Overall risk and risk factors for metachronous peritoneal metastasis after colorectal cancer surgery: a nationwide cohort study.

BACKGROUND: This study aimed to identify the cumulative incidence and risk factors of metachronous peritoneal metastasis (M-PM) from colorectal cancer in patients who had intended curative treatment. METHODS: Patients with colorectal cancer were identified using the Danish Colorectal Cancer Group database for 2006-2015. The Danish Pathology Registry and the Danish National Patient Registry were used to identify M-PM to 2017. Risk factors were estimated by multivariable absolute risk regression, treating death and other cancers as competing risks. Overall risk and risk differences (RDs) were estimated at 1, 3 and 5 years. RESULTS: In 22 586 patients with colorectal cancer, the overall risk of M-PM was reported to be 0·9 (95 per cent c.i. 0·8 to 1·0) per cent at 1 year, 1·9 (1·8 to 2·1) per cent at 3 years and 2·2 (2·0 to 2·4) per cent at 5 years. Advanced tumour category ((y)pT4 versus (y)pT1) increased the RD of both M-PM (2·9 (95 per cent c.i. 2·1 to 3·7) at 1 year and 6·0 (4·9 to 7·2) at 3 years) and lymph node involvement ((y)pN2 versus (y)pN0) (2·5 (1·8 to 3·2) at year and 4·3 (3·2 to 5·3) at 3 years). No further increase in risk was observed at 5 years. In a subanalysis, tumour-involved resection margin (R1 versus R0) was associated with M-PM with a RD of 3·9 (1·6 to 6·2) at 1 year and 5·9 (2·6 to 9·3) at 3 years. CONCLUSION: The overall risk of M-PM in patients with colorectal cancer is low, but is increased in advanced T and N status. Follow-up of at least 3 years after colorectal cancer surgery may be necessary, given the potential curative treatment of early diagnosed M-PM.

ANTECEDENTES: Este estudio tuvo como objetivo identificar la incidencia acumulada y los factores de riesgo de metástasis peritoneales metacrónicas (metachronous peritoneal metastases, M-PM) del cáncer colorrectal en pacientes que se sometieron al tratamiento curativo previsto. MÉTODOS: Se identificaron los pacientes con cáncer colorrectal a partir de la base de datos del grupo danés de cáncer colorrectal (Danish Colorectal Cancer Group) durante el periodo 2006-2015. El Registro Danés de Patología (Danish Pathology Registry) y el Registro Nacional Danés de Pacientes (Danish National Patient Registry) se utilizaron para identificar los casos de M-PM hasta el 2017. Los factores de riesgo se estimaron mediante una regresión de riesgo absoluto multivariable, tratando la muerte y otros tipos de cáncer como riesgos competitivos. El riesgo general y las diferencias de riesgo (risk differences, RD) se estimaron a 1, 3 y 5 años. RESULTADOS: De los 22.586 pacientes con CCR, el riesgo global de M-PM fue del 0,9% (i.c. del 95%: 0,8 a 1,0) al año, 1,9 (i.c. del 95%: 1,8 a 2,1) a los 3 años y 2,2 (i.c. del 95%: 2,0 a 2.4) después de 5 años. El estadio T tumoral avanzado ((y) pT4 versus (y) pT1) aumentó el riesgo de M-PM, DR a 1 año: 2,9% (i.c. del 95%: 2,1 a 3,), 3 años: 6,0 (i.c. 95% 4,9 a 7,2), así como la afectación de los ganglios linfáticos ((y) pN2 versus (y) pN0), 1 año: 2,5 (i.c. 95% 1,8 a 3,2), 3 años: 4,3 (i.c. 95% 3,2 a 5,3). No se observó un aumento adicional en la DR después de 5 años. Los márgenes de resección tumoral (R1 versus R0) se asociaron con una DR a 1 año de 3,9 (i.c. del 95% 1,6 a 6,2), y a 3 años de 5,9 (i.c. del 95% 2,6 a 9,3) de riesgo de M-PM en un subanálisis. CONCLUSIÓN: El riesgo global de M-PM en el cáncer colorrectal en pacientes es bajo, pero aumenta en las categorías de estadios T y N avanzados. Puede ser necesario un seguimiento de al menos 3 años después de la cirugía de CCR, dado el tratamiento potencialmente curativo de la M-PM diagnosticada precozmente.

