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BACKGROUND: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. METHODS: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). RESULTS: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. CONCLUSIONS: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. CLINICALTRIALS: gov Identifier: NCT00628745.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the standard of care for patients with peritoneal dissemination of appendiceal cancer and are increasingly being evaluated for use in patients with carcinomatosis from colon cancer. Mitomycin C (MMC) is one of the most frequently used HIPEC agents in the management of peritoneal-based gastrointestinal malignancies. This study analyzes the incidence and risk factors for developing neutropenia following MMC-HIPEC combined with CRS.All patients undergoing CRS and MMC-HIPEC for appendiceal cancer between January 1993 and October 2006 were retrospectively reviewed. Logistic regression was used to identify risk factors for the development of neutropenia, defined as an absolute neutrophil count (ANC)

The small GTPase Rac1 (Ras‐related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial‐mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1‐SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1‐SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO‐GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co‐localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer‐related deaths, POTEE could represent a potential therapeutic target for these types of cancer. [ABSTRACT FROM AUTHOR]

Despite the increasing number of students in music education graduate programmes, attrition rates suggest a lack of success in retaining and assisting them to the completion of their degree. Based on the expectancy-value theory, the aim of this study was to examine students' motivations (values and competence beliefs) and their complex interaction with the social system. A questionnaire was sent to students from three graduate programmes in Mexico (two traditional, one distance learning), which examined both personal and environmental factors that have enhanced or undermined students' motivational beliefs. The results show gender differences; female students place higher value on graduate school, while male students hold higher expectations of success. Factors affecting motivation positively included perceptions of career development and income increase; the requirement to pursue an academic qualification as a part of an existing job; and interest in research. Factors affecting motivation negatively included the economic impact of study, time constraints and insufficient support and communication coupled with high expectations from advisers. (Contains 7 tables and 1 note.)

Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology. The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts. The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology. As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients. [ABSTRACT FROM AUTHOR]

The majority of cancer patients report malnutrition, with a significant impact on patient's outcome. This study aimed to compare how nutritional assessment is conducted across different surgical oncology sub-specialties. Survey modules were designed for breast, hepato-pancreato-biliary (HPB), upper-gastrointestinal (UGI), sarcoma, peritoneal and surface malignancies (PSM) and colorectal cancer (CRC) surgeries to describe 4 domains: participants' setting, evaluation of clinical factors, use of screening tools and clinical practice. Results were compared among sub-specialties and according to human development index (HDI) in the largest cohorts. Out of 457 answers from 377 global participants (62% European), 35.0% were from breast and 28.9% were from CRC surgeons. Although MDTs management is consistently reported (64–88%), the presence of a nutritionist/dietician ranges from 14.1% to 44.2%. Breast surgeons seldom evaluate albumin (25.6%) and weight loss (30.6%), opposite to HPB, PSM and UGI groups (>70%, p 0.044). Overall, responders declared that the use of screening tools is largely neglected, that nutritional status is often assessed by the surgeons and that nutrition is not consistently modified according to risk factors (range among groups respectively: 1.9%–25.6%, 33.1%–51.4%, 33.1%–60.5%). Less than 20% of breast surgeons assess patients before/after surgery, comparing to >60% of PSM surgeons. However, no statistical differences were documented comparing groups for the majority of the items of the 4 domains. Nutritional evaluation is more often conducted by breast surgeons in medium/low HDI countries comparing very high/high HDI (p 0.04). Nutritional assessment is largely neglected. These results identify target-issues for the implementation of clinical practice. [ABSTRACT FROM AUTHOR]

Colorectal cancer mortality presents world-wide variation. In rectal cancers presenting a complete/nearly-complete tumor response (ypT0/ypTis) following neoadjuvant treatment, the features correlated to nodal metastases and relapses still need to be defined. An international cohort study enrolling ypT0/ypTis rectal cancers surgically treated from 2012 to 2017 was conducted. A propensity matching was used to balance nodal-positive and nodal-negative patients and statistical analyses were performed to investigate survivals, using a bootstrap model for internal validation. The features correlated with nodal metastasis were studied. Countries with participating centers were ranked using the World Bank (WBI), Human Development (HDI) and Global Gender Gap (GGG) indexes to compare survivals. 680 ypT0/ypTis from 52 European, Australian, Indian and American Institutions were analyzed. Mean follow-up was of 30.4 months. 96.5% were treated with total mesorectal excision, 7.2% were nodal-positive and 8.8% relapsed. Distal cancers (HR 0.71 95%CI: 0.56-0.91) and nodal metastasis and nodal metastasis (HR 3.85 95%CI:1.12–13.19) correlated with worse DFS, whereas a younger age was of borderline significance (HR 0.95 95%CI:0.91–0.99). The bootstrap analysis validated the model on 5000 repetitions. A short-course radiotherapy (OR 0.18 95%CI:0.09–0.37) correlated with the occurrence of nodal metastasis. Those countries classified in the low/medium-WBI, medium-HDI and lower-GGG ranks documented worse DFS curves (respectively p < 0.0001, p < 0.0001 and p 0.0002). However, the clinical stages were similar and patients from medium-HDI countries received more adjuvant chemotherapy than the others (p < 0.0001). Sub-groups at risk for relapses and nodal metastasis were identified. A global variation exists also when benchmarking a rectal cancer complete regression. [ABSTRACT FROM AUTHOR]

