The effect of intra-operative hypotension on acute kidney injury, postoperative mortality and length of stay following emergency hip fracture surgery.

The association between intra-operative hypotension and postoperative acute kidney injury, mortality and length of stay has not been comprehensively evaluated in a large single-centre hip fracture population. We analysed electronic anaesthesia records of 1063 patients undergoing unilateral hip fracture surgery, collected from 2015 to 2018. Acute kidney injury, 3-, 30- and 365-day mortality and length of stay were evaluated to assess the relationship between intra-operative hypotension absolute values (≤ 55, 60, 65, 70 and 75 mmHg) and duration of hypotension. The rate of acute kidney injury was 23.7%, mortality at 3-, 30- and 365 days was 3.7%, 8.0% and 25.3%, respectively, and median (IQR [range]) length of stay 8 (6-12 [0-99]) days. Median (IQR [range]) time ≤ MAP 55, 60, 65, 70 and 75 mmHg was 0 (0-0.5[0-72.1]); 0 (0-4.4 [0-104.9]); 2.2 (0-8.7 [0-144.2]); 6.6 (2.2-19.7 [0-198.8]); 17.5 (6.6-37.1 [0-216.3]) minutes, and percentage of surgery time below these thresholds was 1%, 2.5%, 7.9%, 12% and 21% respectively. There were some univariate associations between hypotension and mortality; however, these were no longer evident in multivariable analysis. Multivariable analysis found no association between hypotension and acute kidney injury. Acute kidney injury was associated with male sex, antihypertensive medications and cardiac/renal comorbidities. Three-day mortality was associated with delay to surgery ? 48 hours, whilst 30-day and 365-day mortality was associated with delay to surgery ≥ 48 hours, impaired cognition and cardiac/renal comorbidities. While the rate of acute kidney injury was similar to other studies, use of vasopressors and fluids to reduce the time spent at hypotensive levels failed to reduce this complication. Intra-operative hypotension at the levels observed in this cohort may not be an important determinant of acute kidney injury, postoperative mortality and length of stay.

Factors associated with persistent opioid use 6-12 months after primary total knee arthroplasty.

Persistent pain following knee arthroplasty occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty using a standardised enhanced recovery programme. Opioid prescribing for 12 months before and 12 months after surgery was evaluated and converted to oral morphine equivalents. Demographic, functional, psychological and pain questionnaires were completed along with quantitative sensory testing and genetic analysis. Forty-nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients ≥6 months after surgery. Persistent opioid use ≥6 months after surgery was strongly associated with pre-operative opioid use (RR 3.2, p < 0.001 (95%CI 1.9-5.4)). The median (IQR [range]) oral morphine equivalent daily dose was 3.6 (0.9-10.5 [0-100.0]) mg pre-operatively, 35.0 (22.5-52.5 [4.6-180.0]) mg in hospital, 12.8 (5.1-24.8 [0-57.9]) mg from discharge to 3 months and 5.9 (4.5-12.0 [0-44.5]) mg at ≥6 months following surgery. Predictors of increased daily oral morphine equivalent ≥6 months after surgery included increased average daily oral morphine equivalent dose compared with previous values (lag), increased body mass index and three or more comorbid pain sites. Persistent opioid use was not associated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (RR 1.003, p = 0.655, 95%CI 0.65-1.002) or WOMAC function (RR 1.001, p = 0.99, 95%CI 0.99-1.03) outcomes 6 months after surgery. There was no association between persistent opioid use and pre-operative quantitative sensory testing results or psychological distress. Pre-operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose ≥ 6 months after surgery. Strategies need to be developed to limit dose and duration of persistent opioid use in patients following knee arthroplasty surgery.

Analysis of trimodal and bimodal therapy in a selective-surgery paradigm for locally advanced oesophageal squamous cell carcinoma.

