Clinical features and outcomes of patients with pancreatic cancer requiring unplanned medical ICU admission: A retrospective multicenter study.

BACKGROUND: We sought to describe the reasons for intensive care unit (ICU) admission and outcomes of patients with pancreatic cancer requiring unplanned medical ICU admission. PATIENTS AND METHODS: Retrospective cohort study in five ICUs from 2009 to 2020. All patients with pancreatic cancer admitted to the ICU were included. Patients having undergone recent surgery were excluded (< 4 weeks). RESULTS: 269 patients were included. Tumors were mainly adenocarcinoma (90%). Main reason for admission was sepsis/septic shock (32%) with a biliary tract infection in 44 (51%) patients. Second reason for admission was gastrointestinal bleeding (28%). ICU and 3-month mortality rates were 26% and 59% respectively. Performance status 3-4 (odds ratio OR 3.58), disease status (responsive/stable -ref-, newly diagnosed OR 3.25, progressive OR 5.99), mechanical ventilation (OR 8.03), vasopressors (OR 4.19), SAPS 2 (OR 1.69) and pH (OR 0.02) were independently associated with ICU mortality. Performance status 3-4 (Hazard ratio HR 1.96) and disease status (responsive/stable -ref-, newly diagnosed HR 2.67, progressive HR 4.14) were associated with 3-month mortality. CONCLUSION: Reasons for ICU admissions of pancreatic cancer patients differ from those observed in other solid cancer. Short- and medium-term mortality are strongly influenced by performance status and disease status at ICU admission.

Risk factors related to the appearance of umbilical disorders in dairy calves / [Fatores de risco relacionados ao surgimento de afecções umbilicais em bezerros leiteiros]

The objective of this study was to determine the types of calve housing used in dairy farms, the prevalence of umbilical disorders and related risk factors. The 16 farms studied were visited to characterize the types of installation and possible risk factors, as well as information obtained from a questionnaire applied to the farmers. 806 Holstein calves were physically examined, in addition to collecting blood samples for the evaluation of Failures in Passive Immunity Transfer (FPIT), in animals that manifested inflammatory omphalopathies, and were also submitted to ultrasound examination. The prevalence of omphalopathies was assessed by Fisher's test, and multivariate logistic regression to assess risk factors. Eight types of installation were found: tropical house, suspended cage, collective stall, collective picket, Argentinean type, single-story cage, individual stall, and collective picket with chain. Omphalopathies accounted for 6.45% of the calves. Small size farms (up to 99 lactation cows) had high risk for umbilical disorders, ground floor collective calves, without side protection, with sand floor, in closed sheds and without heatstroke were considered risk factors for omphalopathies. Adequate colostrum and umbilical antisepsis are not associated with disease, its appearance being related to the housing conditions of the animals.(AU)

O objetivo deste estudo foi determinar os tipos de alojamento para bezerros leiteiros, a prevalência de onfalopatias e os fatores de risco relacionados. As 16 fazendas estudadas foram visitadas buscando-se caracterizar os tipos de instalação e os possíveis fatores de risco, além de informações obtidas de um questionário aplicado aos fazendeiros. Foram examinados fisicamente 806 bezerros da raça Holandesa, além da coleta de amostras de sangue, para avaliação da falha de transferência de imunidade passiva (FTIP), nos animais que manifestaram onfalopatias inflamatórias, sendo submetidos também ao exame ultrassonográfico. A prevalência das onfalopatias foi avaliada por teste de Fisher, e foi feita regressão logística multivariada a fim de se avaliarem os fatores de risco. Verificou-se oito tipos de instalação: casinha tropical, gaiola suspensa, baia coletiva, piquete coletivo, bezerreiro tipo argentino, gaiola térrea, baia individual e piquete coletivo com corrente. As onfalopatias corresponderam a 6,45% dos bezerros. Os bezerreiros coletivos térreos, sem proteções laterais, com piso de areia, borracha, concreto ou madeira, em galpões fechados, sem insolação, com alta densidade animal, antissepsia umbilical realizada por três dias e FTIP acima de 50% foram considerados fatores de risco para onfalopatias e possuem relação com o bezerreiro, sendo decisivas para evitar essas condições a colostragem e a antissepsia umbilical adequadas.(AU)

Practical model to identify liver transplant recipients at low risk of postoperative haemorrhage, bile leakage and ascites.

BACKGROUND: This study aimed to identify a subgroup of recipients at low risk of haemorrhage, bile leakage and ascites following liver transplantation (LT). METHODS: Factors associated with significant postoperative ascites (more than 10 ml/kg on postoperative day 5), bile leakage and haemorrhage after LT were identified using three separate multivariable analyses in patients who had LT in 2010-2019. A model predicting the absence of all three outcomes was created and validated internally using bootstrap procedure. RESULTS: Overall, 944 recipients underwent LT. Rates of ascites, bile leakage and haemorrhage were 34.9, 7.7 and 6.0 per cent respectively. The 90-day mortality rate was 7.0 per cent. Partial liver graft (relative risk (RR) 1.31; P = 0.021), intraoperative ascites (more than 10 ml/kg suctioned after laparotomy) (RR 2.05; P = 0.001), malnutrition (RR 1.27; P = 0.006), portal vein thrombosis (RR 1.56; P = 0.024) and intraoperative blood loss greater than 1000 ml (RR 1.39; P = 0.003) were independently associated with postoperative ascites and/or bile leak and/or haemorrhage, and were introduced in the model. The model was well calibrated and predicted the absence of all three outcomes with an area under the curve of 0.76 (P = 0.001). Of the 944 patients, 218 (23.1 per cent) fulfilled the five criteria of the model, and 9.6 per cent experienced postoperative ascites (RR 0.22; P = 0.001), 1.8 per cent haemorrhage (RR 0.21; P = 0.033), 4.1 per cent bile leak (RR 0.54; P = 0.048), 40.4 per cent severe complications (RR 0.70; P = 0.001) and 1.4 per cent 90-day mortality (RR 0.13; P = 0.004). CONCLUSION: A practical model has been provided to identify patients at low risk of ascites, bile leakage and haemorrhage after LT; these patients could potentially qualify for inclusion in non-abdominal drainage protocols.

Changes in fecal microbiota with CFTR modulator therapy: A pilot study.

Studies have demonstrated that people with CF with pancreatic insufficiency (PI) have fecal dysbioses. Evidence suggests the causes of these dysbioses are multifactorial, and that important drivers include antibiotic exposure, dietary intake, and CF gastrointestinal tract dysfunction, including nutrient malabsorption. In this pilot study, we tested whether initiation of the CFTR modulator treatments ivacaftor (in a cohort of pancreatic sufficient (PS) people with CF and an R117H CFTR variant) or lumacaftor/ivacaftor (in a cohort of PI people with CF and an F508del variant) changed fecal measures of malabsorption or fecal microbiomes. While we identified no statistically significant fecal changes with either treatment, we detected trends in the PI cohort when initiating lumacaftor/ivacaftor towards decreased fecal fat content and towards fecal microbiomes that more closely resembled the fecal microbiota of people without PI. While these findings support a model in which nutrient malabsorption resulting from CF-induced PI drives fecal dysbiosis, they must be validated in future, larger studies of fecal microbiome and malabsorption outcomes with highly effective CFTR modulator therapies.

ComBat harmonization for radiomic features in independent phantom and lung cancer patient computed tomography datasets.

This work seeks to evaluate the combatting batch effect (ComBat) harmonization algorithm's ability to reduce the variation in radiomic features arising from different imaging protocols and independently verify published results. The Gammex computed tomography (CT) electron density phantom and Quasar body phantom were imaged using 32 different chest imaging protocols. 107 radiomic features were extracted from 15 spatially varying spherical contours between 1.5 cm and 3 cm in each of the lung300 density, lung450 density, and wood inserts. The Kolmogorov-Smirnov test was used to determine significant differences in the distribution of the features and the concordance correlation coefficient (CCC) was used to measure the repeatability of the features from each protocol variation class (kVp, pitch, etc) before and after ComBat harmonization. P-values were corrected for multiple comparisons using the Benjamini-Hochberg-Yekutieli procedure. Finally, the ComBat algorithm was applied to human subject data using six different thorax imaging protocols with 135 patients. Spherical contours of un-irradiated lung (2 cm) and vertebral bone (1 cm) were used for radiomic feature extraction. ComBat harmonization reduced the percentage of features from significantly different distributions to 0%-2% or preserved 0% across all protocol variations for the lung300, lung450 and wood inserts. For the human subject data, ComBat harmonization reduced the percentage of significantly different features from 0%-59% for bone and 0%-19% for lung to 0% for both. This work verifies previously published results and demonstrates that ComBat harmonization is an effective means to harmonize radiomic features extracted from different imaging protocols to allow comparisons in large multi-institution datasets. Biological variation can be explicitly preserved by providing the ComBat algorithm with clinical or biological variables to protect. ComBat harmonization should be tested for its effect on predictive models.

