Mild Initial Symptoms Research Articles

Early neurological deterioration in acute lacunar ischemic stroke: Systematic review of incidence, mechanisms, and prospects for treatment.

Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischemic strokes. In acute lacunar ischemic stroke, despite often mild initial symptoms, early neurological deterioration (END) occurs in approximately 15-20% of patients and is associated with poor functional outcome, yet its mechanisms are not well understood. In this review, we systematically evaluated data on: (1) definitions and incidence of END, (2) mechanisms of small vessel occlusion, (3) predictors and mechanisms of END, and (4) prospects for the prevention or treatment of patients with END. We identified 67 reports (including 13,407 participants) describing the incidence of END in acute lacunar ischemic stroke. The specified timescale for END varied from <24 h to 3 weeks. The rate of END ranged between 2.3% and 47.5% with a pooled incidence of 23.54% (95% confidence interval (CI) = 21.02-26.05) but heterogeneity was high (I2 = 90.29%). The rates of END defined by National Institutes of Health Stroke Scale (NIHSS) decreases of ⩾1, ⩾2, ⩾3, and 4 points were as follows: 24.17 (21.19-27.16)%, 22.98 (20.48-25.30)%, 23.33 (16.23-30.42)%, and 10.79 (2.09-23.13)%, respectively, with lowest heterogeneity and greatest precision for a cutoff of ⩾2 points. Of the 20/67 studies (30%) reporting associations of END with clinical outcome, 19/20 (95%) reported worse outcomes (usually measured using the modified Rankin score at 90 days or at hospital discharge) in patients with END. In a meta-regression analysis, female sex, hypertension, diabetes, and smoking were associated with END. END occurs in more than 20% of patients with acute lacunar ischemic stroke and might provide a novel target for clinical trials. A definition of an NIHSS ⩾2 decrease is most used and provides the best between-study homogeneity. END is consistently associated with poor functional outcome. Further research is needed to better identify patients at risk of END, to understand the underlying mechanisms, and to carry out new trials to test potential interventions.

Comparative Proteomics Identified EXOSC1 as a Target Protein of Anticancer Peptide LVTX-8 in Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy that usually occurs among the nose and throat. Due to mild initial symptoms, most patients are diagnosed in the late stage, and the recurrence rate of tumors is high, resulting in many deaths every year. Traditional radiotherapy and chemotherapy are prone to causing drug resistance and significant side effects. Therefore, searching for new bioactive drugs including anticancer peptides is necessary and urgent. LVTX-8 is a peptide toxin synthesized from the cDNA library of the spider Lycosa vittata, which is consisting of 25 amino acids. In this study, a series of in vitro cell experiments such as cell toxicity, colony formation, and cell migration assays were performed to exam the anticancer activity of LVTX-8 in NPC cells (5-8F and CNE-2). The results suggested that LVTX-8 significantly inhibited cell proliferation and migration of NPC cells. To find the potential molecular targets for the anticancer capability of LVTX-8, high-throughput proteomic and bioinformatics analysis were conducted on NPC cells. The results identified EXOSC1 as a potential target protein with significantly differential expression levels under LVTX-8+/LVTX-8- conditions. The results in this research indicate that spider peptide toxin LVTX-8 exhibits significant anticancer activity in NPC, and EXOSC1 may serve as a target protein for its anticancer activity. These findings provide a reference for the development of new therapeutic drugs for NPC and offer new ideas for the discovery of biomarkers related to NPC diagnosis. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the data set identifier PXD050542.

