scholarly journals Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management

Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 2080-2091 ◽  
Author(s):  
Benjamin Misselwitz ◽  
Matthias Butter ◽  
Kristin Verbeke ◽  
Mark R Fox

Lactose is the main source of calories in milk, an essential nutriedigestion, patients with visceral hypersensitivity nt in infancy and a key part of the diet in populations that maintain the ability to digest this disaccharide in adulthood. Lactase deficiency (LD) is the failure to express the enzyme that hydrolyses lactose into galactose and glucose in the small intestine. The genetic mechanism of lactase persistence in adult Caucasians is mediated by a single C→T nucleotide polymorphism at the LCTbo −13’910 locus on chromosome-2. Lactose malabsorption (LM) refers to any cause of failure to digest and/or absorb lactose in the small intestine. This includes primary genetic and also secondary LD due to infection or other conditions that affect the mucosal integrity of the small bowel. Lactose intolerance (LI) is defined as the onset of abdominal symptoms such as abdominal pain, bloating and diarrhoea after lactose ingestion by an individual with LM. The likelihood of LI depends on the lactose dose, lactase expression and the intestinal microbiome. Independent of lactose digestion, patients with visceral hypersensitivity associated with anxiety or the Irritable Bowel Syndrome (IBS) are at increased risk of the condition. Diagnostic investigations available to diagnose LM and LI include genetic, endoscopic and physiological tests. The association between self-reported LI, objective findings and clinical outcome of dietary intervention is variable. Treatment of LI can include low-lactose diet, lactase supplementation and, potentially, colonic adaptation by prebiotics. The clinical outcome of these treatments is modest, because lactose is just one of a number of poorly absorbed carbohydrates which can cause symptoms by similar mechanisms.

2021 ◽  
Vol 11 ◽  
Author(s):  
Heather M. Kahalehili ◽  
Nolan K. Newman ◽  
Jamie M. Pennington ◽  
Siva K. Kolluri ◽  
Nancy I. Kerkvliet ◽  
...  

The diet represents one environmental risk factor controlling the progression of type 1 diabetes (T1D) in genetically susceptible individuals. Consequently, understanding which specific nutritional components promote or prevent the development of disease could be used to make dietary recommendations in prediabetic individuals. In the current study, we hypothesized that the immunoregulatory phytochemcial, indole-3-carbinol (I3C) which is found in cruciferous vegetables, will regulate the progression of T1D in nonobese diabetic (NOD) mice. During digestion, I3C is metabolized into ligands for the aryl hydrocarbon receptor (AhR), a transcription factor that when systemically activated prevents T1D. In NOD mice, an I3C-supplemented diet led to strong AhR activation in the small intestine but minimal systemic AhR activity. In the absence of this systemic response, the dietary intervention led to exacerbated insulitis. Consistent with the compartmentalization of AhR activation, dietary I3C did not alter T helper cell differentiation in the spleen or pancreatic draining lymph nodes. Instead, dietary I3C increased the percentage of CD4+RORγt+Foxp3- (Th17 cells) in the lamina propria, intraepithelial layer, and Peyer’s patches of the small intestine. The immune modulation in the gut was accompanied by alterations to the intestinal microbiome, with changes in bacterial communities observed within one week of I3C supplementation. A transkingdom network was generated to predict host-microbe interactions that were influenced by dietary I3C. Within the phylum Firmicutes, several genera (Intestinimonas, Ruminiclostridium 9, and unclassified Lachnospiraceae) were negatively regulated by I3C. Using AhR knockout mice, we validated that Intestinimonas is negatively regulated by AhR. I3C-mediated microbial dysbiosis was linked to increases in CD25high Th17 cells. Collectively, these data demonstrate that site of AhR activation and subsequent interactions with the host microbiome are important considerations in developing AhR-targeted interventions for T1D.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah E. Martchenko ◽  
David Prescott ◽  
Alexandre Martchenko ◽  
Maegan E. Sweeney ◽  
Dana J. Philpott ◽  
...  

AbstractIntestinal functions demonstrate circadian rhythms thought to be entrained, in part, by an organisms’ intrinsic feeding and fasting periods as well as by the intestinal microbiome. Circadian disruption as a result of ill-timed nutrient exposure and obesogenic feeding poses an increased risk to disease. As such, the aim of this study was to assess the relationships between dietary timing, composition, and the microbiome with regard to rhythmic small intestinal structure and mucosal immunity. Rodent chow (RC)-mice exhibited time-dependent increases in small intestinal weight, villus height, and crypt depth as well as an increased proportion of CD8αα+ cells and concomitant decrease in CD8αβ+ cells at the onset of the feeding period (p < 0.05–0.001). Western diet (WD)-animals displayed disrupted time-dependent patterns in intestinal structure and lymphocyte populations (p < 0.05–0.01). Antibiotic-induced microbial depletion abrogated the time- and diet-dependent patterns in both RC- and WD-mice (p < 0.05–0.001). However, although germ-free-mice displayed altered rhythms, fecal microbial transfer from RC-mice was generally unsuccessful in restoring structural and immune changes in these animals. This study shows that adaptive changes in the small intestine at the onset of the feeding and fasting periods are disrupted by WD-feeding, and that these changes are dependent, in part, on the intestinal microbiome.


