non-MC Patients Research Articles

Formation of Polyploid Giant Cancer Cells Involves in the Prognostic Value of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer.

We previously reported that polyploid giant cancer cells (PGCCs) exhibit cancer stem cell properties and can generate daughter cells with the epithelial-mesenchymal transition phenotype. This study investigated the role of PGCC formation in the prognostic value of neoadjuvant chemoradiation therapy (nCRT) in locally advanced rectal cancer (LARC). The morphological characteristics were observed in patients with LARC after nCRT. Colorectal cancer cell lines were treated with irradiation or chemotherapeutic drugs, and the metastasis-related proteins were detected. 304 nCRT cases and 301 paired non-nCRT cases were collected for analysis. More PGCCs and morphologic characteristics related to invasion and metastasis appeared in tumor tissue after nCRT. Irradiation or chemicals could induce the formation of PGCCs with daughter cells exhibiting strong migratory, invasive, and proliferation abilities. In patients after nCRT, pathologic complete remission, partial remission, stable disease, and progressive disease were observed in 29 (9.54%), 125 (41.12%), 138 (45.39%), and 12 (3.95%) patients, respectively. Mucinous adenocarcinomas (MCs) occurred more frequently in nCRT than in non-nCRT patients (χ2 = 29.352, P=0.001), and the prognosis in MC patients was worse than that in non-MC patients (χ2 = 24.617, P=0.001). The difference in survival time had statistical significance for 60 days (χ2 = 5.357, P=0.021) and 70 days (χ2 = 18.830, P=0.001) rest interval time. On multivariable analysis, 60 days rest interval, Duke's stage, and recurrence and/or distant metastasis remained significant predictors of survival. In conclusion, irradiation or chemicals induce the formation of PGCCs and PGCCs produce daughter cells with strong migration and invasion abilities after a long incubation period. Appropriate rest interval (incubation period) is very important for patients with LARC who will receive nCRT.

Prognostic Implications of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer and Potential Mechanisms

BACKGOUND: To evaluate the role of neoadjuvant chemoradiation therapy (nCRT) in locally advanced rectal cancer, we retrospectively analyzed the prognosis and survival in patients treated with and without nCRT, and explored the possible mechanisms of chemoradiation resistance. METHODS: Clinicopathologic data of 304 nCRT cases and 301 paired non-nCRT cases were collected. LoVo and HCT116 cell lines were treated with irradiation and chemotherapeutic drugs, and subsequently the expression levels of metastasis-related proteins before and after treatments were compared. FINDINGS: After nCRT, pathologic complete remission (pCR), partial remission (pPR), stable disease (pSD), and progressive disease (pPD) were observed in 26(8.55%), 127(41.78%), 137(45.07%), and 12(3.95%) patients, respectively. Mucinous adenocarcinomas (MC) occurred more frequently in nCRT than in non-nCRT patients (χ2=29.352, P=0.000) and the prognosis in MC patients was worse than that in non-MC patients (χ2=24.617, P=0.000). The difference of survival rates from three to eight years between the nCRT and non-nCRT groups increased gradually. The difference in survival time had statistical significance for 60 days (χ2=5.357, P=0.021) and 70 days (χ2=18.830, P=0.001) rest interval time. T stage, lymph node metastasis, recurrence and/or distant metastasis, and Duke's stage were associated with poor survival. On multivariable analysis, 60 days rest interval, Duke's stage, and recurrence and/or distant metastasis remained significant predictors of survival. Radiation and chemotherapeutic treatment induced polyploid giant cancer cells (PGCCs) formation, and the PGCCs and their daughter cells exhibited strong migratory, invasive, and proliferation abilities. INTERPRETIATION. Radiation and chemotherapy can induce the formation of PGCCs with cancer stem cell properties. PGCCs and their budding daughter cells display strong migration and invasion abilities, which may be related to the poor prognosis in patients with nCRT. Funding: This work was supported in part by grants from the National Natural Science Foundation of China (81472729 and 81672426), and the foundation of committee on science and technology of Tianjin (17ZXMFSY00120 and 17YFZCSY00700). Declaration of Interest: All authors declare no competing interests. Ethical Approval: Our hospital review board approved the use of data from the colorectal cancer database.

HCV RNA Genomic sequences and HCV-E2 glycoprotein in sural nerve biopsies from HCV-infected patients with peripheral neuropathy.