Reciprocal associations of pain and post-traumatic stress symptoms after whiplash injury: A longitudinal, cross-lagged study.

BACKGROUND: The objectives of the current study were to investigate (1) the longitudinal, reciprocal associations between pain and post-traumatic stress symptoms as proposed by the mutual maintenance model, and (2)  to assess the predictive value of the three clusters of post-traumatic stress, where the model revealed that post-traumatic stress symptoms maintained pain in a consecutive cohort of whiplash-injured. METHODS: Participants (n = 253; 66.4% women) were people with WAD grades I-III following motor vehicle crashes in Australia. Pain and post-traumatic stress symptoms were assessed by questionnaires over the course of a year (at baseline (<4 weeks), 3, 6 and 12 months post-injury). The objectives were tested using auto-regressive cross-lagged modelling and two additional structural equation models. RESULTS: The analyses revealed that post-traumatic stress symptoms at baseline predicted an increase in pain between baseline and 3 months and that post-traumatic stress symptoms at 6 months predicted an increase in pain between 6 and 12 months, beyond the stability of pain over time. Furthermore, hyperarousal at baseline significantly predicted pain at 3 months and hyperarousal at 6 months significantly predicted pain at 12 months with 16 and 23% explained variance, respectively. [Correction added on 2 March 2018 after first online publication: the explained variance for hyperarousal symptoms at 6 months was previously given incorrectly and has been corrected to 23% in this version.] CONCLUSIONS: The results point to a temporal main effect of post-traumatic stress symptoms on pain over and above the stability of pain itself within the first 3 months post-injury and again in the chronic phase from 6 to 12 months with hyperarousal symptoms driving these effects. From 3 to 6 months, there was a slip in the maintenance patterns with no cross-lagged effects. SIGNIFICANCE: Investigating mutual maintenance of pain and PTSS in whiplash, the present study found evidence suggesting a maintaining effect of PTSS on pain within the first 3 months post-injury and from 6 to 12 months driven by hyperarousal, highlighting the importance of addressing PTSS.

Intravenous Infusion of Nitroglycerine Leads to Increased Permeability on Dynamic Contrast-Enhanced MR Imaging in Pig Brains.

BACKGROUND AND PURPOSE: It has been suggested that off-label use of transdermal nitroglycerine patches to prevent frostbite may lead to severe acute mountain sickness and ataxia. The aim of this study was to investigate the effect of nitroglycerine on brain vascular permeability by using dynamic contrast-enhanced MR imaging in a swine model. MATERIALS AND METHODS: Eight Danish Landrace-Yorkshire-Danish Landrace pigs of approximately 20-25 kg were scanned with a dynamic contrast-enhanced MR perfusion protocol with and without nitroglycerine intravenous infusion. Compartmental analysis was performed on the basis of the Tofts model, and voxel-based quantitative values of the volume transfer constants from the vascular to the extracellular space were determined. RESULTS: The scan with nitroglycerine infusion resulted in significantly higher volume transfer constant values than values derived from the first scan without nitroglycerine infusion. Increased volume transfer constant values were observed in 6 of 8 animals. CONCLUSIONS: Infusion of nitroglycerine increases the vascular permeability of the swine brain on the basis of the transfer constant estimated from dynamic contrast-enhanced MR imaging.

POLG mutations in Alpers syndrome.

Described are six patients with Alpers syndrome from four unrelated families. Affected individuals harbored the following combinations of POLG mutations: 1) A467T/W1020X, 2) W748S-E1143G/G848S, 3) A467T/A467T, and 4) A467T/G848S. Homozygosity for the A467T allele in one patient was associated with a later age at onset. Mitochondrial respiratory chain studies in skeletal muscle were normal in each case. Nine combinations of mutant POLG alleles that cause Alpers syndrome are summarized.

Choice of jumping strategy in two standard jumps, squat and countermovement jump--effect of training background or inherited preference?

Six male subjects, three professional ballet dancers and three elite volleyball players, performed maximal vertical jumps from 1) a static preparatory position (squat jump), 2) starting with a countermovement (countermovement jump) and 3) a specific jump for ballet and for volleyball, respectively. The jumps were recorded on highspeed film (500 Hz) combined with registration of ground reaction forces, and net joint moments were calculated by inverse dynamics. The purpose was to investigate the choice of strategy in two standard jumps, squat jump and countermovement jump. The volleyball jump was performed with a sequential strategy and the ballet jump was performed with a simultaneous strategy. In the two standard jumps, the choice of strategy was individual and not related to training background. This was additionally confirmed in a test of seven ballet dancers and seven volleyball players.