Impact of Patency of the Carotid Terminus and Middle Cerebral Artery on Early Clinical Outcomes in Patients with Acute Internal Carotid Artery Occlusion and Mild Symptoms

Introduction: Both collateral flow via the internal carotid artery (ICA) terminus (ICT) and initial mild symptoms might be associated with favorable outcomes in patients with acute ICA occlusion (ICAO). This study aimed to address the association between early clinical outcomes and patency of the ICT and middle cerebral artery (MCA) in patients with acute ICAO with mild symptoms. Methods: Of 1,214 consecutive patients with acute ischemic stroke or transient ischemic attack due to large vessel occlusion, patients with ipsilateral ICAO and initial National Institutes of Health Stroke Scale (NIHSS) score ≤5 were retrospectively enrolled. We examined the associations between clinical factors including patency of the ICT and MCA and recurrence of stroke or early neurological deterioration (REND). Significant early neurological deterioration was defined as increment in NIHSS score ≥1 during hospital stay. Results: Thirteen of the 35 patients who were finally enrolled had REND (37%), and median modified Rankin scale (mRS) score at discharge was 1 (interquartile range, 0–4). Initial NIHSS score (4 vs. 1, p < 0.001) and rates of diabetes mellitus (61.5% vs. 13.6%, p = 0.007), intravenous thrombolysis (IVT) (30.9% vs. 0%, p = 0.014), and mechanical thrombectomy (MT) (23.1% vs. 0%, p = 0.044) were significantly higher in patients with REND rather than in those without. The rate of patent ICT and MCA was comparable between groups. Except for 1 patient who underwent MT promptly after IVT immediately after REND, 3 patients initially treated with IVT deteriorated after the procedure. One patient without patent ICT and MCA did not meet the indications for MT. In 2 other patients with patent ICT and MCA, MT was not initially performed, but was eventually performed because of REND due to thrombus migration, and both were discharged with an mRS score of 5. Conclusion: The overall clinical outcomes of patients with acute ICAO with mild symptoms were not depending on the patency of the ICT and MCA, but initial treatment with IVT alone might risk unfavorable outcomes due to thrombus migration in patients with patent ICT and MCA.

"Atypical" Mild Clinical Presentation in Elderly Patients With Ruptured Intracranial Aneurysm: Causes and Clinical Characteristics.

ObjectiveThunderclap-like severe headache or consciousness disturbance is the common “typical” clinical presentation after aneurysmal subarachnoid hemorrhage (aSAH); however, a slowly developing “atypical” clinical pattern, with mild headache, vomiting, or dizziness, is frequently noted in elderly patients. The aim of this study was to evaluate the clinical characteristics of this “atypical” subgroup, as well as related factors associated with the presence of these mild symptoms.MethodsThe data of 176 elderly patients (≥70 years old) with ruptured intracranial aneurysms (IAs) treated at our center from January 2016 to January 2020 were retrospectively collected and analyzed. The patients were divided into “typical” and “atypical” groups based on their initial and development of clinical symptoms after the diagnosis of aSAH. Intergroup differences were analyzed, and factors related to the presence of these two clinical patterns were explored through multiple logistic regression analyses.ResultsDespite significant admission delay (P < 0.001) caused by mild initial symptoms with slow development, patients in the “atypical” group achieved better clinical prognosis, as indicated by a significantly higher favourable outcome ratio and lower death rate upon discharge and at different time points during the 1-year follow-up, than the “typical” group (P < 0.05). Multiple logistic regression analysis revealed that modified Fisher grade III-IV (OR = 11.182, P = 0.003), brain atrophy (OR = 10.010, P = 0.001), a larger lesion diameter (OR = 1.287, P < 0.001) and current smoking (OR = 5.728, P < 0.001) were independently associated with the presence of “typical” symptoms. Aneurysms with wide necks (OR = 0.013, P < 0.001) were independently associated with the presence of “atypical” symptoms.Conclusions“Atypical” presentations, with mild clinical symptoms and slow development, were commonly recorded in elderly patients after the onset of aSAH. Despite the prolonged admission delay, these “atypical” patients achieved better clinical outcomes than those with “typical” symptoms. Modified Fisher grade (III-IV), current smoking, brain atrophy and larger lesion diameter were factors predictive of “typical” symptoms, while aneurysms with wide necks were independently associated with “atypical” symptoms.

The Greek Collaborative Long COVID Study: Non-Hospitalized and Hospitalized Patients Share Similar Symptom Patterns.

