Chronic subclinical mastitis reduces milk and components yield at the cow level.

We evaluated the effects of chronic subclinical mastitis (CSM) caused by different types of pathogens on milk yield and milk components at the cow level. A total of 388 Holstein cows had milk yield measured and were milk sampled three times at intervals of two weeks for determination of SCC and milk composition, and microbiological culture was performed. Cows were considered healthy if all three samples of SCC were ≤200 000 cells/ml and were culture-negative at the third milk sampling. Cows with one result of SCC > 200 000 cells/ml were considered to suffer non-chronic subclinical mastitis whereas cows with at least 2 out of 3 results of SCC > 200 000 cells/ml had CSM. These latter cows were further sorted according to culture results into chronic negative-culture or chronic positive-culture. This resulted in four udder health statuses: healthy, non-chronic, chronicNC or chronicPC. The milk and components yields were evaluated according to the udder health status and by pathogen using a linear mixed effects model. A total of 134 out of 388 cows (34.5%) were chronicPC, 57 cows (14.7%) were chronicNC, 78 cows (20.1%) were non-chronic and 119 cows (30.7%) were considered healthy, which resulted in a grand total of 1164 cow records included in the statistical model. The healthy cows produced more milk than each of the other groups (+2.1 to +5.7 kg/cow/day) and produced higher milk component yields than the chronicPC cows. The healthy cows produced more milk than cows with chronicPC caused by minor (+5.2 kg/cow/day) and major pathogens (+7.1 kg/cow/day) and losses varied from 5.8 to 11.8 kg/cow/day depending on the pathogen causing chronicPC mastitis. Chronic positive-culture cows had a reduction of at least 24.5% of milk yield and 22.4% of total solids yield.

Impact of Micro- and Macroscopically Positive Surgical Margins on Survival after Resection of Adrenocortical Carcinoma.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare, aggressive cancer; complete surgical resection offers the best chance for long-term survival. The impact of surgical margin status on survival is poorly understood. Our objective was to determine the association of margin status with survival. METHODS: Patients with ACC were identified from the National Cancer Data Base, 1998-2012, and stratified based on surgical margin status (negative vs. microscopically positive [+] vs. macroscopically [+]). Univariate/multivariate regression/survival analyses were utilized to determine factors associated with margin status and overall survival (OS). RESULTS: A total of 1553 patients underwent surgery at 589 institutions: 86% had negative, 12% microscopically (+), and 2% macroscopically (+) margins. Those with microscopically (+) and macroscopically (+) margins more often received adjuvant chemotherapy (39.4% macroscopically (+) vs. 38.5% microscopically (+) vs. 25.2% negative margins, p < 0.001). For unadjusted analysis, there was a significant difference in OS between the groups (log-rank p < 0.001), with median survival times of 58 months (95% confidence interval [CI] 49-66) for those with negative margins, 22 months (95% CI 18-34) microscopically (+), and 14 months (95% CI 6-27) macroscopically (+) margins. After adjustment, both microscopically (+) (HR 1.76, p < 0.001) and macroscopically (+) (HR 2.10, p = 0.0019) margin status were associated with compromised survival. CONCLUSIONS: Having micro- or macroscopically (+) margin status after ACC resection is associated with dose-dependent compromised survival. These results underscore the importance of achieving negative surgical margins for optimizing long-term patient outcomes.

Complete versus culprit-only revascularisation in ST elevation myocardial infarction with multi-vessel disease.

