Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ...‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.
BACKGROUND AND PURPOSE—Plasma GFAP (glial fibrillary acidic protein) has recently emerged as a potential biomarker for the differentiation of acute intracerebral hemorrhage (ICH) from acute ischemic ...stroke (AIS). We prospectively assessed the diagnostic accuracy of GFAP in the differential diagnosis of ICH.
METHODS—Consecutive patients presenting to the emergency department within 6 hours from symptom onset were evaluated. All patients underwent extensive diagnostic work-up and were classified according to discharge diagnosis in AIS, ICH, subarachnoid hemorrhage, and stroke mimics. GFAP was also measured in healthy volunteers (controls). Baseline stroke severity was evaluated using National Institutes of Health Stroke Scale. Receiver operating characteristic curve analysis was used to identify the optimal cutoff point for the differentiation between subgroups. Correlation analyses of GFAP plasma concentrations with baseline National Institutes of Health Stroke Scale and onset to sampling time were performed with the nonparametric Spearman rank test and fractional polynomial regression, respectively.
RESULTS—Our study population consisted of 270 individuals (AIS121, ICH34, stroke mimics31, subarachnoid hemorrhage5, controls79). No differences on baseline stroke severity and onset to sampling time were detected between AIS and ICH. Higher median plasma GFAP values were documented in ICH compared with AIS, stroke mimics, and controls (P<0.001). Receiver operating characteristic analysis highlighted a cutoff value of 0.43 ng/mL as the optimal threshold for the differentiation between ICH and AIS (sensitivity91%, specificity97%). No association was detected between plasma GFAP concentrations and baseline stroke severity for both AIS (P=0.515) and ICH (P=0.387). In the fractional polynomial analysis, the association between GFAP concentration and onset to sampling time was best described by a J-shaped curve for AIS and an inverted U-shaped curve for ICH, with a peak at 2 hours.
CONCLUSIONS—Plasma GFAP seems to be a sensitive and specific biomarker for the differentiation of ICH from both AIS and other acute neurological disorders, with the optimal diagnostic yield being present in the second hour from symptom onset.
Results from landmark diabetes studies have established A1C as the gold standard for assessing long-term glycemic control. However, A1C does not provide "real-time" information about individual ...hyperglycemic or hypoglycemic excursions. Real-time information provided by self-monitoring of blood glucose (SMBG) represents an important adjunct to A1C, because it can differentiate fasting, preprandial, and postprandial hyperglycemia; detect glycemic excursions; identify hypoglycemia; and provide immediate feedback about the effect of food choices, physical activity, and medication on glycemic control. The importance of SMBG is widely appreciated and recommended as a core component of management in patients with type 1 or insulin-treated type 2 diabetes, as well as in diabetic pregnancy, for both women with pregestational type 1 and gestational diabetes. Nevertheless, SMBG in management of non-insulin-treated type 2 diabetic patients continues to be debated. Results from clinical trials are inconclusive, and reviews fail to reach an agreement, mainly because of methodological problems. Carefully designed large-scale studies on diverse patient populations with type 2 diabetes with the follow-up period to investigate long-term effects of SMBG in patients with type 2 diabetes should be carried out to clarify how to make the best use of SMBG, in which patients, and under what conditions.
This correspondence comments on a published article presenting a case of rhombencephalitis following SARS-CoV-2-vaccination with the mRNA vaccine BNT162b2 (Pfizer/BioNTech). We also present the case ...of a 47-year-old man who developed Guillain-Barré-syndrome and a fulminant encephalomyelitis 28 days after immunization with Ad26.COV2.S (Janssen/Johnson & Johnson). Based on the presented cases, we underscore the importance of clinical awareness for early recognition of overlapping neuroimmunological syndromes following vaccination against SARS-CoV-2. Additionally, we propose that that role of autoantibodies against angiotensin-converting enzyme 2 (ACE2) and the cell-surface receptor neuropilin-1, which mediate neurological manifestations of SARS-CoV-2, merit further investigation in patients presenting with neurological disorders following vaccination against SARS-CoV-2.
