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An analysis of the most important changes and provisions of the Maastricht VI consensus published in August 2022 is presented. 41 experts from 29 countries took part in the creation of the consensus. Recommendations have been developed in five areas: (1) indications for treatment and clinical associations of Helicobacter pylori (H. pylori) infection, (2) diagnosis, (3) treatment, (4) prevention of gastric cancer, (5) H. pylori and gastric microbiota -intestinal tract (GIT), taking into account the level of evidence and the strength of recommendations. Emphasis is placed on molecular testing, which is becoming an increasingly accessible research method in the world to identify both H. pylori itself and its sensitivity to antibiotics. The growing resistance of H. pylori strains to previously effective antibacterial agents requires a treatment strategy that implies the ability to determine the sensitivity of H. pylori to antibacterial agents both in the population and in a particular individual. The use of modern diagnostic tests expands the possibilities of individualization of therapy, since it allows determining not only the presence of H. pylori in the gastric mucosa, but also the sensitivity of the infection to antibacterial drugs. Along with individual approaches to treatment, the most effective empirical therapy regimens are given in case of impossibility to determine individual resistance to antibiotics. New data on the effectiveness and results of the use of primary and secondary preventive strategies for gastric cancer are presented. Given the important role of the entire microbiome of the gastrointestinal tract in the functioning of the body, the question of the interaction of H. pylori with other microorganisms is discussed. The critical issues of the near future are related to the global prevention of gastric cancer; the need to control antibiotic resistance, and the development of new methods of therapy and prevention of Helicobacter pylori infection.

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Data used in study analyses

Purpose:Radiotherapy is important in managing pelvic cancers. However, radiation enteropathy may occur and can be dose limiting. The gut microbiota may contribute to the pathogenesis of radiation enteropathy. We hypothesized that the microbiome differs between patients with and without radiation enteropathy.Experimental Design: Three cohorts of patients (n = 134) were recruited. The early cohort (n = 32) was followed sequentially up to 12 months post-radiotherapy to assess early radiation enteropathy. Linear mixed models were used to assess microbiota dynamics. The late cohort (n = 87) was assessed cross-sectionally to assess late radiation enteropathy. The colonoscopy cohort compared the intestinal mucosa microenvironment in patients with radiation enteropathy (cases, n = 9) with healthy controls (controls, n = 6). Fecal samples were obtained from all cohorts. In the colonoscopy cohort, intestinal mucosa samples were taken. Metataxonomics (16S rRNA gene) and imputed metataxonomics (Piphillin) were used to characterize the microbiome. Clinician- and patient-reported outcomes were used for clinical characterization.Results:In the acute cohort, we observed a trend for higher preradiotherapy diversity in patients with no self-reported symptoms (P = 0.09). Dynamically, diversity decreased less over time in patients with rising radiation enteropathy (P = 0.05). A consistent association between low bacterial diversity and late radiation enteropathy was also observed, albeit nonsignificantly. Higher counts of Clostridium IV, Roseburia, and Phascolarctobacterium significantly associated with radiation enteropathy. Homeostatic intestinal mucosa cytokines related to microbiota regulation and intestinal wall maintenance were significantly reduced in radiation enteropathy [IL7 (P = 0.05), IL12/IL23p40 (P = 0.03), IL15 (P = 0.05), and IL16 (P = 0.009)]. IL15 inversely correlated with counts of Roseburia and Propionibacterium.Conclusions:The microbiota presents opportunities to predict, prevent, or treat radiation enteropathy. We report the largest clinical study to date into associations of the microbiota with acute and late radiation enteropathy. An altered microbiota associates with early and late radiation enteropathy, with clinical implications for risk assessment, prevention, and treatment of radiation-induced side-effects.See related commentary by Lam et al., p. 6280

