Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases: A Nationwide Population-Based Study.

BACKGROUND: Before 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks. METHODS: This nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009-2015 and 2016-2021). RESULTS: In total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009-2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016-2021 (30.2% in expert centers, 22.6% in referring centers). In 2009-2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02-2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66-0.96). In 2016-2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76-2.13) and survival (HR 1.00, 95% CI 0.76-1.32). CONCLUSION: Previously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.

Elbow joint loads during simulated activities of daily living: implications for formulating recommendations after total elbow arthroplasty.

BACKGROUND: Overloading of the elbow joint prosthesis following total elbow arthroplasty can lead to implant failure. Joint moments during daily activities are not well contextualized for a prosthesis's failure limits, and the effect of the current postoperative instruction on elbow joint loading is unclear. This study investigates the difference in elbow joint moments between simulated daily tasks and between flexion-extension, pronation-supination, and varus-valgus movement directions. Additionally, the effect of the current postoperative instruction on elbow joint load is examined. METHODS: Nine healthy participants (age 45.8 ± 17 years, 3 males) performed 8 tasks; driving a car, opening a door, rising from a chair, lifting, sliding, combing hair, drinking, emptying cup, without and with the instruction "not lifting more than 1 kg." Upper limb kinematics and hand contact forces were measured. Elbow joint angles and net moments were analyzed using inverse dynamic analysis, where the net moments are estimated from movement data and external forces. RESULTS: Peak elbow joint moments differed significantly between tasks (P < .01) and movement directions (P < .01). The most and least demanding tasks were, rising from a chair (13.4 Nm extension, 5.0 Nm supination, and 15.2 Nm valgus) and sliding (4.3 Nm flexion, 1.7 Nm supination, and 2.6 Nm varus). Net moments were significantly reduced after instruction only in the chair task (P < .01). CONCLUSION: This study analyzed elbow joint moments in different directions during daily tasks. The outcomes question whether postoperative instruction can lead to decreasing elbow loads. Future research might focus on reducing elbow loads in the flexion-extension and varus-valgus directions.

The impact of a multi-hospital network on the inequality in odds of receiving resection or ablation for synchronous colorectal liver metastases.

BACKGROUND: This study investigates whether inequalities in the utilization of resection and/or ablation for synchronous colorectal liver metastases (SCLM) between patients diagnosed in expert and non-expert hospitals changed since a multi-hospital network started. MATERIALS AND METHODS: Patients diagnosed with SCLM between 2009 and 2020 were included. The likelihood of receiving ablation and/or resection was analyzed in the prenetwork (2009-2012), startup (2013-2016), and matured-network (2017-2020) periods. RESULTS: Nationwide, 13.981patients were diagnosed between 2009 and 2020, of whom 1.624 were diagnosed in the network. Of patients diagnosed in the network's expert hospitals, 36.7% received ablation and/or resection versus 28.3% in nonexpert hospitals (p < 0.01). The odds ratio (OR) of receiving ablation and/or resection for patients diagnosed in expert versus nonexpert hospitals increased from 1.38 (p = 0.581, pre-network), to 1.66 (p = 0.108, startup), to 2.48 (p = 0.090, matured-network). Nationwide, the same trend occurred (respectively OR 1.41, p = 0.011; OR 2.23, p < 0.001; OR 3.20, p < 0.001). CONCLUSIONS: Patients diagnosed in expert hospitals were more likely to receive ablation and/or resection for SCLM than patients diagnosed in non-expert hospitals. This difference increased over time despite the startup of a multi-hospital network. Establishing a multi-hospital network did not have an effect on reducing the existing unequal odds of receiving specialized treatment. SYNOPSIS: Specialized oncology treatments are increasingly provided through multi-hospital networks. However, scant empirical evidence on the effectiveness of these networks exists. This study analyzes whether a regional multi-hospital network was able to improve equal access to specialized oncology treatments.

Additional preconditioning program for bariatric surgery: Any benefits? A large cohort study.

