Neurosurgical therapy possibilities in treatment of Huntington disease: An update.

INTRODUCTION: Huntington's disease (HD) is a hereditary condition caused by the expansion of the CAG trinucleotide in the huntingtin gene on chromosome 4, resulting in motor, cognitive, and psychiatric disorders that significantly impact patients' quality of life. Despite the lack of effective treatments for the disease, various surgical strategies have been explored to alleviate symptoms and slow its progression. METHODOLOGY: A comprehensive systematic literature review was conducted, including MeSH terms, yielding only 38 articles that were categorized based on the surgical procedure. The study aimed to describe the types of surgeries performed and their efficacy in HD patients. RESULTS: Deep brain stimulation (DBS) involved 41 predominantly male patients with bilateral implantation in the globus pallidus, showing a preoperative Unified Huntington's Disease Rating Scale (UHDRS) score of 60.25 ± 16.13 and a marked postoperative value of 48.54 ± 13.93 with a p < 0.018 at one year and p < 0.040 at three years. Patients experienced improvement in hyperkinesia but worsening of bradykinesia. Additionally, cell transplantation in 119 patients resulted in a lower preoperative UHDRS score of 34.61 ± 14.61 and a significant postoperative difference of 32.93 ± 15.87 (p < 0.016), respectively, in the first to third years of following. Some now, less used procedures were crucial for understanding brain function, such as pallidotomies in 3 patients, showing only a 25 % difference from their baseline. CONCLUSION: Despite advancements in technology, there is still no curative treatment, only palliative options. Promising treatments like trophic factor implantation offer new prospects for the future.

Immune response of DNA vaccinated-gilthead seabream (Sparus aurata) against LCDV-Sa infection: relevance of the inflammatory process.

Lymphocystis disease is one of the main viral pathologies affecting cultured gilthead seabream (Sparus aurata) in the Mediterranean region. Recently, we have developed a DNA vaccine based on the major capsid protein (MCP) of the Lymphocystis disease virus 3 (LCDV-Sa). The immune response triggered by either LCDV-Sa infection or vaccination have been previously studied and seem to be highly related to the modulation of the inflammatory and the IFN response. However, a comprehensive evaluation of immune-related gene expression in vaccinated fish after viral infection to identify immunogenes involved in vaccine-induced protection have not been carried out to date. The present study aimed to fulfill this objective by analyzing samples of head-kidney, spleen, intestine, and caudal fin from fish using an OpenArray® platform containing targets related to the immune response of gilthead seabream. The results obtained showed an increase of deregulated genes in the hematopoietic organs between vaccinated and non-vaccinated fish. However, in the intestine and fin, the results showed the opposite trend. The global effect of fish vaccination was a significant decrease (p<0.05) of viral replication in groups of fish previously vaccinated, and the expression of the following immune genes related to viral recognition (tlr9), humoral and cellular response (rag1 and cd48), inflammation (csf1r, elam, il1ß, and il6), antiviral response (isg15, mx1, mx2, mx3), cell-mediated cytotoxicity (nccrp1), and apoptosis (prf1). The exclusive modulation of the immune response provoked by the vaccination seems to control the progression of the infection in the experimentally challenged gilthead seabream.

A global phylogenomic analysis of the shiitake genus Lentinula.

Lentinula is a broadly distributed group of fungi that contains the cultivated shiitake mushroom, L. edodes. We sequenced 24 genomes representing eight described species and several unnamed lineages of Lentinula from 15 countries on four continents. Lentinula comprises four major clades that arose in the Oligocene, three in the Americas and one in Asia-Australasia. To expand sampling of shiitake mushrooms, we assembled 60 genomes of L. edodes from China that were previously published as raw Illumina reads and added them to our dataset. Lentinula edodes sensu lato (s. lat.) contains three lineages that may warrant recognition as species, one including a single isolate from Nepal that is the sister group to the rest of L. edodes s. lat., a second with 20 cultivars and 12 wild isolates from China, Japan, Korea, and the Russian Far East, and a third with 28 wild isolates from China, Thailand, and Vietnam. Two additional lineages in China have arisen by hybridization among the second and third groups. Genes encoding cysteine sulfoxide lyase (lecsl) and γ-glutamyl transpeptidase (leggt), which are implicated in biosynthesis of the organosulfur flavor compound lenthionine, have diversified in Lentinula. Paralogs of both genes that are unique to Lentinula (lecsl 3 and leggt 5b) are coordinately up-regulated in fruiting bodies of L. edodes. The pangenome of L. edodes s. lat. contains 20,308 groups of orthologous genes, but only 6,438 orthogroups (32%) are shared among all strains, whereas 3,444 orthogroups (17%) are found only in wild populations, which should be targeted for conservation.