Preclinical data suggest that combined gamma-tocotrienol with pentoxifylline ameliorates radiotherapy-induced gastrointestinal damage.To test whether gastrointestinal symptoms arising after radiotherapy, and persisting after maximal medical therapy, can be improved using Tocovid SupraBio 200 mg and pentoxifylline 400 mg orally twice daily for one year. Patients stratified by severity of symptoms, and randomised to active treatment or matched placebo were assessed after 12 months. The primary end point was improvement in gastrointestinal symptoms measured using the Inflammatory Bowel Disease Questionnaire, bowel subset score. Changes in bio-markers of fibrosis were assessed.62 patients, median age 66, 34(55%) treated for prostate, 21(34%) gynaecological, 6(10%) anal and one(1%) rectal cancer were recruited; 40(65%) randomised to treatment, 22(35%) to placebo, 39 months (median) after radiotherapy completion. Gamma tocotrienol was not detected in serum in 41% of treated patients, despite good compliance with study medication. Treatment was completed in 28(70%) and 17(77%) patients in the treatment and placebo groups respectively. No improvement in symptom scores nor in quality of life was identified. Thirteen serious adverse events occurred. A transient ischaemic attack, was possibly related to pentoxifylline, others were assessed as unlikely to be related to treatment. Levels of EGF, PDGF and FGF were significantly reduced and consistent trends in reduced inflammation were seen during treatment but were not sustained once treatment ended.This single centre study closed prematurely and therefore data interpretation is of necessity limited. No clinical benefit was demonstrated. However, biochemical data suggest that this intervention does have anti-inflammatory and anti-fibrotic effects.

A 66-year-old man was treated for a moderately differentiated T3 N1 M0 adenocarcinoma of the rectum in 2015 with preoperative short course radiotherapy, anterior resection and then adjuvant chemotherapy with oxaliplatin and capecitabine. Following ileostomy reversal, he complained of intense, unremitting anorectal pain. After repeated scans, computed tomography (CT) showed findings suggestive of a longstanding anastomotic leak. Subsequent, magnetic resonance imaging (MRI) revealed osteomyelitis of the sacrum, with the development of sacral osteomyelitis in this context unusual. Our case highlights the importance of appropriate radiological imaging and that clinicians should consider osteomyelitis as a differential diagnosis in patients presenting with severe anorectal pain after treatment for rectal cancer.

Background The underlying mechanisms of chemotherapy-induced gastrointestinal (GI) symptoms are poorly researched. This study characterised the nature, frequency, severity and treatable causes for GI symptoms prospectively in patients undergoing chemotherapy for GI malignancy. Methods Patients receiving chemotherapy for a GI malignancy were assessed pre-chemotherapy, then monthly for 1 year using the Gastrointestinal Symptom Rating Scale, a validated patient-reported outcome measure. Patients with new, troublesome GI symptoms were offered investigations to diagnose the cause(s). Their oncologist was alerted when investigations were abnormal. Results A total of 241 patients, 60% male, median age 63 years (range 30–88), were enrolled; 122 patients were withdrawn, 93%, because of progressive disease or death. During the study, > 20% patients reported chronic faecal incontinence and > 10% reported moderate or severe problems with taste, dysphagia, belching, heartburn, early satiety, appetite, nausea, abdominal cramps, peri-rectal pain, rectal flatulence, borborygmi, urgency of defecation or tenesmus. Thirty percent reported continuing passage of hard stools and 30% on-going diarrhoea. Moderate or severe fatigue affected 40% participants at its peak and persisted in 15% at 1 year. Toxicity dictated change in chemotherapy for 13–29% patients/month. Common Terminology Criteria for Adverse Events underestimated gastrointestinal morbidity. Pre-chemotherapy screening identified previously undiagnosed pathology: exocrine pancreatic insufficiency (9%), vitamin B12 deficiency (12%) and thyroid dysfunction (20%). Patients often refused investigations to diagnose their chemotherapy-induced symptoms; however, for every three investigations performed, one treatable cause was diagnosed: particularly small intestinal bacterial overgrowth (54%), bile acid malabsorption (43%), previously not described after chemotherapy, and unsuspected urinary tract infection (17%). Conclusions Patients undergoing chemotherapy for GI malignancy commonly have difficult GI symptoms requiring active management which does not occur routinely. The underlying causes for these symptoms are often treatable or curable. Randomised trials are urgently needed to show whether timely investigation and treatment of symptoms improve quality of life and survival. Trial registration ClinicalTrials.gov Identifier: NCT02121626

The first determinations of the heat flow density in Uzbekistan, as well as in Central Asia as a whole, were carried out in the middle 1960s. In subsequent years, many researchers, primarily in connection with the search and exploration of oil and natural gas deposits, studied the geothermal field of the region. The data accumulated to date show a significant heterogeneity of the thermal field in both Uzbekistan and the adjacent territory of Central Asia. Rare wells were studied in the desert areas of Kyzyl Kum and Kara Kum. The heat flow in Uzbekistan varies over a wide range from 20–30 to approximately 100 mW/m2. Its high values are characteristic of intermountain depressions and blocks of the earth’s crust with a dense network of deep faults. The heat flow increases significantly in the southern and eastern parts of Uzbekistan, as well as in the neighbouring territories adjacent to the mountain structures of the Tien Shan and Pamir, characterized by high seismicity, tectonic and thermal activation. An updated map of the heat flow density of Uzbekistan was compiled and, separately for the Fergana Depression. They reflect a significant regional variability of the geothermal field. With the transition from the relatively flat territory of the Turanian Plate to mountain structures, the degree of differentiation by the heat flow increases significantly. This is typical of the entire orogenic Alpine-Himalayan Belt.