BACKGROUND: Long-term survival outcomes of trimodal therapy (TMT; chemoradiation plus surgery) and bimodal therapy (BMT; chemoradiation) have seldom been analysed. In a selective-surgery paradigm, the benefit of TMT in patients with a complete clinical response is controversial. Factors associated with survival in patients with a clinical complete response to chemoradiation were evaluated. METHODS: Patients with stage II-III oesophageal squamous cell carcinoma treated with TMT or BMT from 2002 to 2017 were evaluated. The BMT group consisted of patients who were otherwise eligible for surgery but underwent chemoradiation alone followed by observation. This group included patients who later had salvage oesophagectomy. Survival was evaluated and compared between TMT and BMT groups. Elastic net regularization was performed to select co-variables for Cox multivariable survival analysis in patients with a clinical complete response. RESULTS: Of 143 patients, 60 (41.9 per cent) underwent TMT and 83 (58.0 per cent) BMT. Patients who underwent TMT had longer median overall survival than those who had BMT (77 versus 33 months; P = 0.019). For patients with a clinical complete response, TMT achieved longer median overall survival than BMT (123 versus 55 months; P = 0.04). BMT had a high locoregional recurrence rate (48 versus 6 per cent; P < 0.001); 26 of 29 patients with locoregional recurrence in the BMT groupunderwent salvage resection. Cox multivariable analysis demonstrated that upper-mid oesophageal tumour location (hazard ratio (HR) 2.04; P = 0.024) and tumour length (HR 1.18; P = 0.046) were associated with worse survival. Although TMT was not associated with survival, it was a predictor of reduced recurrence (HR 0.28; P = 0.028). The maximum standardized uptake value after chemoradiation also predicted recurrence (HR 1.33; P < 0.001). CONCLUSION: In patients who achieve a clinical complete response, TMT reduces locoregional recurrence but may not prolong survival. The differences in survival outcomes may be due to patient selection; therefore, a selective-surgery strategy in oesophageal squamous cell carcinoma is a reasonable approach.

Steroids to reduce the impact on delirium (STRIDE): a double-blind, randomised, placebo-controlled feasibility trial of pre-operative dexamethasone in people with hip fracture.

Neuro-inflammation may be important in the pathogenesis of postoperative delirium following hip fracture surgery. Studies have suggested a potential role for steroids in reducing postoperative delirium; however, the potential efficacy and safety of pre-operative high-dose dexamethasone in this specific population is largely unknown. Conducting such a study could be challenging, considering the multidisciplinary team involvement and the emergency nature of the surgery. The aim of this study was to assess feasibility and effectiveness of dexamethasone given as early as possible following hospital admission for hip fracture, to inform whether a full-scale trial is warranted. This single-centre, randomised, double-blind, placebo-controlled study randomly allocated 79 participants undergoing hip fracture surgery to dexamethasone 20 mg or placebo pre-operatively. Eligibility and recruitment rates, timing of the intervention and adverse events were recorded. Incidence and severity of postoperative delirium were assessed using the 4AT delirium screening tool and the Memorial Delirium Assessment Scale. Postoperative pain, length of stay and mortality were also assessed. The eligibility rate for inclusion was 178/527 (34%), and 57/178 (32%) of eligible patients presented to hospital when no researcher was available (e.g. after-hours, weekends, public holidays). Recruitment was limited mainly by ethical limitations (not including patients with impaired cognition) and lack of weekend staffing. Median (IQR [range]) time from emergency department admission to drug administration was 13.3 (5.9-17.6 [1.8-139.6]) hours. There was a significant difference in delirium severity scores, favouring the dexamethasone group: median (IQR [range]) 5 (3-6 [3-7]) vs. 9 (6-13 [5-14]) in the placebo group, with the probability of superiority effect size being 0.89, p = 0.010. Delirium incidence did not differ between groups: 6/40 (15%) in the dexamethasone group vs. 9/39 (23%) in the placebo group, relative risk (95%CI) 0.65 (0.22-1.65), p = 0.360). A larger randomised controlled trial is feasible and ideally this should include people with existing cognitive impairment, seven days-a-week cover and a multicentre design.

An evaluation of DistillerSR's machine learning-based prioritization tool for title/abstract screening - impact on reviewer-relevant outcomes.

BACKGROUND: Systematic reviews often require substantial resources, partially due to the large number of records identified during searching. Although artificial intelligence may not be ready to fully replace human reviewers, it may accelerate and reduce the screening burden. Using DistillerSR (May 2020 release), we evaluated the performance of the prioritization simulation tool to determine the reduction in screening burden and time savings. METHODS: Using a true recall @ 95%, response sets from 10 completed systematic reviews were used to evaluate: (i) the reduction of screening burden; (ii) the accuracy of the prioritization algorithm; and (iii) the hours saved when a modified screening approach was implemented. To account for variation in the simulations, and to introduce randomness (through shuffling the references), 10 simulations were run for each review. Means, standard deviations, medians and interquartile ranges (IQR) are presented. RESULTS: Among the 10 systematic reviews, using true recall @ 95% there was a median reduction in screening burden of 47.1% (IQR: 37.5 to 58.0%). A median of 41.2% (IQR: 33.4 to 46.9%) of the excluded records needed to be screened to achieve true recall @ 95%. The median title/abstract screening hours saved using a modified screening approach at a true recall @ 95% was 29.8 h (IQR: 28.1 to 74.7 h). This was increased to a median of 36 h (IQR: 32.2 to 79.7 h) when considering the time saved not retrieving and screening full texts of the remaining 5% of records not yet identified as included at title/abstract. Among the 100 simulations (10 simulations per review), none of these 5% of records were a final included study in the systematic review. The reduction in screening burden to achieve true recall @ 95% compared to @ 100% resulted in a reduced screening burden median of 40.6% (IQR: 38.3 to 54.2%). CONCLUSIONS: The prioritization tool in DistillerSR can reduce screening burden. A modified or stop screening approach once a true recall @ 95% is achieved appears to be a valid method for rapid reviews, and perhaps systematic reviews. This needs to be further evaluated in prospective reviews using the estimated recall.

Morbidity following salvage esophagectomy for squamous cell carcinoma: the MD Anderson experience.

The survival advantage associated with the addition of surgical therapy in esophageal squamous cell carcinoma (ESCC) patients who demonstrate a complete clinical response to chemoradiotherapy is unclear, and many institutions have adopted an organ-preserving strategy of selective surgery in this population. We sought to characterize our institutional experience of salvage esophagectomy (for failure of definitive bimodality therapy) and planned esophagectomy (as a component of trimodality therapy) by retrospectively analyzing patients with ESCC of the thoracic esophagus and GEJ who underwent esophagectomy following chemoradiotherapy between 2004 and 2016. Of 76 patients who met inclusion criteria, 46.1% (35) underwent salvage esophagectomy. Major postoperative complications (major cardiovascular and pulmonary events, anastomotic leak [grade ≥ 2], and 90-day mortality) were frequent and occurred in 52.6% of the cohort (planned resection: 36.6% [15/41]; salvage esophagectomy: 71.4% [25/35]). Observed rates of 30- and 90-day mortality for the entire cohort were 7.9% (planned: 7.3% [3/41]; salvage: 8.6% [3/35]) and 13.2% (planned: 9.8% [4/41]; salvage: 17.1% [6/35]), respectively. In summary, esophagectomy following chemoradiotherapy for ESCC at our institution has been associated with frequent postoperative morbidity and considerable rates of mortality in both planned and salvage settings. Although a selective approach to surgery may permit organ preservation in many patients with ESCC, these results highlight that salvage esophagectomy for failure of definitive-intent treatment of ESCC may also constitute a difficult clinical undertaking in some cases.

Screening questionnaires for substance abuse post brain injury: a review.