Long COVID-19 syndrome refers to persisting symptoms (>12 weeks) after the initial coronavirus infection and is estimated to affect 3% to 12% of people diagnosed with the disease globally. Aim: We conducted a collaborative study with the Long COVID patient organization in Greece, in order to estimate the characteristics, symptoms, and challenges these patients confront. Methods: Data were collected from 208 patients using unstructured qualitative free-text entries in an anonymized online questionnaire. Results: The majority of respondents (68.8%) were not hospitalized and reported lingering symptoms (66.8%) for more than six months. Eighteen different symptoms (fatigue, palpitations, shortness of breath, parosmia, etc.) were mentioned in both hospitalized and community patients. Awareness of Long COVID sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still not included inthe management plan of Long COVID patients. Conclusions: Patients infected with coronavirus with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Long COVID syndrome appears to be a multi-systemic entity and a multidisciplinary medical approach should be adopted in order to correctly diagnose and successfully manage these patients.

Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes

The number of people affected by Type 2 diabetes mellitus (T2DM) is close to half a billion and is on a sharp rise, representing a major and growing public health burden. Given its mild initial symptoms, T2DM is often diagnosed several years after its onset, leaving half of diabetic individuals undiagnosed. While several classical clinical and genetic biomarkers have been identified, improving early diagnosis by exploring other kinds of omics data remains crucial. In this study, we have combined longitudinal data from two population-based cohorts CoLaus and DESIR (comprising in total 493 incident cases vs. 1360 controls) to identify new or confirm previously implicated metabolomic biomarkers predicting T2DM incidence more than 5 years ahead of clinical diagnosis. Our longitudinal data have shown robust evidence for valine, leucine, carnitine and glutamic acid being predictive of future conversion to T2DM. We confirmed the causality of such association for leucine by 2-sample Mendelian randomisation (MR) based on independent data. Our MR approach further identified new metabolites potentially playing a causal role on T2D, including betaine, lysine and mannose. Interestingly, for valine and leucine a strong reverse causal effect was detected, indicating that the genetic predisposition to T2DM may trigger early changes of these metabolites, which appear well-before any clinical symptoms. In addition, our study revealed a reverse causal effect of metabolites such as glutamic acid and alanine. Collectively, these findings indicate that molecular traits linked to the genetic basis of T2DM may be particularly promising early biomarkers.

Bronchiectasis is one of the indicators of severe coronavirus disease 2019 pneumonia.

Bronchiectasis is one of the indicators of severe coronavirus disease 2019 pneumonia.

Looking for fever in nursing home residents with COVID-19: A false friend?

ObjectivesResidents in nursing homes represent a frail, elderly population, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can spread easily in this setting. Despite a frequent severe evolution of coronavirus disease 2019 (COVID-19), these patients often present an atypical course with mild initial symptoms. The aim of this study was to assess the occurrence of fever in elderly patients with COVID-19 residing in nursing homes. MethodsTwo hundred and thirty-one elderly patients from three nursing homes in Pavia and surrounding area were enrolled in April–May 2020. SARS-CoV-2 infection was diagnosed using real-time reverse transcription polymerase chain reaction with nasopharyngeal swab and/or serological assay (LIAISON® SARS-CoV-2 S1/S2 IgG). Patients with a positive result on RT-PCR or serology were classed as positive. ResultsIn total, 170 patients (74%) were SARS-CoV-2-positive on RT-PCR and/or serology, and 61 patients (26%) had negative results on both tests. Fever (body temperature >37.5 °C) was observed in four patients (1.7%): three in the SARS-CoV-2-positive group (1.8%) and one in the SARS-CoV-2-negative group (1.6%). ConclusionsThe prevalence of fever was extremely low in this population of nursing home residents with COVID-19. This finding must be taken into consideration when screening patients without fever in nursing homes.