To assess the prevalence of bowel dysfunctions after treatment for gynaecological cancer and the impact on the quality of life. We identified a cohort of 217 eligible women treated with radiotherapy (RT) with curative intention, alone or as combined treatment, for gynaecological malignancies at three institutions in Catalonia (Spain). Demographic, diagnosis and treatment modality were reviewed. Patients were sent validated questionnaires to assess bowel function and a set of questions asking on the changes after RT in bowel function, urinary function, sexuality, pain and lymphoedema. Questionnaires were returned by 109 patients (50.2%) with a mean age of 65 ± 11 years. Of them, 71.8% had been treated for endometrial cancer and 28.2% for cervical cancer. Overall, 42.7% of patients reported bowel dysfunction, affecting their quality of life in 36% of cases. Symptoms were more frequent in patients who had undergone external beam RT compared to brachytherapy. The most common symptom was defecatory urgency which was reported by more than 40% of patients according to the St Mark’s score, although it was less common in other questionnaires. Overall, faecal incontinence ranged between 10 and 15%, and usual loose stools and diarrhoea were reported by 13.5% and 5.1%, respectively. Prevalence of bowel symptoms after treatment of gynaecological malignancies is high. A systematic evaluation using validated questionnaires should be performed in order to allow the decision-making process and also because there are a number of treatments available to improve the quality of life of cancer survivors.

Background and aim Long-term changes in gastrointestinal function impacting quality of life after treatment for cancer are common. Peer reviewed guidance to investigate and manage GI dysfunction following cancer treatment has been published. This study reviewed gastrointestinal symptoms of women previously treated for gynaecological cancer and considered whether suggested algorithms could be amended to optimise management for this cohort. Methods Demographic and clinical data recorded for patients attending a specialist consequences of cancer treatment gastroenterology service prospectively are reported using median and range. The Wilcoxon signed rank test analysed changes in symptoms between initial assessment to discharge from the service. Results Between April 2013 and March 2016, 220 women, with a median age of 57 years (range 24–83 years), treated for gynaecological cancer (cervical (50%)), endometrial (28%), ovarian (15%), vaginal or vulval (7%) attended. Twelve gastrointestinal symptoms were statistically significantly reduced by time of discharge from the specialist gastroenterology clinic including bowel frequency ≥ 4/day (88%), type 6 or 7 stool consistency (36%), urgency (31%) and incontinence (21%). General quality of life improved from a median score of 4 at first assessment to a median of 6 at discharge (p Conclusion Women with gastrointestinal symptoms after cancer treatment benefit from a systematic management approach. After excluding disease recurrence, a proposed investigational algorithm and the oncology team includes FBC, U&Es, LFTs, thyroid function test, vitamin B12, vitamin D, a hydrogen methane breath test and a SeHCAT scan. If rectal bleeding is present, iron studies, flexible sigmoidoscopy or colonoscopy should be performed. Patients with normal investigations or symptoms not responding to treatment require gastroenterology input.

Treatable gastrointestinal disorders in patients with symptoms typical for irritable bowel syndrome (IBS) may be overlooked. The prevalence of five gastrointestinal conditions—bile acid diarrhoea (BAD), carbohydrate malabsorption (CM), microscopic colitis (MC), pancreatic exocrine insufficiency (PEI) and small intestinal bacterial overgrowth (SIBO) was systematically assessed from studies including consecutive patients meeting diagnostic criteria for IBS. 4 databases were searched from 1978 to 2020. Studies were included if they evaluated the prevalence of these conditions in secondary healthcare setting. Estimated pooled rates were calculated and statistical heterogeneity between studies was evaluated using Q and I2 statistics. Seven studies (n = 597) estimated the pooled prevalence for BAD as 41% (95% CI 29–54). 17 studies (n = 5068) estimated that of MC as 3% (95% CI 2–4%). Two studies (n = 478) suggested a rate of 4.6% (range: 1.8–6.1%) for PEI. Using breath testing, 26 studies (n = 6700) and 13 studies (n = 3415) estimated the prevalence of lactose and fructose malabsorption as 54% (95% CI 44–64%) and 43% (95% CI 23–62%); 36 studies (n = 4630) and 22 studies (n = 2149) estimated that of SIBO as 49% (95% CI 40–57%) with lactulose and 19% (95% CI 13–27%) with glucose. Rates of all conditions were significantly higher than in healthy controls. A significant proportion of patients presenting to secondary care with IBS have an organic condition which may account for their symptoms. Failure to exclude such conditions will deny patients effective treatment.

