Management of monogenic diabetes in pregnancy:A narrative review

Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.

Continuous glucose monitoring metrics in pregnancy with type 1 diabetes mellitus

Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level monitoring and periodic HbA1c tests,the advent of continuous glucose monitoring(CGM)systems has revolutionized the approach.These devices offer a safe and reliable means of tracking glucose levels in real-time,benefiting both women with diabetes during pregnancy and the healthcare providers.Moreover,CGM systems have shown a low rate of side effects and high feasibility when used in pregnancies complicated by diabetes,especially when paired with continuous subcutaneous insulin infusion pump as hybrid closed loop device.Such a combined approach has been demonstrated to improve overall blood sugar control,lessen the occurrence of preeclampsia and neonatal hypoglycaemia,and minimize the duration of neonatal intensive care unit stays.This paper aims to offer a comprehensive evaluation of CGM metrics specifically tailored for pregnancies impacted by type 1 diabetes mellitus.

Diabetes mellitus and stroke: A clinical update

Cardiovascular disease including stroke is a major complication that tremendously increases the morbidity and mortality in patients with diabetes mellitus(DM). DM poses about four times higher risk for stroke. Cardiometabolic risk factors including obesity, hypertension, and dyslipidaemia often co-exist in patients with DM that add on to stroke risk. Because of the strong association between DM and other stroke risk factors, physicians and diabetologists managing patients should have thorough understanding of these risk factors and management. This review is an evidence-based approach to the epidemiological aspects, pathophysiology, diagnostic work up and management algorithms for patients with diabetes and stroke.

Effect of fish oil enriched enteral diet on inflammatory bowel disease tissues in organ culture: Differential effects on ulcerative colitis and Crohn's disease

AIM： To investigate the influence of fish oil enriched enteral diet on intestinal tissues taken from Crohn＇s disease （CD）, ulcerative colitis （UC） and non-inflamed non-IBD control patients in vitro. METHODS： Colonoscopic biopsies from patients with active CD （n = 4）, active UC （n = 7）, and non-inflamed non-IBD control patients （n = 4） were incubated （three dilutions of 1：20, 1：10, and 1：5） with Waymouth＇s culture medium and enteral elemental diet （EO28, SHS, Liverpool, UK） modified in the fatty acid composition with fish oil （EF） in an organ culture system for 24 h. In each experimental set-up, incubation with Waymouth＇s medium alone as control was included. Tissue viability was assessed by adding bromodeoxyuridine （BrdU） to the culture fluid and immunohistochemically staining for BrdU uptake. Cytokine ratio of IL-1ra/IL-1β （low ratio indicative of inflammation） and production of those cytokines as a percentage of medium control were assayed in the culture supernatant. RESULTS： Incubation of CD-affected tissue with EF （1：20, 1：10, and 1：5） modestly and non-significantly increased IL-1ra/IL-1β ratio as compared with medium control （CD 39.1±16.1; 26.5±7.8, 47.1±16.8 vs control 13.0±2.2）, but incubation of UC-affected tissues increased IL-1ra/IL-1β ratio significantly in all three dilutions （UC 69.1±32.2, P〈0.05; 76.1±36.4, P = 0.05; 84.5±37.3, P〈0.02; vs control 10.2±3.7）. Incubation of non-inflamed non-IBD control tissue did not increase the IL-1ra/IL-1β ratio in any dilution compared to medium control （69.3±47.0, 54.1±30.6, 79.4±34.0 vs control 76.1±37.3）. Average percentage production of IL-1β indexed against medium control was significantly less in UC after EF incubation as compared with CD （UC 24.0±4.8 vs CD 51.8±8.1; P〈0.05）. Average percentage production of IL-tra was markedly higher in UC （135.9±3.4） than that in control patients （36.5±4.3） （p〈0.0001）. CONCLUSION： IBD tissues, after incubation with elemental diet modified in its fatty acid composition with fish oil, show an increase in IL-1ra/IL-1β cytokine ratio. This effect of ω-3 fatty acid modulation is significantly more marked in UC compared with CD and is accompanied by both a reduction of IL-1β and increase of IL-1ra. The positive direct anti-inflammatory effect of elemental diet with fish oil in tissue affected with UC suggests dietary treatment of UC may be possible.