A Multicenter Study of 2-year Outcomes Following Hyperthermia Therapy with Mitomycin C in Treating Non-Muscle Invasive Bladder Cancer: HIVEC-E.

INTRODUCTION: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette-Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC. OBJECTIVE: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC. METHODS: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT. RESULTS AND LIMITATIONS: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 -35.8). Median age was 70.4 years (IQR: 62.1 -78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% -60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients. CONCLUSIONS: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile.

Therapeutic drug monitoring of nivolumab in routine clinical practice. A pilot study.

OBJECTIVE: A review of the literature about the anti-programmed death 1 monoclonal antibody nivolumab permits to verify the existence  of several issues still unresolved about their dosing schedule. The aim of the present work was to explore possibilities of nivolumab treatment  personalization through therapeutic drug monitoring, in order to  improve their effectiveness and efficiency. METHOD: Observational, prospective study carried out from May 2017  through June 2019 in patients with different tumor diagnoses treated with nivolumab. Blood samples were obtained in the routine  clinical practice, once nivolumab steady state was reached. Serum  nivolumab levels were determined by means of quantitative ELISA. The  standard schedule of 3 mg/kg every two weeks (Q2W) was modified in  some patients due to different circumstances, and resulting serum  concentrations were compared with those from the non-modified  patients and the published data. RESULTS: Blood samples from 19 patients in treatment with nivolumab were analyzed. A total of 39 samples of nivolumab were  analyzed between 6th and 27th cycles. The standard schedule of 3  mg/kg every two weeks was modified in 12/19 (60%) patients, with  intervals of 3, 4, 5, 6 or 7 weeks, once the steady state was reached.  No statistically significant differences were detected when comparing  every two weeks and every four week intervals. When the intervals  were six or seven weeks, mean plasma concentration showed a  statistically significant difference compared with every two weeks. CONCLUSIONS: Current data contribute to confirm former suspects about the possibilities of exploring new scenarios to improve and  personalize nivolumab dosage. Additional studies to confirm it in bigger  series and correlate it with clinical results, and to better define the role  of therapeutic drug monitoring in the treatment, are warranted, not only by financial concerns but also for improving quality of life of patients  and clinical management aspects.

Objetivo: Una revisión de la literatura sobre nivolumab permite  verificar la existencia de diversos aspectos sin resolver sobre su  intervalo de dosificación. El objetivo del presente estudio ha sido  explorar las posibilidades de personalización del tratamiento con  nivolumab mediante la monitorización terapéutica de sus  concentraciones séricas para mejorar su efectividad y eficiencia.Método: Estudio observacional, prospectivo, realizado entre mayo de 2017 y junio de 2019 en pacientes tratados con nivolumab que  estaban diagnosticados de diferentes tumores. Se obtuvieron muestras  de sangre en la práctica clínica habitual, una vez alcanzado el estado de  equilibrio de nivolumab. Las concentraciones séricas de nivolumab  fueron determinadas mediante ELISA cuantitativo. La pauta posológica  habitual de 3 mg/kg cada dos semanas tuvo que ser modificada en  algunos pacientes debido a diferentes circunstancias, y las  concentraciones séricas resultantes se compararon con las  correspondientes a los pacientes en los que no se modificó y con datos  publicados.Resultados: Se analizaron muestras de 19 pacientes que recibieron inicialmente 3 mg/kg de nivolumab cada dos semanas. Se  analizó un total de 39 muestras, entre los ciclos 6 y 27. La pauta  habitual se modificó, una vez alcanzado el estado de equilibrio, en  12/19 (60%) pacientes, en los que se amplió el intervalo a 3, 4, 5, 6 o 7 semanas. No se encontraron diferencias estadísticamente significativas  al comparar la administración cada dos semanas y cada cuatro  semanas. Cuando los intervalos fueron de seis o siete semanas, la  concentración sérica media mostró una diferencia estadísticamente  significativa en comparación con la administración cada dos semanas.Conclusiones: La información recogida parece confirmar la necesidad de explorar nuevos escenarios para personalizar la  dosificación de nivolumab. Se necesitan estudios adicionales en series  de mayor tamaño para confirmar esta información, correlacionarla con  los resultados clínicos y definir mejor el papel de la monitorización  terapéutica, no solo por motivos económicos, sino también para mejorar  la calidad de vida de los pacientes y facilitar la administración  clínica del tratamiento.