Fission at low excitation energy is an ideal playground to probe the impact of nuclear structure on nuclear dynamics. While the importance of structural effects in the nascent fragments is well established in the (trans-)actinide region, the observation of asymmetric fission in several neutron-deficient pre-actinides can be explained by various mechanisms. To deepen our insight into that puzzle, an innovative approach based on inverse kinematics and an enhanced version of the VAMOS++ heavy-ion spectrometer was implemented at the GANIL facility, Caen. Fission of $^{178}$Hg was induced by fusion of $^{124}$Xe and $^{54}$Fe. The two fragments were detected in coincidence using VAMOS++ supplemented with a new SEcond Detection arm. For the first time in the pre-actinide region, access to the pre-neutron mass and total kinetic energy distributions, and the simultaneous isotopic identification of one the fission fragment, was achieved. The present work describes the experimental approach, and discusses the pre-neutron observables in the context of an extended asymmetricfission island located southwest of $^{208}$Pb. A comparison with different models is performed, demonstrating the importance of this new asymmetric-fission island for elaborating on driving effects in fission. Fission at low excitation energy is an ideal playground to probe the impact of nuclear structure on nuclear dynamics. While the importance of structural effects in the nascent fragments is well-established in the (trans-)actinide region, the observation of asymmetric fission in several neutron-deficient pre-actinides can be explained by various mechanisms. To deepen our insight into that puzzle, an innovative approach based on inverse kinematics and an enhanced version of the VAMOS++ heavy-ion spectrometer was implemented at the GANIL facility, Caen. Fission of $^{178}$Hg was induced by fusion of $^{124}$Xe and $^{54}$Fe. The two fragments were detected in coincidence using VAMOS++ supplemented with a new SEcond Detection arm. For the first time in the pre-actinide region, access to the pre-neutron mass and total kinetic energy distributions, and the simultaneous isotopic identification of one the fission fragment, was achieved. The present work describes the experimental approach, and discusses the pre-neutron observables in the context of an extended asymmetric-fission island located south-west of $^{208}Pb. A comparison with different models is performed, demonstrating the importance of this "new" asymmetric-fission island for elaborating on driving effects in fission.

BackgroundPancreatic exocrine insufficiency is a cause of malabsorption. It is generally diagnosed if faecal elastase-1 (FE-1) levels are below 200 µg/g. Pancreatic function is assumed to be normal when faecal elastase levels are >500 µg/g. The significance of faecal elastase levels above 200 µg/g but less than 500 µg/g is unclear.MethodsThis retrospective study reports the response to treatment in patients who had an FE-1 level between 200 and 500 µg/g.ResultsOf these 82 patients, 28 were offered pancreatic enzyme replacement therapy (PERT). A clinical response, defined as an improvement in their initial symptoms after commencing PERT, was seen in 20 patients (71%), 7 with potentially predisposing conditions and 13 with functional diarrhoea. PERT particularly abolished or improved diarrhoea, steatorrhoea and flatulence.ConclusionClinicians should, therefore, be aware that a trial of PERT given to patients with FE-1 levels between 200 and 500 µg/g may lead to improvement in gastrointestinal symptoms.

A study of the laser-ionized and mass-separated neutron-deficient isotopes Au 176 , 177 , 179 was performed using the Resonance Ionization Laser Ion Source and the Windmill detection setup at ISOLDE, CERN. New and improved data on complex fine-structure α decays of the three isotopes were deduced, providing insight into the low-lying levels in the daughter nuclei Ir 172 , 173 , 175 . New information on the properties of β -decay daughter products Pt 177 , 179 was also obtained. From the first in-source laser spectroscopy measurements of the hyperfine structure in the atomic 267.6-nm transition of Au 176 , the nuclear magnetic moments for both high- and low-spin α -decaying states were deduced. Together with the values determined from the additivity relations, they were used to propose the most probable spins and configurations for both states. The α -decay branching ratios were determined as b α ( Au ls 176 ) = 58 ( 5 ) % and b α ( Au hs 176 ) = 29 ( 5 ) % .