BACKGROUND: Multi-vessel coronary disease in people with ST elevation myocardial infarction (STEMI) is common and is associated with worse prognosis after STEMI. Based on limited evidence, international guidelines recommend intervention on only the culprit vessel during STEMI. This, in turn, leaves other significantly stenosed coronary arteries for medical therapy or revascularisation based on inducible ischaemia on provocative testing. Newer data suggest that intervention on both the culprit and non-culprit stenotic coronary arteries (complete intervention) may yield better results compared with culprit-only intervention. OBJECTIVES: To assess the effects of early complete revascularisation compared with culprit vessel only intervention strategy in people with STEMI and multi-vessel coronary disease. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, World Health Organization International Clinical Trials Registry Platform Search Portal, and ClinicalTrials.gov. The date of the last search was 4 January 2017. We applied no language restrictions. We handsearched conference proceedings to December 2016, and contacted authors and companies related to the field. SELECTION CRITERIA: We included only randomised controlled trials (RCTs), wherein complete revascularisation strategy was compared with a culprit-only percutaneous coronary intervention (PCI) for the treatment of people with STEMI and multi-vessel coronary disease. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of each trial using the Cochrane 'Risk of bias' tool. We resolved the disagreements by discussion among review authors. We followed standard methodological approaches recommended by Cochrane. The primary outcomes were long-term (one year or greater after the index intervention) all-cause mortality, long-term cardiovascular mortality, long-term non-fatal myocardial infarction, and adverse events. The secondary outcomes were short-term (within the first 30 days after the index intervention) all-cause mortality, short-term cardiovascular mortality, short-term non-fatal myocardial infarction, revascularisation, health-related quality of life, and cost. We analysed data using fixed-effect models, and expressed results as risk ratios (RR) with 95% confidence intervals (CI). We used GRADE criteria to assess the quality of evidence and we conducted Trial Sequential Analysis (TSA) to control risks of random errors. MAIN RESULTS: We included nine RCTs, that involved 2633 people with STEMI and multi-vessel coronary disease randomly assigned to either a complete (n = 1381) versus culprit-only (n = 1252) revascularisation strategy. The complete and the culprit-only revascularisation strategies did not differ for long-term all-cause mortality (65/1274 (5.1%) in complete group versus 72/1143 (6.3%) in culprit-only group; RR 0.80, 95% CI 0.58 to 1.11; participants = 2417; studies = 8; I2 = 0%; very low quality evidence). Compared with culprit-only intervention, the complete revascularisation strategy was associated with a lower proportion of long-term cardiovascular mortality (28/1143 (2.4%) in complete group versus 51/1086 (4.7%) in culprit-only group; RR 0.50, 95% CI 0.32 to 0.79; participants = 2229; studies = 6; I2 = 0%; very low quality evidence) and long-term non-fatal myocardial infarction (47/1095 (4.3%) in complete group versus 70/1004 (7.0%) in culprit-only group; RR 0.62, 95% CI 0.44 to 0.89; participants = 2099; studies = 6; I2 = 0%; very low quality evidence). The complete and the culprit-only revascularisation strategies did not differ in combined adverse events (51/2096 (2.4%) in complete group versus 57/1990 (2.9%) in culprit-only group; RR 0.84, 95% CI 0.58 to 1.21; participants = 4086; I2 = 0%; very low quality evidence). Complete revascularisation was associated with lower proportion of long-term revascularisation (145/1374 (10.6%) in complete group versus 258/1242 (20.8%) in culprit-only group; RR 0.47, 95% CI 0.39 to 0.57; participants = 2616; studies = 9; I2 = 31%; very low quality evidence). TSA of long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction showed that more RCTs are needed to reach more conclusive results on these outcomes. Regarding long-term repeat revascularisation more RCTs may not change our present result. The quality of the evidence was judged to be very low for all primary and the majority of the secondary outcomes mainly due to risk of bias, imprecision, and indirectness. AUTHORS' CONCLUSIONS: Compared with culprit-only intervention, the complete revascularisation strategy may be superior due to lower proportions of long-term cardiovascular mortality, long-term revascularisation, and long-term non-fatal myocardial infarction, but these findings are based on evidence of very low quality. TSA also supports the need for more RCTs in order to draw stronger conclusions regarding the effects of complete revascularisation on long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction.

Using milk leukocyte differentials for diagnosis of subclinical bovine mastitis.

This research study aimed to evaluate the use of the milk leukocyte differential (MLD) to: (a) identify quarter milks that are culture-positive; and (b) characterize the milk leukocyte responses to specific groups of pathogens causing subclinical mastitis. The MLD measures the absolute number and relative percentage of inflammatory cells in milk samples. Using the MLD in two dairy herds (170 and 172 lactating cows, respectively), we studied all lactating cows with a most recent monthly Dairy Herd Improvement Association somatic cell count (SCC) >200 × 103 cells/ml. Quarter milk samples from 78 cows meeting study criteria were analysed by MLD and aseptically collected milk samples were subjected to microbiological culture (MC). Based upon automated instrument evaluation of the number and percentage of inflammatory cells in milk, samples were designated as either MLD-positive or - negative for subclinicial mastitis. Positive MC were obtained from 102/156 (65·4%) of MLD-positive milk samples, and 28/135 (20·7%) of MLD-negative milk samples were MC-positive. When MC was considered the gold standard for mastitis diagnosis, the calculated diagnostic Se of the MLD was 78·5% (IC(95%) = 70·4 to 85·2%) and the Sp was 66·5% (IC(95%) = 58·6 to 73·7%). [corrected]. Quarter milks positive on MC had higher absolute numbers of neutrophils, lymphocytes and macrophages, with higher neutrophils% and lymphocytes% but lower macrophages%. The Log10 (N/L) ratios were the most useful ratio to differentiate specific subclinical mastitis quarters from healthy quarters. Use of the MLD on cows with monthly composite SCC > 200 × 103 cells/ml for screening at quarter level identified quarters more likely to be culture-positive. In conclusion, the MLD can provide an analysis of mammary quarter status more detailed than provided by SCC alone; however, the MLD response to subclinical mastitis was not found useful to specifically identify the causative pathogen.

Bovine Staphylococcus aureus: dose response to iodine and chlorhexidine and effect of iodine challenge on antibiotic susceptibility.

Staphylococcus aureus is a gram-positive organism that is frequently associated with clinical or subclinical mastitis. The use of germicidal teat dips is one of the measures taken by the dairy industry to control mastitis. Iodine and chlorhexidine compounds are commonly used disinfectants in teat dips. We determined the minimum inhibitory concentrations (MIC) of iodine for 37 isolates of Staph. aureus and observed variations in MIC. Seven of these Staph. aureus isolates were selected as genotype group representatives based on their pulsed-field gel electrophoresis patterns. Dose responses against iodine and chlorhexidine were determined for the 7 genotype group representatives. The response of these isolates to iodine varied significantly, whereas all isolates were susceptible to chlorhexidine, even at concentrations as low as 0.0002%. We also evaluated whether exposure of Staph. aureus to sublethal levels of iodine influenced subsequent antibiotic susceptibility. No differences in antibiotic susceptibility of Staph. aureus were observed among cultures grown in brain heart infusion broth with and without supplemental iodine. The observed variation in iodine dose responses of Staph. aureus may have implications for the occurrence of Staph. aureus mastitis on dairy farms.

Transmission of methicillin-resistant Staphylococcus aureus between human and hamster.

Transmission of methicillin-resistant Staphylococcus aureus (MRSA) between humans and animals is increasingly recognized. We newly document that the transmission of MRSA between human and hamster is possible.

Simultaneous Versus Sequential Heart-liver Transplantation: Ideal Strategies for Organ Allocation.

BACKGROUND: Simultaneous heart-liver (SHL) transplantation is an efficacious therapeutic modality for patients with combined heart and liver failure. However, the extent to which heart transplantation followed by sequential liver transplantation (LAH) can match the benefit of simultaneous transplantation has not previously been examined. Our objective was to determine if LAH offers comparable survival to SHL. METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing Standard Transplant Analysis and Research file was queried for adult recipients waitlisted for both heart and liver transplantation. The United Network for Organ Sharing thoracic and liver databases were linked to facilitate examination of waitlist and transplant characteristics for simultaneously listed patients. Univariate survival analysis was used to determine overall survival. RESULTS: Of the 236 patients meeting inclusion criteria, 200 underwent SHL, 7 sequentially underwent LAH, and 29 received heart transplantation only (isolated orthotopic heart transplantation [iOHT]). Recipients of SHL were less likely to have an episode of acute rejection before discharge (LAH, 14.2%; SHL, 2.4%; iOHT, 3.6%; P = .019) or be treated for acute rejection within 1 year after transplantation (LAH, 14.3%; SHL, 2.5%; iOHT, 13.8%; P = .007). Otherwise, postoperative hospital length of stay, stroke, need for dialysis, and need for pacemaker placement were comparable across groups. Ten-year survival similarly favored both LAH and SHL over iOHT (LAH: 100%, 71.4%, 53.6%; SHL: 87.1%, 80.4%, 52.1%, iOHT: 70.1%, 51.6%, 27.5% for 1-, 5-, and 10-year survivals, respectively, P = .003). However, median time between heart and liver transplant was 302 days in patients undergoing sequential transplantation. CONCLUSIONS: Although transplantation in a simultaneous or sequential fashion yields equivalent outcomes, a high fraction of patients undergoing initial heart transplant alone fail to proceed to subsequent liver transplantation. Therefore, in patients with combined heart and liver failure with a projected need for 2 allografts, simultaneous transplantation is associated with maximum benefit.

