Increased risk of postoperative wound complications among obesity classes II & III after ALIF in 10-year ACS-NSQIP analysis of 10,934 cases.

BACKGROUND CONTEXT: Anterior lumbar interbody fusion (ALIF) procedures for lumbar spine disease have been increasing amid a growing obese patient population with limited studies available focusing exclusively on risk-factors for post-operative ALIF complications. PURPOSE: The objective of this study was to compare 30-day post-operative complications among different obesity World Health Organization classes according to body mass index (BMI) in comparison to non-obese patients who underwent an ALIF procedure. STUDY DESIGN/SETTING: Retrospective cohort study of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) from 2009 to 2019. PATIENT SAMPLE: A total of 10,934 patients undergoing an ALIF. OUTCOME MEASURES: Primary outcome measures include 30 day cardiac, pulmonary, urinary, infectious, and wound complications. Secondary outcomes included rates of blood transfusion, reintubation, deep vein thrombosis, pulmonary embolism, 30-day return to the operating room (OR), and 30 day mortality. METHODS: Patients were identified by use of the current procedural terminology codes 22558 and 22585 from 2009 to 2019. Patients were divided into the following groups: non-obese (BMI 18.5-29.9 kg/m2), Obese I (BMI 30-34.9 kg/m2), Obese II (BMI 35-39.9 kg/m2), and Obese III (BMI ≥40 kg/m2). Age, gender, race, American Society of Anesthesiologists status, smoking status, hypertension requiring medication, steroid used, chronic obstructive pulmonary disease, history of a bleeding disorder, and diabetes was identified as risk factors after a univariate analysis conducted for demographic variables and pre-operative comorbidities. A multivariate logistic regression analysis was then performed to adjust for these preoperative risk factors and compare obesity classes I-III to non-obese patients. RESULTS: Obesity classes II and III had a significant odds ratio (OR) for superficial infection (OR:2.7, 95%CI(1.7-4.5); OR:2.8, 95%CI(1.5-5.2) respectively), organ space infection (OR:3.8, 95%CI(1.6-7.4); OR:3.2, 95%CI(1.1-9.9) respectively), wound disruption (OR:2.8, 95%CI(1.1-7.4); OR:4.6, 95%CI(1.6-13.6) respectively), and total wound complication (OR:2.6, 95%CI(1.8-3.9); OR:3.4, 95%CI(2.2-5.4) respectively) following a multivariate logistic regression analysis. CONCLUSIONS: Risk for post-operative wound complications following an ALIF were found to be significantly higher for obesity classes II-III in comparison to non-obese patients. These findings can further support the use of additional wound care in the perioperative setting for certain levels of obesity.

A four-gene LincRNA expression signature predicts risk in multiple cohorts of acute myeloid leukemia patients.

Prognostic gene expression signatures have been proposed as clinical tools to clarify therapeutic options in acute myeloid leukemia (AML). However, these signatures rely on measuring large numbers of genes and often perform poorly when applied to independent cohorts or those with older patients. Long intergenic non-coding RNAs (lincRNAs) are emerging as important regulators of cell identity and oncogenesis, but knowledge of their utility as prognostic markers in AML is limited. Here we analyze transcriptomic data from multiple cohorts of clinically annotated AML patients and report that (i) microarrays designed for coding gene expression can be repurposed to yield robust lincRNA expression data, (ii) some lincRNA genes are located in close proximity to hematopoietic coding genes and show strong expression correlations in AML, (iii) lincRNA gene expression patterns distinguish cytogenetic and molecular subtypes of AML, (iv) lincRNA signatures composed of three or four genes are independent predictors of clinical outcome and further dichotomize survival in European Leukemia Net (ELN) risk groups and (v) an analytical tool based on logistic regression analysis of quantitative PCR measurement of four lincRNA genes (LINC4) can be used to determine risk in AML.

Testosterone and trenbolone enanthate increase mature myostatin protein expression despite increasing skeletal muscle hypertrophy and satellite cell number in rodent muscle.