Adeno-associated viral overexpression of neuroligin 2 in the mouse hippocampus enhances GABAergic synapses and impairs hippocampal-dependent behaviors.

The cell adhesion molecule neuroligin2 (NLGN2) regulates GABAergic synapse development, but its role in neural circuit function in the adult hippocampus is unclear. We investigated GABAergic synapses and hippocampus-dependent behaviors following viral-vector-mediated overexpression of NLGN2. Transducing hippocampal neurons with AAV-NLGN2 increased neuronal expression of NLGN2 and membrane localization of GABAergic postsynaptic proteins gephyrin and GABAARγ2, and presynaptic vesicular GABA transporter protein (VGAT) suggesting trans-synaptic enhancement of GABAergic synapses. In contrast, glutamatergic postsynaptic density protein-95 (PSD-95) and presynaptic vesicular glutamate transporter (VGLUT) protein were unaltered. Moreover, AAV-NLGN2 significantly increased parvalbumin immunoreactive (PV+) synaptic boutons co-localized with postsynaptic gephyrin+ puncta. Furthermore, these changes were demonstrated to lead to cognitive impairments as shown in a battery of hippocampal-dependent mnemonic tasks and social behaviors.

Implementation of buffy-coat-derived pooled platelet concentrates for internal quality control of light transmission aggregometry: a proof of concept study.

Essentials In platelet function testing, standardized internal controls (IQC) are not commercially provided. Platelet function testing was performed daily on aliquoted pooled platelet concentrates. Pooled platelet concentrates showed stability for control purposes from Monday to Friday. Pooled platelet concentrates provide the necessary steadiness to serve as IQC material. SUMMARY: Background Standardized commercially available control material for internal quality control (IQC) of light transmission aggregometry (LTA) is still lacking. Moreover, the availability of normal blood donors to provide fresh platelets is difficult in small laboratories, where 'volunteers' may be in short supply. Objectives To evaluate the implementation of buffy-coat-derived pooled platelet concentrates (PCs) for IQC material for LTA. Methods We used buffy-coat-derived pooled PCs from the blood bank as IQC material for LTA. On each weekend one PC was prepared (> 200 mL) and aliquoted from the original storage bag on a daily basis in four baby bags (40-50 mL), which were delivered from Monday to Friday to our laboratory. The IQC measurements of at least 85 work-weeks (from Monday to Friday) were evaluated with this new IQC material. LTA was performed on a four-channel Chronolog 700 Aggregometer (Chronolog Corporation, Havertown, PA, USA) (agonists: collagen, adenosine diphosphate [ADP], arachidonic acid [AA] and thrombin receptor activator peptide-6 [TRAP-6]). Results The medians of platelet aggregation from IQC measurements with collagen, ADP and AA from Monday to Friday were 68.0-59.5, 3.0-2.0 and 51.0-50.0%, respectively, and the mean of platelet aggregation with TRAP-6 was 71.2-66.4%. Conclusions Buffy-coat-derived pooled PCs serve as a reliable and robust IQC material for LTA measurements and would be beneficial for the whole laboratory procedure and employees' safety.

Characterization of non-dialyzable constituents from cranberry juice that inhibit adhesion, co-aggregation and biofilm formation by oral bacteria.

An extract prepared from cranberry juice by dialysis known as nondialyzable material (NDM) has been shown previously to possess anti-adhesion activity toward microbial species including oral bacteria, uropathogenic Escherichia coli and Helicobacter pylori. Bioassay-guided fractionation of cranberry NDM was therefore undertaken to identify the anti-adhesive constituents. An aqueous acetone-soluble fraction (NDMac) obtained from Sephadex LH-20 inhibited adhesion-linked activities by oral bacteria, including co-aggregation of oral bacteria Fusobacterium nucleatum with Streptococcus sanguinis or Porphyromonas gingivalis, and biofilm formation by Streptococcus mutans. Analysis of NDMac and subsequent subfractions by MALDI-TOF MS and 1H NMR revealed the presence of A-type proanthocyanidin oligomers (PACs) of 3-6 degrees of polymerization composed of (epi)catechin units, with some (epi)gallocatechin and anthocyanin units also present, as well as quercetin derivatives. Subfractions containing putative xyloglucans in addition to the mixed polyphenols also inhibit biofilm formation by S. mutans (MIC = 125-250 µg mL-1). These studies suggest that the anti-adhesion activities of cranberry NDM on oral bacteria may arise from a combination of mixed polyphenol and non-polyphenol constituents.

