Performance of commercial SARS-CoV-2 wild-type and Omicron BA.1 antibody assays compared with pseudovirus neutralization tests.

BACKGROUND: Commercially available ELISA-based antibody tests are used to approximate vaccination success against SARS-CoV-2 in at-risk patients, but it is unclear whether they correlate with neutralization of the Omicron variant. METHODS: 269 serum samples of a cohort of 44 non-immunosuppressed participants and 65 MTX-treated rheumatic patients taken before and after COVID-19 booster vaccinations were measured using COVID-19 antibody testing systems with wild-type and Omicron BA.1 antigens developed by three different manufacturers (surrogate virus neutralization test cPass, and binding antibody tests QuantiVac and SeraSpot), as well as with a pseudovirus neutralization test (pVNT). The pVNT was considered the gold standard for determining the presence and level of anti-SARS-CoV-2 antibodies. RESULTS: All three wild-type ELISAs showed excellent test performance compared with wild-type neutralization in pVNT. However, out of 56 samples without Omicron BA.1 neutralization in pVNT, 71.4% showed positive results in at least one and 28.6% in all three wild-type ELISAs at the manufacturer-defined cut-offs. Omicron ELISAs showed either decreased specificity (57.1% and 55.4% for binding ELISAs) or sensitivity (51.2% in cPass) compared to Omicron neutralization in pVNT. The proportion of any false positive results among all samples decreased from 26.5% before to 3.2% after booster vaccination, however binding antibody test specificities remained below 70%. CONCLUSIONS: We found a poorer test performance of new Omicron antibody test systems compared to wild-type tests in detecting neutralizing antibodies against the corresponding SARS-CoV-2 variants. Decisions for booster vaccination or passive immunization of at-risk patients should not be based solely on antibody test results.

Combined APRI/ALBI score to predict mortality after hepatic resection.

BACKGROUND: Aspartate aminotransferase/platelet ratio index (APRI) and albumin-bilirubin grade (ALBI) are validated prognostic indices implicated as predictors of postoperative liver dysfunction after hepatic resection. The aim of this study was to evaluate the relevance of the combined APRI/ALBI score for postoperative clinically meaningful outcomes. METHODS: Patients undergoing hepatectomy were included from the American College of Surgeons National Surgical Quality Improvement Program database. The association between APRI/ALBI score and postoperative grade C liver dysfunction, liver dysfunction-associated and overall 30-day mortality was assessed. RESULTS: A total of 12 055 patients undergoing hepatic resection from 2014 to 2017 with preoperative blood values and detailed 30-day postoperative outcomes were included (exploration cohort: January 2014 to December 2016; validation cohort: 2017). In the exploration cohort (8538 patients), the combination of both scores (APRI/ALBI) was significantly associated with postoperative grade C liver dysfunction, 30-day mortality, and liver dysfunction-associated 30-day mortality, and was superior to either score alone. The association with postoperative 30-day mortality was confirmed in multivariable analysis. A predictive model was generated using the exploration cohort. The predicted incidence of events closely followed the observed incidence in the validation cohort (3517 patients). Subgroup analyses of tumour types were used to generate disease-specific risk models to assess risk in different clinical scenarios. These findings informed development of a smartphone application (https://tellaprialbi.37binary.com). CONCLUSION: The predictive potential of the combined APRI/ALBI score for clinically relevant outcomes such as mortality was demonstrated. An evidence-based smartphone application will allow clinical translation and facilitation of risk assessment before hepatic resection using routine laboratory parameters.

Biological subtype, treatment response and outcomes in inflammatory breast cancer using data from the National Cancer Database.