The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week-1 ) or ORX + trenbolone (TREN; 1.0 mg week-1 ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.

A ribosome-related signature in peripheral blood CLL B cells is linked to reduced survival following treatment.

We have used polysome profiling coupled to microarray analysis to examine the translatome of a panel of peripheral blood (PB) B cells isolated from 34 chronic lymphocytic leukaemia (CLL) patients. We have identified a 'ribosome-related' signature in CLL patients with mRNAs encoding for ribosomal proteins and factors that modify ribosomal RNA, e.g. DKC1 (which encodes dyskerin, a pseudouridine synthase), showing reduced polysomal association and decreased expression of the corresponding proteins. Our data suggest a general impact of dyskerin dysregulation on the translational apparatus in CLL and importantly patients with low dyskerin levels have a significantly shorter period of overall survival following treatment. Thus, translational dysregulation of dyskerin could constitute a mechanism by which the CLL PB B cells acquire an aggressive phenotype and thus have a major role in oncogenesis.

MAPK/ERK2 phosphorylates ERG at serine 283 in leukemic cells and promotes stem cell signatures and cell proliferation.

Aberrant ERG (v-ets avian erythroblastosis virus E26 oncogene homolog) expression drives leukemic transformation in mice and high expression is associated with poor patient outcomes in acute myeloid leukemia (AML) and T-acute lymphoblastic leukemia (T-ALL). Protein phosphorylation regulates the activity of many ETS factors but little is known about ERG in leukemic cells. To characterize ERG phosphorylation in leukemic cells, we applied liquid chromatography coupled tandem mass spectrometry and identified five phosphorylated serines on endogenous ERG in T-ALL and AML cells. S283 was distinct as it was abundantly phosphorylated in leukemic cells but not in healthy hematopoietic stem and progenitor cells (HSPCs). Overexpression of a phosphoactive mutant (S283D) increased expansion and clonogenicity of primary HSPCs over and above wild-type ERG. Using a custom antibody, we screened a panel of primary leukemic xenografts and showed that ERG S283 phosphorylation was mediated by mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling and in turn regulated expression of components of this pathway. S283 phosphorylation facilitates ERG enrichment and transactivation at the ERG +85 HSPC enhancer that is active in AML and T-ALL with poor prognosis. Taken together, we have identified a specific post-translational modification in leukemic cells that promotes progenitor proliferation and is a potential target to modulate ERG-driven transcriptional programs in leukemia.

[Workplace Health Promotion in Germany: Prevalence and Utilisation. Analyses on Labour Force Surveys of the Federal Institute for Occupational Safety and Health in 2006 and 2012]. / Betriebliche Gesundheitsförderung in Deutschland: Verbreitung und Inanspruchnahme. Ergebnisse der BIBB/BAuA-Erwerbstätigenbefragungen 2006 und 2012.

BACKGROUND AND METHODS: This article describes representative data on the availability of and individual participation in workplace health promotion (WHP) in Germany. These data are based on responses of 17 870 employees which were collected within the Labour Force Survey 2011/12 of the Federal Institute for Vocational Education and Training and the Federal Institute for Occupational Safety and Health. By comparison with data from the previous wave of the survey carried out in 2005/06 (N=17 803), medium-term trends in WHP are identified. RESULTS: In 2012, 44% of the employees reported WHP activities in their companies, as against 38% in 2006. Increasing WHP prevalences were observed in all company sizes and economic sectors. In both surveys, employees in small companies reported significantly less WHP than those in large companies. Of all economic sectors, industrial manufacturing still showed the largest diffusion of WHP, even though the gap to other sectors has narrowed since 2006. The proportion of respondents who individually participated in WHP (if available) has slightly declined. The most striking difference in participation rates - which has even increased over time - is between small and large companies. CONCLUSIONS: Our findings indicate a moderately increased prevalence of WHP in Germany. At the same time, data still suggest a considerable need for WHP-related advice and support, particularly in small companies. On the basis of the analysed data, however, no statements can be made about qualitative characteristics of WHP activities in Germany.