颈动脉狭窄:无创伤性检查的准确性——个体病人数据的Meta分析

目的评价临床相关的无创伤性影像学检查——US、CT血管成像、MR血管成像和MR增强血管成像对于诊断重度和中度有症状的颈动脉狭窄的准确性；确定先期各种特异性临床因素和临床表现对诊断准确性的影响：评估两种无创性检查的一致性。方法利用原始检查资料得到伦理委员会认可。所有的资料都是匿名的。利用个体病例无创性影像学检查的资料（IPDS）评估有症状的颈动脉狭窄的敏感度、特异度和一致性：比较同侧与对侧动脉：比较IPDs与文献的评估结果；

Novel susceptibility genes in inflammatory bowel disease

The inflammatory bowel disease, Crohn's disease and ulcerative colitis, are polygenic disorders with important environmental interactions. To date, the most widely adopted approach to identifying susceptibility genes in complex diseases has involved genome wide linkage studies followed by studies of positional candidate genes in loci of interest. This review encompasses data from studies into novel candidate genes implicated in the pathogenesis of inflammatory bowel disease. Novel techniques to identify candidate genes-genome wide association studies, yeast-two hybrid screening, microarray gene expression studies and proteomic profiling, are also reviewed and their potential role in unravelling the pathogenesis of inflammatory bowel disease are discussed.

65～70岁和75～80岁大脑MR正常参考影像的研制和初步测试

解读老年人的大脑影像需要了解正常健康老年人大脑的变化。本研究制作和测试了一个老年人参考模板，用65～70岁和75～80岁正常人的MR影像制定了一般年龄特定的影像。根据脑组织减少程度将T2加权影像分级，建立一个百分位数图表。2位神经放射学专家在常规报告时测试模板；8位放射学专家先阅读99份MR影像，然后与模板对比。

Colonoscopy quality with Entonox? vs intravenous conscious sedation:18608 colonoscopy retrospective study

AIM To compare colonoscopy quality with nitrous oxide gas(Entonox?) against intravenous conscious sedation using midazolam plus opioid.METHODS A retrospective analysis was performed on a prospectively held database of 18608 colonoscopies carried out in Lothian health board hospitals between July 2013 and January 2016.The quality of colonoscopies performed with Entonox was compared to intravenous conscious sedation(abbreviated in this article as IVM).Furthermore,the quality of colonoscopies performed with an unmedicated group was compared to IVM.The study used the following key markers of colonoscopy quality:(1) patient comfort scores;(2) caecal intubation rates(CIRs); and (3) polyp detection rates (PDRs).We used binary logistic regression to model the data.RESULTS There was no difference in the rate of moderate-toextreme discomfort between the Entonox and IVM groups (17.9% vs 18.8%; OR = 1.06,95%CI: 0.95-1.18,P = 0.27).Patients in the unmedicated group were less likely to experience moderate-to-extreme discomfort than those in the IVM group(11.4% vs 18.8%; OR = 0.71,95%CI: 0.60-0.83,P < 0.001).There was no difference in caecal intubation between the Entonox and IVM groups(94.4% vs 93.7%; OR = 1.08,95%CI: 0.92-1.28,P = 0.34).There was no difference in caecal intubation between the unmedicated and IVM groups (94.2% vs 93.7%; OR = 0.98,95%CI: 0.79-1.22,P = 0.87).Polyp detection in the Entonox group was not different from IVM group (35.0% vs 33.1%; OR = 1.01,95%CI: 0.93-1.10,P = 0.79).Polyp detection in the unmedicated group was not significantly different from the IVM group (37.4% vs 33.1%; OR = 0.97,95%CI: 0.87-1.08,P = 0.60).CONCLUSION The use of Entonox was not associated with lower colonoscopy quality when compared to intravenous conscious sedation using midazolam plus opioid.