The parasite Cryptosporidium hominis is a leading cause of the diarrheal disease cryptosporidiosis, whose incidence in the United States has increased since 2005. Here, we show that the newly emerged and hyper-transmissible subtype IfA12G1R5 is now dominant in the United States. In a comparative analysis of 127 newly sequenced and 95 published C. hominis genomes, IfA12G1R5 isolates from the United States place into three of the 14 clusters (Pop6, Pop13, and Pop14), indicating that this subtype has multiple ancestral origins. Pop6 (IfA12G1R5a) has an East Africa origin and has recombined with autochthonous subtypes after its arrival. Pop13 (IfA12G1R5b) is imported from Europe, where it has recombined with the prevalent local subtype, whereas Pop14 (IfA12G1R5c) is a progeny of secondary recombination between Pop6 and Pop13. Selective sweeps in invasion-associated genes have accompanied the emergence of the dominant Pop14. These observations offer insights into the emergence and evolution of hyper-transmissible pathogens. [Display omitted] • Newly emerged IfA12G1R5 has become the dominant C. hominis subtype in the United States • IfA12G1R5 originates from subtypes in East Africa and Europe • IfA12G1R5 has gone through genetic recombination with local US subtypes • Natural selection played an additional role in shaping the evolution of IfA12G1R5 A newly emerged Cryptosporidium hominis subtype is associated with increased incidence of cryptosporidiosis in the United States. Huang et al. use comparative genomics to trace this subtype's evolutionary history involving multiple imports and secondary recombination. Adaptive selection in invasion-associated genes has led to the dominance of one of the three variants. [ABSTRACT FROM AUTHOR]

The Transthyretin Amyloidosis Outcomes Survey (THAOS) is a global, longitudinal, observational study of patients with transthyretin amyloidosis (ATTR amyloidosis), including both inherited (ATTRv amyloidosis) and wild-type (ATTRwt amyloidosis) disease, and asymptomatic patients with transthyretin (TTR) mutations (NCT00628745). This descriptive analysis provides a consolidated overview of 14 years of global demographics and clinical characteristics of patients with ATTR amyloidosis enrolled in THAOS as of January 4, 2021. The data period spans 2007 to 2021. There were 3604 symptomatic patients and 1772 asymptomatic carriers enrolled in THAOS. Of the symptomatic patients, 1055 had ATTRwt amyloidosis (93.8% male) and 2549 had ATTRv amyloidosis (61.6% male); the most prevalent TTR mutation was Val30Met (1493/2549; 58.6%). Median age at symptom onset was higher in patients with ATTRwt amyloidosis (73.0 years) vs patients with Val30Met (40.0 years), non-Val30Met (excluding cardiac; 51.5 years), and cardiac (64.5 years) mutations. In North America, the majority of patients had ATTRwt amyloidosis (58.8%), whereas in Europe, South America, and Japan ATTRv amyloidosis was more common. The most common phenotype was cardiac in North America (73.1%) and neurologic in South America (66.1%), Europe (52.1%), and Japan (56.9%). Of the asymptomatic carriers, 41.9% were male and median age at enrollment was 39.8 years. The most prevalent mutation was Val30Met (70.9%), followed by non-Val30Met (excluding cardiac; 18.3%), and cardiac (10.8%) mutations. These results revealed regional differences in relative rates of ascertainment of ATTRwt vs ATTRv amyloidosis and predominant phenotypes. However, this registry analysis may be limited by under-ascertainment and underreporting. [ABSTRACT FROM AUTHOR]

Abstract: Aims: A new treatment strategy combining maximal cytoreductive surgery for treatment of macroscopic disease and maximal perioperative intraperitoneal chemotherapy for residual microscopic disease, suggests that in a selected group of patients benefit is possible. The purpose of this study was to report our experience with this combined treatment and to identify the principal prognostic factors. Methods: The study included 266 patients from 9 institutions operated on between July 1990 and July 2004. The median age was 55 years. Results: The mortality rate was 7.8% and the morbidity rate 37.5%. The overall median survival was 13.7 months. Positive independent prognostic factors by multivariate analysis were gender, perioperative intraperitoneal chemotherapy and treatment by the second-look procedure. Conclusions: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with an acceptable morbidity and mortality. [Copyright &y& Elsevier]