Peripheral neuropathy (PN), the major neurological complication of chronic HCV infection, is frequently associated with mixed cryoglobulinaemia (MC) and small-vessel systemic vasculitis. While humoral and cell-mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of HCV remains largely speculative. The possible demonstration of HCV in peripheral nerve tissue would obviously assume important pathogenic implications. We studied sural nerve biopsies from 11 HCV-positive patients with neuropathic symptoms: five with and six without MC. In situ hybridization (ISH) and immunofluorescence studies were carried out to detect genomic and antigenomic HCV RNA sequences and HCV-encoded E2-glycoprotein, respectively. Epineurial vascular deposits of E2-glycoprotein were found in four (80%) MC and in two (33.3%) non-MC patients, respectively. These findings were enhanced by the perivascular deposition of positive-, though not negative-strand replicative RNA, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and/or complement proteins were revealed around small vessels, without distinct vasculitis changes between MC and non-MC patients. These results indicate that nerve vascular HCV RNA/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically HCV-infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate HCV productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus-triggered immune-mediated mechanisms.

Clinical significance of anti-HLA antibodies associated with ventricular assist device use in pediatric patients: A United Network for Organ Sharing database analysis.

While VAD use in pediatric patients has previously been associated with anti-HLA antibody production, the clinical significance of these antibodies is unclear. We investigated the clinical impact of anti-HLA antibodies associated with VAD use in a large cohort of pediatric HTx recipients. From 2004 to 2011, pediatric cardiomyopathy patients post-HTx (N=1288) with pre-HTx PRA levels were identified from the United Network for Organ Sharing database. PRA levels were compared between VAD patients and those with no history of MCS. Incidence of rejection and overall survival were compared between VAD and non-MCS groups after stratification by PRA and age. VAD recipients were more likely to produce anti-HLA antibodies than non-MCS patients (25.5% vs 10.5% had PRA>10%, P<.0001). Sensitized VAD patients (PRA>10%) had a higher incidence of rejection within 15 months of HTx compared to sensitized non-MCS patients (57.1% vs 35.9%, P=.02). There was no intergroup difference in 15-month mortality. Among pediatric cardiomyopathy patients supported with a VAD, the presence of anti-HLA antibodies prior to HTx is associated with an increased risk of rejection. The mechanism of the association between VAD-associated antibodies and early rejection is unclear and warrants further investigation.

Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation

Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial. Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts. We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis. MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.

ABO blood group antibody levels in infants exposed to mechanical circulatory support.

ABO sensitization is a barrier to ABO-incompatible heart transplantation in infants. We investigate the development of ABO antibodies in infants with and without mechanical circulatory support (MCS) during their waiting period. Although the proportion of patients with antibodies was similar between the groups, the median age at antibody detection was only 9 days (6-198) for MCS vs. 223 days (28-367) for non-MCS patients (P = 0.028), suggesting MCS is associated with earlier ABO antibody detection.

Perioperative mechanical circulatory support in children: An analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database

Analyses of mechanical circulatory support (MCS) in pediatric heart surgery have primarily focused on single-center outcomes or narrow applications. We describe the patterns of use, patient characteristics, and MCS-associated outcomes across a large multicenter cohort. Patients (aged <18 years) in the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database (2000-2010) were included. The characteristics and outcomes of those receiving postoperative MCS were described, and bayesian hierarchical models were used to examine variations in the adjusted MCS rates across institutions. Of 96,596 operations (80 centers), MCS was used in 2.4%. The MCS patients were younger (13 vs 195 days, P < .0001) and more often had STS-defined preoperative risk factors (57.2% vs 32.7%, P < .0001). The operations with the greatest MCS rates included the Norwood procedure (17%) and complex biventricular repairs (arterial switch, ventricular septal defect, and arch repair [14%]). More than one half of the MCS patients did not survive to hospital discharge (53.2% vs 2.9% of non-MCS patients; P < .0001). MCS-associated mortality was greatest for truncus arteriosus and Ross-Konno operations (both 71%). The hospital-level MCS rates adjusted for patient characteristics and case mix varied by 15-fold across institutions, with both high- and low-volume hospitals having substantial variation in MCS rates. Perioperative MCS use varied widely across centers. The MCS rates were greatest overall for the Norwood procedure and complex biventricular repairs. Although MCS can be a life-saving therapy, more than one half of MCS patients will not survive to hospital discharge, with mortality >70% for some operations. Future studies aimed at better understanding the appropriate indications, optimal timing, and management of MCS could help to reduce the variation in MCS use across hospitals and improve outcomes.