BACKGROUND: Although inflammatory breast cancer (IBC) is postulated to be a distinct biological entity, practice guidelines and previous data suggest that treatment and outcomes are influenced by standard approximated biological subtype. The aim of this study was validation in a large recent National Cancer Database (NCDB) patient cohort. METHODS: Patients with non-metastatic IBC treated in 2010-2015 with neoadjuvant systemic therapy and surgery were identified from the NCDB. Approximated biological subtypes were categorized as oestrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), ER-/HER2- and HER2+. Total pathological complete response (pCR) was defined as ypT0/ypTis, ypN0. χ2 tests were used to compare pCR rates, and Kaplan-Meier curves and Cox proportional hazards regression to analyse overall survival. RESULTS: Among 4068 patients with IBC (median age 56 years), the approximated biological subtype was ER+/HER2- in 1575 (38·7 per cent), HER2+ in 1323 (32·5 per cent) and ER-/HER2- in 1170 (28·8 per cent). A total of 3351 patients (84·0 per cent) were cN+ at presentation, with no differences across subtypes. Total pCR rates varied significantly by subtype: ER+/HER2- (6·2 per cent), HER2+ (38·8 per cent), ER-/HER2- (19·1 per cent) (P < 0·001), as did breast pCR rates (10·4, 44·5 and 25·2 per cent respectively) and nodal pCR rates (16·9, 56·9 and 33·1 per cent). The 5-year overall survival rate varied significantly across subtypes (ER+/HER2- 64·9 per cent, HER2+ 74·0 per cent, ER-/HER2- 44·0 per cent; P < 0·001) and by pCR within subtypes (all P < 0·001). In multivariable analysis, ER-/HER2- subtype (hazard ratio 2·89 versus HER2+ as reference; P < 0·001) and absence of total pCR (hazard ratio 3·23; P < 0·001) predicted worse survival. CONCLUSION: Both treatment response and survival in patients with IBC varied with approximated biological subtype, as among other invasive breast cancers. These data support continued tailoring of systemic treatment to approximated biological subtype and highlight the recent improved outcomes in patients with HER2+ disease.

ANTECEDENTES: En tanto que el cáncer inflamatorio de mama (inflammatory breast cancer, IBC) se ha postulado como una entidad biológica distinta, las guías de práctica clínica y datos previos sugieren que el tratamiento y los resultados están influenciados por aproximación al subtipo biológico estándar. El objetivo de este estudio fue la validación en una cohorte reciente de pacientes incluidas en una extensa Base de Datos Nacional de Cáncer (National Cancer Database, NCDB). MÉTODOS: A partir de la NCDB, se identificaron las pacientes con IBC no metastásico tratadas en con neoadyuvancia sistémica y cirugía durante el periodo 2010-2015. El subtipo biológico aproximado se categorizó como ER+/HER2-, ER-/HER2- y HER2+. La respuesta patológica completa total (pathologic complete response, pCR) se definió como ypT0/ypTis, ypN0. Se utilizaron pruebas de ji al cuadrado para comparar las tasas de pCR y las curvas de Kaplan-Meier y la regresión de riesgos proporcionales de Cox para analizar la supervivencia global (overall survival, OS). RESULTADOS: En las 4.068 pacientes con IBC (mediana de edad 56 años), el subtipo biológico aproximado fue ER+/HER2- en 1.575 (39%), HER2+ en 1.323 (33%) y ER-/HER2- en 1.170 (29%). Un total de 3.351 pacientes (84%) eran cN+ en el momento de la presentación, sin diferencias entre los subtipos. Las tasas totales de pCR variaron significativamente en función del subtipo: ER+/HER2- (6%), HER2+ (39%), ER-/HER2- (19%), P < 0,001, así como las tasas de pCR de la mama (10%, 45%, 25%) y las tasas de pCR de los ganglios linfáticos (17%, 57%, 33%). La OS a los 5 años varió significativamente según los subtipos (ER+/HER2- 65%, HER2+ 74%, ER-/HER2- 44%, P < 0,001) y según la pCR en cada uno de los subtipo (en cada uno P < 0,01). En el análisis multivariable, el subtipo ER-/HER2- (cociente de riesgos instantáneos, hazard ratio, HR 2,9, P < 0,001 versus HER2+) y la ausencia de pCR total (HR 3,2, P < 0,001) predijeron una peor supervivencia. CONCLUSIÓN: Tanto la respuesta al tratamiento del IBC y como la supervivencia variaron en función del subtipo biológico aproximado, tal como sucede en otros cánceres de mama invasivos. Estos datos apoyan la importancia de continuar ajustando el tratamiento sistémico al subtipo biológico aproximado y resaltan la mejoría reciente de los resultados en las pacientes HER2+.

A 25 year experience of perineal hernia repair.