Relevance of surgery in patients with non-variceal upper gastrointestinal bleeding.

INTRODUCTION: Upper GI bleeding remains one of the most common emergencies with a substantial overall mortality rate of up to 30%. In severe ill patients, death does not occur due to failure of hemostasis, either medical or surgical, but mainly from comorbidities, treatment complications, and decreased tolerated blood loss. Management strategies have changed dramatically over the last two decades and include primarily endoscopic intervention in combination with acid-suppressive therapy and decrease in surgical intervention. Herein, we present one of the largest patient-based analysis assessing clinical parameters and outcome in patients undergoing endoscopy with an upper GI bleeding. Data were further analyzed to identify potential new risk factors and to investigate the role of surgery. PATIENTS AND METHODS: In this retrospective study, we aimed to analyze outcome of patients with an UGIB and data were analyzed to identify potential new risk factors and the role of surgery. Data collection included demographic data, laboratory results, endoscopy reports, and details of management including blood administration, and surgery was carried out. Patient events were grouped and defined as "overall" events and "operated," "non-operated," and "operated and death" as well as "non-operated and death" where appropriate. Blatchford, clinical as well as complete Rockall-score analysis, risk stratification, and disease-related mortality rate were calculated for each group for comparison. RESULTS: Overall, 253 patients were eligible for analysis: endoscopy was carried out in 96% of all patients, 17% needed surgical intervention after endoscopic failure of bleeding control due to persistent bleeding, and the remaining 4% of patients were subjected directly to surgery. The median length of stay to discharge was 26 days. Overall mortality was 22%; out of them, almost 5% were operated and died. Anticoagulation was associated with a high in-hospital mortality risk (23%) and was increased once patients were taken to surgery (43%). Patients taking steroids presented with a risk of death of 26%, once taken to surgery the risk increased to 80%. Patients with liver cirrhosis had a risk of death of 42%; we observed a better outcome for these patients once taken to theater. Clinically, once scored with Blatchford score, statistical correlation was found for initial need for blood transfusion and surgical intervention. Clinical as well as complete Rockall score revealed a correlation between need for blood transfusion as well as surgical intervention in addition with a decreased outcome with increasing Rockall scores. Risk factor analysis including comorbidity, drug administration, and anticoagulation therapy introduced the combination of tumor and non-steroidal antirheumatic medication as independent risk factors for increased disease-related mortality. CONCLUSION: UGIB remains challenging and endoscopy is the first choice of intervention. Care must be taken once a patient is taking antirheumatic non-steroidal pain medication and suffers from cancer. In patients with presence of liver cirrhosis, an earlier surgical intervention may be considered, in particular for patients with recurrent bleeding. Embolization is not widely available and carries the risk of necrosis of the affected organ and should be restricted to a subgroup of patients not primarily eligible for surgery once endoscopy has failed. Taken together, an interdisciplinary approach including gastroenterologists as well as surgeons should be used once the patient is admitted to the hospital to define the best treatment option.

Teaching mandibular implant-Supported overdentures in dental schools in North America - a survey.

INTRODUCTION: Mandibular two-implant overdentures are considered the minimum standard of care for edentulous patients and provide an excellent performance, as well as satisfaction to the patients. Dental schools are required to promote the teaching of current treatment options in order to enable students to master state-of-the-art procedures. AIMS: The purpose of this study was to examine how the theoretical and practical aspects of mandibular two-implant overdentures are taught in dental schools in North America. METHODS: Data were collected via an online questionnaire that included questions regarding the theoretical and clinical courses, surgical procedure and imaging method. RESULTS: Of 75 schools, 36 responded to the survey. Almost all the schools teach the subject theoretically, but it is not mandatory for students to perform in most of the schools. Only a minority (23%) of the mandibular dentures made by students are implant-supported. Almost all of the schools (94%) use two implants to support overdentures, and Locator abutment is used almost exclusively. The prevalent imaging for the surgical procedure is CT scans, although 30% of the schools use panoramic radiograph. None of the schools loads the implants immediately after surgery. CONCLUSION: Some clear trends are apparent in the current survey: the use of two implants, no use of bar connectors and delayed loading of the implants. It is likely that graduates will not have sufficient clinical skills and will need continuing education to be familiar with the required procedures, both surgical and prosthetic.

