Does Ileus Represent the Forgotten End Organ Failure in Critical Illness?

PURPOSE OF REVIEW: This review evaluates the current literature on ileus, impaired gastrointestinal transit (IGT), and acute gastrointestinal injury (AGI) and its impact on multiple organ dysfunction syndrome. RECENT FINDINGS: Ileus is often under recognized in critically ill patients and is associated with significant morbidity and is potentially a marker of disease severity as seen in other organs like kidneys (ATN).

Transitions of care from the womb to the world: Implementation of inpatient neonatal med rec.

BACKGROUND: Medication use during pregnancy is common. Safety of fetal medication exposures is an important consideration for pregnancy and for pharmacologic management and care of newborns. OBJECTIVES: The objective of this study was to describe the impact of implementing a neonatal medication reconciliation service at an acute-care hospital. PRACTICE DESCRIPTION: A neonatal medication reconciliation process was implemented at the University of New Mexico Hospital, a level 4 maternity center in a 500-bed academic medical center. Pharmacy personnel identified inpatient pregnant and postpartum patients who required medication reconciliation. In addition to performing maternal medication reconciliation, clinically significant medication exposures that occurred during pregnancy were recorded for neonates. PRACTICE INNOVATION: Our neonatal medication reconciliation process evaluated prenatal "medication use" via a maternal medication history. We considered our medication reconciliation to be occurring during a "transition" from in utero to being born, which, to the best of our knowledge, has not been commonly reported as a transition of care in which pharmacists may play a role. EVALUATION METHODS: We conducted a retrospective descriptive chart review of patients who had both maternal and neonatal medication reconciliation services performed. We collected demographics, comorbidities, medications, and clinically significant exposures from the medication reconciliation note. RESULTS: A total of 384 charts were included in the final analysis. Of these, 167 medication reconciliations (43.5%) identified at least one medication history problem and 97 medication histories (25.3%) identified at least one potentially clinically significant neonatal medication exposure. PRACTICE IMPLICATIONS: Although several limitations exist, a neonatal medication reconciliation process can be implemented in any inpatient setting with pharmacy staff available to perform and record reconciliation. CONCLUSION: Opportunities for pharmacist involvement in pregnancy, postpartum, and neonatal care are expected to increase. Further research is warranted to more clearly determine the maternal and neonatal benefits of this medication reconciliation process and to link fetal exposures to outcomes.

Enriched East Asian oxygen isotope of precipitation indicates reduced summer seasonality in regional climate and westerlies.

Speleothem oxygen isotope records over East Asia reveal apparently large and rapid paleoclimate changes over the last several hundred thousand years. However, what the isotopic variation actually represent in terms of the regional climate and circulation is debated. We present an answer that emerges from an analysis of the interannual variation in amount-weighted annual δ18O of precipitation over East Asia as simulated by an isotope-enabled model constrained by large-scale atmospheric reanalysis fields. 18O-enriched years have reduced summer seasonality both in terms of precipitation isotopes and in the large-scale circulation. Changes occur between June and October, where the δ18O of precipitation (δ18Op) transitions from the isotopically heavier winter to the lighter summer regime. For 18O-enriched years, this transition is less pronounced. Variations in precipitation amount alone are insufficient to explain the amount-weighted annual δ18Op between 18O-enriched and 18O-depleted years. Reduced summer seasonality is also expressed in the low-level monsoonal southerlies and upper-level westerlies; for the latter, the northward migration across the Tibetan Plateau in the summer is less pronounced. Our result thus implicates the westerlies across the plateau as the proximate cause of East Asian paleomonsoon changes, manifested as a modulation of its summer peak.

Severity of neonatal opioid withdrawal syndrome with prenatal exposure to serotonin reuptake inhibitors.