肠内管饲时机及方法对卒中伴吞咽困难患者的影响(FOOD):一项多中心随机对照试验

Background Undernutrition is common in patients admitted with stroke. We aimed to establish whether the timing and route of enteral tube feeding after stroke affected patients’outcomes at 6 months. Methods The FOOD trials consist of thre e pragmatic multicentre randomized controlled trials, two of which included dysp hagic stroke patients. In one trial, patients enrolled within 7 days of admissio n were randomly allocated to early enteral tube feeding or no tube feeding for m ore than 7 days (early versus avoid). In the other, patients were allocated perc utaneous endoscopic gastrostomy (PEG) or nasogastric feeding. The primary outcom e was death or poor outcome at 6 months. Analysis was by intention to treat.Find ings Between Nov 1, 1996, and July 31, 2003, 859 patients were enrolled by 83 ho spitals in 15 countries into the early versus avoid trial. Early tube feeding wa s associated with an absolute reduction in risk of death of 5.8%(95%CI -0.8 t o 12.5, p=0.09) and a reduction in death or poor outcome of 1.2%(-4.2 to 6.6, p=0.7). In the PEG versus nasogastric tube trial, 321 patients were enrolled by 47 hospitals in 11 countries. PEG feeding was associated with an absolute increa se in risk of death of 1.0%(-10.0 to 11.9, p=0.9) and an increased risk of dea th or poor outcome of 7.8%(0.0 to 15.5, p=0.05). Interpretation Early tube feed ing might reduce case fatality, but at the expense of increasing the proportion surviving with poor outcome. Our data do not support a policy of early initiatio n of PEG feeding in dysphagic stroke patients.

Does a melatonin supplement alter the course of gastroesophageal reflux disease?

Symptomatic gastro-esophageal reflux disease(GERD) is a very common disease.The consequence of GERD is not only erosive esophagitis,but also esophageal stricture,Barrett's esophagus and extra-esophageal damage(including the lungs,throat,sinuses,middle ear and teeth).GERD and Barrett's esophagus are also identif ied as major risk factors for esophageal carcinoma.Therapy with melatonin prevents esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals,then further studies are required in humans to establish whether a melatonin supplement is able to protect the patients with GERD from erosions,Barrett's and neoplasia.

对结肠癌DNA错配修复基因突变携带者的识别及存活率的评估

BACKGROUND:The identification of mutations in germ-line DNA mismatch-repair genes at the time of diagnosis of colorectal cancer is important in the management of the disease.METHODS:Without preselection and regardless of family history,we recruited 870 patients under the age of 55 years soon after they received a diagnosis of colorectal cancer.We studied these patients for germ-line mutations in the DNA mismatch-repair genes MLH1,MSH2,and MSH6 and developed a two-stage model by multivariate logistic regression for the prediction of the presence of mutations in these genes.Stage 1 of the model incorporated only clinical variables;stage 2 comprised analysis of the tumor by immunohistochemical staining and tests for microsatellite instability.The model was validated in an independent population of patients.We analyzed 2938 patient-years of follow-up to determine whether genotype influenced survival.RESULTS:There were 38 mutations among the 870 participants(4 percent) :15 mutations in MLH1,16 in SH2,and 7 in MSH6.Carrier frequencies in men(6 percent) and women(3 percent) differed significantly(P < 0.04) .The addition of immunohistochemical analysis in stage 2 of the model had a sensitivity of 62 percent and a positive predictive value of 80 percent.There were 35 mutations in the validation series of 155 patients(23 percent) :19 mutations in MLH1,13 in MSH2,and 3 in MSH6.The performance of the model was robust among a wide range of cutoff probabilities and was superior to that of the Bethesda and Amsterdam criteria for hereditary nonpolyposis colorectal cancer.Survival among carriers was not significantly different from that among noncarriers.CONCLUSIONS:We devised and validated a method of identifying patients with colorectal cancer who are carriers of mutations in DNA repair genes.Survival was similar among carriers and noncarriers.