Postbariatric outcomes may improve by providing an additional preconditioning program (APP) in targeted patients. However, APPs are a demand for health resources while only little and inconsistent evidence consists to support their effectiveness. This cohort study aims to evaluate the effectiveness of APP, by comparing outcomes of patients with and without such APP. We carried out a retrospective single-centre cohort study in a before-after design. Patients signing up for primary gastric bypass or sleeve gastrectomy and eligible for surgery were included if screened as vulnerable patients. Vulnerable patients screened between September 2017 and March 2018 followed an APP and formed the APP-group. Due to a policy change, APPs were no longer performed since September 2018. Vulnerable patients screened between September 2018 and March 2019 thus did not receive an APP (comparator-group). Multidisciplinary follow-up remained unchanged. Endpoints included percentage total weight loss (%TWL), bodyweight, evolution of comorbidities, protein intake, and number of no-shows. The APP-group comprised 231 patients and the comparator-group 153. %TWL differed statistically significantly at 7 (Δ1.5%, p = .01) and 12 months postoperative (Δ2.8%, p < .01) in favour of the comparator-group, as did bodyweight 12 months postoperative (Δ1.8 kg, p < .01). Statistically significant differences were also found in the evolution of comorbidities, protein intake, and the number of no-shows, most in favour for the comparator-group. APP proofed not to be superior to Non-App. It is debatable whether statically significant differences are clinically relevant given their small magnitude. A care pathway without an APP seems at least as effective as a care pathway without.

Why the long face? A comparative study of feeding kinematics of two pipefishes with different snout lengths.

This study showed that the mouth of Doryrhamphus dactyliophorus, a species with a relatively long snout, travels a greater distance compared with Doryrhamphus melanopleura, a species with a considerably shorter snout, allowing it to strike at prey that are farther away from the mouth. The long-snouted species also tended to reach significantly higher linear velocities of the mouth approaching the prey. On the other hand, D. melanopleura needed less time to capture its prey. A striking difference in prey-capture success was observed between species: D. melanopleura and D. dactyliophorus had a prey-capture success of 91 and 31%, respectively. The small prey size and the relatively large distance between eyes and prey are potential reasons why directing the mouth accurately to the prey is difficult in D. dactyliophorus, hence possibly explaining the lower prey-capture success in this long-snouted species.

Wilms' tumour 1 can suppress hTERT gene expression and telomerase activity in clear cell renal cell carcinoma via multiple pathways.

BACKGROUND: Wilms' tumour 1 (WT1) gene was discovered as a tumour suppressor gene. Later findings have suggested that WT1 also can be oncogenic. This complexity is partly explained by the fact that WT1 has a number of target genes. METHOD: WT1 and its target gene human telomerase reverse transcriptase (hTERT) were analysed in clear cell renal cell carcinoma (ccRCC). In vitro experiments were performed to examine the functional link between WT1 and hTERT by overexpression of WT1 isoforms in the ccRCC cell line, TK-10. RESULTS: WT1 demonstrated lower RNA expression in ccRCC compared with renal cortical tissue, whereas hTERT was increased, showing a negative correlation between WT1 and hTERT (P=0.005). These findings were experimentally confirmed in vitro. The WT1 generated effect on hTERT promoter activity seemed complex, as several negative regulators of hTERT transcription, such as SMAD3, JUN (AP-1) and ETS1, were activated by WT1 overexpression. Downregulation of potential positive hTERT regulators, such as cMyc, AP-2α, AP-2γ, IRF1, NFX1 and GM-CSF, were also observed. Chromatin immunoprecipitation analysis verified WT1 binding to the hTERT, cMyc and SMAD3 promoters. CONCLUSION: The collected data strongly indicate multiple pathways for hTERT regulation by WT1 in ccRCC.

Increased abdominal obesity, adverse psychosocial factors and shorter telomere length in subjects reporting early ageing; the MONICA Northern Sweden Study.

BACKGROUND: The rate of biological ageing is individual and represents the steady decrease in physiological and mental functions. Adverse social factors have been shown to influence this process. Self-perceived early ageing (SEA) might be a useful indicator of early biological ageing and increased mortality risk. The aim of this population-based study was to identify markers of SEA, including telomere length. METHODS: We studied 1502 subjects (744 men, 758 women) from Northern Sweden. These subjects underwent a physical examination, blood sampling (including telomere length) and completed a self-administered questionnaire about their subjective age, social situation, lifestyle, and self-rated health (SRH). Age- and SRH-adjusted statistical analyses were made comparing SEA subjects with same-sex controls. RESULTS: In all, 7.9% of men and 12.1% of women reported SEA. These subjects had significantly (p<0.0001) wider waist circumference and higher body mass index than controls. SEA men showed higher fasting glucose and SEA women showed higher total cholesterol levels than controls (p=0.020 and p=0.015, respectively). In addition, SEA women more often reported infrequent physical exercise (p=0.006), mental problems (p=0.064) and worse SRH (p=0.001) than controls. In a random sub-sample, telomere length was significantly shorter in SEA subjects (n=139) than controls (n=301; p=0.02), but not after full adjustment for BMI. CONCLUSIONS: Self-perceived early ageing is not uncommon and is associated with abdominal obesity, poor self-rated health, lower education, and shorter telomere length. This could link adverse social factors with features of the metabolic syndrome as well as with early biological ageing, of importance for targeting preventive programmes.