Postmenopausal hormone replacement therapy--clinical implications.

The menopause is defined as cessation of menstruation, ending the fertile period. The hormonal changes are a decrease in progesterone level, followed by a marked decrease in estrogen production. Symptoms associated with these hormonal changes may advocate for hormonal replacement therapy. This review is based on the English-language literature on the effect of estrogen therapy and estrogen plus progestin therapy on postmenopausal women. The advantages of hormone replacement therapy are regulation of dysfunctional uterine bleeding, relief of hot flushes, and prevention of atrophic changes in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin. Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke, and there is no increased risk of venous thrombosis or hypertension. A disadvantage of hormone replacement therapy is an increased risk of forming gall-bladder stones and undergoing cholecystectomy. Unopposed estrogen therapy gives a higher incidence of endometrial cancer in women with an intact uterus, but the contribution of progestins for about 10 days every month excludes this risk. Breast cancer in relation to estrogen-progestogen therapy has been given much concern, and the problem is still not fully solved. If there is a risk, it is small, and only after prolonged use of estrogen (15-20 years). The decision whether or not to use hormone replacement therapy should, of course, be taken by the individual woman in question, but her decision should be based on the available scientific information. It is the opinion of the authors that the advantages of hormone replacement therapy far exceed the disadvantages. We suggest that every woman showing any signs of hormone deprivation should be treated with hormone replacement therapy. This includes women with subjective or objective vaso-motor symptoms, genito-urinary symptoms, women at risk of osteoporosis (fast bone losers), and women at risk of cardiovascular diseases.

Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes. A typical housekeeping gene family.

Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous modulator of the GABAA receptor in brain membranes. ACBP/DBI, or proteolytically derived polypeptides of ACBP/DBI, have also been implicated in the control of steroidogenesis in mitochondria and glucose-stimulated insulin secretion. Thus, it appears that ACBP/DBI is a remarkable, versatile protein. Now we have molecularly cloned and characterized the ACBP/DBI gene family in rat. The rat ACBP/DBI gene family comprises one expressed gene and four processed pseudogenes of which one was shown to exist in two allelic forms. The expressed gene is organized into four exons and three introns. There is a remarkable correspondence between the structural modules of ACBP/DBI as determined by 1H nuclear magnetic resonance spectroscopy and the exon-intron architecture of the ACBP/DBI gene. Detailed analyses of transcription of the ACBP/DBI gene in brain and liver were performed to map transcription initiation sites and to examine if transcripts from the ACBP/DBI gene were subject to alternative processing. In both brain and liver, transcription is initiated from two major and multiple minor initiation sites. No evidence for alternative splicing was obtained. The promoter region of the ACBP/DBI gene is located in a CpG island and lacks a canonical TATA box. Thus, the ACDB/DBI gene exhibits all the hallmarks of a typical housekeeping gene.

Bambuterol: clinical effects of three doses of bambuterol once daily in asthmatic patients.

Twenty-two asthmatics received bambuterol solution, a terbutaline pro-drug, once every evening. The following doses were each given orally for 7 days in a double-blind cross-over study: 0.185, 0.270 and 0.400 mg/kg. Bambuterol 0.270 mg/kg was preferable regarding clinical effects and side effects. The plasma concentration of generated terbutaline showed a slow linear decrease at all doses. Tests of two methods for objective measurements of tremor in five patients did not add any new data compared with the subjective recordings.

Bambuterol: clinical effects of different doses of a long-acting bronchodilator prodrug.

Sixty-eight asthmatics participated in a dose-finding study on bambuterol, a terbutaline prodrug, administered once every evening. Bambuterol administrations of 0.185, 0.270 and 0.400 mg/kg gave effective and long-lasting bronchodilation, for at least 24 h, with the two higher doses probably close to the maximal effect of the drug. Bambuterol 0.400 mg/kg was associated with more adverse effects than bambuterol 0.185 mg/kg. The side effects were those expected in oral beta 2-agonist treatment and mainly experienced by patients who had not been on oral beta 2-agonists before. The most favourable of the investigated doses was found to be 0.270 mg/kg. It can not be excluded, however, that a somewhat lower dose may still be as beneficial. This will be investigated in forthcoming studies.