OBJECTIVE: To evaluate the severity of neonatal opioid withdrawal syndrome (NOWS) in infants prenatally exposed to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). METHODS: A prospective cohort included 148 maternal-infant pairs categorized into MOUD (n = 127) and MOUD + SRI (n = 27) groups. NOWS severity was operationalized as the infant's need for pharmacologic treatment with opioids, duration of hospitalization, and duration of treatment. The association between prenatal SRI exposure and the need for pharmacologic treatment (logistic regression), time-to-discharge, and time-to-treatment discontinuation (Cox proportional hazards modeling) was examined after adjusting for the type of maternal MOUD, use of hydroxyzine, other opioids, benzodiazepines/sedatives, alcohol, tobacco, marijuana, gestational age, and breastfeeding. RESULTS: Infants in the MOUD + SRI group were more likely to receive pharmacologic treatment for NOWS (OR = 3.58; 95% CI: 1.31; 9.76) and had a longer hospitalization (median: 11 vs. 6 days; HR = 0.54; 95% CI: 0.33; 0.89) compared to the MOUD group. With respect to time-to-treatment discontinuation, no association was observed in infants who received treatment (HR = 0.59; 95% CI: 0.26, 1.32); however, significant differences were observed in the entire sample (HR = 0.55; 95% CI: 0.34, 0.89). CONCLUSIONS: Use of SRIs among pregnant women on MOUD might be associated with more severe NOWS. IMPACT: A potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin has been hypothesized but not carefully evaluated in clinical studies. Results of this prospective cohort indicate that the use of SRIs among pregnant women on MOUD is associated with more severe neonatal opioid withdrawal syndrome. This is the first prospective study which carefully examined effect modification between the type of maternal MOUD and SRI use on neonatal outcomes. This report lays the foundation for treatment optimization in pregnant women with co-occurring mental health and substance use disorders.

Phase II clinical trial of cabozantinib for the treatment of recurrent hepatocellular carcinoma after liver transplantation.

Recurrent hepatocellular carcinoma (HCC) develops in 15-20% of liver transplant recipients, and it tends to be more aggressive due to underlying immunosuppression. The multikinase inhibitor cabozantinib has been shown to be effective for the treatment of advanced HCC. However, there is no study evaluating this medication in patients with recurrent HCC. Adult patients with measurable biopsy-proven recurrent HCC are eligible for enrollment provided they are not amenable to curative treatments and no prior treatment with cabozantinib. In this study, 60 mg once daily cabozantinib will be administered orally. Participants will receive study treatment as long as they continue to experience clinical benefit or until there is unacceptable toxicity. Tumor measurements will be repeated every 8 weeks to evaluate response. The primary end point of this study will be the disease control rate at 4 months after treatment. The secondary end points will be overall survival, progression-free survival and safety profile of cabozantinib. Furthermore, potential biomarkers will be evaluated to identify their role in tumor progression. The total duration of this trial is expected to be 3 years. We anticipate that this trial will show the effectiveness and safety of cabozantinib in the treatment of post-liver transplant recurrent HCC. Cabozantinib is expected to be an effective treatment due to its activity against many protein kinases, including MET and AXL which are not inhibited by sorafenib.

Liver cancer is the sixth most diagnosed cancer worldwide with few available curative treatments. Liver transplantation (LT) is considered as one of the treatments for liver cancer especially in earlier stages of cancer. However, after LT, cancer develops again in 15­20% of the patients who undergo transplant for liver cancer. Compared with liver cancer in the nontransplant population, recurrent cancer grows faster and spreads in the body very quickly. Therefore, unfortunately, to date there are limited treatment options for these patients without significant effect on their survival. In this study, we aim to evaluate the effect of a new medication called cabozantinib on patients who develop recurrent liver cancer after their LT. Cabozantinib has been already tested in patients with liver cancer and was shown to be effective and safe in nontransplant patients. However, this is the first study to evaluate the effect of cabozantinib in liver transplant recipients with recurrent liver cancer. Clinical Trial Registration: NCT04204850 (ClinicalTrials.gov).

Photobiomodulation as an Adjunctive Treatment to Physiotherapy for Reduction of Anterior Knee Pain in Combat Soldiers: A Prospective, Double-Blind, Randomized, Pragmatic, Sham-Controlled Trial.