Overexpression of ERG in cord blood progenitors promotes expansion and recapitulates molecular signatures of high ERG leukemias.

High expression of the ETS family transcription factor ERG is associated with poor clinical outcome in acute myeloid leukemia (AML) and acute T-cell lymphoblastic leukemia (T-ALL). In murine models, high ERG expression induces both T-ALL and AML. However, no study to date has defined the effect of high ERG expression on primary human hematopoietic cells. In the present study, human CD34+ cells were transduced with retroviral vectors to elevate ERG gene expression to levels detected in high ERG AML. RNA sequencing was performed on purified populations of transduced cells to define the effects of high ERG on gene expression in human CD34+ cells. Integration of the genome-wide expression data with other data sets revealed that high ERG drives an expression signature that shares features of normal hematopoietic stem cells, high ERG AMLs, early T-cell precursor-ALLs and leukemic stem cell signatures associated with poor clinical outcome. Functional assays linked this gene expression profile to enhanced progenitor cell expansion. These results support a model whereby a stem cell gene expression network driven by high ERG in human cells enhances the expansion of the progenitor pool, providing opportunity for the acquisition and propagation of mutations and the development of leukemia.

Timing of colonoscopy after resection for colorectal cancer: are we looking too soon?

BACKGROUND: Based on current National Comprehensive Cancer Network guidelines, colonoscopic surveillance after colorectal cancer resection should begin at 1 year. OBJECTIVE: The aim of this study was to determine whether the incidence of cancer or advanced polyp detection rate was high enough to justify colonoscopy at 1 year. DESIGN: The Ochsner Clinic Tumor Registry Database was queried for patients who underwent a segmental colectomy or proctectomy between 2002 and 2010. Patients who had a preoperative colonoscopy and at least 1 documented postoperative colonoscopy were included. We considered new cancer or polyps of ≥1 cm as missed on the preoperative colonoscopy. Patients with an identified genetic trait causing a predisposition to colorectal cancer were excluded. RESULTS: Five hundred twelve patients underwent resection, and 155 met our inclusion criteria. The average age was 64 years, and 53% patients were male. There were 32.9% with stage I disease, 35% with stage II disease, 27.1% with stage III disease, and 5.2% with stage IV disease. Of these patients, 52.2% had a right colectomy, 7.1% had a left colectomy, 16.8% had a sigmoid colectomy, 22% had a low anterior resection, and 1.3% had a transanal resection. The average time to first postoperative colonoscopy was 478 days (SD ±283 days). Twenty-four patients had adenomatous polyps detected on their first surveillance colonoscopy, but only 5 (3.2%) polyps were ≥1 cm, and there was no correlation between stage of cancer and finding a polyp. No new cancers were detected, but 3 (1.9%) had an anastomotic recurrence. CONCLUSIONS: The performance of surveillance colonoscopy at 1 year resulted in the detection of only 5 missed polyps ≥1 cm and no metachronous cancers. Anastomotic recurrences were rare, and the majority were in patients who had rectal cancer that could be evaluated by in-office flexible sigmoidoscopy. Extending the time to first colonoscopy appears to be safe and would help conserve valuable resources, including physician and facility time, which is imperative in the current health care climate.

Synergistic effects of secretory phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus with cancer chemotherapeutic agents.

Healthy cells typically resist hydrolysis catalyzed by snake venom secretory phospholipase A2. However, during various forms of programmed cell death, they become vulnerable to attack by the enzyme. This observation raises the question of whether the specificity of the enzyme for dying cells could be used as a strategy to eliminate tumor cells that have been intoxicated but not directly killed by chemotherapeutic agents. This idea was tested with S49 lymphoma cells and a broad range of antineoplastic drugs: methotrexate, daunorubicin, actinomycin D, and paclitaxel. In each case, a substantial population of treated cells was still alive yet vulnerable to attack by the enzyme. Induction of cell death by these agents also perturbed the biophysical properties of the membrane as detected by merocyanine 540 and trimethylammonium-diphenylhexatriene. These results suggest that exposure of lymphoma cells to these drugs universally causes changes to the cell membrane that render it susceptible to enzymatic attack. The data also argue that the snake venom enzyme is not only capable of clearing cell corpses but can aid in the demise of tumor cells that have initiated but not yet completed the death process.