First Case of 2019 Novel Coronavirus in the United States

SummaryAn outbreak of novel coronavirus (2019-nCoV) that began in Wuhan, China, has spread rapidly, with cases now confirmed in multiple countries. We report the first case of 2019-nCoV infection confirmed in the United States and describe the identification, diagnosis, clinical course, and management of the case, including the patient’s initial mild symptoms at presentation with progression to pneumonia on day 9 of illness. This case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels, as well as the need for rapid dissemination of clinical information related to the care of patients with this emerging infection.

DWI-pc-ASPECT score in basilar artery occlusion: is 6 points or less always indicative of a bad outcome?

The prognosis of patients with acute basilar arterial occlusion after endovascular reperfusion therapy with diffusion-weighted imaging - posterior circulation-Alberta Stroke Program Early Computed Tomography Score (DWI-pc-ASPECTS) of 6 or less remains unclear. We aimed to assess the characteristics and prognosis of endovascular reperfusion therapy in patients with acute basilar arterial occlusion and DWI-pc-ASPECTS of 6 or less. We analysed data collected from 1 January 2012 to 31 January 2018 in a prospective neuro-interventional registry of consecutive patients treated with endovascular reperfusion therapy. Clinical and imaging data on patients with DWI-pc-ASPECTS of 6 or less who underwent endovascular reperfusion therapy for acute basilar arterial occlusion were collected for this study. A good clinical outcome was defined as a modified Rankin scale of 2 or less at 90 days. Forty-five acute basilar arterial occlusion patients with DWI-pc-ASPECTS of 6 or less were included. Among them, 11 (24.4%) patients had a good clinical outcome at 90 days. Patients with a good clinical outcome had less severe neurological symptoms at presentation (National Institutes of Health Stroke Scale (NIHSS) 19.0 (12.0-25.0) vs. 8.0 (6.0-11.5); P = 0.003) and were younger (72.5 years (57.0-80.0 years) vs. 63.0 years (55.5-69.0 years), P = 0.096) than those with a poor clinical outcome. The symptomatic intracranial haemorrhage rate was significantly higher in the poor clinical outcome group (13 (38.2%)) than in the good clinical outcome group (0 (0.0%)) (P = 0.045). In particular, in patients aged over 70 years, a favourable outcome was low (18 (52.9%) vs. 1 (9.1%); P = 0.027) even after successful recanalisation. In a multivariate model, a low initial NIHSS score (odds ratio 1.21; 95% confidence interval 1.07-1.44; P = 0.0093) and age over 70 years (odds ratio 15.27; 95% confidence interval 1.85-379.79; P = 0.0321) were independent predictors of poor clinical outcome. Even with DWI-pc-ASPECTS of 6 or less, good clinical outcome can be achieved after endovascular reperfusion therapy. Relatively mild initial symptoms and younger age can predict a better outcome in acute basilar arterial occlusion patients with DWI-pc-ASPECTS of 6 or less.

Customizing Anaphylaxis Guidelines for Emergency Medicine

BackgroundMost episodes of anaphylaxis are managed in emergency medical settings, where the cardinal signs and symptoms often differ from those observed in the allergy clinic. Data suggest that low recognition of anaphylaxis in the emergency setting may relate to inaccurate coding and lack of a standard, practical definition. ObjectiveDevelop a simple, consistent definition of anaphylaxis for emergency medicine providers, supported by clinically relevant consensus statements. DiscussionDefinitions of anaphylaxis and criteria for diagnosis from current anaphylaxis guidelines were reviewed with regard to their utilization in emergency medical settings. The agreed-upon working definition is: Anaphylaxis is a serious reaction causing a combination of characteristic findings, and which is rapid in onset and may cause death. It is usually due to an allergic reaction but can be non-allergic. The definition is supported by Consensus Statements, each with referenced discussion. For a positive outcome, quick diagnosis and treatment of anaphylaxis are critical. However, even in the emergency setting, the patient may not present with life-threatening symptoms. Because mild initial symptoms can quickly progress to a severe, even fatal, reaction, the first-line treatment for any anaphylaxis episode—regardless of severity—is intramuscular injection of epinephrine into the anterolateral thigh; delaying its administration increases the potential for morbidity and mortality. When a reaction appears as “possible anaphylaxis,” it is generally better to err on the side of caution and administer epinephrine. ConclusionWe believe that this working definition and the supporting Consensus Statements are a first step to better management of anaphylaxis in the emergency medical setting.