BACKGROUND AND OBJECTIVES: Anterior knee pain (AKP) is the most common knee pathology in athletes and occurs in 15% of army recruits of elite units during basic training. Of these, 50% are symptomatic 6 years later. Photobiomodulation (PBM) is a nonthermal red-to-near-infrared irradiation used for pain reduction of a variety of etiologies. This study was designed to determine whether addition of PBM to physiotherapy (PT) for AKP in combat soldiers is superior to PT alone. STUDY DESIGN/MATERIALS AND METHODS: In this prospective, double-blind, sham-controlled, randomized clinical trial (NCT02845869), 26 combat soldiers/policemen (male:female, 15:11; body mass index [BMI] = 24.2 ± 3.9, n = 46 knees), with AKP due to overuse/load, received 4 weeks of PT + sham (PT + Sham) or active PBM (wavelength = 660 and 850 nm, pulsing = 2.5 Hz, LED power = 50 mW/cm2 [local tissue/regional lymph nodes]; 810 nm continuous beam, laser cluster 6 W/cm2 [analgesia] and laser pointer 4.75 W/cm2 [trigger points]) (PT + PBM). The main outcome measures were subjective pain by visual analog scale (VAS) (0 [none]-100 [intolerable]) and functional disability by Kujala score (0 [worst]-100 [best]). Evaluations were carried out at baseline, end of treatments, and 3-month follow-up. RESULTS: All participants completed the treatment protocol without any reported adverse device effects. Post-treatment pain was significantly reduced in the PT+PBM group, compared with baseline and sham (Δpain, VAS, mean ± SD: PT + PBM = -19 ± 23, P = 0.002; PT + Sham = -6 ± 21, P = 0.16; between groups, P = 0.032). At 3-month follow-up, pain reduction was similar between groups; however, the Kujala score was significantly improved only in the PBM-treated group (ΔKujala: PT + PBM = 11 ± 10, P = 0.003; PT + Sham = 5 ± 7, P = 0.059). CONCLUSIONS: Addition of PBM to PT for AKP resulted in earlier reduction in pain and improved functionality, compared with PT alone. This noninvasive, nonpharmacologic, adjunctive therapeutic modality can be easily incorporated into team healthcare frameworks or end units and may lead to earlier return to competition or combat-level service. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Reduce Patient Treatment wait time in a Proton Beam Facility - A Gatekeeper Approach.

Patient wait time can negatively impact treatment quality in a proton therapy center, where multiple treatment rooms share one proton beam. Wait time increases patient discomfort that can lead to patient motion, dissatisfaction, and longer treatment delay. This study was to develop a patient call-back model that reduced patient wait while efficiently utilizing the proton beam. A "Gatekeeper" logic allowing therapists to adjust the time of a patient's call-back to the treatment room was developed. It uses a two-pronged approach to minimize overlap of long treatment and the possibility of excessive wait in the queue to receive the proton beam. The goal was to reduce the maximum wait time to less than eight minutes per field for a four-room facility. The effectiveness of this logic was evaluated through simulation, and five scenarios were compared. Four scenarios implementing various levels of gatekeeper logic were compared with the original scenario without the logic. The best performing model provided a reduction of the maximum field wait by 26% and met the predefined goal. Adjusting call-back extended the treatment day length by an average of 6 min and a maximum of 12 min in total. The use of this gatekeeper logic significantly reduces patient field wait with minimal impact on treatment day length for a four-room proton facility. A sample interface that adopts this logic for therapists to make informed decision on patient call-back time is demonstrated.

Identification and characterization of differentially expressed genes in Caenorhabditis elegans in response to pathogenic and nonpathogenic Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes infection in immunocompromised patients. S. maltophilia isolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of the Stenotrophomonas genus are part of the native microbiome of C. elegans, being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate within C. elegans. Thus, study of the C. elegans-Stenotrophomonas interaction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed the C. elegans transcriptomic response to S. maltophilia strains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. RESULTS: Overall, we found 145 genes that are commonly differentially expressed in response to pathogenic S. maltophilia strains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences in C. elegans survival in response to at least one S. maltophilia strain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. CONCLUSIONS: Variation in observed pathogenicity and differences in host transcriptional responses to S. maltophilia strains reveal that strain-specific mechanisms play important roles in S. maltophilia pathogenesis. Furthermore, utilizing bacteria closely related to strains found in C. elegans natural environment provides a more realistic interaction for understanding host-pathogen response.

AAPM medical physics practice guideline 7.a.: Supervision of medical physicist assistants.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee May 28, 2019.

Association of two BRM promoter polymorphisms and smoking status with malignant pleural mesothelioma risk and prognosis.