T cell receptor variable β gene repertoire in liver and peripheral blood lymphocytes of chronically hepatitis C virus-infected patients with and without mixed cryoglobulinaemia

To characterize the repertoire of T lymphocytes in chronically hepatitis C virus (HCV)-infected patients with and without mixed cryoglobulinaemia (MC). T cell receptor (TCR) variable (V) β clonalities in portal tracts isolated from liver biopsy sections with a laser capture microdissection technique in 30 HCV-positive MC patients were studied by size spectratyping. Complementarity-determining region 3 (CDR3) profiles of liver-infiltrating lymphocytes (LIL) were also compared with those circulating in the blood. The representative results of TCR Vβ by CDR3 were also obtained from liver tissues and peripheral blood lymphocytes (PBL) of 21 chronically HCV-infected patients without MC. LIL were highly restricted, with evidence of TCR Vβ clonotypic expansions in 23 of 30 (77%) and in 15 of 21 (71%) MC and non-MC patients, respectively. The blood compartment contained TCR Vβ expanded clones in 19 (63%) MC and 12 (57%) non-MC patients. The occurrence of LIL clonalities was detected irrespective of the degree of liver damage or circulating viral load, whereas it correlated positively with higher levels of intrahepatic HCV RNA. These results support the notion that TCR Vβ repertoire is clonally expanded in HCV-related MC with features comparable to those found in chronically HCV-infected patients without MC.

The Nordic Maintenance Care Program: Maintenance care – what happens during the consultation? Observations and patient questionnaires

BackgroundBecause maintenance care (MC) is frequently used by chiropractors in the management of patients with back pain, it is necessary to define the rationale, frequency and indications for MC consultations, and the contents of such consultations. The objectives of the two studies described in this article are: i) to determine the typical spacing between visits for MC patients and to compare MC and non-MC patients, ii) to describe the content of the MC consultation and to compare MC and non-MC patients and iii) to investigate the purposes of the MC program.MethodIn two studies, chiropractors who accepted the MC paradigm were invited to assist with the data collection. In study 1, patients seen by seven different chiropractors were observed by two chiropractic students. They noted the contents of the observed consultations. In study 2, ten chiropractors invited their MC patients to participate in an anonymous survey. Participants filled in a one page questionnaire containing questions on their view of the purposes and contents of their MC consultations. In addition, information was obtained on the duration between appointments in both studies.ResultsThere were 178 valid records in study 1, and in study 2 the number of questionnaires received was 373. The time interval between MC visits was close to nine weeks and for non-MC consultations it was two weeks.The content of the consultations in study 1 was similar for MC and non-MC patients with treatment being the most time-consuming element followed by history taking/examination. MC consultations were slightly shorter than non-MC consultations.In study 2, the most common activities reported to have taken place were history taking and manipulative therapy. The most commonly reported purposes were to prevent recurring problems, to maintain best possible function and /or to stay as pain free as possible.ConclusionsThe results from these two studies indicate that MC consultations commonly take place with around two months intervals, and that history taking, examination and treatment are as important components in MC as in non-MC consultations. Further, the results demonstrate that most patients consider the goal to be secondary or tertiary prevention.

The Nordic Maintenance Care Program - Time intervals between treatments of patients with low back pain: how close and who decides?

BackgroundThe management of chiropractic patients with acute and chronic/persistent conditions probably differs. However, little is known on this subject. There is, for example, a dearth of information on maintenance care (MC). Thus it is not known if patients on MC are coerced to partake in a program of frequent treatments over a long period of time, or if they are actively involved in designing their own individualized treatment program.ObjectivesIt was the purpose of this study to investigate how chiropractic patients with low back pain were scheduled for treatment, with special emphasis on MC. The specific research questions were: 1. How many patients are on maintenance care? 2) Are there specific patterns of intervals between treatments for patients and, if so, do they differ between MC patients and non-MC patients? 3. Who decides on the next treatment, the patient, the chiropractor or both, and are there any differences between MC patients and non-MC patients?MethodsChiropractic students, who during their summer holidays were observers in chiropractic clinics in Norway and Denmark, recorded whether patients were classified by the treating chiropractor as a MC-patient or not, dates for last and subsequent visits, and made a judgement on whether the patient or the chiropractor decided on the next appointment.ResultsObservers in the study were 16 out of 30 available students. They collected data on 868 patients from 15 Danish and 13 Norwegian chiropractors. Twenty-two percent and 26%, respectively, were classified as MC patients. Non-MC patients were most frequently seen within 1 week. For MC patients, the previous visit was most often 2-4 weeks prior to the actual visit, and the next appointment between 1 and 3 months. This indicates a gradual increase in intervals. The decision of the next visit was mainly made by the chiropractor, also for MC patients. However, the study samples of chiropractors appear not to be representative of the general Danish and Norwegian chiropractic profession and the patients may also have been non-representative.ConclusionThere were two distinctly different patterns for the time period between visits for MC patients and non-MC patients. For non-MC patients, the most frequent interval between visits was one week and for MC patients, the period was typically between two weeks and three months. It was primarily the chiropractor who made the next visit-decision. However, these results can perhaps not be extrapolated to other groups of patients and chiropractors.