OBJECTIVE: To assess the psychometric properties of the available assessment questionnaires for substance abuse studied within a brain injury population. METHODS: A literature search was conducted on MEDLINE, PsycINFO, CINAHL, and Embase databases. Articles published in English from inception through March 2018 on the screening questionnaires used to identify substance abuse post brain injury were reviewed. Eligible primary studies had to include: adults (participants ≥18 years old) post brain injury; and report measures of diagnostic accuracy (e.g., sensitivity, specificity, and diagnostic odds ratio). RESULTS: Six screening questionnaires were included: Alcohol Use Disorders Identification Test, Brief Michigan Alcohol Screening Test, CAGE, Drug Abuse Screening Test, Substance Abuse Screening Inventory and the Short Michigan Alcohol Screening Test (SMAST). All questionnaires, except the SMAST, used the Diagnostic and Statistical Manual of Mental Disorders as the criterion measure. While report measures of diagnostic accuracy were reported and summarized, none of the studies provided reliability information or subgroup analysis among those with brain injury. CONCLUSIONS: Concerns of social desirability, population demographics, responsiveness to treatment effects, and administrative burden are important when selecting a questionnaire. Research examining the reliability of substance abuse screening questionnaires in the brain injury population is lacking and future research is warranted.

Persistent postoperative pain after total knee arthroplasty: a prospective cohort study of potential risk factors.

BACKGROUND: Persistent postoperative pain (PPP) is common after total knee arthroplasty (TKA). The primary aim of this prospective cohort study was to identify important predictors of moderate to severe PPP 6 and 12 months after TKA. METHODS: Consenting patients (n=300) undergoing primary unilateral TKA attended a preoperative session to collect clinical information (age, gender, BMI, preoperative knee pain, comorbid pain, likely neuropathic pain) and psychological variables (depression, anxiety, catastrophising, expected pain). Quantitative sensory testing (pressure pain thresholds, temporal summation, conditioned pain modulation) was performed, and blood samples were obtained for subsequent genotyping of OPRM1 and COMT. Acute postoperative pain was measured at rest and during movement. Surgical factors (surgery time, patella resurfacing, anaesthetic type) were collected after operation. Follow-up questionnaires were sent 6 and 12 months after surgery. Multivariate logistic regression was used to identify predictors of PPP. RESULTS: The prevalence of moderate to severe PPP was 21% (n=60) and 16% (n=45) 6 and 12 months after surgery, with 55% (n=33) and 60% (n=31) of PPP likely neuropathic in nature. At 6 months, a combination of preoperative pain intensity, expected pain, trait anxiety, and temporal summation (Akaike information criterion, 309.9; area under receiver operating characteristic (ROC) curve, 0.70) was able to correctly classify 66% of patients into moderate to severe PPP and no to mild PPP groups. At 12 months, preoperative pain intensity, expected pain, and trait anxiety (Akaike information criterion, 286.8; area under ROC curve, 0.66) correctly classified 66% of patients. CONCLUSIONS: Findings from this study highlight several factors that may be targeted in future intervention studies to reduce the development of PPP. TRIAL REGISTRY NUMBER: ACTRN12612001089820.

Label-free multimodal coherent anti-Stokes Raman scattering analysis of microparticles in unconstrained microfluidics.

Fast, label-free optical identification and quantification of biomolecules and other relevant biological materials in microfluidic devices and the vascular system will play a major role in liquid biopsy and related diagnoses. An optical microscope probing simultaneously non-linear coherent anti-Stokes Raman scattering (CARS) and linear scattering (LS) was used to probe microparticles in aqueous solutions flowed unconstrained in microfluidic channels. Despite the optical complexity of these systems, where out-of-focus microparticles randomly impede CARS and LS, and where water CARS generates a substantial background, we demonstrate that in-focus microparticles can be individually and unambiguously detected when CARS and LS are co-analyzed. The ability to chemically discriminate microscale features in optically realistic flows supports the relevance of multimodal CARS platforms for liquid biopsy.

TENS Alleviates Muscle Weakness Attributable to Attenuation of Ia Afferents.