Bone marrow fibrosis in childhood acute lymphoblastic leukemia correlates to biological factors, treatment response and outcome.

We retrospectively evaluated reticulin fiber density (RFD) in 166 diagnostic bone marrow (BM) biopsies and 62 biopsies obtained at treatment day 29 from children with acute lymphoblastic leukemia (ALL). Patients with B-cell precursor (BCP)-ALL showed higher RFD as compared to patients with T-cell ALL (P<0.001). RFD correlated negatively with white blood cell count (P=0.008) in BCP-ALL patients. Patients with high-hyperdiploid ALL (51-61 chromosomes), no high-risk criteria and low RFD showed a favorable outcome when compared to similar patients with high RFD (P=0.002). In BCP-ALL patients, RFD at diagnosis correlated to the levels of minimal residual disease (MRD) analyzed by flow cytometry on treatment day 29 (P=0.001). Accordingly, patients with MRD > or = 10(-4) presented higher RFD at diagnosis compared to patients with MRD < 10(-4) (P=0.003). BCP-ALL patients with low RFD at diagnosis and a rapid reduction of RFD on day 29 had a favorable outcome compared to patients with the same baseline RFD level at diagnosis but a slow RFD reduction (P=0.041). To our knowledge, these findings are novel and may indicate BM fibrosis as a new valuable prognostic marker in childhood ALL. Expanded use of BM biopsy both at diagnosis and during follow-up is suggested.

The BCL-2 promoter (-938C>A) polymorphism does not predict clinical outcome in chronic lymphocytic leukemia.

The (-938C>A) polymorphism in the promoter region of the BCL-2 gene was recently associated with inferior time to treatment and overall survival in B-cell chronic lymphocytic leukemia (CLL) patients displaying the -938A/A genotype and may thus serve as an unfavorable genetic marker in CLL. Furthermore, the -938A/A genotype was associated with increased expression of Bcl-2. To investigate this further, we analyzed the -938 genotypes of the BCL-2 gene in 268 CLL patients and correlated data with treatment status, overall survival and known prognostic factors, for example, Binet stage, immunoglobulin heavy-chain variable (IGHV) mutational status and CD38 expression. In contrast to the recent report, the current cohort of CLL patients showed no differences either in time to treatment or overall survival in relation to usage of a particular genotype. In addition, no correlation was evident between the (-938C>A) genotypes and IGHV mutational status, Binet stage or CD38. Furthermore, the polymorphism did not appear to affect the Bcl-2 expression at the RNA level. Taken together, our data do not support the use of the (-938C>A) BCL-2 polymorphism as a prognostic marker in CLL and argue against its postulated role in modulating Bcl-2 levels.

The G(-248)A polymorphism in the promoter region of the Bax gene does not correlate with prognostic markers or overall survival in chronic lymphocytic leukemia.

The G(-248)A polymorphism in the promoter region of the Bax gene was recently associated with low Bax expression, more advanced stage, treatment resistance and short overall survival in B-cell chronic lymphocytic leukemia (CLL), the latter particularly in treated patients. To investigate this further, we analyzed 463 CLL patients regarding the presence or absence of the G(-248)A polymorphism and correlated with overall survival, treatment status and known prognostic factors, for example, Binet stage, VH mutation status and genomic aberrations. In this material, similar allele and genotype frequencies of the Bax polymorphism were demonstrated in CLL patients and controls (n=207), where 19 and 21% carried this polymorphism, respectively, and no skewed distribution of the polymorphism was evident between different Binet stages and VH mutated and unmutated CLLs. Furthermore, no difference in overall survival was shown between patients displaying the G(-248)A polymorphism or not (median survival 85 and 102 months, respectively, P=0.21), and the polymorphism did not influence outcome specifically in treated CLL. Neither did the polymorphism affect outcome in prognostic subsets defined by VH mutation status or genomic aberrations. In conclusion, the pathogenic role and clinical impact of the Bax polymorphism is limited in CLL.

Analysis of plant extracts by NIRS: simultaneous determination of kavapyrones and water in dry extracts of Piper methysticum Forst.

A near-infrared reflection spectroscopy (NIRS) method was developed to determine the total content of kavapyrones, kavain and water in dry extracts of Piper methysticum Forst. (kava kava, Piperaceae). Based on the recorded spectra and the reference data, performed by HPLC and Karl Fischer titration, a chemometrical analysis was calculated using PLS 2 algorithm. In general, good calibration statistics are obtained for the prediction of the different contents presenting high correlation coefficients (r(2) > 0.9913) and low root mean square errors of prediction (RMSEP < 0.094%). Usually the main water bands are "cut out" of the spectra to improve the model, however this is associated with the loss of relevant spectroscopic information. Thus, the entire spectrum including the OH bands is used, as these are not only found in water but also in the kavapyrones. The use of this new strategy succeeds in overcoming the difficulties in NIRS and establishes NIRS as a valid alternative in the routine quality control of plant extracts.