Giant Cell Tumor of the Tendon Sheath in the Knee of an 11-year-old Girl

Giant cell tumors are commonly found over the flexor tendon sheath of the hand and wrist. However, giant cell tumors in the knee joint are rare, especially in children. We report an interesting case of an 11-year-old girl who presented with a painful lump on her right knee that enlarged over time. Clinically, she had fullness over the anterolateral part of her knee. Magnetic resonance imaging revealed an encapsulated mass inferior to the patella. The tumor measured 3 x 3.5 x 1.5 cm. Histopathological findings confirmed that it was a tenosynovial giant cell tumor. Because of initial mild symptoms, there was a delay of 2 years from the initial symptoms until tumor excision. Her follow-up period was 35 months, and her health to date is excellent with no recurrence. We believe that reporting this rare case will help clinicians update their knowledge on possible causes of lumps in the knee, and avoid diagnostic delay. It could also prove to be beneficial in arriving at a diagnosis in future cases.

Characteristics of Asthma among Elderly Adults in a Sample of the General Population

This article describes the characteristics and course of asthma among subjects who were older than 65 years at the time of enrollment in a longitudinal study of a general population sample. It was present in 3.8 percent of men and 7.1 percent of women. An additional 4.1 percent of men reported having "asthma," but they also had seen a physician for "emphysema" and had smoked significantly; their "asthma" diagnosis is regarded as highly questionable. They did not show the elevated rate of allergy skin test reactivity of high serum IgE levels that were characteristic of other asthmatics. Many of the elderly asthmatics (mean age, 72 years) had severe disease with marked ventilatory impairment. There was a close relationship between the severity of wheezing complaints and impairment of the FEV1. Of the 46 patients, 48 percent reported an onset before age 40 years. There was no relationship between severity and age of onset or duration of disease. A second diagnosis of "chronic bronchitis" was reported by 46 percent of the asthmatics, but this did not delineate a distinctive group with late-onset, smoking-related disease. Death rates in the asthmatics tended to be higher than in nonasthmatics (odds ratio, 1.9; CI, 0.998 to 3.70, after stratifying by sex). Over a mean follow-up of 7.44 years, most symptoms as well as the FEV1 remained relatively stable. Chronic productive cough did tend to remit (p less than 0.01), but this was noted in the nonasthmatics as well. We estimate that no more than 19 percent of the asthmatics went into complete remission during follow-up. Most of these had mild initial symptoms; there were no remissions in subjects with severe disease at the time of entry. We concluded that asthma in the elderly is not a rare disease and may be associated with severe symptoms and chronic airways obstruction. If severe, it rarely goes into complete remission but tends to remain a severe, disabling disorder.

High-pressure injection injury: A hand-threatening emergency

A variety of tools mounted with high-pressure nozzles cause a typical pattern of hand injuries. Often the relatively mild initial symptoms conceal the actual degree of tissue damage and the need for prompt treatment. As illustrated by a case of dye impression, early extensive surgical exploration and radical removal of the injected agent are mandatory to minimize sequelae and to avoid mutilating complications. Pathophysiology and surgical management of this hand-threatening emergency are outlined.

Transmission of Creutzfeldt-Jakob disease to the stumptail macaque (Macaca arctoides).

The successful transmission of Creutzfeldt-Jakob disease from both affected human and chimpanzee brain to stumptail macaques has been accomplished. The incubation period of 5 yr was the same for both animals; however, the course of the disease was longer in the animal receiving the human brain. In both cases, initial mild symptoms slowly remitted only to reappear some 4 mo later. Muscle biopsies revealed changes suggestive of a mild neuropathy. In addition, there appeared to be an increased ability to incorporate 3H-thymidine in untreated cultures of lymphocytes from peripheral blood.