Quadriceps weakness is a notable problem following knee damage. Research has shown effectiveness of TENS in improving Quadriceps weakness associated with arthrogenic muscle inhibition. However, these studies were not focused upon short term delivery of TENS, nor did they examine the potential mechanism(s). The present study examined the effect of 25-30 s of TENS upon weakness induced temporarily by a prolonged vibration. Subjects performed eccentric MVCs under 2 conditions (TENS and no-TENS). First, MVC was measured at baseline. For the TENS condition, TENS was applied to each subject's knee joint during a second MVC measurement after vibration. For no-TENS condition, TENS was not applied during the 2nd MVC measurement. MVC between pre-and post-vibration stimulation were compared across the 2 conditions. The results showed that MVC and EMG of TENS-condition was larger than that of no-TENS condition. Our results suggest that TENS could partially restore α-motoneuron activation, despite the induced dysfunctional γ-loop. These results suggest that mechanisms independent of the γ-loop such as a direct facilitation of the QF α-motoneuron pool by a long latency spinal-reflex and/or supraspinal mechanisms appear more likely to be responsible. The findings provide further support for utilizing TENS, even when γ-loop dysfunction is present following joint damage.

Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Several studies have identified clinical, psychosocial, patient characteristic, and perioperative variables that are associated with persistent postsurgical pain; however, the relative effect of these variables has yet to be quantified. The aim of the study was to provide a systematic review and meta-analysis of predictor variables associated with persistent pain after total knee arthroplasty (TKA). METHODS: Included studies were required to measure predictor variables prior to or at the time of surgery, include a pain outcome measure at least 3 months post-TKA, and include a statistical analysis of the effect of the predictor variable(s) on the outcome measure. Counts were undertaken of the number of times each predictor was analysed and the number of times it was found to have a significant relationship with persistent pain. Separate meta-analyses were performed to determine the effect size of each predictor on persistent pain. Outcomes from studies implementing uni- and multivariable statistical models were analysed separately. RESULTS: Thirty-two studies involving almost 30 000 patients were included in the review. Preoperative pain was the predictor that most commonly demonstrated a significant relationship with persistent pain across uni- and multivariable analyses. In the meta-analyses of data from univariate models, the largest effect sizes were found for: other pain sites, catastrophizing, and depression. For data from multivariate models, significant effects were evident for: catastrophizing, preoperative pain, mental health, and comorbidities. CONCLUSIONS: Catastrophizing, mental health, preoperative knee pain, and pain at other sites are the strongest independent predictors of persistent pain after TKA.

Expression profiling stratifies mesothelioma tumors and signifies deregulation of spindle checkpoint pathway and microtubule network with therapeutic implications.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal neoplasm exhibiting resistance to most treatment regimens and requires effective therapeutic options. Though an effective strategy in many cancer, targeted therapy is relatively unexplored in MPM because the therapeutically important oncogenic pathways and networks in MPM are largely unknown. MATERIALS AND METHODS: We carried out gene expression microarray profiling of 53 surgically resected MPMs tumors along with paired normal tissue. We also carried out whole transcriptomic sequence (RNA-seq) analysis on eight tumor specimens. Taqman-based quantitative Reverse-transcription polymerase chain reaction (qRT-PCR), western analysis and immunohistochemistry (IHC) analysis of mitotic arrest deficient-like 1 (MAD2L1) was carried out on tissue specimens. Cell viability assays of MPM cell lines were carried out to assess sensitivity to specific small molecule inhibitors. RESULTS: Bioinformatics analysis of the microarray data followed by pathway analysis revealed that the mitotic spindle assembly checkpoint (MSAC) pathway was most significantly altered in MPM tumors with upregulation of 18 component genes, including MAD2L1 gene. We validated the microarray data for MAD2L1 expression using quantitative qRT-PCR and western blot analysis on tissue lysates. Additionally, we analyzed expression of the MAD2L1 protein by IHC using an independent tissue microarray set of 80 MPM tissue samples. Robust clustering of gene expression data revealed three novel subgroups of tumors, with unique expression profiles, and showed differential expression of MSAC pathway genes. Network analysis of the microarray data showed the cytoskeleton/spindle microtubules network was the second-most significantly affected network. We also demonstrate that a nontaxane small molecule inhibitor, epothilone B, targeting the microtubules have great efficacy in decreasing viability of 14 MPM cell lines. CONCLUSIONS: Overall, our findings show that MPM tumors have significant deregulation of the MSAC pathway and the microtubule network, it can be classified into three novel molecular subgroups of potential therapeutic importance and epothilone B is a promising therapeutic agent for MPM.