Enhanced external counterpulsation improves peripheral artery function and glucose tolerance in subjects with abnormal glucose tolerance.

BACKGROUND: In coronary artery disease patients, enhanced external counterpulsation (EECP) improves peripheral arterial function and nitric oxide (NO) bioavailability, which have been implicated in the pathogenesis of abnormal glucose tolerance (AGT). We sought to evaluate the effects of EECP on outcomes of arterial function, glucose tolerance, and skeletal muscle morphology in subjects with AGT. METHODS AND RESULTS: 18 subjects with AGT were randomly (2:1 ratio) assigned to receive either 7 wk (35 1-h sessions) of EECP (n = 12) or 7 wk of standard care (control; n = 6). Peripheral vascular function, biochemical assays, glucose tolerance, and skeletal muscle morphology were evaluated before and after EECP or control. EECP increased normalized brachial artery (27%) and popliteal artery (52%) flow-mediated dilation. Plasma nitrite/nitrate (NOx) increased (30%) and 8-isoprostane-PGF-F(2α), a marker of lipid peroxidation in the plasma, decreased (-23%). Fasting plasma glucose declined (-16.9 ± 5.4 mg/dl), and the homeostasis model assessment of insulin resistance (HOMA-IR) decreased (31%) following EECP. Plasma glucose 120 min after initiation of oral glucose tolerance testing decreased (-28.3 ± 7.3 mg/dl), and the whole body composite insulin sensitivity index (C-ISI) increased (21%). VEGF concentrations increased (75%), and vastus lateralis skeletal muscle biopsies demonstrated improvements in capillary density following EECP. No change was observed in cellular signaling pathways, but there was a significant increase GLUT-4 protein expression (47%) following EECP. CONCLUSIONS: Our findings provide novel evidence that EECP has a beneficial effect on peripheral arterial function and glucose tolerance in subjects with AGT.

[Interstitial lung disease]. / Interstitielle Lungenerkrankungen.

This concise article summarizes recent advances in the field of interstitial lung disease (ILD) with particular focus on clinically relevant findings. As a novel treatment option for idiopathic pulmonary fibrosis (IPF), pirfenidone has been granted marketing authorization in the European Union for the treatment of mild to moderate IPF. In contrast, the FDA refused to approve pirfenidone for the US market. Promising study results for the treatment of IPF were published for the triple tyrosine kinase inhibitor intedanib, other drugs such as the endothelin receptor antagonist (ERA) macitentan are currently investigated in clinical trials. Further studies that investigated the ERA bosentan, the phosphodiesterase 5 inhibitor sildenafil, or the tyrosine kinase inhibitor imatinib in IPF failed to show a benefit for the pertinent primary endpoint. Additionally, an evidence-based guideline for the diagnosis and management of IPF has very recently been published. The European Respiratory Society established a guideline for the management of lymphangioleiomyomatosis (LAM), while another study showed the cost effectiveness of HRCT screening for LAM in selected female patients suffering from spontaneous pneumothorax. Data from a scleroderma-ILD study show the prognostic relevance of antitopoisomerase antibodies in the progression of this form of ILD. Bosentan treatment did not significantly enhance exercise capacity in patients with scleroderma-ILD in the absence of pulmonary hypertension. With regard to sarcoidosis with mediastinal lymphadenopathy the diagnostic sensitivity can be significantly improved by endobronchial ultrasonography-guided transbronchial needle aspiration vs. conventional needle aspiration. As a possible future treatment option for sarcoidosis vasointestinal peptide has been successfully evaluated in a phase 2 tolerability trial.

