Модификации арефлюксного холедохоеюноанастомоза с восстановлением пассажа желчи в двенадцатиперстную кишку

Разработаны модификации формирования холедохоеюноанастомоза, способствующие восстановлению желчетока с пассажем желчи в двенадцатиперстную кишку, что предупреждает развитие в ней пептической язвы. Предложена специальная методика мобилизации отключенного по Ру сегмента тощей кишки, обеспечивающая его полноценную моторику.Modifications of forming choledochoanastomosis promoting restoration of bile passage to the duodenum, which prevented development of peptic ulcer, were worked out. A special technique for mobilization of the switched off segment of the jejunum according to Roux promoting an adequate motility was suggested

A Single-Lumen Central Venous Catheter for Continuous and Direct Intra-abdominal Pressure Measurement

Background: Abdominal compartment syndrome (ACS) is associated with high morbidity and mortality rates. Therefore, the need for a good diagnostic tool to predict intra-abdominal hypertension (IAH) and progression to ACS is paramount. Bladder pressure (BP) has been used for several years for intra-abdominal pressure (IAP) measurement but has the disadvantage that it is not a continuous measurement. In this study, a single-lumen central venous catheter (CVC) is placed through the abdominal wall into the abdominal cavity to continuously and directly monitor the intra-abdominal pressure (CDIAP). The aim of this study was to evaluate the use of CDIAP to measure BP as a representative of the true IAP. Methods: Both BP and CDIAP were prospectively recorded on a variety of surgical patients admitted to the intensive care unit (ICU) from March 2003 up to December 2004. At the end of the surgical procedure, the CVC was placed through the abdominal wall and connected to a pressure transducer. In addition, the BP was measured through the urine drainage port after clamping the catheter and filling the bladder with 50 ml of 0.9% saline. At least three paired measurements (BP and CDIAP) were performed for at least one day on the ICU in a standardized manner at preset time intervals on each patient. The paired measurements were compared using the Bland-Altman (B-A) method. Data are presented as mean ± standard deviation. Results: Over a period of 22 months (March 2003 until December 2004), 125 paired measurements of both BP and CDIAP were recorded on 25 patients. The mean age was 72.4 ± 6.6 years. Eighteen patients underwent central vascular surgery, and seven patients with peritonitis received laparotomy. The mean CDIAP was 11.4 ± 4.8 (range 2-30) mmHg, and the BP was 12.9 ± 5.3 (range 3-37) mmHg. The mean difference between CDIAP and BP was 1.6 ± 2.7 mmHg. There was an acceptable level of agreement (intraclass correlation 0.82) between IAP measured by BP and IAP measured via CDIAP. Conclusion: Continuous direct intra-abdominal pressure measurement proved that the BP measurement approach of Kron is representative of the IAP. CDIAP measurement is accurate and makes it easier for the nursing staff to be informed of the IAP

Spontaneous speech:a robust measurement before, during and after awake brain surgery in patients with glioma

BackgroundPatients with glioma often report language complaints with devastating effect on daily life. Analysing spontaneous speech can help to understand underlying language problems. Spontaneous speech monitoring is also of importance during awake brain surgery: it can guide tumour resection and contributes to maintaining language function. We aimed to investigate the spontaneous speech of patients with glioma in the perioperative period and the additional value of spontaneous speech analyses compared to standardised language testing.MethodsWe elicited and transcribed spontaneous speech of eight patients with glioma elected for awake brain surgery preoperatively, intraoperatively and 2.0-3.5 months postoperatively. Linguistic errors were coded. Type Token Ratio, Mean Length of Utterance of words, minimal utterances, and errors were extracted from the transcriptions. Patients were categorised based on total error patterns: stable, decrease or increase during surgery. Reliable Change Index scores were calculated for all spontaneous speech variables to objectify changes between time points. Language performance on language tests was compared to spontaneous speech variables.ResultsMost errors occurred in lexico-syntax, followed by phonology/articulation, syntax, and semantics. The predominant errors were Repetitions, Self-corrections, and Incomplete sentences. Most patients remained stable over time in almost all spontaneous speech variables, except in Incomplete sentences, which deteriorated in most patients postoperatively compared to intraoperatively. Some spontaneous speech variables (total errors, MLUw, TTR) gave more information on language change than a standard language test.ConclusionsWhile the course of spontaneous speech over time remained relatively stable in most patients, Incomplete sentences seems to be a robust marker of language difficulties patients with glioma. These errors can be prioritised in spontaneous speech analysis to save time, especially to determine intra- to postoperative deterioration. Importantly, spontaneous speech analyses can give more information on language change than standardised language testing and should therefore be used in addition to standardised language tests

Effect of corticosteroid injection for trochanter pain syndrome: design of a randomised clinical trial in general practice

Background. Regional pain in the hip in adults is a common cause of a general practitioner visit. A considerable part of patients suffer from (greater) trochanteric pain syndrome or trochanteric bursitis. Local corticosteroid injections is one of the treatment options. Although clear evidence is lacking, small observational studies suggest that this treatment is effective in the short-term follow-up. So far, there are no randomised controlled trials available evaluating the efficacy of injection therapy. This study will investigate the efficacy of local corticosteroid injections in the trochanter syndrome in the general practice, using a randomised controlled trial design. The cost effectiveness of the corticosteroid injectio