Low- vs. High-Dose Neoadjuvant Radiation in Trimodality Treatment of Locally Advanced Esophageal Cancer.

BACKGROUND: The optimal dose of neoadjuvant radiation for locally advanced, resectable esophageal cancer remains controversial in the absence of randomized clinical trials, with conventional practice favoring the use of 50.4 vs. 41.4 Gy. METHODS: Retrospective analysis of adults with non-metastatic esophageal cancer in the National Cancer Database (2004-2015) treated with neoadjuvant chemoradiotherapy. Outcomes were compared between patients undergoing 41.4, 45, or 50.4 Gy. Primary outcome was overall survival. Secondary outcomes included T and N downstaging and perioperative mortality adjusted for demographics, clinicopathologic factors, and facility volume. RESULTS: Eight thousand eight hundred eighty-one patients were included: 439 (4.9%) received low-dose (41.4 Gy), 2194 (24.7%) received moderate-dose (45 Gy), and 6248 (70.4%) received high-dose (50.4 Gy) neoadjuvant radiation. Compared to high-dose, low-dose radiation was associated with superior median overall survival (52.6 vs. 40.7 months) and 5-year survival (48.3% vs. 40.2%), and lower unadjusted 90-day mortality (2.3% vs. 6.5%, all p ≤ 0.01). Multivariable proportional hazards models confirmed an increased hazard of death associated with high-dose radiation therapy (HR = 1.38, 95% CI 1.10-1.72, p = 0.005). There was no significant difference in T and/or N downstaging between low-dose vs. high-dose therapy (p > 0.1 for both). Patients receiving 45 Gy exhibited the lowest median overall survival (37.2 months) and 5-year survival (38.7%, log-rank p = 0.04). CONCLUSIONS: Compared to 50.4 Gy, 41.4 Gy is associated with reduced perioperative mortality and superior overall survival with similar downstaging in locally advanced esophageal cancer. In the absence of randomized clinical data, our findings support the use of 41.4 Gy in patients with chemoradiation followed by esophagectomy. Prospective trials are warranted to further validate these results.

Proof of concept of a method that assesses the spread of microbial infections with spatially explicit and non-spatially explicit data.

BACKGROUND: A method that assesses bacterial spatial dissemination was explored. It measures microbial genotypes (defined by electrophoretic patterns or EP), host, location (farm), interfarm Euclidean distance, and time. Its proof of concept (construct and internal validity) was evaluated using a dataset that included 113 Staphylococcus aureus EPs from 1126 bovine milk isolates collected on 23 farms between 1988 and 2005. RESULTS: Construct validity was assessed by comparing results based on the interfarm Euclidean distance (a spatially explicit measure) and those produced by the (non-spatial) interfarm number of isolates reporting the same EP. The distance associated with EP spread correlated with the interfarm number of isolates/EP (r = .59, P < 0.02). Internal validity was estimated by comparing results obtained with different versions of the same indices. Concordance was observed between: (a) EP distance (estimated microbial dispersal over space) and EP speed (distance/year, r = .72, P < 0.01), and (b) the interfarm number of isolates/EP (when measured on the basis of non-repeated cow testing) and the same measure as expressed by repeated testing of the same animals (r = .87, P < 0.01). Three EPs (2.6% of all EPs) appeared to be super-spreaders: they were found in 26.75% of all isolates. Various indices differentiated local from spatially disseminated infections and, within the local type, infections suspected to be farm-related were distinguished from cow-related ones. CONCLUSION: Findings supported both construct and internal validity. Because 3 EPs explained 12 times more isolates than expected and at least twice as many isolates as other EPs did, false negative results associated with the remaining EPs (those erroneously identified as lacking spatial dispersal when, in fact, they disseminated spatially), if they occurred, seemed to have negligible effects. Spatial analysis of laboratory data may support disease surveillance systems by generating hypotheses on microbial dispersal ability.