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Survival after neoadjuvant chemotherapy with or without bevacizumab or everolimus for HER2-negative primary breast cancer (GBG 44-GeparQuinto)†.

BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.

Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression.

BACKGROUND: Taxane-based adjuvant chemotherapy is standard in node-positive (N+) early breast cancer (BC). The magnitude of benefit in intermediate-risk N+ early BC is still unclear. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc is a large trial evaluating modern taxane-based chemotherapy in patients with 1-3 positive lymph nodes (LNs) only. PATIENTS AND METHODS: A total of 2011 BC patients (18-65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel 100 q3w (n = 1008) with the current standard: 6 × F500E100C500 q3w (n = 828) or C600M40F600 d1, 8× q4w (n = 175). Primary end point was event-free survival (EFS); secondary end points were overall survival (OS), toxicity, translational research, and quality of life. Central tumor bank samples were evaluable in a representative collective (n = 772; 40%). Ki-67 was assessed centrally in hormone receptor-positive disease as a surrogate marker for the distinction of luminal A/B-like tumors. RESULTS: Baseline characteristics were well balanced between study arms in both main study and central tumor bank subset. At 59-month median follow-up, superior efficacy of EC-Doc [versus FEC (a combination of 5-fluorouracil, epirubicin, and cyclophosphamide)] was seen in EFS and OS: 5-year EFS: 89.8% versus 87.3% (P = 0.038); 5-year OS: 94.5% versus 92.8% (P = 0.034); both tests one-tailed. EC-Doc caused more toxicity. In hormone receptor-positive (HR)+ disease, only high-Ki-67 tumors (≥ 20%) derived significant benefit from taxane-based therapy: hazard ratio = 0.39 (95% CI 0.18-0.82) for EC-Doc versus FEC (test for interaction; P = 0.01). CONCLUSION: EC-Doc significantly improved EFS and OS versus FEC in intermediate-risk BC (1-3 LNs) within all subgroups as defined by local pathology. In HR+ disease, patients with luminal A-like tumors may be potentially over-treated by taxane-based chemotherapy. CLINICAL TRIAL NUMBER: ClinicalTrials.gov, NCT02115204.

Use of the Nexfin™ device to detect acute arterial pressure variations during anaesthesia induction.

BACKGROUND: Standard non-invasive arterial pressure (AP) measurements are discontinuous. By providing non-invasive beat-to-beat AP measurements, Nexfin™ might limit duration of intraoperative hypotension and hypertension. We assessed the ability of Nexfin™ to detect AP variations by comparing its trending ability with invasive AP monitoring. METHODS: Thirty-one subjects undergoing elective surgery under general anaesthesia were included. During induction, simultaneous pairs of AP measurements were collected every 5 s from the Nexfin™ finger sensor and a homolateral radial artery catheter. Magnitude and time lags of AP variations from baseline to nadir and peak were calculated for both methods. Concordance analysis was performed by the Bland-Altman method (for comparison of repeated measures when appropriate). RESULTS: Nexfin™ detected 100% of AP changes with the median delays of 0 s (-13 to 7) and 0 s (-5 to 12) for nadir and peak, respectively. Bias [limits of agreement (LOA)] of systolic AP (SAP) variations was -0.5 mm Hg (-31.2 to 30.2) and -9.4 mm Hg (-31.3 to 12.6) from baseline to nadir and from baseline to peak, respectively. For 3479 analysed paired measurements, bias was -3.8 and -8.8 mm Hg for SAP and diastolic AP, with LOA of (-36.0 to 28.5) and (-29.8 to 12.3), respectively. CONCLUSIONS: Nexfin™ detects AP variations accurately and can be a useful warning device during anaesthesia. However, it is not interchangeable with invasive monitoring, given the large LOA between the two measurements. CLINICAL TRIAL REGISTRATION: NCT01658631.

Preoperative depression and hospital length of stay in surgical patients.