卒中住院患者常规口服营养补充(FOOD):一项多中心随机对照试验

Background Undernutrition is common in hospital patients with stroke, can deve lop or worsen in hospital, and is associated with poor outcomes. We aimed to est ablish whether routine oral nutritional supplements improve outcome after stroke . Methods The FOOD trials are a family of three pragmatic, multicentre, randomis ed controlled trials.We measured the outcomes of stroke patients who could swall ow and who were randomly allocated normal hospital diet or normal hospital diet plus oral nutritional supplements until hospital discharge. The primary outcome was death or poor outcome (modified Rankin scale [MRS] grade 3-5), 6 months aft er enrolment, measured unaware of treatment allocation. Analysis was by intentio n to treat. Findings Between Nov 1, 1996, and July 31, 2003, 4023 patients were enrolled by 125 hospitals in 15 countries. Only 314 (8%) patients were judged t o be undernourished at baseline. Vital status and MRS at the end of the trial we re known for 4012 and 4004 patients, respectively. Supplemented diet was associa ted with an absolute reduction in risk of death of 0.7%(95%CI-1.4 to 2.7) and an increased risk of death or poor outcome of 0.7%(-2.3 to 3.8). Interpretati on We could not confirm the anticipated 4%absolute benefit for death or poor ou tcome from routine oral nutritional supplements for mainly well nourished stroke patients in hospital. Our results would be compatible with a 1%or 2%absolute benefit or harm from oral supplements. These results do not support a policy of routine oral supplementation after stroke.

无证据表明颈内动脉卒中的严重程度与其相关动脉有关

Background/Aim:The neurological effects of internal carotid artery(ICA)occlusion vary between patients.The authors investigated whether the severity of symptoms in a large group of patients with ipsilateral or/and contralateral ICA occlusion at presentation with ocular or cerebral ischaemic symptoms could be explained by patency of other extra or intracranial arteries to act as collateral pathways.Methods:The authors prospectively identified all patients(n=2881)with stroke,cerebral transient ischaemic attack(TIA),retinal artery occlusion(RAO),and amaurosis fugax(AFx)presenting to our hospital over five years,obtained detailed history and examination,and examined the intra and extracranial arteries with carotid and colour-power transcranial Doppler ultrasound.For this analysis,all those with intracranial haemorrhage on brain imaging and cerebral events without brain imaging were excluded.Results:Among 2228/2397 patients with brain imaging(1713 ischaemic strokes,401 cerebral TIAs,193 AFx,and 90 RAO)who underwent carotid Doppler,195(9%)had ICA occlusion.Among those patients with cortical events,disease in potential collateral arteries(contralateral ICA,external carotid,ipsilateral or contralateral vertebral or intracranial arteries)was equally distributed among patients with severe and mild ischaemic presenting symptoms.Conclusion:The authors found no evidence that the clinical presentation associated with an ICA occlusion was related to patency of other extra or intracranial arteries to act as collateral pathways.Further work is required to investigate what determines the clinical effects of ICA occlusion.

c-MET immunohistochemical expression in sporadic and inflammatory bowel disease associated lesions