Comparison of the pharmacokinetics of plant-based treatments in milk and plasma of USDA organic dairy cattle with and without mastitis.

Organic dairy products are the second largest sector of the organic food market. Organic dairy products come from United States Department of Agriculture (USDA) certified organic dairy cattle that meet USDA organic standards. Organic dairy cattle in the US cannot be treated with antibiotics for mastitis, one of the costliest diseases of dairy cattle, and thus effective alternatives are needed. When any compound (medication or other non-food product) is used in a food producing animal, a withhold time for that compound that meets US Food and Drug Administration (FDA) standards for food safety must be applied to the animal and its products (like milk). However, there are no US FDA products approved for mastitis that maintain USDA certified organic dairy cattle's organic status. Thus, we studied the pharmacokinetics of 3 compounds (garlic, thymol and carvacrol) used on organic both healthy and mastitic organic dairy cattle. We also used this information to estimate a milk withhold time using methods consistent with US FDA requirements. For thymol intra-mammary and carvacrol intra-mammary or topical administration, all compounds were partially absorbed into the body from the milk or skin. Thymol and carvacrol are measurable in plasma (at 0.0183 and 0.0202 µg/mL, respectively) after intramammary administration with similar elimination half lives of 1.7 h. Milk concentrations of thymol and carvacrol are much higher at 2.958 and 4.487 µg/mL in healthy cattle, respectively. Concentrations are not significantly different in cows with mastitis as compared to those in healthy cows. Despite these compounds being natural products, they should have a withhold time for milk of at least 24 h after administration. For garlic, levels remained below the limit of detection in milk and plasma and thus no withdrawal time appears to be needed for milk.

Each procedure matters: threshold for surgeon volume to minimize complications and decrease cost associated with adrenalectomy.

BACKGROUND: An association has been suggested between increasing surgeon volume and improved patient outcomes, but a threshold has not been defined for what constitutes a "high-volume" adrenal surgeon. METHODS: Adult patients who underwent adrenalectomy by an identifiable surgeon between 1998-2009 were selected from the Healthcare Cost and Utilization Project National Inpatient Sample. Logistic regression modeling with restricted cubic splines was utilized to estimate the association between annual surgeon volume and complication rates in order to identify a volume threshold. RESULTS: A total of 3,496 surgeons performed adrenalectomies on 6,712 patients; median annual surgeon volume was 1 case. After adjustment, the likelihood of experiencing a complication decreased with increasing annual surgeon volume up to 5.6 cases (95% confidence interval, 3.27-5.96). After adjustment, patients undergoing resection by low-volume surgeons (<6 cases/year) were more likely to experience complications (odds ratio 1.71, 95% confidence interval, 1.27-2.31, P = .005), have a greater hospital stay (relative risk 1.46, 95% confidence interval, 1.25-1.70, P = .003), and at increased cost (+26.2%, 95% confidence interval, 12.6-39.9, P = .02). CONCLUSION: This study suggests that an annual threshold of surgeon volume (≥6 cases/year) that is associated with improved patient outcomes and decreased hospital cost. This volume threshold has implications for quality improvement, surgical referral and reimbursement, and surgical training.

Multifactorial relationships between intramammary invasion by Staphylococcus aureus and bovine leukocyte markers.