BACKGROUND: The association of depression and hospital length of stay (LOS) has rarely been examined in surgical patients outside of cardiovascular surgery. This study investigates whether clinically significant preoperative depression shows an independent association with LOS in patients from various surgical fields after adjusting for age, gender and important somatic factors. METHODS: A total of 2624 surgical patients were included in this prospective observational study. Data were collected before the preoperative anesthesiological examination within a computer-assisted psychosocial self-assessment including screening for depression (Center for Epidemiologic Studies Depression Scale, CES-D). Data on peri- and postoperative somatic parameters were obtained from the electronic patient management system of the hospital six months after the preoperative assessment. RESULTS: LOS of patients with clinically significant depression (N.=296; median: 5 days, interquartile range: 3-8 days) was longer than LOS of patients without depression (N.=2328; median: 4 days, interquartile range: 2-6 days) (P<0.001). A multivariate logistic regression model with the binary dependent variable 'above versus below or equal to the median LOS' revealed that the significant association between depression and LOS persisted (OR: 1.822 [95% CI 1.360-2.441], P<0.001) when simultaneously including the covariates age, gender, ASA classification, Charlson Comorbidity Index, surgical field and POSSUM operative severity rating. CONCLUSION: Data suggest that the association of depression and LOS is independent of the impact of age, gender, surgical field, preoperative physical health, severity of medical comorbidity and extent of surgical procedure. Integration of depression therapy into routine care of surgical patients might be an option to improve outcomes.

Phantom rectum following abdominoperineal excision for rectal neoplasm: appearance and disappearance.

AIM: The sensation that the rectum remains or is functioning after abdominoperineal excision (APE) is called phantom rectum (PR). Its postoperative and long-term morbidity are not well documented. Informed consent may not include the risk and consequences of this condition. We assessed the incidence and morbidity of PR after APE and compared those with vs those without vertical rectus abdominis myocutaneous flaps. METHOD: Patients who underwent APE between 1 January 2004 and 31 December 2008 were identified. Preoperative radiation and operative reconstruction by vertical rectus abdominis myocutaneous (VRAM) flaps were noted. Patients were interviewed by telephone to assess the presence and timing of PR symptoms and their effect on quality of life. RESULTS: Thirty-six of 80 patients who underwent APE were available for follow-up. Twenty-three (64%) described PR symptoms including urgency to evacuate [22 (61%)], sensation of faeces in the rectum [19 (52%)] and sensation of passing flatus [17 (48%)]. Eleven (47%) who had VRAM vs 25 who did not, reported having symptoms of PR at < 3 months after APE. Patients described their symptoms as 'unchanged over time' [20 (56%)], 'gradually decreasing and ultimately disappearing' [13 (35%)] or 'worsening' [3 (9%)]. Preoperative radiation and laparoscopic approach were not associated with PR symptoms. Significantly more patients having a VRAM flap reported early PR symptoms [7/11 (64%) vs 4/25 (16%)] (P = 0.008). CONCLUSION: PR sensations were experienced by 23 (64%) patients who underwent APE for rectal cancer. VRAM reconstruction was associated with early PR presentation. The possibility of PR should be discussed preoperatively in patients undergoing APE for anorectal neoplasm.

Are postoperative complications more common following colon and rectal surgery in patients with chronic kidney disease?

AIM: According to National Kidney Foundation guidelines, early stages of chronic kidney disease (CKD) can be detected through the estimated glomerular filtration rate (eGFR). We assessed complications following colorectal surgery (CRS) in patients with CKD Stages 3 and 4, as defined by the eGFR. METHOD: Patients with CKD were identified within our database. Patients with an eGFR of 15-59 ml/min (CKD Stages 3 and 4) formed the CKD group and were compared with American Society of Anesthesiology (ASA) score-matched controls with an eGFR of ≥ 60 ml/min. Assessments included demographics, comorbidity, ASA score, operative details and 30-day postoperative outcome. RESULTS: Seventy patients in the CKD group were matched with 70 controls. ASA scores and length of stay did not differ significantly between the groups. CKD patients were older (mean age 76.5 years vs 71.1 years; P < 0.001) and had a lower mean body mass index (24.3 vs 28.2; P < 0.001) compared with controls. Compared with the CKD group, the mean operation time was longer in the control group (181.5 min vs 151.6 min; P = 0.02) and the estimated blood loss was greater (232 ml vs 165 ml; P = 0.004). Postoperative infection was more common in the CKD group (60%vs 40%; P = 0.01). There were no significant differences in reoperation rates, 30-day readmissions or the incidence of acute renal failure (ARF). CONCLUSION: Patients with CKD Stages 3 and 4 had a higher incidence of postoperative infections than matched controls after colorectal surgery. ARF developed in 18.6% of patients. Preoperative optimization should include adequate hydration and assessment of potentially nephrotoxic substances for bowel preparation, preoperative antibiotics and pain control.