Brahma (BRM), of the SWI/SNF complex, has two 6 to 7 bp insertion promoter polymorphisms (BRM-741/BRM-1321) that cause epigenetic BRM suppression, and are associated with risk of multiple cancers. BRM polymorphisms were genotyped in malignant pleural mesothelioma (MPM) cases and asbestos-exposed controls. Multivariable logistic regression (risk) and Cox regression (prognosis) were performed, including stratified analyses by smoking status to investigate the effect of polymorphisms on MPM risk and prognosis. Although there was no significant association overall between BRM-741/BRM-1321 and risk in patients with MPM, a differential effect by smoking status was observed (P-interaction < .001), where homozygous variants were protective (aOR of 0.18-0.28) in ever smokers, while never smokers had increased risk when carrying homozygous variants (aOR of 2.7-4.4). While there was no association between BRM polymorphisms and OS in ever-smokers, the aHR of carrying homozygous-variants of BRM-741, BRM-1321 or both were 4.0 to 8.6 in never-smokers when compared to wild-type carriers. Mechanistically, lower mRNA expression of BRM was associated with poorer general cancer prognosis. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (ChIP) revealed high BRM insertion variant homology to MEF2 regulatory binding sites. ChIP experimentation confirmed MEF2 binding only occurs in the presence of insertion variants. DNA-affinity purification assays revealed YWHA scaffold proteins as vital to BRM mRNA expression. Never-smokers who carry BRM homozygous variants have an increased chance of developing MPM, which results in worse prognosis. In contrast, in ever-smokers, there may be a protective effect, with no difference in overall survival. Mechanisms for the interaction between BRM and smoking require further study.

Optimization of motion management parameters in a synchrotron-based spot scanning system.

PURPOSE: To quantify the effects of combining layer-based repainting and respiratory gating as a strategy to mitigate the dosimetric degradation caused by the interplay effect between a moving target and dynamic spot-scanning proton delivery. METHODS: An analytic routine modeled three-dimensional dose distributions of pencil-beam proton plans delivered to a moving target. Spot positions and weights were established for a single field to deliver 100 cGy to a static, 15-cm deep, 3-cm radius spherical clinical target volume with a 1-cm isotropic internal target volume expansion. The interplay effect was studied by modeling proton delivery from a clinical synchrotron-based spot scanning system and respiratory target motion, patterned from surrogate patient breathing traces. Motion both parallel and orthogonal to the beam scanning direction was investigated. Repainting was modeled using a layer-based technique. For each of 13 patient breathing traces, the dose from 20 distinct delivery schemes (combinations of four gate window amplitudes and five repainting techniques) was computed. Delivery strategies were inter-compared based on target coverage, dose homogeneity, high dose spillage, and delivery time. RESULTS: Notable degradation and variability in plan quality were observed for ungated delivery. Decreasing the gate window reduced this variability and improved plan quality at the expense of longer delivery times. Dose deviations were substantially greater for motion orthogonal to the scan direction when compared with parallel motion. Repainting coupled with gating was effective at partially restoring dosimetric coverage at only a fraction of the delivery time increase associated with very small gate windows alone. Trends for orthogonal motion were similar, but more complicated, due to the increased severity of the interplay. CONCLUSIONS: Layer-based repainting helps suppress the interplay effect from intra-gate motion, with only a modest penalty in delivery time. The magnitude of the improvement in target coverage is strongly influenced by individual patient breathing patterns and the tumor motion trajectory.

Clinical implementation of respiratory-gated spot-scanning proton therapy: An efficiency analysis of active motion management.

PURPOSE: The aim of this work is to describe the clinical implementation of respiratory-gated spot-scanning proton therapy (SSPT) for the treatment of thoracic and abdominal moving targets. The experience of our institution is summarized, from initial acceptance and commissioning tests to the development of standard clinical operating procedures for simulation, motion assessment, motion mitigation, treatment planning, and gated SSPT treatment delivery. MATERIALS AND METHODS: A custom respiratory gating interface incorporating the Real-Time Position Management System (RPM, Varian Medical Systems, Inc., Palo Alto, CA, USA) was developed in-house for our synchrotron-based delivery system. To assess gating performance, a motion phantom and radiochromic films were used to compare gated vs nongated delivery. Site-specific treatment planning protocols and conservative motion cutoffs were developed, allowing for free-breathing (FB), breath-holding (BH), or phase-gating (Ph-G). Room usage efficiency of BH and Ph-G treatments was retrospectively evaluated using beam delivery data retrieved from our record and verify system and DICOM files from patient-specific quality assurance (QA) procedures. RESULTS: More than 70 patients were treated using active motion management between the launch of our motion mitigation program in October 2015 and the end date of data collection of this study in January 2018. During acceptance procedures, we found that overall system latency is clinically-suitable for Ph-G. Regarding room usage efficiency, the average number of energy layers delivered per minute was <10 for Ph-G, 10-15 for BH and ≥15 for FB, making Ph-G the slowest treatment modality. When comparing to continuous delivery measured during pretreatment QA procedures, the median values of BH treatment time were extended from 6.6 to 9.3 min (+48%). Ph-G treatments were extended from 7.3 to 13.0 min (+82%). CONCLUSIONS: Active motion management has been crucial to the overall success of our SSPT program. Nevertheless, our conservative approach has come with an efficiency cost that is more noticeable in Ph-G treatments and should be considered in decision-making.