We explored the hypothesis that the outcome of bacterial invasion (infection or no infection) may depend on immunologic factors when bacterial and environmental factors are kept constant. Leukocyte surface molecules (CD3, CD2, CD4, CD8, CD11b, and CD45r) were assessed before and 3 times after intramammary infusion of Staphylococcus aureus in 5 dairy cows. The somatic cell count (SCC/mL), bacterial count (colony-forming units [CFUs]/mL), ratio of milk phagocytes (mononuclear [Mphi] plus polymorphonuclear [PMN] cells) to lymphocytes (P/L index), and ratio of PMN to Mphi cells (PMN/Mphi index) were determined. Although all cows showed evidence of inflammation resulting from the infusion (the median P/L ratio was 11 times greater 1 d after infusion than before infusion), bacteria were not obtained from the milk of 2 cows. Threshold-like responses, resulting in bacterial counts that approached zero (indicating no infection) and SCCs of less than 500000/mL, were observed when the milk CD2+ lymphocyte proportion exceeded 73% (P < or = 0.007). At 1 d after infusion, 7 immune factors distinguished infected cows from those without infection with more than 95% confidence: compared with infected cows, uninfected cows had higher proportions of CD3+, CD2+, CD4+, and CD8+ T cells, higher densities of CD3 and CD2 molecules per cell, and a higher density of CD11b molecules on milk Mphi cells. At 7 d after infusion, the PMN/Mphi index was lower (94% confidence) in uninfected than in infected cows. At 14 d, the CD2, CD8, and CD45r marker densities were lower than those at 1 d (P < 0.02), findings compatible with memory function. Synergism was suggested by the combined effects of the proportions of CD3+, CD2+, and CD11b+ cells, which explained 75.5% of the bacterial-count variability (P < 0.001); alone, none of these markers predicted CFU variability. These results support further studies aimed at identifying cows capable (or incapable) of early bacterial clearance.

Impact of minimally invasive vs. open distal pancreatectomy on use of adjuvant chemoradiation for pancreatic adenocarcinoma.

BACKGROUND: Published data examining the impact of minimally invasive distal pancreatectomy (MIDP) on survival are generally limited to experiences from high-volume institutions. Our aim was to compare utilization of adjuvant chemoradiation and time from surgery until its initiation following MIDP vs. open surgery (ODP) at a national level. METHODS: Adult patients undergoing distal pancreatectomy for Stage I and II pancreatic adenocarcinoma were identified from the National Cancer Data Base, 2010-2012. RESULTS: A total of 1807 patients underwent distal pancreatectomy for adenocarcinoma at 506 institutions (27.9% MIDP). After adjustment, those who underwent MIDP were more likely to have complete tumor resections and a shorter hospital length of stay. Patients undergoing MIDP vs. ODP were more likely to receive adjuvant chemotherapy; time to initiation of adjuvant chemotherapy or radiation was not different between groups. After adjustment, overall survival for MIDP vs. ODP remained similar (HR 0.85, CI 0.67-1.10, p = 0.21). CONCLUSION: MIDP is associated with increased use of adjuvant chemotherapy; further study is needed to understand the etiology and impact of this association.

Pharmacokinetic analysis of thymol, carvacrol and diallyl disulfide after intramammary and topical applications in healthy organic dairy cattle.

Mastitis is among the most costly concerns for dairy producers whether cattle are managed conventionally or organically. Unfortunately, there are no USFDA-approved mastitis treatments that allow dairy cows in the United States to maintain organic dairy status. We investigated the plasma pharmacokinetics of three organic mastitis products currently used by organic producers and organic dairy veterinarians. Those products include intramammary, topical and intravaginal preparations, each dosed at two levels. Additionally, tissue data were collected for kidney, liver and fat in order to estimate a withholding time for each of the products. The lower limit of quantification (LOQ) and lower limit of detection (LOD) were 0.001 and 0.0005 µg ml-1, respectively, in plasma and all tissues except fat for both thymol and carvacrol. Fat had an LOQ of 0.01 µg ml-1 and an LOD of 0.005 µg ml-1 for thymol and carvacrol. Diallyl disulfide had an LOQ of 0.005 µg ml-1 and LOD of 0.001 µg ml-1 in all tissues. For diallyl disulfide (garlic), no levels above 0.001 µg ml-1 were measurable in plasma or tissues. For topical and intramammary products, levels were measurable in the plasma, liver, kidney and fat up to 72 h after the last dose. The plasma half-lives were short for thymol (approximately 1.6 h) and carvacrol (approximately 1.5 h), whereas the estimated half-lives for these substances in tissues ranged from 13.9 to 31.5 h for thymol and from 16.9 to 25 h for carvacrol. The predicted amount of time that the molecules would be found in the body based on the slowest depletion time of liver tissue was 13 days for thymol and 10 days for carvacrol. The apparent half-life of topically applied carvacrol was approximately 4.5 h in plasma, with an estimated withhold time of 10 days. These times were calculated using the USFDA's tolerance limit method for meat withdrawal times.

