Colorectal cancer(CRC)is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors.CRC develops through a gradual accumulation of genetic and epigenetic changes,leading to the...Colorectal cancer(CRC)is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors.CRC develops through a gradual accumulation of genetic and epigenetic changes,leading to the transformation of normal colonic mucosa into invasive cancer.CRC is one of the most prevalent and incident cancers worldwide,as well as one of the most deadly.Approximately 1235108 people are diagnosed annually with CRC,and 609051 die from CRC annually.The World Health Organization estimates an increase of77%in the number of newly diagnosed cases of CRCand an increase of 80%in deaths from CRC by 2030.The incidence of CRC can benefit from different strategies depending on its stage:health promotion through health education campaigns(when the disease is not yet present),the implementation of screening programs(for detection of the disease in its early stages),and the development of nearly personalized treatments according to both patient characteristics(age,sex)and the cancer itself(gene expression).Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application,not all strategies meet the criteria required for screening tests in population programs;the three most accepted tests are the fecal occult blood test(FOBT),colonoscopy and sigmoidoscopy.FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe.Due to its non-invasive nature and low cost,it is one of the most accepted techniques by population.CRC is a very heterogeneous disease,and with a few exceptions(APC,p53,KRAS),most of the genes involved in CRC are observed in a small percentage of cases.The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy.In recent years,the use of DNA,RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis.Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA,RNA or proteins in the blood or stool,it is likely that given the quick progression of technology tools in molecular biology,increasingly sensitive and less expensive,these tools will gradually be employed in clinical practice and will likely be developed in mass.展开更多
This study was conducted to identify the number and density of active licensed acupuncturists(LAcs),as well as the number of accredited schools in acupuncture and Oriental medicine(AOM),as of January 1,2023,in the Uni...This study was conducted to identify the number and density of active licensed acupuncturists(LAcs),as well as the number of accredited schools in acupuncture and Oriental medicine(AOM),as of January 1,2023,in the United States(U.S.).The number of active LAcs as of January 1,2023 was 34,524,potentially33,364 after removing license duplication in multiple states,among which the largest three states were California(with 7317 LAcs[21.19%of the total]),New York(5024[14.55%])and Florida(2644[7.66%]).The total number of LAcs decreased by 8.87%from 2018,and fell short of our projected number of LAcs in 2023 by 9037,or 20.75%.The overall LAc density in the U.S.Dmeasured as the number of LAcs per 100,000 populationDwas 10.36,less than in 2018.There were 56 active,accredited AOM schools which offered a total of 147 programs(121 at the level necessary for licensing[entry-level],12 for an advanced practicing degree[advanced-level],and 14 for certifications).Broken down further,offerings included 50 master's degrees in acupuncture,40 master's degrees in Oriental medicine,31 entry-level doctorate degrees(10 in acupuncture and 21 in acupuncture plus Chinese herbal medicine),and 12advanced-level doctorate degrees in AOM.The certification programs included one in East-Asian Medical Bodywork and 13 in CHM.Among these schools in 2023,institutions in the West and East Coast states comprised 67.86%(decreased from 77.42%in 2018)of the national total.California,Florida and Illinois represented 39.29%.There were 48 jurisdictions with acupuncture practice laws in place.The data suggests that the acupuncture profession in the U.S.has been significantly impacted during the coronavirus disease 2019 pandemic.展开更多
Adolescents and young adults(AYA)with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to addr...Adolescents and young adults(AYA)with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to address reproductive concerns,especially fertility.The opportunity for genetic counselors to provide important risk information is relevant to both the newly diagnosed as well as to unaffected carriers and survivors.However,genetic counselors may need additional training in reproductive options related to AYA cancer to provide this valuable counsel.This commentary uses hereditary breast and ovarian cancer syndrome as a model to highlight important considerations when discussing preimplanatation genetic diagnosis and prenatal diagnosis,particularly in the context of expanded testing for hereditary cancer risk including multigene panels or whole exome or whole genome sequencing.Other hereditary cancers are also addressed;however,less is known about the psychosocial and fertility concerns in these AYA populations.Additionally,we provide an overview of the concept of"oncofertility"-the linkage between cancer care and reproductive medicine that aims to expand the reproductive opportunities of cancer patients-and offer support for the expansion of guidelines to include genetic counselors in AYA cancer patients’treatment planning related to reproductive health and fertility.展开更多
Background: Monoclonal antibody treatments for metastatic colorectal cancer (mCRC) have distinct treatment-related safety profiles. This study aimed to elucidate the hospitalisation costs of adverse events (AEs) commo...Background: Monoclonal antibody treatments for metastatic colorectal cancer (mCRC) have distinct treatment-related safety profiles. This study aimed to elucidate the hospitalisation costs of adverse events (AEs) commonly associated with monoclonal antibodies when administered to patients with mCRC. Methods: This study extracted data for patients newly diagnosed with mCRC from a large US claims database from January 2005 to June 2008. The first distant metastasis diagnosis date was defined as the index date. Main outcomes were length of hospital stay (days) and hospitalisation costs (2010 US$) for AEs (identified by primary discharge diagnoses). All analyses are presented descriptively. Results: The study population (aged ≥18 years;n = 12,648) was balanced according to gender and was mainly aged 50 years or older (90.1%). Most patients had colon cancer (70.1%) as opposed to rectal cancer. Gastrointestinal (GI) perforation incurred the longest median length of stay (11.5 days) for hospitalisations, followed by wound-healing complications (7 days), arterial and venous thromboembolism (5.5 and 4 days, respectively), and congestive heart failure (4 days). The highest inpatient cost per event was for GI perforations (mean $66,224 and median $ 34,027), followed by arterial thromboembolism ($40,992 and $18,587), wound-healing complications ($36,440 and $21,163), interstitial lung disease ($26,705 and $19,111) and acute myocardial infarction ($22,395 and $15,223). Skin toxicity (mean $6475 and median $6110) and hypertension ($14,108 and $6047) were associated with relatively low costs. Conclusions: Hospital costs for monoclonal antibody treatment-related AEs in patients with mCRC vary greatly. This study provides source data for economic evaluations of head-to-head comparisons of monoclonal antibody treatments.展开更多
AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC)mice with dextran sodium sulfate(DSS)-induced inflammation.METHODS Inflammation driven colorectal carcinogenesis...AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC)mice with dextran sodium sulfate(DSS)-induced inflammation.METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC)mice by administering DSS in their drinking water.Mice were fed a diet supplemented with plecanatide(0-20 ppm)and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated.Plecanatide-mediated activation of guanylate cyclase-C(GC-C)signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP)by ELISA,protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting.Ki-67,c-myc and cyclin D1 were used as markers of proliferation.Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry,respectively.Uroguanylin(UG)and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR).A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures.RESULTS Oral treatment of Apc^(+/Min-FCCC)mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid,flat and indeterminate dysplasias.This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation.Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6,IL-1 TNF),chemokines(MIP-1,IP-10)and growth factors(GCSF and GMCSF)from colon explants derived from mice with acute DSS-induced inflammation.The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues.Although GC-C expression was not altered appreciably,a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon,potentially due to a reduction in intestinal inflammation and/or neoplasia.Taken together,these results suggest that reductions in endogenous UG,accompanied by dysregulation in GC-C signaling,may be an early event in inflammation-promoted colorectal neoplasia;an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice,demonstrating the utility for developing GC-C agonists as chemopreventive agents.展开更多
基金Supported by Partially funded by the Carlos Ⅲ Health Institute No.PI11/01593
文摘Colorectal cancer(CRC)is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors.CRC develops through a gradual accumulation of genetic and epigenetic changes,leading to the transformation of normal colonic mucosa into invasive cancer.CRC is one of the most prevalent and incident cancers worldwide,as well as one of the most deadly.Approximately 1235108 people are diagnosed annually with CRC,and 609051 die from CRC annually.The World Health Organization estimates an increase of77%in the number of newly diagnosed cases of CRCand an increase of 80%in deaths from CRC by 2030.The incidence of CRC can benefit from different strategies depending on its stage:health promotion through health education campaigns(when the disease is not yet present),the implementation of screening programs(for detection of the disease in its early stages),and the development of nearly personalized treatments according to both patient characteristics(age,sex)and the cancer itself(gene expression).Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application,not all strategies meet the criteria required for screening tests in population programs;the three most accepted tests are the fecal occult blood test(FOBT),colonoscopy and sigmoidoscopy.FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe.Due to its non-invasive nature and low cost,it is one of the most accepted techniques by population.CRC is a very heterogeneous disease,and with a few exceptions(APC,p53,KRAS),most of the genes involved in CRC are observed in a small percentage of cases.The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy.In recent years,the use of DNA,RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis.Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA,RNA or proteins in the blood or stool,it is likely that given the quick progression of technology tools in molecular biology,increasingly sensitive and less expensive,these tools will gradually be employed in clinical practice and will likely be developed in mass.
文摘This study was conducted to identify the number and density of active licensed acupuncturists(LAcs),as well as the number of accredited schools in acupuncture and Oriental medicine(AOM),as of January 1,2023,in the United States(U.S.).The number of active LAcs as of January 1,2023 was 34,524,potentially33,364 after removing license duplication in multiple states,among which the largest three states were California(with 7317 LAcs[21.19%of the total]),New York(5024[14.55%])and Florida(2644[7.66%]).The total number of LAcs decreased by 8.87%from 2018,and fell short of our projected number of LAcs in 2023 by 9037,or 20.75%.The overall LAc density in the U.S.Dmeasured as the number of LAcs per 100,000 populationDwas 10.36,less than in 2018.There were 56 active,accredited AOM schools which offered a total of 147 programs(121 at the level necessary for licensing[entry-level],12 for an advanced practicing degree[advanced-level],and 14 for certifications).Broken down further,offerings included 50 master's degrees in acupuncture,40 master's degrees in Oriental medicine,31 entry-level doctorate degrees(10 in acupuncture and 21 in acupuncture plus Chinese herbal medicine),and 12advanced-level doctorate degrees in AOM.The certification programs included one in East-Asian Medical Bodywork and 13 in CHM.Among these schools in 2023,institutions in the West and East Coast states comprised 67.86%(decreased from 77.42%in 2018)of the national total.California,Florida and Illinois represented 39.29%.There were 48 jurisdictions with acupuncture practice laws in place.The data suggests that the acupuncture profession in the U.S.has been significantly impacted during the coronavirus disease 2019 pandemic.