Multiple Regions of Interest on Multiparametric Magnetic Resonance Imaging are Not Associated with Increased Detection of Clinically Significant Prostate Cancer on Fusion Biopsy.

PURPOSE: We sought to determine the association between multiple regions of interest on prebiopsy magnetic resonance imaging and the detection of clinically significant prostate cancer in men undergoing magnetic resonance imaging-ultrasound fusion biopsy. MATERIALS AND METHODS: We performed a retrospective, single institution analysis of men who underwent fusion biopsy. Men with prior positive biopsies, magnetic resonance imaging performed elsewhere and/or magnetic resonance imaging prior to release of the PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 were excluded from study, resulting in 381 participants. Modeled independent variables included patient age, number of regions of interest with a PI-RADS categorization of 3 or greater, body mass index, prostate specific antigen, prostate volume and PI-RADS categorization. Multivariable logistic regression was performed to determine factors associated with finding clinically significant prostate cancer (Gleason 7 or greater) on biopsy. RESULTS: Median age was 67.2 years (IQR (61.6-73.0) and median prostate specific antigen was 6.6 ng/ml (5.0-10.0). Adjusted analysis demonstrated that age (OR 1.10, 95% CI 1.06-1.15, p ≤0.001), body mass index (OR 1.08, 95% CI 1.01-1.16, p = 0.038) and prostate specific antigen (OR 1.06, 95% CI 1.01-1.10, p = 0.015) were associated with detection of clinically significant prostate cancer. PI-RADS categories 4 (OR 4.62, 95% CI 2.23-9.33) and 5 (OR 6.75, 95% CI 2.72-16.71, each p <0.001) were associated with greater odds of clinically significant prostate cancer. Multiple regions of interest were not associated with the detection of clinically significant prostate cancer (OR 1.05, 95% CI 0.60-1.84, p = 0.857). CONCLUSIONS: Multiple regions of interest do not portend a greater likelihood of finding clinically significant prostate cancer. Physicians should recognize that multiple regions of interest should not influence the decision to perform fusion biopsy. Our findings may ease patient anxiety concerning these findings.

EUS-guided fine-needle core liver biopsy sampling using a novel 19-gauge needle with modified 1-pass, 1 actuation wet suction technique.

BACKGROUND AND AIMS: EUS-guided fine-needle core biopsy sampling is a safe and effective technique for diagnosis of focal liver lesions. However, data are limited in its role in parenchymal disease. We evaluated the utility of EUS-guided parenchymal liver biopsy sampling with a modified 1-pass wet suction technique (EUS-modified liver biopsy sampling [EUS-MLB]) in patients with unexplained increase in liver-associated tests. METHODS: We retrospectively evaluated the safety and efficacy of EUS-MLB in patients referred for EUS to evaluate for biliary obstruction and pancreatic disorders but with associated unexplained liver tests. EUS-MLB was performed during the same session after biliary obstruction was excluded. RESULTS: One hundred sixty-five consecutive patients underwent EUS-MLB. The median age was 52 years (interquartile range [IQR], 42-65). Sixty-eight patients (41%) were men. The median of the maximum intact core tissue length was 2.4 cm (IQR, 1.8-3.5). The median total specimen length (TSL) was 6 cm (IQR, 4.3-8). The median number of complete portal tracts (CPTs) per TSL was 18 (IQR, 13- 24). The mean number of CPTs per sample length was 7.5 cm. Adverse events were uncommon (1.8%) and included abdominal pain and self-limited hematoma. CONCLUSIONS: EUS-guided fine-needle biopsy sampling using a novel 19-gauge core needle with a modified 1-pass 1 actuation wet suction technique (EUS-MLB) is a safe and effective way to evaluate patients with unexplained liver tests abnormalities who are undergoing EUS for exclusion of biliary obstruction.