Potential of phytoceuticals to affect antibiotic residue detection tests in cow milk in a randomised trial.

Mastitis is a costly disease for dairy farmers. Some dairy farmers use herbal products, or phytoceuticals, to treat mastitis. Phytoceuticals have not been approved for this use by the United States Food and Drug Administration, and have not been tested to determine how they impact antibiotic residue detection testing. The current study tested the potential for phytoceuticals to cause positive results on two milk antibiotic residue screening tests, the Delvotest P and Charm SL Beta-lactam test, or to interfere with the detection of antibiotics by these tests. The three phytoceuticals tested were labelled for intramammary, topical or intravulvar administration. Testing was performed in vitro using the products diluted in milk obtained from healthy organic dairy cows. Phytoceuticals were tested at concentrations ranging from 1.5 per cent to 100 per cent. Concentration levels were replicated at least twice on each milk antibiotic residue screening test. The Delvotest P is based on detection of bacterial inhibitors and no positive results were obtained for any product at concentrations less than 50 per cent. The Charm SL Beta-lactam test uses a receptor for the detection of beta-lactam antibiotics and no concentration of phytoceuticals caused an interference with these tests. Based on dilution of the products in bovine milk at physiologically achievable levels, phytoceutical products tested at levels expected after treatment do not cause positive test results for the Delvotest P nor do they interfere with the Charm SL Beta-lactam test in detection of various antibiotics.

Induction chemotherapy for T3N0M0 non-small-cell lung cancer increases the rate of complete resection but does not confer improved survival.

OBJECTIVES: The objective of this study was to evaluate outcomes of induction therapy prior to an operation in patients with cT3 non-small-cell lung cancer (NSCLC). METHODS: Patients diagnosed with cT3N0M0 NSCLC from 2006 to 2011 in the National Cancer Database who were treated with lobectomy or pneumonectomy were stratified by treatment strategy: an operation first versus induction chemotherapy. Propensity scores were developed and matched cohorts were generated. Short-term outcomes included margin status, 30- and 90-day mortality rates, readmission and length of stay. Survival analyses using Kaplan-Meier methods were performed on both the unadjusted and propensity matched cohorts. RESULTS: A total of 3791 cT3N0M0 patients were identified for inclusion, of which 580 (15%) were treated with induction chemotherapy. Prior to adjustment, patients treated with induction chemotherapy were younger, had a higher comorbidity burden and were more likely to have private insurance (all P < 0.001). Following matching, patients receiving induction chemotherapy were more likely to subsequently undergo an open procedure (87.3 vs 77.8%, P = 0.005). These patients were more likely to obtain R0 resection (93.1% vs 90.0%, P = 0.04) and were thereby less likely to have positive margins at the time of resection (6.9% vs 10.0%, P = 0.03). Patients who received induction therapy had higher rates of 90-day mortality (6.6% vs 3.4%) but there was no difference in long-term survival between the groups. CONCLUSIONS: Despite yielding increased rates of R0 resection, induction chemotherapy for cT3N0M0 NSCLC is not associated with improved survival and should not be considered routinely. Further studies are warranted to elucidate cohorts that may benefit from induction therapy.

Adjuvant Chemotherapy Does Not Confer Superior Survival in Patients With Atypical Carcinoid Tumors.