PURPOSE: Though perineal hernias remain rare, the incidence is reportedly rising. Secondary to the historical rarity, optimal method of repair and outcomes after repair remain poorly understood. Therefore, we reviewed the past 25 years of our institutional experience with perineal hernia repair. METHODS: A retrospective review of an institution-maintained database was conducted from January 1, 1994 to January 31, 2018 for patients undergoing perineal hernia repair. Data were collected on patient characteristics, operative technique, and post-operative outcomes. RESULTS: Twenty-one patients (n = 12 male) underwent perineal hernia repair in the study period with two-thirds of the operations occurring in the most recent 7 years (since January 1, 2011). The median time to repair was 13 months (range 2-127) after index operation. The approach was transabdominal in nine, perineal in nine, and combined in three. Mesh, a tissue flap, or a combination of these was used in 19 of the cases and 6 additional abdominal wall hernias were repaired concurrently. Post-operative complications consisted of superficial surgical-site infection (n = 2), infected seroma (n = 1), and a missed enterotomy (n = 1). Follow-up ranged from 0 to 112 months (median 2 months) and only one recurrence was noted. CONCLUSION: Presentation for repair of perineal hernia has increased at our instituion over the past 2 decades. Outcomes did not differ between the three repair approaches and the choice of mesh or tissue-based repair. Surgeons should base these decisions on hernia complexity and local tissue conditions.

Evidence-based wound classification for vulvar surgery: Implications for risk adjustment.

OBJECTIVES: The correct wound classification for vulvar procedures (VP) is ambiguous according to current definitions, and infection rates are poorly described. We aimed to analyze rates of surgical site infection (SSI) in women who underwent VP to correctly categorize wound classification. METHODS: Patients who underwent VP for dysplasia or carcinoma were collected from the National Surgical Quality Improvement Program database (NSQIP). SSI rates of vulvar cases were compared to patients who underwent abdominal hysterectomy via laparotomy, stratified by the National Academy of Sciences wound classification. Descriptive analyses and trend tests of categorical variables were performed. RESULTS: Between 2008 and 2016, 2116 and 31,506 patients underwent a VP or TAH, respectively. Among VP, 1345 (63.6%), 364 (17.2%), and 407 (19.2%) women underwent simple vulvectomy, radical vulvectomy, or radical vulvectomy with lymphadenectomy, respectively. The overall rate of SSI for VP was higher than that observed for TAH (5.6% vs. 3.8%; p < 0.0001). While patients undergoing TAH displayed a corresponding increase in the rate of SSI with wound type (type I: 3.4%; type II: 3.8%, type III: 6.8%; type IV 10.6%; p < 0.001), no such correlation was observed for simple VP (type I: 3.3%, type II: 3.0%; type III: 3.2%; type IV: 0%; p = 0.40). On the other hand, a non-significant correlation was observed for radical VP (type I: 4.0%, type II: 10.1%; type III: 14.3%; type IV: 20.0%; p = 0.08). The overall rate of SSI in patients undergoing any radical VP was similar to patients undergoing hysterectomy with a type IV wound (10.1% vs 10.6%, p = 0.87). CONCLUSION: Patients undergoing VP are at high risk of infection. Simple vulvectomy should be classified as a type II and radical vulvectomy as a type III wound. These recommendations are important for proper risk adjustment.

2019 John Charnley Award: Increased risk of prosthetic joint infection following primary total knee and hip arthroplasty with the use of alternative antibiotics to cefazolin: the value of allergy testing for antibiotic prophylaxis.

AIMS: The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. PATIENTS AND METHODS: We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. RESULTS: Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. CONCLUSION: PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9-15.

Surgical trends of groin hernia repairs performed for recurrence in medicare patients.