BACKGROUND Post-colonoscopy colorectal cancer(CRC)rates for patients with inflammatory bowel disease(IBD)are unacceptably high.During colonoscopy,an intravenous fluorescent anti-c-MET probe may improve endoscopic detection of lesions.However,c-MET expression in IBD lesions is poorly defined,limiting translational studies.AIM To comprehensively define c-MET expression in sporadic and IBD-associated colorectal carcinogenesis.METHODS c-MET expression was immunohistochemically assessed in 319 formalin-fixed paraffin-embedded tissue specimens,colonoscopically or surgically retrieved between 1994-2017.Tissue included:30 normal colorectal biopsies,30 hyperplastic polyps(HP),31 sessile serrated lesions(SSL),55 tubular/tubulovillous adenomas with low(TA-LGD,n=32)or high grade dysplasia(TA-HGD,n=23),26 sporadic(s)-CRCs,16 quiescent IBD biopsies,11 active/inflamed IBD biopsies,18 IBDassociated dysplastic lesions(IBD-dys),and 102 IBD-CRCs.Expression was scored by two independent observers as:0=absent,1=weak,2=moderate or 3=strong.Mann-Whitney U and Kruskal-Wallis tests were used to assess significance.RESULTS Positive epithelial cytoplasmic and membranous c-MET expression was observed in all tissues,indicating there is ubiquitous expression in the colorectum.c-MET expression was weak in normal colonic epithelium compared with each of the sporadic colonic lesions,including TA-LGD(P<0.001),TA-HGD(P=0.004),HP(P<0.001),SSL(P<0.001),and s-CRC(P<0.001).Specifically,in sporadic(non-IBD)lesions,expression was stronger in TA-LGD compared with normal mucosa(P<0.001),and stronger in s-CRC compared with TA-HGD(P=0.004).However,there was no significant difference between TA-LGD and TA-HGD(P=0.852).Further,there was no difference in c-MET expression between HP and SSL(P=0.065).In IBD,expression was weaker in quiescent colonic mucosa compared with inflamed colonic mucosa(P<0.001).There was no difference between inflamed colonic mucosa and IBD-dys(P=0.512)or IBD-CRC(P=0.296).However,expression was stronger in IBD-dys(P<0.001)and IBD-CRC(P<0.001)compared with quiescent IBD colonic mucosa.CONCLUSION The characterisation of c-MET expression suggest that an intravenous probe may improve the endoscopic detection of lesions in both non-IBD patients and IBD patients with quiescent disease.

Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity

AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers.METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80&#x02005;&#x000b0;C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 &#x003bc;g/g in 2 participants, and above 50 &#x003bc;g/g in a further 5 participants.CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.

Pre-Operative MRI in HER-2 Receptor Positive and Her-2 Receptor Negative Breast Cancer: A Comparison

Objectives: MRI is the most sensitive modality for local staging of breast cancer. Herceptin receptor over-expression is seen in 15% - 30% of breast tumours, and is associated with increased aggression, poorer prognosis, higher grade at diagnosis and increased lymphatic dissemination. This study aimed at evaluating the role of MRI in Herceptin receptor positive vs negative tumours. Methods: 193 pre-operative MRIs were performed in 2021 for staging of 162 Her-2 negative and 37 Her-2 positive tumours. Recall rates and further biopsies (ipsilateral/contralateral) were assessed in both groups, and MRI largest size was compared to pathological size of invasive cancer and DCIS. Results: 36.4% of Her-2 negative tumours were recalled;further ipsilateral malignancy was identified in 13.6%. Contralateral malignancy was identified in 1.2%. 29.7% of Her-2 positive tumours were recalled;further ipsilateral malignancy was identified in 16.2%. No contralateral malignancy was seen in Her-2 positive tumours. The OR of Her-2 positive tumours having ipsilateral foci of malignancy on MRI is 0.83 (CI 0.3, 2.2). Pathological size concordance with MRI size was seen in 70.3% of Her-2 negative, and 48.6% of Her-2 positive tumours. Discordance in both groups was due to MRI size overestimation (70.8% of Her-2 negative discordance;89.4% of Her-2 positive discordance). Conclusions: Pre-operative MRI did not detect significant increased additional foci in Her-2 positive tumours. Significant concordance with pathological size was not seen in both groups;MRI overestimation was the most frequent cause for discordance in both groups. Advances in Knowledge: This study compares MRI features of Her-2 positive and Her-2 negative tumours. It demonstrates that there is no significant increased multifocality or multicentricity of Her-2 positive tumours, but MRI over-estimates size in 30% of Her-2 negative and 51% of Her-2 positive cancers.