High-performance liquid chromatography-coordination ion spray-mass spectrometry (HPLC-CIS/MS): a new tool for the analysis of non-polar compound classes in plant extracts using the example of Piper methysticum Forst.

An efficient method to characterise complex plant extracts is described using the example of Piper methysticum Forst. (kava; Piperaceae). The method is based on the on-line coupling of high-performance liquid chromatography to a new detection technique: coordination ion spray-mass spectrometry (CIS/MS). CIS/MS is a universal, novel ionisation technique improving selectivity as well as sensitivity. Charged complexes were formed through addition of central complexing ions such as sodium, silver and cobalt. The advantages of CIS/MS detection compared with the electrospray ionisation detection are discussed. The experimental set-up and the application of this simple and robust technique is described to show the its various fields of application in the analysis of plant extracts.

A systematic review of socioeconomic differences in food habits in Europe: consumption of cheese and milk.

OBJECTIVE: To assess differences in cheese and milk consumption across socioeconomic groups in representative samples from several European countries. DESIGN: A meta-analysis of published and unpublished surveys of food habits performed in nine European countries between 1985 and 1999. Educational and occupational levels were used as indicators of socio-economic status. RESULTS: A higher socioeconomic status was associated with a greater consumption of cheese. The pooled estimate of the difference in cheese consumption between women in the highest vs the lowest educational level was 9.0 g/day (95% CI: 7.1 to 11.0). The parallel observation in men was 6.8 g/day (95% CI: 3.4 to 10.1). Similar results were obtained using occupation as an indicator of socioeconomic status. The pooled estimates of the higher cheese consumption among subjects belonging to the highest (vs the lowest) occupational level were 5.1 g/day (95% CI: 3.7 to 6.5) in women and 4.6 g/day (95% CI: 2.1 to 7.0) in men. No statistically significant associations were found for milk consumption concerning educational or occupational level. CONCLUSIONS: Our findings suggest that consumption of cheese is likely to be higher among subjects belonging to higher socioeconomic levels. We did not find enough evidence to support that milk intake is different according to educational or social levels.

Expression of cyclin D1, D3, E, and p27 in human renal cell carcinoma analysed by tissue microarray.

Aberrations in the G1/S transition of the cell cycle have been observed in many malignancies and seem to be critical in the transformation process. Few studies have delineated the presence of G1/S regulatory defects and their clinical relevance in renal cell carcinoma (RCC). Therefore, we have examined the protein contents of cyclin D1, D3, E, and p27 in 218 RCCs, using tissue microarray and immunohistochemistry. The results from a subset of tumours were confirmed by Western blotting and immunohistochemical staining of regular tissue sections. Interestingly, low protein contents of cyclin D1 and p27 were associated with high nuclear grade, large tumour size, and poor prognosis for patients with conventional tumours. We further observed substantial differences in the pattern of G1/S regulatory defects between the different RCC subtypes. The majority of both conventional and papillary cases expressed p27; however, chromophobe tumours generally lacked p27 staining. In addition, conventional RCCs often expressed high cyclin D1 protein levels, while papillary RCCs exhibited high cyclin E. In summary, we have shown that G1/S regulatory defects are present in RCC and are associated with clinico-pathological parameters. The pattern of cell cycle regulatory defects also differed between RCC subtypes.

Expression of p53, PCNA, Ki-67 and bcl-2 in relation to risk factors in oral cancer - a molecular epidemiological study.

A group of 133 primary oral squamous cell carcinomas were studied concerning a relationship between exposure factors and tumour biological parameters with a focus on the TP53 gene and p53 protein status. Tumours were evaluated using immunohistochemistry (IHC) for expression of p53, PCNA, Ki-67 and bcl-2 proteins. The TP53 gene was studied for mutations using PCR amplification of exons 5-9 and single strand conformation polymorphism (SSCP) analysis. The collected data were correlated to the exposure factors smoking, oral snuff, liquor, oral infections, dental factors, dental X-ray and iron deficiency. When compared with matched controls only oral infections, and reported HSV-infections in particular, gave statistically significant ORs (odds ratio) for all tumours (OR 8.0) as well as for the group of IHC p53 positive tumours (OR 12). No association between smoking and p53 positivity was found (OR 1.0).