Despite significant progress by genome-wide association studies, the ability of genetic variants to conduce to the prediction or prognosis of type-2 diabetes (T2D) is weak. Expression analysis of the ...corresponding genes may suggest possible links between single-nucleotide polymorphisms and T2D phenotype and/or risk. Herein, we investigated the expression patterns of 24 T2D-susceptibility genes, and their individual transcript variants (tv), in peripheral blood of T2D patients and controls (CTs), applying RNA-seq and real-time qPCR methodologies, and explore possible associations with disease features. Our data revealed the deregulation of certain transcripts in T2D patients. Among them, the down-regulation of CAPN10 tv3 was confirmed as an independent predictor for T2D. In patients, increased expression of CDK5 tv2, CDKN2A tv3 or THADA tv5 correlated positively with serum insulin levels, of CDK5 tv1 positively with % HbA1c levels, while in controls, elevated levels of TSPAN8 were associated positively with the presence of T2D family history. Herein, a T2D-specific expression profile of specific transcripts of disease-susceptibility genes is for the first time described in human peripheral blood. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.
Resistin and the proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, produced by adipocytes, and macrophages, are considered to be important modulators of chronic inflammation contributing to ...the development of obesity and atherosclerosis. Human monocyte-enriched mononuclear cells, from ten healthy individuals, were exposed to high concentrations of insulin, leptin, and glucose (alone or in combination) for 24 hours in vitro. Resistin, TNF-α, IL-6, and IL-1β production was examined and compared to that in untreated cells. High insulin and leptin concentrations significantly upregulated resistin and the cytokines. The subsequent addition of high glucose significantly upregulated resistin and TNF-α mRNA and protein secretion, while it did not have any effect on IL-6 or IL-1β production. By comparison, exposure to dexamethasone reduced TNF-α, IL-6, and IL-1β production, while at this time point it increased resistin protein secretion. These data suggest that the expression of resistin, TNF-α, IL-6, and IL-1β from human mononuclear cells, might be enhanced by the hyperinsulinemia and hyperleptinemia and possibly by the hyperglycemia in metabolic diseases as obesity, type 2 diabetes, and atherosclerosis. Therefore, the above increased production may contribute to detrimental effects of their increased adipocyte-derived circulating levels on systemic inflammation, insulin sensitivity, and endothelial function of these patients.
Background: Although insulin resistance in thyroid hormone excess is well documented, information on insulin action in hypothyroidism is limited.
Methods: To investigate this, a meal was given to 11 ...hypothyroid (HO; aged 45 ± 3 yr) and 10 euthyroid subjects (EU; aged 42 ± 4 yr). Blood was withdrawn for 360 min from veins (V) draining the anterior abdominal sc adipose tissue and the forearm and from the radial artery (A). Blood flow (BF) in adipose tissue was measured with 133Xe and in forearm with strain-gauge plethysmography. Tissue glucose uptake was calculated as (A-V)glucose(BF), lipoprotein lipase as (A-V)Triglycerides(BF), and lipolysis as (V-A)glycerol(BF)-lipoprotein lipase.
Results: The HO group had higher glucose and insulin levels than the EU group (P < 0.05). In HO vs. EU after meal ingestion (area under curve 0–360 min): 1) BF (1290 ± 79 vs. 1579 ± 106 ml per 100 ml tissue in forearm and 706 ± 105 vs. 1340 ± 144 ml per 100 ml tissue in adipose tissue) and glucose uptake (464 ± 74 vs. 850 ± 155 μmol per 100 ml tissue in forearm and 208 ± 42 vs. 406 ± 47 μmol per 100 ml tissue in adipose tissue) were decreased (P < 0.05), but fractional glucose uptake was similar (28 ± 6 vs. 33 ± 6% per minute in forearm and 17 ± 4 vs. 14 ± 3% per minute in adipose tissue); 2) suppression of lipolysis by insulin was similar; and 3) plasma triglycerides were elevated (489 ± 91 vs. 264 ± 36 nmol/liter·min, P < 0.05), whereas adipose tissue lipoprotein lipase (42 ± 11 vs. 80 ± 21 μmol per 100 ml tissue) and triglyceride clearance (45 ± 10 vs. 109 ± 21 ml per 100 ml tissue) were decreased in HO (P < 0.05).