Treatable gastrointestinal disorders in patients with symptoms typical for irritable bowel syndrome (IBS) may be overlooked. The prevalence of five gastrointestinal conditions-bile acid diarrhoea (BAD), carbohydrate malabsorption (CM), microscopic colitis (MC), pancreatic exocrine insufficiency (PEI) and small intestinal bacterial overgrowth (SIBO) was systematically assessed from studies including consecutive patients meeting diagnostic criteria for IBS. 4 databases were searched from 1978 to 2020. Studies were included if they evaluated the prevalence of these conditions in secondary healthcare setting. Estimated pooled rates were calculated and statistical heterogeneity between studies was evaluated using Q and I

ObjectiveBile acid diarrhoea (BAD), which includes bile acid malabsorption, causes a variety of digestive symptoms. Diagnostic rates and management vary considerably. We conducted a survey of current practice to review expert opinion and provide guidance on diagnosis and management.Design/methodAn online survey was conducted of clinical members of the UK Bile Acid Related Diarrhoea Network, who had all published research on BAD (n=21). Most were National Health Service consultants who had diagnosed over 50 patients with the condition.ResultsThe preferred terminology was to use BAD, with primary and secondary to classify causes. A wide range of presenting symptoms and associated conditions were recognised. SeHCAT (tauroselcholic acid) was the preferred diagnostic test, and 50% of respondents thought general practitioners should have access to this. Patients who met the Rome IV diagnostic criteria for functional diarrhoea, irritable bowel syndrome (IBS) with predominant diarrhoea or postcholecystectomy diarrhoea were usually investigated by SeHCAT, which was used sometimes in other types of IBS. Treatment with a bile acid sequestrant was offered to patients with low SeHCAT values, with expected response rates >70% in the most severe. Colestyramine was the usual sequestrant, starting between 2 g and 8 g daily; colesevelam was an alternative. In patients who had an incomplete response, increasing the dose, changing to an alternative sequestrant, use of loperamide and a low fat diet were suggested. Recommendations for follow-up and to improve the overall patient experience were made.ConclusionThis expert survey indicates current best practice in the diagnosis and management of BAD.

The structure of Po-208 populated through the EC/beta(+) decay of At-208 is investigated using gamma-ray spectroscopy at the ISOLDE Decay Station. The presented level scheme contains 27 new excited states and 43 new transitions, as well as a further 50 previously observed. rays which have been (re)assigned a position. The level scheme is compared to shell model calculations. Through this analysis approximately half of the beta-decay strength of At-208 is found to proceed via allowed decay and half via first-forbidden decay. The first-forbidden transitions predominantly populate core excited states at high excitation energies, which is qualitatively understood using shell model considerations. This mass region provides an excellent testing ground for the competition between allowed and first-forbidden beta-decay calculations, important for the detailed understanding of the nucleosynthesis of heavy elements.

A new α-emitting isotope ^{214}U, produced by the fusion-evaporation reaction ^{182}W(^{36}Ar,4n)^{214}U, was identified by employing the gas-filled recoil separator SHANS and the recoil-α correlation technique. More precise α-decay properties of even-even nuclei ^{216,218}U were also measured in the reactions of ^{40}Ar, ^{40}Ca beams with ^{180,182,184}W targets. By combining the experimental data, improved α-decay reduced widths δ^{2} for the even-even Po-Pu nuclei in the vicinity of the magic neutron number N=126 are deduced. Their systematic trends are discussed in terms of the N_{p}N_{n} scheme in order to study the influence of proton-neutron interaction on α decay in this region of nuclei. It is strikingly found that the reduced widths of ^{214,216}U are significantly enhanced by a factor of two as compared with the N_{p}N_{n} systematics for the 84≤Z≤90 and N126 even-even nuclei. The abnormal enhancement is interpreted by the strong monopole interaction between the valence protons and neutrons occupying the π1f_{7/2} and ν1f_{5/2} spin-orbit partner orbits, which is supported by the large-scale shell model calculation.

Cancer survival is improving rapidly due to advances in treatments that will often involve radiotherapy, chemotherapy and novel biological agents in addition to surgery. This comes at the price of living with chronic symptoms, of which diarrhoea is particularly common. There is good evidence that for many patients these symptoms become part of everyday life, their "normality" is adjusted and symptoms are tolerated even when limiting activities severely. Clinicians often fail to appreciate the impact of these problems, as the focus of follow up tends to be on cancer recurrence. However, the rapid identification of patients in significant trouble can lead to earlier diagnosis of treatable pathologies and improvement of patients' symptoms. The aim of this review is to highlight the mechanisms which cause oncology patients to develop diarrhoea and highlight useful investigational and treatment strategies.