A mobile device application (app) to improve adherence to an enhanced recovery program for colorectal surgery: a randomized controlled trial.

BACKGROUND: Increased adherence with enhanced recovery pathways (ERP) is associated with improved outcomes. However, adherence to postoperative elements that rely on patient participation remains suboptimal. Mobile device apps may improve delivery of health education material and have the potential to foster behavior change and improve patient compliance. The objective of this study was to estimate the extent to which a novel mobile device app affects adherence to an ERP for colorectal surgery in comparison to standard written education. METHODS: This was a superiority, parallel-group, assessor-blind, sham-controlled randomized trial involving 97 patients undergoing colorectal resection. Participants were randomly assigned with a 1:1 ratio into one of two groups: (1) iPad including a novel mobile device app for postoperative education and self-assessment of recovery, or (2) iPad without the app. The primary outcome measure was mean adherence (%) to a bundle of five postoperative ERP elements requiring patient participation: mobilization, gastrointestinal motility stimulation, breathing exercises, and consumption of oral liquids and nutritional drinks. RESULTS: In the intervention group, app usage was high (94% completed surveys on POD0, 82% on POD1, 72% on POD2). Mean overall adherence to the bundle on the two first postoperative days was similar between groups: 59% (95% CI 52-66%) in the intervention group and 62% (95% CI 56-68%) in the control group [Adjusted mean difference 2.4% (95% CI - 5 to 10%) p = 0.53]. CONCLUSIONS: In this randomized trial, access to a mobile health application did not improve adherence to a well-established enhanced recovery pathway in colorectal surgery patients, when compared to standard written patient education. Future research should evaluate the impact of applications integrating novel behavioral change techniques, particularly in contexts where adherence is low.

Is there a gender bias in the advancement to SAGES leadership?

BACKGROUND: The proportion of women in surgery has risen significantly yet there remains gender discrepancies in upper leadership positions in academia. Specialty societies play an important role in academic advancement but the progression of women in surgical societies has not been studied. The purpose of this study was to determine if there are gender differences in advancement within the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) leadership. METHODS: A retrospective audit of all SAGES committee members (CM) from 1992 to 2018 was performed. The overall membership gender distribution was available from 2010 to 2018. Leadership positions included Committee Chair/Co-chair, Board of Governors, and Executive Committee. Three phenomena were investigated: "pipeline," by determining the change in women CMs compared to overall membership over time; "sticky floors," by comparing advancement beyond CM by gender; "glass-ceiling," by analyzing the promotion trajectory and time to leadership positions between genders. Statistical analysis comparing trends over time was performed using Kendall-tau. RESULTS: There were 1546 surgeons who served on at least one committee during the study period. Women represented 21% of CMs, 18% of chairs/co-chairs, 16% of board members and 14% of executives, with one woman President. The proportion of women CMs has significantly increased over time from 3% in 1992 to 27% in 2018 (p-trend < 0.001). A similar proportion of women and men advanced beyond CM (17% vs. 14%, p = 0.194), with no difference in time to advancement. From 2010 to 2018, the increase in the proportion of women CMs and board members outpaced that of overall women members (p < 0.05). Women executives surpassed overall women members in 2018 (29% vs. 19%). A similar proportion of men and women "skipped ranks" to reach the Board/Executive (37% vs. 25%, p = 0.307). CONCLUSION: The proportion of women in leadership positions within SAGES is higher than in the overall membership. There were no gender differences in the advancement of CMs to leadership positions. While these data are encouraging, SAGES should continue to foster the advancement of women surgeons.

Preoperative Exercise Rehabilitation in Cardiac and Vascular Interventions.