Effects of chemotherapy on contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers:A nationwide cohort study

AIM: BRCA1/2 mutation carriers with primary breast cancer (PBC) are at high risk of contralateral breast cancer (CBC). In a nationwide cohort, we investigated the effects of chemotherapeutic agents given for PBC on CBC risk separately in BRCA1 and BRCA2 mutation carriers. PATIENTS AND METHODS: BRCA1 or BRCA2 mutation carriers with an invasive PBC diagnosis from 1990 to 2017 were selected from a Dutch cohort. We estimated cumulative CBC incidence using competing risks analysis. Hazard ratios (HR) for the effect of neo-adjuvant or adjuvant chemotherapy and different chemotherapeutic agents on CBC risk were estimated using Cox regression. RESULTS: We included 1090 BRCA1 and 568 BRCA2 mutation carriers; median follow-up was 8.9 and 8.4 years, respectively. Ten-year cumulative CBC incidence for treatment with and without chemotherapy was 6.7% [95%CI: 5.1–8.6] and 16.7% [95%CI: 10.8–23.7] in BRCA1 and 4.8% [95%CI: 2.7–7.8] and 16.0% [95%CI: 9.3–24.4] in BRCA2 mutation carriers, respectively. Chemotherapy was associated with reduced CBC risk in BRCA1 (multivariable HR: 0.46, 95%CI: 0.29–0.74); a similar trend was observed in BRCA2 mutation carriers (HR: 0.63, 95%CI: 0.29–1.39). In BRCA1, risk reduction was most pronounced in the first 5 years (HR: 0.32, 95%CI: 0.17–0.61). Anthracyclines and the combination of anthracyclines with taxanes were associated with substantial CBC risk reduction in BRCA1 carriers (HR: 0.34, 95%CI: 0.17–0.68 and HR: 0.22, 95%CI: 0.08–0.62, respectively). CONCLUSION: Risk-reducing effects of chemotherapy are substantial for at least 5 years and may be used in personalised CBC risk prediction in any case for BRCA1 mutation carriers

Long-Term Morbidity and Health After Early Menopause Due to Oophorectomy in Women at Increased Risk of Ovarian Cancer:Protocol for a Nationwide Cross-Sectional Study With Prospective Follow-Up (HARMOny Study)

Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited. Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer. Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery. Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study. Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to offer health recommendations after RRSO

Breast cancer genomes from CHEK2 c.1100delC mutation carriers lack somatic TP53 mutations and display a unique structural variant size distribution profile

BackgroundCHEK2 c.1100delC was the first moderate-risk breast cancer (BC) susceptibility allele discovered. Despite several genomic, transcriptomic and functional studies, however, it is still unclear how exactly CHEK2 c.1100delC promotes tumorigenesis. Since the mutational landscape of a tumor reflects the processes that have operated on its development, the aim of this study was to uncover the somatic genomic landscape of CHEK2-associated BC.MethodsWe sequenced primary BC (pBC) and normal genomes of 20 CHEK2 c.1100delC mutation carriers as well as their pBC transcriptomes. Including pre-existing cohorts, we exhaustively compared CHEK2 pBC genomes to those from BRCA1/2 mutation carriers, those that displayed homologous recombination deficiency (HRD) and ER- and ER+ pBCs, totaling to 574 pBC genomes. Findings were validated in 517 metastatic BC genomes subdivided into the same subgroups. Transcriptome data from 168 ER+ pBCs were used to derive a TP53-mutant gene expression signature and perform cluster analysis with CHEK2 BC transcriptomes. Finally, clinical outcome of CHEK2 c.1100delC carriers was compared with BC patients displaying somatic TP53 mutations in two well-described retrospective cohorts totaling to 942 independent pBC cases.ResultsBC genomes from CHEK2 mutation carriers were most similar to ER+ BC genomes and least similar to those of BRCA1/2 mutation carriers in terms of tumor mutational burden as well as mutational signatures. Moreover, CHEK2 BC genomes did not show any evidence of HRD. Somatic TP53 mutation frequency and the size distribution of structural variants (SVs), however, were different compared to ER+ BC. Interestingly, BC genomes with bi-allelic CHEK2 inactivation lacked somatic TP53 mutations and transcriptomic analysis indicated a shared biology with TP53 mutant BC. Moreover, CHEK2 BC genomes had an increased frequency of > 1 Mb deletions, inversions and tandem duplications with peaks at specific sizes. The high chromothripsis frequency among CHEK2 BC genomes appeared, however, not associated with this unique SV size distribution profile.ConclusionsCHEK2 BC genomes are most similar to ER+ BC genomes, but display unique features that may further unravel CHEK2-driven tumorigenesis. Increased insight into this mechanism could explain the shorter survival of CHEK2 mutation carriers that is likely driven by intrinsic tumor aggressiveness rather than endocrine resistance.Hereditary cancer genetic

Differential overexpression of SERPINA3 in human prion diseases

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann-Sträussler-Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans