Multimorbidity and functional impairment–bidirectional interplay,synergistic effects and common pathways

This review discusses the interplay between multimorbidity (i.e. co‐occurrence of more than one chronic health condition in an individual) and functional impairment (i.e. limitations in mobility, strength or cognition that may eventually hamper a person's ability to perform everyday tasks). On the one hand, diseases belonging to common patterns of multimorbidity may interact, curtailing compensatory mechanisms and resulting in physical and cognitive decline. On the other hand, physical and cognitive impairment impact the severity and burden of multimorbidity, contributing to the establishment of a vicious circle. The circle may be further exacerbated by people's reduced ability to cope with treatment and care burden and physicians’ fragmented view of health problems, which cause suboptimal use of health services and reduced quality of life and survival. Thus, the synergistic effects of medical diagnoses and functional status in adults, particularly older adults, emerge as central to assessing their health and care needs. Furthermore, common pathways seem to underlie multimorbidity, functional impairment and their interplay. For example, older age, obesity, involuntary weight loss and sedentarism can accelerate damage accumulation in organs and physiological systems by fostering inflammatory status. Inappropriate use or overuse of specific medications and drug–drug and drug–disease interactions also contribute to the bidirectional association between multimorbidity and functional impairment. Additionally, psychosocial factors such as low socioeconomic status and the direct or indirect effects of negative life events, weak social networks and an external locus of control may underlie the complex interactions between multimorbidity, functional decline and negative outcomes. Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age‐related health deterioration; this review provides an overview of knowledge gaps and future directions.     

The differential roles of contralesional frontoparietal areas in cortical reorganization after stroke

BackgroundStudies examining the contribution of contralesional brain regions to motor recovery after stroke have revealed conflicting results comprising both supporting and disturbing influences. Especially the relevance of contralesional brain regions beyond primary motor cortex (M1) has rarely been studied, particularly concerning the temporal dynamics post-stroke.MethodsWe, therefore, used online transcranial magnetic stimulation (TMS) interference to longitudinally assess the role of contralesional (right) frontoparietal areas for recovery of hand motor function after left hemispheric stroke: contralesional M1, contralesional dorsal premotor cortex (dPMC), and contralesional anterior intraparietal sulcus (IPS). Fourteen stroke patients and sixteen age-matched healthy subjects performed motor tasks of varying complexity with their (paretic) right hand. Motor performance was quantified using three-dimensional kinematic data. All patients were assessed twice, (i) in the first week, and (ii) after more than three months post-stroke.ResultsWhile we did not observe a significant effect of TMS interference on movement kinematics following the stimulation of contralesional M1 and dPMC in the first week post-stroke, we found improvements of motor performance upon interference with contralesional IPS across motor tasks early after stroke, an effect that persisted into the later phase. By contrast, for dPMC, TMS-induced deterioration of motor performance was only evident three months post-stroke, suggesting that a supportive role of contralesional premotor cortex might evolve with reorganization.ConclusionWe here highlight time-sensitive and region-specific effects of contralesional frontoparietal areas after left hemisphere stroke, which may influence on neuromodulation regimes aiming at supporting recovery of motor function post-stroke.     

以肺动脉高压为首发表现的先天性中枢性低通气综合征临床特征和基因分析

目的探讨先天性中枢性低通气综合征(CCHS)的临床和基因变异特征。方法分析1例首发表现为不明原因肺动脉高压的CCHS患儿的临床资料,并总结国内外文献中CCHS病例的临床特点、致病机制和基因变异情况。结果11月龄女婴,主要表现为浮肿、尿少、低血压、嗜睡、发绀、抽搐及颅内压增高。B型脑利钠肽、丙氨酸氨基转移酶升高,凝血酶原时间延长。颅脑磁共振示右侧额叶出血;超声心动图示中重度肺动脉高压。靶向捕获二代测序未发现可能的致病基因。采用Sanger法验证示患儿PHOX 2 B基因第3外显子存在多聚丙氨酸重复扩展变异,基因型为20/25。患儿入院后采用无创通气,睡眠时呼吸浅慢、微弱,伴血氧下降;血气分析提示二氧化碳潴留。随后改用夜间无创通气、降肺压药物治疗。复查肺动脉压力明显下降,生命体征稳定。随访至24月龄,夜间只需较低压力水平的无创通气,生长发育无异常。结论对于不明原因的肺动脉高压伴撤机困难患儿,需警惕CCHS。疑诊者应尽早针对CCHS相关基因进行靶向捕获二代测序及PHOX 2 B基因Sanger法验证。早期给予无创通气有望改善预后。     

Prevalence and correlates of mild cognitive impairment among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.     

糖尿病肾病内热证与肾功能及炎症因子的相关性研究

目的:观察糖尿病肾病不同分期内热证与肾功能及炎症指标的相关性。方法:收集202例糖尿病肾病患者的临床资料,采用酶联免疫吸附法检测微炎症指标,包括超敏C反应蛋白(high-sensitivity C-reactive protein,HS-CRP)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),进行统计分析。结果:与非内热证组比较,中期、晚期内热证组24小时尿蛋白定量明显升高;晚期内热证组的血清肌酐明显升高,肾小球滤过率(glomerular filtration rate,GFR)明显降低;炎症因子CRP、IL-6、TNF-α随疾病进展均呈上升趋势;晚期内热证组与非内热证组比较,IL-6、TNF-α升高;中期HS-CRP与内热积分呈正相关,晚期TNF-α与内热积分呈正相关。结论:内热病机贯穿于糖尿病肾病的始终,与糖尿病肾病肾功能以及疾病进展密切相关;同时,内热积分与炎症因子HS-CRP、TNF-α的表达存在一定的相关性,这种相关性在疾病中期、晚期表现更加明显。     

Developing a Brief Neuropsychological Battery for Early Diagnosis of Cognitive Impairment

ObjectivesEarly diagnosis of cognitive impairment is increasingly emphasized in the literature to facilitate timely preventive interventions. Although bedside cognitive tests such as the Montreal Cognitive Assessment (MoCA) are widely used for such early diagnostic purposes, they may not have comparable performance to a full neuropsychological battery (FNB) in diagnosing early cognitive impairment. This study investigated whether a small subset of neuropsychological tests can be added on to MoCA to match its performance to that of the FNB in discriminating mild cognitive impairment and dementia (MCI/dementia) from normal cognition.DesignCross-sectional diagnostic study.SettingAlzheimer's Disease Centers across the United States.ParticipantsOlder participants (≥50 years) who completed MoCA and the FNB (N = 9187).MeasuresThe study sample was split into two: the derivation sample (n = 1837) was used to develop a brief neuropsychological battery that best discriminated MCI/dementia (using the best-subset approach with 10-fold cross-validation); while the validation sample (n = 7350) verified its actual performance in discriminating MCI/dementia.ResultsA 3-item neuropsychological battery was identified, comprising MoCA, Benson Complex Figure Recall, and Craft Story 21 Delayed Recall. It had excellent performance in discriminating MCI/dementia from normal cognition (area under the receiver operating characteristic curve [AUROC] 90.0%, 95% confidence interval [CI] 89.2%-90.7%), which was comparable to that of the FNB (AUROC 88.4%, 95% CI 87.6%-89.2%). By contrast, MoCA alone had significantly worse AUROC (86.9%, 95% CI 86.0%-87.7%) than that of the FNB.Conclusions/ImplicationsUsing rigorous methods, this study developed a brief neuropsychological battery that maintained the brevity of a bedside cognitive test, while rivaling the diagnostic performance of an FNB in early cognitive impairment. This brief battery offers a viable alternative when the FNB is needed but cannot be feasibly administered in nonspecialty clinics. It can have a wider health systems effect of improving patients’ access to accurate diagnosis in early cognitive impairment and facilitating timely interventions to delay the progression of cognitive impairment.     

重症心源性肺水肿伴休克患者的机械通气治疗

目的研究重症心源性肺水肿伴休克患者机械通气(MV)治疗时通气压力的选择对预后的影响。方法将符合标准的22例患者分为两组对照组9例,常规给予较低通气压力和加强药物治疗;治疗组13例,适当增加通气压力。观察血压、临床症状和动脉血气的变化。结果调整MV后30分钟时,治疗组收缩压迅速由(95±12)mmHg升至(130±15)mmHg(P<0.001),呼吸频率(RR)由(38±11)次/min降至(27±6)次/min(P<0.005),心率(HR)由(126±15)次/min降至(105±12)次/min(P<0.001);对照组上述指标变化不明显。2小时后治疗组的升压药用量减少(70±15)%,对照组则增加(20±5)%;同时在吸氧浓度不变的情况下,治疗组的PaO2由(81±12)mmHg升至(140±15)mmHg(P<0.001),明显高于对照组PaO2的改善。24~48小时内治疗组11例患者(85%)停用升压药,对照组2例(22%)停用。最终治疗组100%的患者好转出院,对照组为45%(P<0.05)。结论与低压力通气相比,适当增加MV通气压力不仅可迅速改善重症心源性水肺肿伴休克患者的低氧血症,也可迅速升高血压,改善心功能,降低病死率。