Clinical translation of neuro-regenerative medicine in India: A study on barriers and enabling strategies

We present the findings of a study of barriers and enabling strategies to clinical translation of Neuro-Regenerative Medicine (Neuro-RM) technologies in India. Twenty-three people were included in this qualitative study, including researchers, clinicians, firm representatives and policy makers working in Neuro-RM. The study has identified barriers that may arise at each stage of translation and how these are being addressed. Understanding of the molecular and cellular basis of Neuro-RM is being supported through government investment in existing neuroscience centres and the creation of new centres with regenerative medicine expertise. Clinical trials benefit from the support of clinicians who partner with researchers in study design and data collection. Government agencies have developed guidelines to inform best practices in preclinical and clinical studies. Addressing the barriers to Neuro-RM translation identified in this study can be achieved through continued support for capacity building and priority setting in preclinical studies, international efforts to achieve clinical trial protocol standardization, and multidisciplinary collaborations between clinicians, researchers, government and industry.

关于苏格兰新生儿死亡队列脑损伤和轴突损害的研究

Despite the clinical and medicolegal significance attached to perinatal asphyx ia, the neuropathological basis of this condition remains obscure. There are ver y few studies in the literature which correlate the pathological findings in neo natal brains with detailed epidemiological data, and none which are population b ased. In a Scotland-wide study of neonatal deaths, 70 brains have been examined . On the basis of glial and macrophage reactions, we previously identified infan ts with putative antepartum brain damage in this cohort and have related these r eactions to signs of birth asphyxia. The present study explores the extent of ne uronal/axonal injury in these infants since this is likely to be the basis for n eurological deficits in surviving infants. We have also investigated these brain s for β-amyloid precursor protein (βAPP) positivity to determine whether this is a useful marker of neuronal injury in neonates. Neuronal eosinophilia and ka ryorrhexes were detected in 43%and 27%of the cohort, respectively; maximally i n the subiculum and ventral pons, but often present elsewhere. White matter dama ge was detected in 24%of cases but without classic cystic lesions of periventri cular leucomalacia. βAPP positivity was present in neuronal soma in 52%of case s and, in axons, in 27%of cases, and was seen from as early as 25-weeks gestat ion. Axonal bulbs were clearly delineated by βAPP positivity and were usually l ocated in the cerebral white matter and internal capsule, and infrequently in th e brain stem. Although white matter damage and βAPP axonal positivity were ofte n detected in the same cases (P=0.034), these features also occurred independent ly of each other. Both neuronal karyorrhexes and white matter βAPP positivity w ere significantly correlated with the features of birth asphyxia, particularly a history of seizures. Immunocytochemistry for both βAPP and glial fibrillary ac idic protein proved useful in detecting neuropathological features which escaped detection on routine examination, particularly in preterm infants. The presence together of recent and older damage in individual brains suggests that there is an ongoing neuronal response to cerebral insults. We find that βAPP is a usefu l marker of white matter damage in the neonatal brain. Immunopositivity for βAP P in these circumstances is not attributable to inflicted or accidental trauma. While birth-related trauma cannot be ruled out, hypoxia/ischaemia is a likely c ause in these infants. However, the exact pathogenesis of neuro-nal/axonal inju ry in the neonatal brain remains unclear.

散发性克雅病及其他人类遗传性海绵状脑病患者存活率的预测因素

A collaborative study of human transmissible spongiform encephalopathies has b een carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictor s of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfel dt Jakob disease (n = 86) and in cases associated with mutations of the prion p rotein gene (n=278), including Gerstmann Strussler Scheinker syndrome (n = 24) and fat al familial insomnia (n = 41). Overall survival for each disease type was assess ed by the .Kaplan Meier method and the multivariate analyses by the Cox proport ional hazards model. In sporadic disease, longer survival was correlated with yo unger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of thera py, will be an important starting point for the assessment of potential therapeu tic agents in the future.