BACKGROUND: The recurrence rate after groin hernia repair (GHR) has been estimated to be between 1-10% in adult patients. Neither national rates nor trends in recurrence over time have been reliably established for Medicare patients in the USA. MATERIALS: We evaluated patients undergoing GHR (inguinal = IHR; femoral = FHR) from 2011 to 2014 from the Medicare Provider Analysis and Review database. Patients were identified using ICD-9 diagnosis and ICD-9 and CPT procedure codes, stratified both by primary vs. recurrent hernia repair and by sex. One-tailed Cochran-Armitage tests evaluated trends over time and a generalized estimating equation model estimated factors associated with recurrent IHR or FHR. RESULTS: We identified 407,717 patients (87.0%, ≥ 65 years) who underwent an IHR and 11,578 (91.0%, ≥ 65 years) who underwent a FHR. The proportion of IHRs for recurrence decreased statistically from 14.3% in 2011 to 13.9% in 2014 (p < 0.01) in males and was increased, but not statistically so (7.0-7.4%) in females (p = 0.08). The proportion of FHRs for recurrence was decreased, but not statistically so (16.3-14.8%, p = 0.29) in males and increased in females (5.3-6.3%, p = 0.02). On multivariable analysis, males were more than twice as likely as females to undergo recurrent repair (IHR or FHR, both p < 0.01). CONCLUSIONS: Within the Medicare population, recurrence rates after groin hernia repairs were found to be higher than previously reported but have remained clinically stable over time. Establishing and reducing this rate is important for patient outcomes and expectations.

Proportion of femoral hernia repairs performed for recurrence in the United States.

PURPOSE: Recurrence rates after femoral hernia repair (FHR) have not been reliably established in the USA. We sought to determine this trend over time. METHODS: The proportion of primary and recurrent FHRs was determined for patients age ≥ 18 from: ACS-NSQIP (1/2005-12/2014), Premier (1/2010-09/2015), and institutional (1/2005-12/2014) data. Trends were analyzed using a one-tailed Cochran-Armitage test. RESULTS: In the NSQIP database, 6649 patients underwent a FHR. In females, the proportion of FHRs performed for recurrence decreased from 14.0% in 2005 to 6.2% in 2014, p = 0.02. In males, there was no change: 16.7-16.1% 2005-2014 (p = 0.18). The Premier database included 4495 FHRs and our institution 315 FHRs. There was no difference for either gender over time in either data source, all p > 0.05. CONCLUSIONS: The proportion of femoral hernia repairs performed for recurrence in the USA remained relatively constant in males in two large national databases between 2005 and 2015. In females, a decrease was seen in one of the large national databases.

Antioxidant activity and phenol content of extracts of bark, stems, and young and mature leaves from Blepharocalyx salicifolius (Kunth) O. Berg / Atividade antioxidante e teor de polifenóis de extratos de cascas (súber), caule, folhas jovens e folhas maduras de Blepharocalyx salicifolius (Kunth) O. Berg (Murta)

Abstract Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber) and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC). A correlation was observed between TPC and antioxidant activity index (AAI) with a correlation coefficient (r2) of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies.

Resumo Os polifenóis são um grupo de metabólitos secundários vegetais que possuem uma variedade de bioatividades conhecidas, dentre elas a capacidade de funcionar como antioxidantes. Devido aos efeitos colaterais do uso excessivo de substâncias sintéticas, a busca por compostos naturais e menos tóxicos têm aumentado significativamente. Esse estudo teve por objetivo avaliar a atividade antioxidante e o teor de polifenóis dos extratos hexânicos, acetato de etila e aquosos de cascas (súber), caules, folhas jovens e folhas maduras de Blepharocalyx salicifolius. Os extratos foram obtidos por meio de extração com solventes orgânicos e subsequente fracionamento em cromatografia por coeficiente de partição. Testes preliminares da presença de compostos com atividade antioxidante foram realizados por meio de bioautografia em cromatografia de camada delgada. Os extratos foram submetidos ao teste da capacidade sequestrante do radical 2,2-difenil-1-picrilhidrazil (DPPH) para quantificação da atividade antioxidante e submetidos ao teste com o reagente de Folin-Ciocalteu para quantificação dos polifenóis. Os resultados mostraram que dos 12 extratos avaliados, 9 apresentaram atividade antioxidante muito forte e 3 atividade moderada. Os extratos aquosos de folhas jovens e cascas e o extrato acetato de etila de folhas jovens apresentaram os maiores índices de atividade antioxidante e teor de polifenóis (TPC). A correlação entre TPC e o índice de atividade antioxidante (AAI) observada foi de r2 = 0,7999. Dessa forma, ficou evidenciado o elevado teor de polifenóis e sua correlação com a atividade antioxidante nos extratos de B. salicifolius, fornecendo subsídios para novos estudos.