BACKGROUND: Exercise-based interventions have become part of the standard of care in rehabilitation programs for cardiovascular risk reduction and the promotion of a healthy lifestyle. The systematic review describes the current state of knowledge of the effects of preoperative exercise training (prehabilitation) on perioperative clinical outcomes in patients undergoing cardiac and vascular interventions. METHODS: Studies were systematically searched within 14 databases from inception to October 2016. Only studies that assessed a preoperative exercise program in adult patients undergoing cardiac or vascular interventions with clinical or patient-centered endpoints were included in the review. Two independent reviewers selected studies for inclusion, extracted data, and assessed quality using Cochrane Collaboration's tool for RCTs11111111111111111 and ROBINS-I tool for nonrandomized studies. RESULTS: Nine studies met our inclusion criteria and were stratified for qualitative analyses by cardiac (n = 7) and vascular (n = 2) procedures. Prehabilitation was associated with decreased length of stay, reduced postoperative complications, improved objective physical functioning, and improved subjective quality of life (SF-36 physical and mental health domains) measures in patients undergoing cardiac and vascular procedures. Given the amount of heterogeneity that was present in the designs, populations, and comparators among the included studies, we were unable to statistically pool data across trials. CONCLUSIONS: Our qualitative findings suggest that prehabilitation may improve clinical outcomes, physical performance, and health-related quality-of-life measures in patients undergoing cardiac and vascular surgery procedures.

Incidence and predictors of prolonged postoperative ileus after colorectal surgery in the context of an enhanced recovery pathway.

BACKGROUND: Prolonged postoperative ileus (PPOI) is common after colorectal surgery but has not been widely studied in the context of enhanced recovery pathways (ERPs) that include interventions aimed to accelerate gastrointestinal recovery. The aim of this study is to estimate the incidence and predictors of PPOI in the context of an ERP for colorectal surgery. METHODS: We analyzed data from an institutional colorectal surgery ERP registry. Incidence of PPOI was estimated according to a definition adapted from Vather (intolerance of solid food and absence of flatus or bowel movement for ≥ 4 days) and compared to other definitions in the literature. Potential risk factors for PPOI were identified from previous studies, and their predictive ability was evaluated using Bayesian model averaging (BMA). Results are presented as posterior effect probability (PEP). Evidence of association was categorized as: no evidence (PEP < 50%), weak evidence (50-75%), positive evidence (75-95%), strong evidence (95-99%), and very strong evidence (> 99%). RESULTS: There were 323 patients analyzed (mean age 63.5 years, 51% males, 74% laparoscopic, 33% rectal resection). The incidence of PPOI was 19% according to the primary definition, but varied between 11 and 59% when using other definitions. On BMA analysis, intraoperative blood loss (PEP 99%; very strong evidence), administration of any intravenous opioids in the first 48 h (PEP 94%; strong evidence), postoperative epidural analgesia (PEP 56%; weak evidence), and non-compliance with intra-operative fluid management protocols (3 ml/kg/h for laparoscopic and 5 ml/kg/h for open; PEP 55%, weak evidence) were predictors of PPOI. CONCLUSIONS: The incidence of PPOI after colorectal surgery is high even within an established ERP and varied considerably by diagnostic criteria, highlighting the need for a consensus definition. The use of intravenous opioids is a modifiable strong predictor of PPOI within an ERP, while the role of epidural analgesia and intraoperative fluid management should be further evaluated.

Neoadjuvant chemohyperthermia: Our experience after 10 years. / Quimiohipertermia neoadyuvante: nuestra experiencia después de 10 años.

Neoadjuvant chemohyperthermia (QHT) with MMC has demonstrated its efficacy in NMIBC both in the level of complete response at the time of TURBT and reduction of recurrences after several years of follow up. We present our experience with this treatment. METHODS: We performed a case control study in a group of 104 patients with middle-high risk NMIBC. 43 of them received neoadjuvant recirculated intravesical QHT and 61 passively administered standard adjuvant MMC. Patient follow up was 43 months (3 - 108) evaluating their clinical efficacy and adverse effects in both groups. RESULTS: After neoadjuvant QHT, 27 patients showed CR (63%), 13 PR (30.2%) and 3 NR (6.9%). 5 year recurrence rate after QHT passive MMC were 16.2% and 26.2% respectively. No patient in the QHT group presented tumor progression compared to 5% progressions in the group treated with MMC at room temperature and 1.6% deaths due to metastatic disease. 94% QHT programmed doses were administered in comparison to 97%in the group of standard MMC. In the QHT group there were 60.5% grade 1-2 AEs in comparison with 49% in the standard MMC group (p<0.4). Likewise, 9.3% cases in the QHT group presented Grade 3 AEs versus 6.5% in the standard MMC (p<0,06). CONCLUSIONS: Recirculating neoadjuvant QHT achieves a reduction in tumor recurrence after 4 years with a similar AE rate in comparison with passive instillation of MMC.