文摘Adolescents and young adults(AYA)with a cancer diagnosis or those at risk for cancer due to hereditary cancer syndromes may benefit from genetic counseling and testing not only to manage personal risk but also to address reproductive concerns,especially fertility.The opportunity for genetic counselors to provide important risk information is relevant to both the newly diagnosed as well as to unaffected carriers and survivors.However,genetic counselors may need additional training in reproductive options related to AYA cancer to provide this valuable counsel.This commentary uses hereditary breast and ovarian cancer syndrome as a model to highlight important considerations when discussing preimplanatation genetic diagnosis and prenatal diagnosis,particularly in the context of expanded testing for hereditary cancer risk including multigene panels or whole exome or whole genome sequencing.Other hereditary cancers are also addressed;however,less is known about the psychosocial and fertility concerns in these AYA populations.Additionally,we provide an overview of the concept of"oncofertility"-the linkage between cancer care and reproductive medicine that aims to expand the reproductive opportunities of cancer patients-and offer support for the expansion of guidelines to include genetic counselors in AYA cancer patients’treatment planning related to reproductive health and fertility.
文摘Background: Monoclonal antibody treatments for metastatic colorectal cancer (mCRC) have distinct treatment-related safety profiles. This study aimed to elucidate the hospitalisation costs of adverse events (AEs) commonly associated with monoclonal antibodies when administered to patients with mCRC. Methods: This study extracted data for patients newly diagnosed with mCRC from a large US claims database from January 2005 to June 2008. The first distant metastasis diagnosis date was defined as the index date. Main outcomes were length of hospital stay (days) and hospitalisation costs (2010 US$) for AEs (identified by primary discharge diagnoses). All analyses are presented descriptively. Results: The study population (aged ≥18 years;n = 12,648) was balanced according to gender and was mainly aged 50 years or older (90.1%). Most patients had colon cancer (70.1%) as opposed to rectal cancer. Gastrointestinal (GI) perforation incurred the longest median length of stay (11.5 days) for hospitalisations, followed by wound-healing complications (7 days), arterial and venous thromboembolism (5.5 and 4 days, respectively), and congestive heart failure (4 days). The highest inpatient cost per event was for GI perforations (mean $66,224 and median $ 34,027), followed by arterial thromboembolism ($40,992 and $18,587), wound-healing complications ($36,440 and $21,163), interstitial lung disease ($26,705 and $19,111) and acute myocardial infarction ($22,395 and $15,223). Skin toxicity (mean $6475 and median $6110) and hypertension ($14,108 and $6047) were associated with relatively low costs. Conclusions: Hospital costs for monoclonal antibody treatment-related AEs in patients with mCRC vary greatly. This study provides source data for economic evaluations of head-to-head comparisons of monoclonal antibody treatments.
基金Supported by National Cancer Institute(CA133689 to Kunwar Shailubhai,CA006927 to Fox Chase Cancer Center)an appropriation from the Commonwealth of Pennsylvania(Fox Chase Cancer Center)
文摘AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC)mice with dextran sodium sulfate(DSS)-induced inflammation.METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC)mice by administering DSS in their drinking water.Mice were fed a diet supplemented with plecanatide(0-20 ppm)and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated.Plecanatide-mediated activation of guanylate cyclase-C(GC-C)signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP)by ELISA,protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting.Ki-67,c-myc and cyclin D1 were used as markers of proliferation.Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry,respectively.Uroguanylin(UG)and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR).A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures.RESULTS Oral treatment of Apc^(+/Min-FCCC)mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid,flat and indeterminate dysplasias.This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation.Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6,IL-1 TNF),chemokines(MIP-1,IP-10)and growth factors(GCSF and GMCSF)from colon explants derived from mice with acute DSS-induced inflammation.The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues.Although GC-C expression was not altered appreciably,a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon,potentially due to a reduction in intestinal inflammation and/or neoplasia.Taken together,these results suggest that reductions in endogenous UG,accompanied by dysregulation in GC-C signaling,may be an early event in inflammation-promoted colorectal neoplasia;an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice,demonstrating the utility for developing GC-C agonists as chemopreventive agents.