Author(s):  
Alexander Younsi ◽  
Lennart Riemann ◽  
Cleo Habel ◽  
Jessica Fischer ◽  
Christopher Beynon ◽  
...  

AbstractIn an aging Western society, the incidence of chronic subdural hematomas (cSDH) is continuously increasing. In this study, we reviewed our clinical management of cSDH patients and identified predictive factors for the need of reoperation due to residual or recurrent hematomas with a focus on the use of antithrombotic drugs. In total, 623 patients who were treated for cSDH with surgical evacuation between 2006 and 2016 at our department were retrospectively analyzed. Clinical and radiological characteristics and laboratory parameters were investigated as possible predictors of reoperation with univariate and multivariate analyses. Additionally, clinical outcome measures were compared between patients on anticoagulants, on antiplatelets, and without antithrombotic medication. In univariate analyses, patients on anticoagulants and antiplatelets presented significantly more often with comorbidities, were significantly older, and their risk for perioperative complications was significantly increased. Nevertheless, their clinical outcome was comparable to that of patients without antithrombotics. In multivariate analysis, only the presence of comorbidities, but not antithrombotics, was an independent predictor for the need for reoperations. Patients on antithrombotics do not seem to necessarily have a significantly increased risk for residual hematomas or rebleeding requiring reoperation after cSDH evacuation. More precisely, the presence of predisposing comorbidities might be a key independent risk factor for reoperation. Importantly, the clinical outcomes after surgical evacuation of cSDH are comparable between patients on anticoagulants, antiplatelets, and without antithrombotics.


2002 ◽  
Vol 20 (11) ◽  
pp. 2672-2679 ◽  
Author(s):  
Poul H.B. Sorensen ◽  
James C. Lynch ◽  
Stephen J. Qualman ◽  
Roberto Tirabosco ◽  
Jerian F. Lim ◽  
...  

PURPOSE: Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue malignancy of children and adolescents. Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) or t(1;13) translocations, respectively. We wished to confirm the diagnostic specificity of gene fusion detection in a large cohort of RMS patients and to evaluate whether these alterations influence clinical outcome in ARMS. PATIENTS AND METHODS: We determined PAX3-FKHR or PAX7-FKHR fusion status in 171 childhood rhabdomyosarcoma (RMS) patients entered onto the Intergroup Rhabdomyosarcoma Study IV, including 78 ARMS patients, using established reverse transcriptase polymerase chain reaction assays. All patients received central pathologic review and were treated using uniform protocols, allowing for meaningful outcome analysis. We examined the relationship between gene fusion status and clinical outcome in the ARMS cohort. RESULTS: PAX3-FKHR and PAX7-FKHR fusion transcripts were detected in 55% and 22% of ARMS patients, respectively; 23% were fusion-negative. All other RMS patients lacked transcripts, confirming the specificity of these alterations for ARMS. Fusion status was not associated with outcome differences in patients with locoregional ARMS. However, in patients presenting with metastatic disease, there was a striking difference in outcome between PAX7-FKHR and PAX3-FKHR patient groups (estimated 4-year overall survival rate of 75% for PAX7-FKHR v 8% for PAX3-FKHR; P = .0015). Multivariate analysis demonstrated a significantly increased risk of failure (P = .025) and death (P = .019) in patients with metastatic disease if their tumors expressed PAX3-FKHR. Among metastatic ARMS, bone marrow involvement was significantly higher in PAX3-FKHR–positive patients. CONCLUSION: Not only are PAX-FKHR fusion transcripts specific for ARMS, but expression of PAX3-FKHR and PAX7-FKHR identifies a very high-risk subgroup and a favorable outcome subgroup, respectively, among patients presenting with metastatic ARMS.