[Prevalence and utilisation of health promotion in German enterprises]. / Verbreitung und Inanspruchnahme von Massnahmen zur Gesundheitsförderung in Betrieben in Deutschland.

The aim of this study was to estimate the prevalence of health promotion in German enterprises, differentiated by size, sector, and the companies' business situations. Representative data were analysed from the survey of working conditions in Germany (n=20,000) that was conducted by the Federal Institute for Vocational Education and Training (BIBB) and the Federal Institute of Occupational Safety and Health (BAuA). Thirty-eight percent of interviewed employees confirmed that health promotion activities had been carried out in their company during the last two years. The prevalence varied significantly, depending on the company's size, sector, and business situation. In cases of implementation, a higher percentage of employees participated in micro and small companies than in medium-sized or large companies. With respect to the implementation of health promotion, more advice and support are needed, particularly in micro and small enterprises. There is still a need for health promotion activities which meet the special needs of micro and small enterprises. Furthermore there is still a need to invest in an infrastructure which allows their adequate supply.

Colonoscopy in the patient requiring anticoagulation.

PURPOSE: The aim of this study was to assess perioperative warfarin management and complications in patients requiring colonoscopy. METHODS: We retrospectively reviewed 109 cases of colonoscopies performed on 94 patients requiring anticoagulation with warfarin. Patients stopped their warfarin three days before colonoscopy. Coagulation profiles obtained just before the colonoscopy showed a median prothrombin time of 13.4 seconds with a range of 11.1 to 29.1 (normal range, 10.9-13) and a median international normalized ratio of 1.2 with a range of 0.9 to 2.6. Patients restarted warfarin the day after the examination. RESULTS: During the 109 colonoscopies, 47 percent of the patients underwent either hot biopsy or snare polypectomy. One examination that included several biopsies was associated with a hemorrhagic complication (0.92 percent) requiring hospitalization and transfusion. Subset analysis of the therapeutic (biopsy and snare polypectomy) group indicated a slightly higher complication rate (1.96 percent) with a median international normalized ratio of 1.3 (range, 1-2.3) and a median prothrombin time of 13.7 (range, 11.6-25.9). CONCLUSION: Patients taking warfarin for anticoagulation may safely undergo colonoscopy. The risk of hemorrhagic complications increases slightly with hot biopsy or snare procedures. Further studies are needed to refine guidelines for colonoscopy in the patient requiring anticoagulation.

Consolidation radiation therapy following cytoreductive surgery, chemotherapy and second-look laparotomy for epithelial ovarian carcinoma: long-term follow-up.

BACKGROUND: From 1979-1987, 139 stage IC-IV ovarian cancer patients who had undergone cytoreductive surgery received 6-11 cycles of cisplatin and adriamycin. STUDY DESIGN: Eighty-four clinically complete responders underwent second-look laparotomy, and 60 of them received consolidation abdominal irradiation. The patients were then followed for a median follow-up of 39 months. RESULTS: Five- and 10-year actuarial survival for all patients was 43% and 24%, for no residuum at primary surgery, 80% and 35%, for residual tumor <2 cm, 45% and 35%, and for residual tumor >2 cm, 20% and 4%. Median survival for stage III-IV patients negative at second-look laparotomy was 72 months in irradiated compared to 25 months in non-irradiated patients (P = 0.14) and 77 months in irradiated patients with microscopic disease at second-look laparotomy. Median survival in patients with macroscopic disease at second-look laparotomy was 23.5 months if irradiated compared to 18 months if not (P = 0.05). CONCLUSIONS: Consolidation whole abdominal irradiation in advanced stages of ovarian cancer may be of value in patients with negative or microscopic disease at second-look laparotomy. Unfortunately, despite the initial survival advantage observed in irradiated patients, owing to late recurrences there was no significant difference in their long-term survival probability.