Phytotoxic potential of young leaves from Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) / Potencial fitotóxico de folhas jovens de Blepharocalyx salicifolius (Kunth) O. Berg

Abstract The loss of leaves by plant species found in the Cerrado (Brazilian savanna) is an energetically expensive process due to adverse environmental conditions and predation by herbivory. The mature leaves have adaptations which minimize these events. However, the young individuals lack these structures and produce high leaf concentrations of secondary metabolites as a form of protection. These compounds can be used in bioprospection of natural herbicides. Thus, this study aimed to evaluate the phytotoxicity of hexane, ethyl acetate and aqueous extracts of young leaves from Blepharocalyx salicifolius (Kunth) O. Berg on the elongation of wheat coleoptiles (Triticum aestivum L.) and evaluate the potential phytotoxic of ethyl acetate extract on germination, growth and cell size of metaxylem of sesame (Sesamum indicum L.) seedlings. The hexane and ethyl acetate extracts inhibited the elongation of wheat coleoptiles at all concentrations; however, the most promising results were observed in coleoptile fragments treated with the ethyl acetate extract. This treatment changed the mean germination time and the synchrony of sesame seeds, inhibited the growth of shoots and roots, reduced the dry weight of seedlings, led to abnormalities in the seedlings and reduced the length of the metaxylem cells in the sesame seedlings. These results demonstrated the phytotoxic potential of young leaf extracts of B. salicifolius and the high phytotoxicity of the ethyl acetate extract in the initial development of S. indicum.

Resumo A perda das folhas pelas plantas do Cerrado é um processo energeticamente custoso devido às condições ambientais adversas e intensa predação por herbivoria. As folhas maduras possuem adaptações que minimizam esses eventos. Entretanto, os indivíduos jovens carecem dessas estruturas e produzem elevadas concentrações foliares de metabólitos secundários como forma de proteção. Esses compostos podem ser utilizados na bioprospecção de herbicidas naturais. Dessa forma, objetivamos com este estudo avaliar a fitotoxicidade dos extratos hexânico, acetato etílico e aquoso de folhas jovens de Blepharocalyx salicifolius (Kunth) O. Berg sobre o alongamento de coleóptilos estiolados de Triticum aestivum L. (trigo) e avaliar o potencial fitotóxico do extrato acetato etílico sobre a germinação, crescimento e comprimento das células do metaxilema de Sesamum indicum (gergelim). Os extratos hexânico e acetato etílico inibiram o alongamento dos coleóptilos em todas as concentrações testadas, entretanto os resultados mais promissores foram observados nos fragmentos submetidos ao extrato acetato etílico. Este extrato alterou o tempo médio de germinação e a sincronia das sementes de gergelim, inibiu o crescimento da parte aérea e subterrânea com redução da massa seca das plântulas, levou ao surgimento acentuado de anomalias e causou redução no comprimento médio das células do metaxilema de plântulas de gergelim. Assim, ficou comprovado o potencial fitotóxico dos extratos de folhas jovens de B. salicifolius e a acentuada fitotoxicidade do extrato acetato etílico sobre o desenvolvimento inicial de S. indicum.

Antioxidant activity and phenol content of extracts of bark, stems, and young and mature leaves from Blepharocalyx salicifolius (Kunth) O. Berg.

Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber) and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC). A correlation was observed between TPC and antioxidant activity index (AAI) with a correlation coefficient (r2) of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies.

Phytotoxic potential of young leaves from Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae).

The loss of leaves by plant species found in the Cerrado (Brazilian savanna) is an energetically expensive process due to adverse environmental conditions and predation by herbivory. The mature leaves have adaptations which minimize these events. However, the young individuals lack these structures and produce high leaf concentrations of secondary metabolites as a form of protection. These compounds can be used in bioprospection of natural herbicides. Thus, this study aimed to evaluate the phytotoxicity of hexane, ethyl acetate and aqueous extracts of young leaves from Blepharocalyx salicifolius (Kunth) O. Berg on the elongation of wheat coleoptiles (Triticum aestivum L.) and evaluate the potential phytotoxic of ethyl acetate extract on germination, growth and cell size of metaxylem of sesame (Sesamum indicum L.) seedlings. The hexane and ethyl acetate extracts inhibited the elongation of wheat coleoptiles at all concentrations; however, the most promising results were observed in coleoptile fragments treated with the ethyl acetate extract. This treatment changed the mean germination time and the synchrony of sesame seeds, inhibited the growth of shoots and roots, reduced the dry weight of seedlings, led to abnormalities in the seedlings and reduced the length of the metaxylem cells in the sesame seedlings. These results demonstrated the phytotoxic potential of young leaf extracts of B. salicifolius and the high phytotoxicity of the ethyl acetate extract in the initial development of S. indicum.