Analysis of tolerance and security of chemo hyperthermia with Mitomycin C for the treatment of non-muscle invasive bladder cancer. / Aálisis de tolerancia y seguridad de la quimiohipertermia con Mitomicina C en el tratamiento del cúncer de vejiga no músculo invasivo.

OBJECTIVES: The treatment of non muscle invasive bladder cancer (NMIBC) continues to be a challenge. Hyperthermia (HT) combined with intravesical chemotherapy is used to enhance the effects of chemotherapy. METHODS: A review of the publications was carried out to synthesize the adverse effects (AE) reported by the use of chemohyperthermia (QHT) with Mitomycin-C (MMC). The most relevant data are exposed for each of the devices currently used in the QHT. RESULTS: SYNERGO®: The dropout rate varied between 3-40%, and the AE rate is up to 88%. The most common AEs were pain (2-40%), thermal reaction of the posterior wall (13-100%), bladder spasms (2-32%), dysuria (3-60%) and hematuria (2-62%). COMBAT BRS®: The dropout rate is 3-11%. The AEs reported were CTCAE Grade 1-2: Pain 13-27%, bladder spasms 6-27%and hematuria 3-20% are the most relevant. In general, CTCAE grade 3-4 toxicity is not reported. UNITHERMIA®: The dropout rate is 7-12%. The AEs described are: Pain 6-23%, bladder spasms 6-23%, hematuria 9-11, frequency 15-25% and allergy 6-11%. The majority of toxicities are CTCAE grade 1-2 (17-53%), with grade 3-4 in 9-15% and Grade 5 in 0-2%. QHT adds little to the AEs of the treatment with MMC. It neither adds severe effects, nor increases dropouts significantly, and does not increase the incidence of allergic reactions. The comparative study between BCG and QHT-MMC, is less likely to present urinary frequency, nocturia, incontinence, hematuria, fever, fatigue and arthralgia in patients in the QHT group. CONCLUSIONS: QHT has proven to be a safe alternative for the treatment of intermediate and high risk NMIBC, with AE mainly grade 1-2. The AEs reported have little variation with respect to the dose of MMC used, presenting different "profiles" related to the device used for its administration. The treatments with QHTMMC are well tolerated, without adding significantly more AE than the instillations of MMC alone and presenting a better toxicity profile than those reflected in the literature with respect to the treatment with BCG.

Incisional Hernia After Midline Versus Transverse Specimen Extraction Incision: A Randomized Trial in Patients Undergoing Laparoscopic Colectomy.

OBJECTIVE: To compare the incidence of incisional hernia (IH) between midline and transverse specimen extraction site in patients undergoing laparoscopic colectomy. BACKGROUND: Midline specimen extraction incision is most commonly used in laparoscopic colectomy, but has high IH risk. IH may be lower for transverse incision. METHODS: A single-center superiority trial was conducted. Eligible patients undergoing laparoscopic colectomy were randomly assigned to midline or transverse specimen extraction. Primary outcome was IH incidence at 1 year. Power calculation required 76 patients per group to detect a reduction in IH from 20% to 5%. Secondary outcomes included perioperative outcomes, pain scores, health-related quality of life (SF-36), and cosmesis (Body Image Questionnaire). RESULTS: A total of 165 patients were randomly assigned to transverse (n = 79) or midline (n = 86) specimen extraction site, of which 141 completed 1-year follow-up (68 transverse, 73 midline). Patient, tumor, surgical data, and perioperative morbidity were similar. Pain scores were similar on each postoperative day. On intention-to-treat analysis, there was no difference in the incidence of IH at 1 year (transverse 2% vs midline 8%, P = 0.065) or after mean 30.3 month (standard deviation 9.4) follow-up (6% vs 14%, P = 0.121). On per-protocol analysis there were more IH after midline incision with longer follow-up (15% vs 2%, P = 0.013). On intention-to-treat analysis, SF-36 domains body pain and social functioning were improved after transverse incision. Cosmesis was higher after midline incision on per-protocol analysis, but without affecting body image. CONCLUSIONS: Per-protocol analysis of this trial demonstrates that a transverse specimen extraction site has a lower incidence of IH compared to midline with longer follow-up but has worse cosmesis.