2012 ◽  
Vol 107 (02) ◽  
pp. 346-355 ◽  
Author(s):  
Grzegorz Dworacki ◽  
Joanna Kufel-Grabowska ◽  
Cezary Watala ◽  
Wojciech Kozubski ◽  
Maria Lukasik

SummaryThe white blood cell count and mean platelet volume determined shortly after the symptom onset are known as independent predictors for clinical outcome after stroke. In the present study we sought to evaluate the prognostic value of platelet-derived inflammatory biomarkers measured prospectively after an ischaemic event. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P and subpopulations of leukocyte-platelet aggregates were assessed in 93 stroke patients on the first (V0), 10th (V1) and 90th (V2) day after stroke, and once in 65 disease controls. The clinical outcome was evaluated using the Scandinavian Stroke Scale (SSS) and modified Rankin Scale (mRS) at the same time points as blood sampling and 24 months after the event. Patients with either CD40L surface expression or the percentage of monocyte-platelet aggregates (M-plt) in the third tertile (T3) at V0 had a significantly lower score on the SSS at V1. Patients with the percentage M-plt at V0 higher than the median value of M-plt in controls were at increased risk of SSS < 40 at V1 (odds ratio: 2.6; 95% confidence interval [CI]: 1.4 – 8.7; p=0.006). Patients with the percentage of M-plt in T3 at V0 showed progressive decline in survival (hazard ratio [HR]: 1.6; 95% CI: 1.1–1.9; p=0.02) and a significantly higher number of recurrent vascular events (HR: 2.64; 95% CI: 1.3–3.2; p=0.02) when compared to the first tertile. In conclusion, increased levels of M-plt could be a predictive marker for both early outcome and long-term prognosis while increased CD40L was correlated with worse clinical outcome.The preliminary results of this study were presented in part during a poster session at the 62nd Annual Meeting of the American Academy of Neurology in Toronto, 7–17 April 2010.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Shun Li ◽  
Juan Li ◽  
Jiawei Tian ◽  
Ranran Dong ◽  
Jin Wei ◽  
...  

CDKN1C and NAP1L4 in human CDKN1C/KCNQ1OT1 imprinted domain are two key candidate genes responsible for BWS (Beckwith-Wiedemann syndrome) and cancer. In order to increase understanding of these genes in pigs, their cDNAs are characterized in this paper. By the IMpRH panel, porcine CDKN1C and NAP1L4 genes were assigned to porcine chromosome 2, closely linked with IMpRH06175 and with LOD of 15.78 and 17.94, respectively. By real-time quantitative RT-PCR and polymorphism-based method, tissue and allelic expression of both genes were determined using F1 pigs of Rongchang and Landrace reciprocal crosses. The transcription levels of porcine CDKN1C and NAP1L4 were significantly higher in placenta than in other neonatal tissues (P<0.01) although both genes showed the highest expression levels in the lung and kidney of one-month pigs (P<0.01). Imprinting analysis demonstrated that in pigs, CDKN1C was maternally expressed in neonatal heart, tongue, bladder, ovary, spleen, liver, skeletal muscle, stomach, small intestine, and placenta and biallelically expressed in lung and kidney, while NAP1L4 was biallelically expressed in the 12 neonatal tissues examined. It is concluded that imprinting of CDKN1C is conservative in mammals but has tissue specificity in pigs, and imprinting of NAP1L4 is controversial in mammalian species.


2021 ◽  
pp. neurintsurg-2021-017771
Author(s):  
Carlos Perez-Vega ◽  
Ricardo A Domingo ◽  
Shashwat Tripathi ◽  
Andres Ramos-Fresnedo ◽  
Samir Kashyap ◽  
...  

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; I2=13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; I2=0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; I2=0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013198
Author(s):  
Arturo Renú ◽  
Carlos Laredo ◽  
Alejandro Rodríguez-Vázquez ◽  
Daniel Santana ◽  
Mariano Werner ◽  
...  

Background and Objectives:The presence of post-interventional subarachnoid hyperdensities (SA-HD) is a relatively common finding after mechanical thrombectomy (MT). We aimed to assess the incidence, characteristics, clinical relevance and predictors of SA-HD after MT as categorized through the use of post-interventional Dual Energy-CT (DE-CT).Methods:A single-center consecutive series of acute stroke patients treated with MT were retrospectively reviewed. Post-treatment SA-HD were defined as incident extra-axial hyperdensities in a follow-up DE-CT performed within a median of 8 hours after MT. SA-HD were further classified according to their content (isolated contrast extravasation versus blood extravasation) and extension [diffuse (hyperdensities in more than one extraparenchymal compartments) versus non-diffuse]. Adjusted logistic regression models assessed the association of SA-HD with pretreatment and procedural variables and with bad clinical outcome (shift towards worse categories in the ordinal Rankin Scale at 90 days).Results:SA-HD were observed in 120 (28%) of the 424 included patients (isolated contrast extravasation n=22, blood extravasation n=98). In this group, SA-HD were diffuse in 72 (60%) patients (isolated contrast extravasation n=7, blood extravasation n=65) and non-diffuse in 48 (40%) patients (isolated contrast extravasation n=15, blood extravasation n=33). Diffuse SA-HD were significantly associated with worse clinical outcome in adjusted models (cOR=2.3, 95%CI=1.36-4.00, p=0.002), unlike the specific SA-HD content alone. In contrast with the absence of SA-HD, only the diffuse pattern with blood extravasation was significantly associated with worse clinical outcome (cOR=2.4, 95%CI=1.36-4.15, p=0.002). Diffuse SA-HD patterns were predicted by M2 occlusions, more thrombectomy passes and concurrent parenchymal hematomas.Discussion:In our cohort of patients imaged within a median of 8 hours after MT, post-interventional SA-HD showed a diffuse pattern in 17% of thrombectomies and were associated with more arduous procedures. Diffuse SA-HD but not local collections of blood or contrast extravasations were associated with an increased risk of poor outcome and death. These findings reinforce the need for improvement in reperfusion strategies.Classification of Evidence:This study provides Class II evidence that in individuals with proximal carotid artery territory occlusions treated with mechanical thrombectomy, diffuse post-interventional subarachnoid hyperdensities on imaging 8 hours post-procedure are associated with worse clinical outcomes at 90 days.