BACKGROUND: Although the use of adjuvant chemotherapy in patients with pathologically node-positive (pN+) atypical carcinoid tumor of the lung is an accepted practice, controversy exists about its use in pathologically node-negative (pN0) patients. Our aim was to determine whether a survival advantage exists in patients receiving chemotherapy postoperatively for pN0 or pN+ atypical carcinoid tumors of the lung. METHODS: Adult patients treated with lobectomy or pneumonectomy for pulmonary atypical carcinoid tumor were identified using the National Cancer Data Base, 2006 to 2011. Propensity scoring (4:1 nearest neighbor algorithm) and survival analysis were used to examine the association between adjuvant chemotherapy and pN+ versus pN0 atypical carcinoid tumors. RESULTS: Of the total 581 patients identified with a diagnosis of atypical carcinoid of the lung, 363 (62.5%) were found to be node negative at the time of operation and 218 (37.5%) had node-positive disease. Adjuvant chemotherapy was used in 15 patients (4.1%) with pN0 disease and 89 patients (40.8%) with pN+ disease. Unadjusted survival, at 12 and 60 months, was similar between pN+ patients who were treated with adjuvant chemotherapy versus patients who received operation alone (adjuvant chemotherapy: 98.9% at 12 months and 47.9% at 60 months versus operation alone: 98.4% and 12 months and 67.1% at 60 months, p = 0.46) and for propensity-matched pN0 (adjuvant chemotherapy: 86.7% at 12 months and 73.3% at 60 months versus operation alone: 87.9% at 12 months and 72.3% at 60 months, p = 0.54). CONCLUSIONS: In a national-level analysis, the use of adjuvant chemotherapy postoperatively in patients with pN+ and pN0 disease conferred no survival advantage; further study is needed to determine proper chemotherapy use for these patients.

The Role of Extent of Surgical Resection and Lymph Node Assessment for Clinical Stage I Pulmonary Lepidic Adenocarcinoma: An Analysis of 1991 Patients.

BACKGROUND: This study examined the association of extent of lung resection, pathologic nodal evaluation, and survival for patients with clinical stage I (cT1-2N0M0) adenocarcinoma with lepidic histologic features in the National Cancer Data Base. METHODS: The association between extent of surgical resection and long-term survival for patients in the National Cancer Data Base with clinical stage I lepidic adenocarcinoma who underwent lobectomy or sublobar resection was evaluated using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: Of the 1991 patients with cT1-2N0M0 lepidic adenocarcinoma who met the study criteria, 1544 underwent lobectomy and 447 underwent sublobar resection. Patients treated with sublobar resection were older, more likely to be female, and had higher Charlson/Deyo comorbidity scores, but they had smaller tumors and lower T status. Of the patients treated with lobectomy, 6% (n = 92) were upstaged because of positive nodal disease, with a median of seven lymph nodes sampled (interquartile range 4-10). In an analysis of the entire cohort, lobectomy was associated with a significant survival advantage over sublobar resection in univariate analysis (median survival 9.2 versus 7.5 years, p = 0.022, 5-year survival 70.5% versus 67.8%) and after multivariable adjustment (hazard ratio = 0.81, 95% confidence interval: 0.68-0.95, p = 0.011). However, lobectomy was no longer independently associated with improved survival when compared with sublobar resection (hazard ratio = 0.99, 95% confidence interval: 0.77-1.27, p = 0.905) in a multivariable analysis of a subset of patients in which only those patients who had undergone a sublobar resection including lymph node sampling were compared with patients treated with lobectomy. CONCLUSIONS: Surgeons treating patients with stage I lung adenocarcinoma with lepidic features should cautiously utilize sublobar resection rather than lobectomy, and they must always perform adequate pathologic lymph node evaluation.

Relationships between the phagocytic ability of milk macrophages and polymorphonuclear cells and somatic cell counts in uninfected cows.

Phagocyte numbers and activities were compared in milk from 2 groups of uninfected mammary-gland quarters from 3 cows each: 6 quarters with a high (> or = 200 000/mL) somatic cell concentration (SCC), analyzed as 4 individual quarters and 1 pooled sample; and 12 quarters with a low SCC (< 200 000/mL), analyzed as 6 paired samples. The concentrations and ability of macrophages and polymorphonuclear (PMN) cells to phagocytize fluorescent microspheres were determined by flow cytometry after exposure of the cells to the microspheres. The macrophages and PMNs contained 2 major subpopulations, characterized by low phagocytic (LP) or high phagocytic (HP) ability. The quarters with high SCCs had significantly lower percentages of HP cells than did the quarters with low SCCs (P < 0.01). Whether mammary-gland quarters or cows were the unit of analysis, the HP/LP ratio was negatively related to the SCC (P < 0.04), which explained more than 50% of the SCC variability. Thus, poor bovine mammary-gland phagocytic ability may be associated with high SCC. Longitudinal studies are suggested to further explore and characterize these relationships.