Effects of RN Age and Experience on Transformational Leadership Practices.

OBJECTIVE: This study reported the evolution of transformational leadership (TL) practices and behaviors across years of age, management experience, and professional nursing practice within a professional nursing leadership organization. BACKGROUND: Recent studies of CNO TL found valuations peak near age 60 years. This study reported on a wider range of management positions, correlating years of RN practice and management experience and age to TL metrics. METHOD: This study used Kouzes and Posner's Leadership Practices Inventory-Self-Assessment (LPI-S) to survey a nursing leadership organization, the Association of California Nurse Leaders (ACNL). Anonymous responses were analyzed to identify leadership trends in age and years of professional service. RESULTS: On average, LPI-S metrics of leadership skills advance through years of management, RN experience, and age. The TL scores are statistically higher in most LPI-S categories for those with more than 30 years of RN or management experience. Decade-averaged LPI-S TL metrics in the ACNL survey evolve linearly throughout age before peaking in the decade from age 60 to 69 years. A similar evolution of TL metrics is seen in decades of either years of management experience or years of RN experience. Transformational leadership increased with nursing maturity particularly for LPI-S categories of "inspire a shared vision," "challenge the process," and "enable others to act." CONCLUSION: In the ACNL population studied, decade-averaged leadership metrics advanced. Leadership evolution with age in the broader RN population peaked in age bracket 60 to 69 years. The LPI-S averages declined when older than 70 years, coinciding with a shift from full-time work toward retirement and part-time employment.

A Stenotrophomonas maltophilia Strain Evades a Major Caenorhabditis elegans Defense Pathway.

Stenotrophomonas maltophilia is a ubiquitous bacterium and an emerging nosocomial pathogen. This bacterium is resistant to many antibiotics, associated with a number of infections, and a significant health risk, especially for immunocompromised patients. Given that Caenorhabditis elegans shares many conserved genetic pathways and pathway components with higher organisms, the study of its interaction with bacterial pathogens has biomedical implications. S. maltophilia has been isolated in association with nematodes from grassland soils, and it is likely that C. elegans encounters this bacterium in nature. We found that a local S. maltophilia isolate, JCMS, is more virulent than the other S. maltophilia isolates (R551-3 and K279a) tested. JCMS virulence correlates with intestinal distension and bacterial accumulation and requires the bacteria to be alive. Many of the conserved innate immune pathways that serve to protect C. elegans from various pathogenic bacteria also play a role in combating S. maltophilia JCMS. However, S. maltophilia JCMS is virulent to normally pathogen-resistant DAF-2/16 insulin-like signaling pathway mutants. Furthermore, several insulin-like signaling effector genes were not significantly differentially expressed between S. maltophilia JCMS and avirulent bacteria (Escherichia coli OP50). Taken together, these findings suggest that S. maltophilia JCMS evades the pathogen resistance conferred by the loss of DAF-2/16 pathway components. In summary, we have discovered a novel host-pathogen interaction between C. elegans and S. maltophilia and established a new animal model with which to study the mode of action of this emerging nosocomial pathogen.

Elective neck management for squamous cell carcinoma metastatic to the parotid area lymph nodes.

The objective of this study is to determine if radiotherapy (RT) alone to the cervical lymphatics is a suitable alternative to elective neck dissection (END) in patients who undergo parotidectomy and postoperative RT for squamous cell carcinoma metastatic to the parotid area lymph nodes (PALN). We retrospectively reviewed the medical records of 107 patients consecutively treated from November 1969 to March 2012 for cutaneous squamous cell carcinoma metastatic to the PALN with a clinically node-negative neck. Primary therapy consisted of parotidectomy in all cases. We compared regional (cervical) control in two subgroups: 42 patients treated with END and RT and 65 patients treated with elective neck irradiation (ENI) alone. The median time of follow-up was 5.5 years (range 0.3-30 years) for all patients and 11 years for living patients (range 1.8-26 years). There was 1 neck recurrence in each subgroup: END and RT, 1/42 (2 %); and ENI alone, 1/65 (1.5 %). No patient experienced a complication related to neck RT. ENI to a dose of approximately 50-60 Gy is a suitable alternative to END and postoperative RT in patients with squamous cell carcinoma metastatic to the PALN.

Radiotherapy alone or combined with chemotherapy as definitive treatment for squamous cell carcinoma of the tonsil.