Author(s):  
Ossama Y Mansour ◽  
Aser Goma

Introduction : Acute dissecting aneurysms are among the uncommon causes of subarachnoid hemorrhage. Established endovascular treatment options include parent artery occlusion and stent‐assisted coiling, but appear to be associated with an increased risk of ischemic stroke. reconstruction of the vessels with flow diverters is an alternative therapeutic option. Methods : This is a retrospective analysis of 53 consecutive acutely ruptured dissecting aneurysms treated with flow diverters. The primary end point was favorable aneurysm occlusion, defined as OKM C1‐3 and D . Secondary end points were procedure‐related complications and clinical outcome. Results : 23 aneurysms (43.4%%) arose from the intradural portion of the vertebral artery, 10 (18.8%) were located on the posterior inferior cerebellar artery and 3 (5.6%) posterior cerebral artery, 7 (13.2%) MCA, (18.8%) ICA . 45 aneurysms presented by SAH while 8 presented by Ischemic manifestation. Flow diverter placement was technically successful in all cases . immediate postoperative rerupture occurred in two case (3.7%), thromboembolic complications in 3 cases (5.7%). Median clinical follow‐up was 640 days and median angiographic follow‐up was 690 days. ten patients (18.9%) with poor‐grade subarachnoid hemorrhage died in the acute phase. Favorable clinical outcome (modified Rankin scale ≤2) was observed in 27 of 53 patients (51%) and a moderate outcome (modified Rankin scale 3/4) was observed in 12 of 53 patients (22.6%). All aneurysms showed complete occlusion at follow‐up. Conclusions : Flow diverters might be a feasible, alternative treatment option for acutely symptomatic dissecting aneurysms and may effectively prevent rebleeding in ruptured aneurysms.


2021 ◽  
pp. 1-10
Author(s):  
Wen Pan ◽  
Min Zhang ◽  
Zhenping Guo ◽  
Wenfeng Xiao ◽  
Chao You ◽  
...  

<b><i>Backgrounds:</i></b> Previous studies reported inconsistent results regarding associations between apolipoprotein E (<i>APOE</i>) polymorphism and clinical outcomes after ischemic stroke (IS), intracerebral hemorrhage (ICH), or subarachnoid hemorrhage (SAH). Thus, the study was designed to make a systematic review and meta-analysis regarding the association between <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH. <b><i>Methods:</i></b> To identify studies eligible for this meta-analysis, we searched for articles published before August 2021 in the databases (PubMed, Web of Science, and Google Scholar). We used STATA 12.0 software to compute hazard ratios (HRs) and their 95% confidence intervals (CIs) regarding <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH. <b><i>Results:</i></b> Meta-analysis showed no significant association between <i>APOE</i> polymorphism and functional outcome after IS with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.00; 95% CI: 0.83–1.21, <i>I</i><sup>2</sup> = 29.4%, <i>p</i> = 0.183; ε2 carrier vs. non-ε2 carrier: HR, 0.92; 95% CI: 0.72–1.16, <i>I</i><sup>2</sup> = 15.6%, <i>p</i> = 0.307). Meta-analysis showed that ICH patients carrying ε4 allele have increased risk of poor outcome in Caucasian population with fixed effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.75; 95% CI: 1.19–2.57, <i>I</i><sup>2</sup> = 0.0%, <i>p</i> = 0.543). Meta-analysis showed no significant association between <i>APOE</i> polymorphism and functional outcomes after SAH with random effects models (ε4 carrier vs. non-ε4 carrier: HR, 1.51; 95% CI: 0.80–2.84, <i>I</i><sup>2</sup> = 57.1%, <i>p</i> = 0.022). <b><i>Conclusions:</i></b> In conclusion, the present study demonstrated <i>APOE</i> ε4 carriers show worse functional outcomes after ICH, but not after IS or SAH. More large-scale studies were critical to explore the association between <i>APOE</i> polymorphism and clinical outcome after IS, ICH, and SAH.


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