Is Chemotherapy or Radiation Therapy in Addition to Surgery Beneficial for Locally Advanced Rectal Cancer in the Elderly? A National Cancer Data Base (NCDB) Study.

INTRODUCTION: Current National Comprehensive Cancer Network guidelines for Stages II and III rectal cancer recommend neoadjuvant chemoradiation followed by curative intent surgery and adjuvant chemotherapy. It is unclear whether therapies in addition to surgery are truly beneficial in elderly patients. Our aim was to compare the survival of patients over 80 with Stages II and III rectal cancer undergoing curative intent surgery with or without additional therapy. MATERIALS AND METHODS: The National Cancer Data Base (NCDB 2006-2011) was queried for patients over 80 with Stages II and III rectal cancer. The primary outcome was overall survival. Patients were stratified based upon therapy group. Univariate group comparisons were made. Unadjusted Kaplan-Meier and multivariable Cox proportional hazards modeling survival analyses were performed. RESULTS: The query yielded 3098 patients over 80 with Stage II (N = 1566) or Stage III (N = 1532) disease. Approximately, half of the patients received surgery only. Kaplan-Meier analysis showed improved survival for patients receiving neoadjuvant and/or adjuvant therapy in addition to surgery, but there was no significant difference between those that received guideline concordant care (GCC), neoadjuvant chemoradiation only, or post-operative chemotherapy only. Cox proportional hazard modeling identified age >90 and margin positivity as independent risk factors for decreased overall survival. CONCLUSION: Analysis of NCDB data for Stages II and III rectal cancer in patients over 80 shows a survival benefit of adjuvant and/or neoadjuvant therapy over surgery alone. There does not appear to be a difference in survival between patients who received neoadjuvant chemoradiation, post-resection adjuvant chemotherapy, or GCC.

Outcomes with multimodal therapy for elderly patients with rectal cancer.

BACKGROUND: Treatment guidelines for stage II and III rectal cancer include neoadjuvant chemoradiotherapy, surgery and postoperative adjuvant chemotherapy. Although data support this recommendation in younger patients, it is unclear whether this benefit can be extrapolated to elderly patients (aged 75 years or older). METHODS: This was a retrospective review of patients aged at least 75 years with stage II or III rectal cancer who underwent surgery with curative intent from 1996 to 2013 at the Mayo Clinic. Kaplan-Meier analysis and log rank test were used to compare overall survival between therapy groups. Cox proportional hazards model was used to estimate the independent effect of treatment group on survival. RESULTS: A total of 160 elderly patients (median age 80 years) with stage II (66) and stage III (94) rectal cancer underwent surgical resection. Only 30·0 and 33·8 per cent received neoadjuvant or adjuvant therapy respectively. Among patients with stage II disease, there was no significant difference in 60-month survival between patients who received any additional therapy and those who had surgery alone (55 versus 38 per cent respectively; P = 0·184), whereas additional therapy improved survival in patients with stage III tumours (58 versus 30 per cent respectively; P = 0·007). Multivariable analysis found a survival benefit for additional therapy in elderly patients with stage III disease (hazard ratio 0·58, 95 per cent c.i. 0·34 to 0·98). CONCLUSION: A multimodal approach in elderly patients with stage III rectal cancer improved oncological outcomes.

Surgery alone is adequate treatment for early stage soft tissue sarcoma of the extremity.