This study is aimed at updating our institution's experience with definitive radiotherapy (RT) for squamous cell carcinoma of the tonsil. We reviewed 531 patients treated between 1983 and 2012 with definitive RT for squamous cell carcinoma of the tonsil. Of these, 179 patients were treated with either induction (n = 19) or concomitant (n = 160) chemotherapy. Planned neck dissection was performed on 217 patients: unilaterally in 199 and bilaterally in 18 patients. Median follow-up was 5.2 years for all patients (range 0.1-31.6 years) and 8.2 years for living patients (range 1.9-31.6 years). The 5-year local control rates by T stage were as follows: T1, 94 %; T2, 87 %; T3 79 %; T4, 70 %; and overall, 83 %. Multivariate analysis revealed that local control was significantly influenced by T stage and neck dissection. The 5-year cause-specific survival rates by overall stage were as follows: I, 94 %; II, 88 %; III, 87 %; IVA, 75 %; IVB, 52 %; and overall, 78 %. Multivariate analysis revealed that cause-specific survival was significantly influenced by T stage, N stage, overall stage, fractionation, neck dissection, sex, and ethnicity. Of 77 patients treated with ipsilateral fields only, contralateral neck failure occurred in 1 %. The rate of severe complications was 12 %. Definitive RT for patients with tonsillar squamous cell carcinoma provides control rates equivalent to other modalities with a comparatively low incidence of late complications. Patients with anterior tonsillar pillar or tonsillar fossa primaries that are well lateralized with no base of tongue or soft palate extension may be treated with ipsilateral fields.

Ipsilateral radiotherapy for squamous cell carcinoma of the tonsil.

The purpose of this study is to update our institution's experience with ipsilateral radiation therapy (RT) for squamous cell carcinoma of the tonsillar area. Outcome study of 76 patients treated between 1984 and 2012 with ipsilateral RT for squamous cell carcinoma of the tonsil. Patients had either cT1 (n = 41, 54 %) or cT2 (n = 35, 46 %) primaries and cN0 (n = 27, 36 %), cN1 (n = 15, 20 %), cN2a (n = 8, 11 %), or cN2b (n = 26, 34 %) nodal disease. Of these, 32 (42 %) patients underwent a planned neck dissection and 21 (28 %) patients received concomitant chemotherapy. Median follow-up for all patients was 7.1 years (range 0.1-27.2) and 7.8 years (range 2.1-27.2 years) for living patients. The 2- and 5-year control and survival rates were as follows: local control, 98.6 and 96.9 %; local-regional control 95.8 and 92.6 %; cause-specific survival 95.9 and 93.1 %; and overall survival, 92.1 and 83.8 %. One patient failed in the contralateral, non-radiated neck 3 years after primary treatment. Univariate analysis revealed that overall survival was significantly influenced by whether the patient had a primary tumor in the anterior tonsillar pillar versus the tonsillar fossa with the latter performing better. The incidence of severe late complications was 16 %. Ipsilateral RT for patients with squamous cell carcinoma of the anterior tonsillar pillar or tonsillar fossa with no base of tongue or soft palate extension is an efficacious treatment that provides excellent control rates with a relatively low incidence of late complications.

Treatment planning for metals using an extended CT number scale.

Metal implants which saturate the CT number scale may require dosimetrist and physicist involvement to manually contour and assign an appropriate value to the metal for accurate dose calculation. This study investigated dose calculation based directly on extended CT scale images for different metals and geometries. The aim was to evaluate extended CT accuracy as a suitable alternative to standard CT methods in the presence of high-Z materials and artifacts, despite the reduced HU resolution of extended CT. Gafchromic film measurements were made for comparison to calculated doses. The method of direct dose calculation on extended CT scale was compared to our institution's standard method of manually contouring and assigning metal values on saturated CT images for each of the metal samples. Clinical patient plans with metal implants were investigated and DVHs were compared between standard CT and extended CT dose calculations. Dose calculations showed agreement within 2% between the two methods of metal characterization and the film measurement in the case of the strongest metal attenuator, cobalt-chromium. In the clinical treatment plans, the greatest dose discrepancy between the two methods was 1.2%. This study suggests that direct dose calculation on an extended scale CT image in the presence of metal implants can produce accurate clinically viable treatment plans, thereby improving efficiency of clinical workflow and eliminating a potential source of human error by manual CT number assignment.