Thymosin beta 15A (TMSB15A) is a predictor of chemotherapy response in triple-negative breast cancer.

BACKGROUND: Biomarkers predictive of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) of breast cancer are urgently needed. METHODS: Using a training/validation approach for detection of predictive biomarkers in HER2-negative breast cancer, pre-therapeutic core biopsies from four independent cohorts were investigated: Gene array data were analysed in fresh frozen samples of two cohorts (n=86 and n=55). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in formalin-fixed, paraffin-embedded (FFPE) samples from two neoadjuvant phase III trials (GeparTrio, n=212, and GeparQuattro, n=383). RESULTS: A strong predictive capacity of thymosin beta 15 (TMSB15A) gene expression was evident in both fresh frozen cohorts (P<0.0001; P<0.0042). In the GeparTrio FFPE training cohort, a significant linear correlation between TMSB15A expression and pCR was apparent in triple-negative breast cancer (TNBC) (n=61, P=0.040). A cutoff point was then defined that divided TNBC into a low and a high expression group (pCR rate 16.0% vs 47.2%). Both linear correlation of TMSB15A mRNA levels (P=0.017) and the pre-defined cutoff point were validated in 134 TNBC from GeparQuattro (pCR rate 36.8% vs 17.0%, P=0.020). No significant predictive capacity was observed in luminal carcinomas from GeparTrio and GeparQuattro. CONCLUSION: In TNBC, TMSB15A gene expression analysis might help to select patients with a high chance for pCR after NACT.

A method to evaluate dose errors introduced by dose mapping processes for mass conserving deformations.

PURPOSE: To present a method to evaluate the dose mapping error introduced by the dose mapping process. In addition, apply the method to evaluate the dose mapping error introduced by the 4D dose calculation process implemented in a research version of commercial treatment planning system for a patient case. METHODS: The average dose accumulated in a finite volume should be unchanged when the dose delivered to one anatomic instance of that volume is mapped to a different anatomic instance-provided that the tissue deformation between the anatomic instances is mass conserving. The average dose to a finite volume on image S is defined as d(S)=e(s)/m(S), where e(S) is the energy deposited in the mass m(S) contained in the volume. Since mass and energy should be conserved, when d(S) is mapped to an image R(d(S→R)=d(R)), the mean dose mapping error is defined as Δd(m)=|d(R)-d(S)|=|e(R)/m(R)-e(S)/m(S)|, where the e(R) and e(S) are integral doses (energy deposited), and m(R) and m(S) are the masses within the region of interest (ROI) on image R and the corresponding ROI on image S, where R and S are the two anatomic instances from the same patient. Alternatively, application of simple differential propagation yields the differential dose mapping error, Δd(d)=|∂d∂e*Δe+∂d∂m*Δm|=|(e(S)-e(R))m(R)-(m(S)-m(R))m(R) (2)*e(R)|=α|d(R)-d(S)| with α=m(S)/m(R). A 4D treatment plan on a ten-phase 4D-CT lung patient is used to demonstrate the dose mapping error evaluations for a patient case, in which the accumulated dose, D(R)=∑(S=0) (9)d(S→R), and associated error values (ΔD(m) and ΔD(d)) are calculated for a uniformly spaced set of ROIs. RESULTS: For the single sample patient dose distribution, the average accumulated differential dose mapping error is 4.3%, the average absolute differential dose mapping error is 10.8%, and the average accumulated mean dose mapping error is 5.0%. Accumulated differential dose mapping errors within the gross tumor volume (GTV) and planning target volume (PTV) are lower, 0.73% and 2.33%, respectively. CONCLUSIONS: A method has been presented to evaluate the dose mapping error introduced by the dose mapping process. This method has been applied to evaluate the 4D dose calculation process implemented in a commercial treatment planning system. The method could potentially be developed as a fully-automatic QA method in image guided adaptive radiation therapy (IGART).