Effects of sevoflurane and propofol on pulmonary shunt fraction during one-lung ventilation for thoracic surgery.

Forty patients requiring one-lung ventilation (OLV) for thoracic surgery were randomly assigned to receive propofol (4-6 mg kg(-1) h(-1)) or sevoflurane (1 MAC) for maintenance of anaesthesia. Three sets of measurements were taken: (i) after 30 min of two-lung ventilation (TLV), (ii) after 30 min of one-lung ventilation (OLV-1) in the supine position and (iii) during OLV in the lateral position (OLV-2) with the chest open and before surgical manipulation of the lung. There were no differences between groups in patient characteristics or preoperative condition. Increases in shunt fraction during OLV-1 were 17.4% and 17.2% (P=0.94), those during OLV-2 were 18.3% and 16.5% (P=0.59) for the propofol and sevoflurane group, respectively. Cardiac index and other haemodynamic and respiratory variables were similar for the two groups. We conclude that inhibition of hypoxic pulmonary vasoconstriction by sevoflurane may only account for small increases in shunt fraction and that much of the overall shunt fraction during OLV has other causes.

Membrane activity of (Cys48Ser) lung surfactant protein B increases with dimerisation.

One of the possible functions of lung surfactant protein B (SP-B), an hydrophobic membrane-associated saposin-like protein, is to reduce the alveolar surface tension by promoting insertion of phospholipids into the air/liquid interface of the lung. SP-B is a covalent homodimer; Cys48 of two polypeptides form an intermolecular disulphide bond. In order to test whether dimerisation of SP-B is important for surfactant function, transgenic mice which express (Cys48Ser) human SP-B in a mouse SP-B null background were generated. In previous studies (Cys48Ser)SP-B showed a concentration-dependent in vitro activity, suggesting that it may form non-covalent dimers. Here (Cys48Ser)SP-B isolated from bronchoalveolar lavage of transgenic mice was studied at different concentrations by circular dichroism (CD) spectroscopy, pulsating bubble surfactometry, mass spectrometry and reversed-phase HPLC. The results indicate that (Cys48Ser)SP-B, both in a phospholipid environment and in organic solvents, is largely monomeric and exhibits low activity at concentrations lower than 1 -2 microM, while at higher concentrations it forms non-covalent dimers, which are nearly functionally equivalent to native SP-B in vitro. Furthermore, electrospray mass spectrometry showed that more dimers were found relative to the monomer when the polarity of the solvent was decreased, and when the concentration of SP-B increased. (Cys48Ser)SP-B also eluted earlier than native SP-B in reversed-phase HPLC. Taken together, these results indicate that a polar surface is buried upon dimerisation, thereby promoting formation of interchain ion pairs between Glu51-Arg52' and Glu51'-Arg52.

A randomized controlled double-blind trial comparing piritramide and morphine for analgesia after hysterectomy.

BACKGROUND AND OBJECTIVE: Efficacy and side-effects of piritramide (pirinitramide) and morphine, given intravenously for postoperative analgesia after hysterectomy, were compared in a randomized controlled double-blind trial in 92 ASA class I-III patients. METHODS: Administration was investigator-controlled during the first 90 min and subsequently via a patient-controlled device. Visual analogue scales for pain intensity and verbal rating scales for side-effects were taken repeatedly. RESULTS: Median visual analogue scores for pain intensity on a 100-mm scale 4, 8 and 24 h after surgery were 10, 8.5 and 5 mm in the piritramide group and 18, 10 and 8.5 mm in the morphine group. These differences are neither statistically nor clinically significant. Median values for nausea on a verbal rating scale from 0 to 3 were zero for both groups at all times with similar ranges. There was no difference in number of episodes of vomiting and retching and usage of antiemetics. The mean amount of piritramide used for initial titration was 15.2 mg; the respective amount of morphine was 15.4 mg. CONCLUSIONS: In this setting the two agents are equally effective and show a similar profile of side-effects.