BACKGROUND: Evolving evidence suggests that, in selected patients with tumour category 1 (T1) extremity soft tissue sarcoma (ESTS), surgery alone offers satisfactory results without decreasing survival. This study assessed the effect of sarcoma treatments on survival outcomes of T1 ESTS in a population-based data set. METHODS: Using the Surveillance, Epidemiology, and End Results database, 1618 patients with primary ESTS underwent limb-sparing surgery. Multivariable analysis was used to assess the impact of radiotherapy on overall survival (OS) and sarcoma-specific survival (SSS), adjusting for co-variables. RESULTS: Some 803 patients (49.6 per cent) underwent surgery alone for T1 ESTS. Radiotherapy in patients with low- and high-grade tumours did not result in any significant difference in OS or SSS. When stratified by grade, multivariable analysis showed that adjuvant radiotherapy was not an independent predictor of SSS (hazard ratio (HR) 1.05; P = 0.906) or OS (HR 0.89; P = 0.695) in low-grade tumours. Neither was radiotherapy a significant predictor of SSS (HR 0.87; P = 0.608) or OS (HR 0.67; P = 0.071) in high-grade tumours. CONCLUSION: This population-based appraisal validated previous evidence supporting a role for surgery alone in the treatment of T1 ESTS. Future policies should be tailored to offer patients minimal yet effective therapy, rather than maximum tolerated therapy.

[Poison and nocebo--2 aspects of toxicology]. / Gift und Nocebo--zwei Aspekte der Toxikologie.

BACKGROUND: Erroneously it is assumed that drugs promote health exclusively by interacting with the organism through chemical or physical forces. However, placebo phenomena are omnipresent in patients who believe in the value of a treatment, be it medical or paramedical. Conversely, nocebo phenomena originate from fear of detrimental effects attributed to a putative poison. Thus, both drugs and poisons release two different messages, the one being physicochemical, the other psychosocial. The latter is fostered by the public opinion, and man is a sensitive receiver. TYPICAL NOCEBO PHENOMENA: Here some epidemiological examples of nocebo phenomena will be presented. Each society selects the matching nocebos, today mainly as chemical exposures from oecological sources such as environment, buildings, emissions and industrial products. THERAPEUTICAL APPROACH: Suspicion of nocebo should not hamper the search for chemical poisons. Anxiety and fear furnish the neurobiological and evolutionary basis of the nocebo phenomena. Hence behavioural and conversational therapy, supported by antidepressants if needed, should be tried. Unfortunately, most patients expect their psychosocial problems instead to be declared as chemical.

Inhibition by clostridial neurotoxins of calcium-independent [3H]noradrenaline outflow from freeze-thawed synaptosomes: comparison with synaptobrevin hydrolysis.

Clostridial neurotoxins are known to inhibit regulated, i.e. calcium-dependent exocytosis. In the present study we have investigated their potential role in also inhibiting calcium-independent exocytosis. Synaptosomes from rat forebrain were preloaded with [3H]noradrenaline and permeabilized reversibly by freezing in Ca(2+)-free potassium glutamate containing dimethyl sulfoxide and the toxins to be assayed. Subsequently, outflow of radioactivity was measured in isotonic calcium-free potassium glutamate. The synaptic vesicle protein synaptobrevin-2/VAMP-2 and its toxin-dependent degradation were analysed by Western blotting. The light chain of tetanus toxin reduced the synaptosomal outflow of radioactivity, whereas the activity of the heavy chain was at the detection limit. The respective activities of the dichain toxins from Clostridium tetani and C. botulinum A, B and E were enhanced by pretreatment with dithiothreitol. Reduced single-chain tetanus toxin was less potent than reduced dichain tetanus toxin. Pretreatment with ethylene diamine tetraacetic acid as an inhibitor of Zn(2+)-proteases abolished the actions of the tetanus toxin light chain and of the reduced dichain toxins. Hydrolysis of synaptobrevin-2/VAMP-2 was obtained with tetanus toxin light chain, reduced dichain tetanus toxin and C. botulinum B toxin. Its hydrolysis by single-chain tetanus toxin was less pronounced, and it was absent with botulinum toxins A and E. It is concluded that clostridial neurotoxins can not only inhibit calcium-dependent release but also affect calcium-independent outflow from synaptosomes. Since this is accompanied by selective intrasynaptosomal proteolysis of synaptobrevin, calcium-independent outflow may at least in part involve the vesicular release apparatus.