Predictors of adherence to enhanced recovery pathway elements after laparoscopic colorectal surgery.

INTRODUCTION: Enhanced recovery pathways (ERP) include a bundle of evidence-based preoperative, intraoperative, and postoperative interventions that together reduce morbidity and length of stay after colorectal surgery. Increased adherence with the bundle is associated with better postoperative outcomes, but adherence is lowest in the postoperative period. Identifying risk factors for lower adherence may help design quality improvement strategies. The aim of this study was to estimate the extent to which patient, procedural, and organizational factors predict adherence to postoperative ERP elements in laparoscopic colorectal surgery. METHODS: Patients in an institutional ERP registry undergoing elective laparoscopic colorectal surgery between 2012 and 2014 were analyzed. The ERP included 10 postoperative ERP elements classified into 2 groups: those requiring patient participation (PP, 5 elements, including nutritional intake and mobilization) and those provided by the clinical team (CT, 5 elements, including removal of catheters and type of analgesia). The impact of baseline and intraoperative factors on adherence was estimated using stepwise linear regression. RESULTS: A total of 223 patients were included (mean age 60, 48% male). Mean adherence was 79% to the PP bundle (range 65-93% for individual elements), and 82% for the CT bundle (range 68-98% for individual elements). The occurrence of nausea/vomiting in the first 24 h was associated with lower adherence to both bundles. In the PP bundle, patients who arrived at the ward after 6 p.m. had lower adherence. In the CT bundle, patients who had rectal resection had lower adherence while thoracic epidural was associated with higher adherence. CONCLUSIONS: With the exception of postoperative nausea and vomiting, predictors of adherence to ERP elements after colorectal surgery differed for elements requiring patient participation and those provided by the clinical team. Strategies to improve ERP adherence should target staff education and engagement of patients at risk for lower adherence.

Dual RNA Processing Roles of Pat1b via Cytoplasmic Lsm1-7 and Nuclear Lsm2-8 Complexes.

Pat1 RNA-binding proteins, enriched in processing bodies (P bodies), are key players in cytoplasmic 5' to 3' mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the spliceosomal U6 small nuclear RNA (snRNA). Furthermore, we establish the set of interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6.U5 tri-small nuclear ribonucleoprotein particle (tri-snRNP) components in Cajal bodies, the site of snRNP biogenesis. RNA sequencing following Pat1b depletion revealed the preferential upregulation of mRNAs normally found in P bodies and enriched in 3' UTR AU-rich elements. Changes in >180 alternative splicing events were also observed, characterized by skipping of regulated exons with weak donor sites. Our data demonstrate the dual role of a decapping enhancer in pre-mRNA processing as well as in mRNA decay via distinct nuclear and cytoplasmic Lsm complexes.

Economic Impact of an Enhanced Recovery Pathway for Lung Resection.

BACKGROUND: Multimodal enhanced recovery pathways (ERP) improve clinical outcomes and hospital length of stay for patients undergoing lung resection. However, data supporting their economic impact is lacking. This study evaluated the effect of an ERP on costs of lung resection. METHODS: Adult patients undergoing elective lung resection from August 2011 to August 2013 at a single university-affiliated institution were prospectively recruited. Pneumonectomies and extended resections were excluded. Beginning in September 2012, patients were enrolled in a multimodal ERP. Outcomes were recorded until 90 days after discharge. Total costs from institutional, health care system, and societal perspectives are reported in 2016 Canadian dollars, with uncertainty expressed as 95% confidence intervals derived using bootstrapped estimates (10,000 repetitions). RESULTS: The study included 133 patients (conventional care: n = 58; ERP: n = 75). Patient and operative characteristics were similar between the groups. The ERP group had shorter median (interquartile range) length of stay (4 [3 to 6] days vs 6 [4 to 9] days, p < 0.01), decreased total complications (32% vs 52%, p = 0.02), and decreased pulmonary complications (16% vs 34%, p = 0.01), with no difference in readmissions. After discharge, there was a trend towards less caregiver burden for the ERP group (53 ± 90 hours vs 101 ± 252 hours, p = 0.17). Overall societal costs were lower in the ERP group (mean difference per patient: -$4,396 Canadian; 95% confidence interval -$8,674 to $618 Canadian). CONCLUSIONS: A multidisciplinary ERP is associated with improved clinical outcomes and societal cost savings compared with conventional perioperative management for elective lung resection.

A simple flow-cytometry method to evaluate peripheral blood contamination of bone marrow aspirates.

Bone marrow (BM) aspirates used for flow-cytometry (FCM) studies are usually obtained from a second aspiration, as the primary aspirate is used for morphological assessment. For this reason, the FCM samples unavoidably contain some blood; although, good-quality samples contain only a small amount. It is of utmost importance to assess the quality of samples prior to FCM analysis; yet, contamination with peripheral blood (PB) is not evaluated in most laboratories, possibly because the methods available are either qualitative or too complex for daily practice. Here, we propose a simple FCM method to quantitatively evaluate PB contamination in BM aspirates, by analyzing the percentage of plasma cells and CD34+ cells - two cell populations nearly absent from PB - and CD10+ granulocytes, which comprise the majority of the PB granulocyte population. We analyzed these three populations in 122 BM aspirates from subjects without hematological disease, and identified samples with PB contamination by performing a hierarchical cluster analysis. A discriminant analysis yielded a function, which we named the PB contamination index (PBCI). This index value gives a quantitative indication about the degree of hemodilution of a given sample. A threshold was identified that discriminates low-quality samples. The method and the threshold proved to be useful in BM aspirates infiltrated with malignant cells, with the exception of cases where hematological disease altered two of the three parameters included in the index. We have easily implemented the PBCI calculation in our daily routine, and find it very helpful for an accurate interpretation of FCM results in a large proportion of BM specimens. Limitations of the technique are discussed.

An enhanced recovery pathway reduces duration of stay and complications after open pulmonary lobectomy.

BACKGROUND: Few studies have investigated the effectiveness of enhanced recovery pathways (ERP) for lung resection. This study estimates the impact of an ERP for lobectomy on duration of stay, complications, and readmissions. METHODS: Patients undergoing open lobectomy were identified from an OR database between 2011 and 2013. Beginning September 2012, all patients were managed according to a 4-day multidisciplinary ERP with written daily patient education treatment plans, multimodal analgesia, early diet, structured mobilization and standardized drain management. Pre-pathway (PRE) and post-pathway (POST) patients were compared in terms of duration of stay, complications, and readmissions. RESULTS: We identified 234 patients (PRE, 127; POST, 107). Groups were similar with respect to age, gender, American Society of Anesthesiologists score, and baseline pulmonary function. Compared with the PRE group, the POST group had decreased duration of stay (median, 6 [interquartile range (IQR), 5-7] vs 7 [6-10] days; P < .05), total complications (40 [37%] vs 64 [50%]; P < .05), urinary tract infections (3 [3%] vs 15 [12%]; P < .05), and chest tube duration (median, 4 [IQR, 3-6] vs 5 [4-7] days; P < .05), with no difference in readmissions (7 [7%] vs 6 [5%]; P < .05) or chest tube reinsertion (4 [4%] vs 6 [5%]; P < .05). Decreased duration of stay was driven by patients without complications (median, 5 [IQR, 4-6] vs 6 [5-7] days; P < .05). CONCLUSION: Implementation of a multimodal ERP for lobectomy was associated with decreased duration of stay and complications with no difference in readmissions.

Validity of the EuroQol-5 dimensions as a measure of recovery after pulmonary resection.