Comparison of broiler performance and carcass yields when fed diets containing genetically modified canola meal from event DP-Ø73496-4, near-isogenic canola meal, or commercial canola meals.

Genetically modified (GM) canola (Brassica napus L.) line containing event DP-Ø73496-4 (hereafter referred to as 73496 canola) was produced by the insertion of the glyphosate acetyltransferase (gat4621) gene derived from Bacillus licheniformis. Expression of the GAT4621 protein present in 73496 canola plants confers in planta tolerance to the herbicidal active ingredient glyphosate. The objective of this study was to compare the nutritional performance of broiler chickens fed canola meal from 73496 canola seed with that of broiler chickens fed non-GM canola meal in a 42-d feeding trial. Diets were prepared using meal processed from seed from unsprayed 73496 plants or from plants sprayed with an in-field application of glyphosate herbicide [73496(S)]. For comparison, additional diets were produced with canola meal obtained from the non-GM near-isogenic control or non-GM commercial reference DuPont Pioneer brand varieties 42H72, 42H73, 46A65, and 44A89. Diets were fed to Ross 708 broilers (n = 120/group, 50% male and 50% female) in 3 phases: starter and grower phases containing 10 or 20% canola meal, respectively, and a finisher phase with a common corn-soybean meal diet without any canola meal. No statistically significant differences were observed in growth performance measures or organ and carcass yields between broilers consuming diets produced with canola meal from unsprayed or sprayed 73496 seed and those consuming diets produced with canola meal from control seed. Additionally, all performance, organ, and carcass measures from control, 73496, and 73496(S) canola treatment groups were within tolerance intervals constructed using data from the reference canola groups. It was concluded from these results that meal processed from 73496 canola seed (unsprayed plants or plants sprayed with glyphosate) was nutritionally equivalent to meal processed from non-GM near-isogenic control canola seed.

Risk factors for local and regional recurrence in patients with resected N0-N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy.

BACKGROUND: The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. PATIENTS AND METHODS: Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. RESULTS: Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. CONCLUSION: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.

Association between clinical complete response and pathological complete response after preoperative chemoradiation in patients with gastroesophageal cancer: analysis in a large cohort.

BACKGROUND: Chemoradiation followed by surgery is the preferred treatment of localized gastroesophageal cancer (GEC). Surgery causes considerable life-altering consequences and achievement of clinical complete response (clinCR; defined as postchemoradiation [but presurgery] endoscopic biopsy negative for cancer and positron emission tomographic (PET) scan showing physiologic uptake) is an enticement to avoid/delay surgery. We examined the association between clinCR and pathologic complete response (pathCR). PATIENTS AND METHODS: Two hundred eighty-four patients with GEC underwent chemoradiation and esophagectomy. The chi-square test, Fisher exact test, t-test, Kaplan-Meier method, and log-rank test were used. RESULTS: Of 284 patients, 218 (77%) achieved clinCR. However, only 67 (31%) of the 218 achieved pathCR. The sensitivity of clinCR for pathCR was 97.1% (67/69), but the specificity was low (29.8%; 64/215). Of the 66 patients who had less than a clinCR, only 2 (3%) had a pathCR. Thus, the rate of pathCR was significantly different in patients with clinCR than in those with less than a clinCR (P < 0.001). CONCLUSIONS: clinCR is not highly associated with pathCR; the specificity of clinCR for pathCR is too low to be used for clinical decision making on delaying/avoiding surgery. Surgery-eligible GEC patients should be encouraged to undergo surgery following chemoradiation despite achieving a clinCR.