Conclusions: In hypothyroidism: 1) glucose uptake in muscle and adipose tissue is resistant to insulin; 2) suppression of lipolysis by insulin is not impaired; and 3) hypertriglyceridemia is due to decreased clearance by the adipose tissue.
ObjectiveAlthough clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited.Design and methodsTo ...investigate this, we assessed the sensitivity of glucose metabolism to insulin in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR.ResultsHR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC0–300 32 190±1067 and 31 497±716 mg/dl min respectively) versus EU (27 119±1156 mg/dl min, P<0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC0–300 11 020±985 and 9565±904 mU/l min respectively) compared with EU subjects (AUC0–300 7588±743 mU/l min, P<0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81±0.3 and 2.43±0.38 respectively) compared with EU subjects (1.27±0.16, P<0.05), while Matsuda and Belfiore indices were decreased in HR (4.21±0.41 and 0.77±0.05 respectively, P<0.001) and SHR patients (4.47±0.33 and 0.85±0.05 respectively, P<0.05 versus EU (7.76±0.87 and 1 respectively). At 100 μU/ml insulin, i) GLUT3 levels on the monocyte plasma membrane were increased in HR (468.8±7 mean fluorescence intensity (MFI)) and SHR patients (522.2±25 MFI) compared with EU subjects (407±18 MFI, P<0.01 and P<0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8±5%) versus EU subjects (61.26±10%, P<0.05).ConclusionsInsulin-stimulated glucose transport in isolated monocytes of patients with HR was decreased compared with EU subjects. Insulin resistance was comparable in patients with both HR and SHR.
Alzheimer's disease is the most common type of dementia, reaching 60-80% of case totals, and is one of the major global causes of the elderly population's decline in functionality concerning daily ...life activities. Epidemiological research has already indicated that, in addition to several others metabolic factors, diabetes mellitus type 2 is a risk factor of Alzheimer's disease. Many molecular pathways have been described, and at the same time, there are clues that suggest the connection between type 2 diabetes mellitus and Alzheimer's disease, through specific genes, autophagy, and even inflammatory pathways. A systematic review with meta-analysis was conducted, and its main goal was to reveal the multilevel connection between these diseases.
The COVID-19 pandemic caused a rise in healthcare demands leading to significant restructuring of hospital emergency departments worldwide. The aim of the present study is twofold: firstly, to ...discern any differences in regard to reason for surgical emergency department (SED) attendance and hospital admission during the pandemic and pre-pandemic eras in Greece, and secondly, to assess the impact of the lockdown measures implemented during the pandemic on SED patient attendance.
Since the beginning of the COVID-19 pandemic in Greece (1 March 2020) and up to 15 December 2020, the charts of all adult patients arriving at the SED of the third surgical department of the "Attikon" University Hospital (a tertiary referral center for surgical and COVID-19 cases) were retrospectively reviewed and broken down in four periods reflecting two nationwide lockdown (period A 1/3/2020 to 30/4/2020 and period D 16/10/2020 to 15/12/2020) and two interim (period B 1/5/2020 to 15/6/2020 and period C 15/9/2020 to 30/10/2020) periods. Demographic and clinical data were compared to those obtained from the same time periods of the year 2019.
The total number of patients attending the SED decreased by 35.9% during the pandemic (from 2839 total patients in 2019 to 1819 in 2020). During the first lockdown, there was statistically significant reduction of motor vehicle accidents (p=0.04) and torso injuries (p=0.01). Contrarily, the rate of head injuries (p<0.001) and abdominal pain (p=0.04) were significantly increased. The same effect was observed regarding the rate of hospital admissions (p=0.002), although in terms of absolute numbers, admissions remained unchanged. During the second lockdown, there was a reduction in the number of perianal abscess cases (p=0.04) and hernia-related problems (p=0.001). An increase in the rate of fall injuries was also demonstrable (p=0.02). Overall, application of the lockdown led to a significant decrease in minor (p<0.001) and torso (p=0.001) injuries.
The burden of the new COVID-19 disease has left a noticeable imprint in the function of emergency departments worldwide. In Greece, SED attendance was significantly reduced during the pandemic, an effect that was even more pronounced during the lockdown implementation; nevertheless, the overall rate of hospital admissions remained the same, denoting that patient care was not altered.
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