BACKGROUND: Surgical innovations advocated to improve patient recovery are often costly. Economic evaluation requires preference-based measures that reflect the construct of patient recovery. We investigated the responsiveness and construct validity of the EuroQol-5 dimensions (EQ-5D) as a measure of postoperative recovery after planned pulmonary resection for suspected malignant tumors. METHODS: Patients undergoing pulmonary resection completed the EQ-5D questionnaire and visual analog scales (VAS) for pain and fatigue at baseline (preoperatively) and at 1 and 3 mo postoperatively. Responsiveness and construct validity (discriminant and convergent) were investigated by testing a priori hypotheses. RESULTS: Fifty-five patients were analyzed (45% male, 62 ± 12 y, 29% video-assisted). There was no significant difference between median EQ-5D scores obtained at baseline (0.83 [interquartile range {IQR 0.80-1}]) compared to scores at 1 mo (0.83 [0.80-1], P = 0.86) and 3 mo after surgery (1 [0.83-1]; P = 0.09). At 1 mo after surgery, EQ-5D scores were significantly lower in patients undergoing thoracotomy versus video-assisted surgery (0.82 [IQR 0.77-0.89] versus 1 [0.83-1], P = 0.003), but there were no significant differences between patients ≥ 70-y old versus younger (0.95 [IQR 0.82-1] versus 0.83 [0.77-1], P = 0.09) or between patients with versus without complications (0.82 [IQR 0.79-0.95] versus 0.83 [0.80-1], P = 0.10). There was a low but significant correlation between EQ-5D and VAS scores of pain and fatigue (Rho -0.30 to -0.47, P ≤ 0.01). CONCLUSIONS: Despite evidence of convergent validity, the EQ-5D was not sensitive to the hypothesized trajectory of postoperative recovery and showed limited discriminant validity. This study suggests that the EQ-5D may not be appropriate to value recovery after lung resection.

Cost-effectiveness of Enhanced Recovery Versus Conventional Perioperative Management for Colorectal Surgery.

OBJECTIVE: To determine the cost-effectiveness of enhanced recovery pathways (ERPs) versus conventional care for patients undergoing elective colorectal surgery. BACKGROUND: ERPs for colorectal surgery are clinically effective, but their cost-effectiveness is unknown. METHODS: A multi-institutional prospective cohort cost-effectiveness analysis was performed. Adult patients undergoing elective colorectal resection at 2 university-affiliated institutions from October 2012 to October 2013 were enrolled. One center used an ERP, whereas the other did not. Postoperative outcomes were recorded up to 60 days. Total costs were reported in 2013 Canadian dollars. Effectiveness was measured using the SF-6D, a health utility measure validated for postoperative recovery. Uncertainty was expressed using bootstrapped estimates (10,000 repetitions). RESULTS: A total of 180 patients were included (conventional care: n = 95; ERP: n = 95). There were no differences in patient characteristics except for a higher proportion of laparoscopy in the ERP group. Mean length of stay was shorter in the ERP group (6.5 vs 9.8 days; P = 0.017), but there were no differences in complications or readmissions. Patients in the ERP group returned to work quicker and had less caregiver burden. There was no difference in quality of life between the 2 groups. The cost of the ERP program was $153 per patient. Overall societal costs were lower in the ERP group (mean difference = -2985; 95% confidence interval, -5753 to -373). The ERP had a greater than 99% probability of cost-effectiveness. The results were insensitive to a range of assumptions and subgroups. CONCLUSIONS: Enhanced recovery is cost-effective compared with conventional perioperative management for elective colorectal resection.

A comparison of the validity of two indirect utility instruments as measures of postoperative recovery.

BACKGROUND: Cost-effectiveness analyses of surgical interventions require valid measures of postoperative recovery. The objective of this study was to compare the validity of two indirect utility instruments, the Short Form 6D (SF-6D) and EuroQol 5D (EQ-5D), as measures of postoperative recovery. MATERIALS AND METHODS: A prospective cohort of patients undergoing elective colorectal resection at two university-affiliated institutions from October 2012-October 2013 completed the SF-6D and EQ-5D (including the EQ-visual analog scale [EQ-VAS]) at baseline (before surgery), and at 4 and 8 wk after surgery. Responsiveness and construct validity were assessed through a priori hypotheses. RESULTS: A total of 165 patients were included. The SF-6D was the most responsive to the expected postoperative changes at 4 and 8 wk compared with the EQ-5D and the EQ-VAS. The 4-wk SF-6D, EQ-5D, and EQ-VAS discriminated between patients with and without complications after controlling for confounders with adjusted mean differences of -0.070 (95% confidence interval [CI] -0.126 to -0.015), -0.133 (95% CI -0.231, -0.030), and -7.91 (95% CI -14.77, -1.04), respectively. Mean SF-6D and EQ-5D values were significantly different from the US population norms at all time points, but the magnitude of change was highest for the SF-6D. The strength of correlation between all three instruments was moderate at all time points (r=0.550-0.684, all P<0.05). CONCLUSIONS: The SF-6D preference-based health index appears to be a more valid measure of postoperative recovery than the EQ-5D and EQ-VAS in surgical cost-effectiveness analyses.