Results of the baseline positron emission tomography can customize therapy of localized esophageal adenocarcinoma patients who achieve a clinical complete response after chemoradiation.

BACKGROUND: Patients with localized esophageal adenocarcinoma (EAC) who achieve a clinical complete response (clinCR) after preoperative chemoradiation (trimodality therapy; TMT) or definitive chemoradiation (bimodality therapy; BMT) live longer than those who achieve a

A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: The contribution of induction chemotherapy (IC) before preoperative chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC would increase the rate of pathologic complete response (pathCR). METHODS: Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ∼5-6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality, overall survival (OS), and toxic effects were assessed. Bayesian methods and Fisher's exact test were used. RESULTS: One hundred twenty-six patients were randomized dynamically to balance the two arms for histology, baseline stage, gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months [95% confidence interval (CI), 27.63-NA], with median OS 45.62 months (95% CI 25.56-NA) in Arm A and 43.68 months (95% CI 27.63-NA) in Arm B (P = 0.69). The pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided Fisher's exact test, P = 0.094). Safety was similar in both arms. CONCLUSIONS: These data suggest that IC produces non-significant increase in the pathCR rate and does not prolong OS. Further development of IC before chemoradiation may not be beneficial. Clinical trial no.: NCT 00525915 (www.clinicaltrials.gov).

Affinity filtration coupled with capillary-based affinity purification for the isolation of protein complexes.

The isolation of complex macromolecular assemblies at the concentrations required for structural analysis represents a major experimental challenge. Here we present a method that combines the genetic power of site-specific recombination in order to selectively "tag" one or more components of a protein complex with affinity-based rapid filtration and a final step of capillary-based enrichment. This modified form of tandem affinity purification produces highly purified protein complexes at high concentrations in a highly efficient manner. The application of the method is demonstrated for the yeast Arp2/3 heptameric protein complex involved in mediating reorganization of the actin cytoskeleton.

Open-lung biopsy in patients with undiagnosed lung lesions referred at a tertiary cancer center is safe and reveals noncancerous, noninfectious entities as the most common diagnoses.

We evaluated the diagnostic yield of open-lung biopsies (OLBs) in a large tertiary cancer center to determine the role of infectious diseases as causes of undiagnosed pulmonary lesions. All consecutive adult patients with either single or multiple pulmonary nodules or masses who underwent a diagnostic OLB over a period of 10 years (1998-2007) were retrospectively identified. Their risk factors for malignancy and clinical and radiological characteristics were reviewed, and their postoperative complications were assessed. We evaluated 155 patients with a median age of 57 years (range, 19-83 years). We identified infectious etiologies in 29 patients (19 %). The most common diagnosis in this group was histoplasmosis (12 [41 %]), followed by nontuberculous mycobacterial infection (7 [24 %]) and aspergillosis (4 [14 %]). The majority of the 126 remaining patients had nonmalignant diagnoses, the most prevalent being nonspecific granuloma (26 %), whereas only 17 % had malignant diagnoses. We observed no significant differences among the patients with infectious, malignant, or both noninfectious and nonmalignant final diagnoses regarding their demographic, laboratory, and clinical characteristics. Six percent of the patients had at least one post-OLB complication, and the post-OLB mortality rate was 1 %. OLB is a safe diagnostic procedure which frequently identifies a wide variety of infectious and inflammatory diseases.

Clinical parameters model for predicting pathologic complete response following preoperative chemoradiation in patients with esophageal cancer.

BACKGROUND: Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (≥60%) probability. PATIENTS AND METHODS: We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model. RESULTS: The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline (EUS)T stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662-0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643-0.728). CONCLUSION: Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR.