Days Of Onset Research Articles

Clinical impact of ceftazidime/avibactam on the treatment of suspected or proven infections in a large cohort of patients with haematological malignancies: a multicentre observational real-world study.

To evaluate clinical impact of ceftazidime/avibactam on treating infections due to MDR Gram-negative bacteria in patients with haematological malignancies (HMs). We conducted a retrospective, observational study at 17 Italian haematological wards that included patients with HMs receiving ceftazidime/avibactam for the treatment of suspected or proven infections. The primary endpoint was all-cause mortality 30 days after infection onset. Secondary endpoints included the development of in vitro ceftazidime/avibactam resistance, adverse reactions and infection relapse. Of 198 patients enrolled, 66 had fever of unknown origin and 132 had microbiologically proven infections (MPIs). Enterobacterales were responsible for 98 MPIs, with KPC producers accounting for 75% of these, and carbapenem-resistant Pseudomonas aeruginosa caused 25% of MPIs. The overall 30-day mortality rate was 17.7%. Infection relapse occurred in four patients with MPI. Patients who died within 30 days of infection onset tended to have pre-existing cerebrovascular diseases, a Charlson Comorbidity Index > 4 and septic shock at infection onset and had received inadequate initial antibiotic therapy. Thirty-day mortality was independently associated with septic shock at infection onset and inappropriate initial antibiotic therapy. Our study provides further evidence about the effectiveness of ceftazidime/avibactam in treating infections in patients with HMs.

Therapeutic Potential of Neutralizing Monoclonal Antibodies (nMAbs) against SARS-CoV-2 Omicron Variant.

The COVID-19 pandemic has spurred significant endeavors to devise treatments to combat SARS-CoV-2. A limited array of small-molecule antiviral drugs, specifically monoclonal antibodies and interferon therapy, have been sanctioned to treat COVID-19. These treatments typically necessitate administration within ten days of symptom onset. There have been reported reductions in the effectiveness of these medications due to mutations in non-structural protein genes, particularly against Omicron subvariants. This underscores the pressing requirement for healthcare systems to continually monitor pathogen variability and its impact on the efficacy of prevention and treatments. This review aimed to comprehend the therapeutic benefits and recent progress of nMAbs for preventing and treating the Omicron variant of SARS-CoV-2. Neutralizing monoclonal antibodies (nMAbs) provide a treatment avenue for severely affected individuals, especially those at high risk for whom vaccination is not viable. With their specific epitope affinity, they pose no significant risk of severe adverse effects. The degree of reduction in neutralization varies significantly across different monoclonal antibodies and variant combinations. For instance, Sotrovimab maintained its neutralization effectiveness against Omicron BA.1, but exhibited diminished efficacy against BA.2, BA.4, BA.5, and BA.2.12.1. Bebtelovimab has been observed to preserve its efficacy against all subtypes of the Omicron variant. Subsequently, WKS13, mAb-39, 19n01, F61-d2 cocktail, etc., have become effective. This review has highlighted the therapeutic implications of nMAbs in SARS-CoV-2 Omicron treatment and the progress of COVID-19 drug discovery.

The minimally clinically important difference in the 2-minute walk test for people in the subacute phase after a stroke

ABSTRACT Background The 2-Minute Walk Test (2MWT) is a simple and reliable test used by clinicians to assess gait function in people with stroke (pwST). No studies established the minimal clinically important difference (MCID) of the 2MWT. Objective To determine the MCID of the 2MWT in subacute pwST using data from a longitudinal cohort study. Methods PwST within 180 days of stroke onset were recruited from the Italian National Health System (NHS) rehabilitation services across the country. Participants underwent physical therapy to improve balance and gait according to their specific needs. The 2MWT was used to assess gait performance at the beginning (T0) and after a minimum of 10 rehabilitation sessions (T1). The Global Perceived Effect (GPE), Activities-specific Balance Confidence Scale (ABC) and the ABC_gait were used to assess balance confidence and the perceived effect of the intervention at T1. Results 51 pwST (69 ± 12 years; 66.7% males) were included in the analysis. Statistically significant improvements were observed in 2MWT, ABC, and ABC_gait scores after rehabilitation using the Wilcoxon signed-rank test. Using an anchor-based approach the receiver operating characteristic (ROC) curves were calculated to establish the MCID. The MCID of the 2MWT was 31 meters with an Area under the curve (AUC) = 0.74 [0.60–0.89], a specificity of 71% and a sensitivity of 63%. Conclusions An improvement of 31 meters on the 2MWT can be considered clinically significant in subacute pwST undergoing rehabilitation. This study provides valuable insights for clinicians to assess walking performance in pwST and determine clinically meaningful changes post-rehabilitation.

Cutaneous manifestations and sequelae of Chikungunya fever: a single centre experience

Background: Chikungunya fever is a common viral illness in the tropical and subtropical areas. Various cutaneous manifestations can develop during the acute phase and post-febrile convalescent phase. Objective: To determine the frequency and types of cutaneous manifestations associated with chikungunya fever in acute and post-febrile phase. Methods: We conducted a prospective, observational study including 20 patients with laboratory-confirmed chikungunya fever. All the patients were followed up for 1 year to detect any cutaneous sequelae. Results: Pruritic maculopapular rash was the most common cutaneous manifestation during the acute febrile phase, noted in 60% of the patients. The rash usually appeared within 1–3 days of fever onset and spread in cephalo-caudal direction. Cutaneous hyperpigmentation was the most common dermatologic sequelae in the post-febrile period, occurring in 3 (15%) patients. In all patients, pigmentation appeared 3–4 weeks after resolution of fever, and started on the nose, gradually spreading to the forehead. The pigmentation improved significantly with topical hydroquinone after 4 weeks. Other additional manifestations of chikungunya fever included joint pain and joint swelling. None of our patients presented with mucosal or systemic involvement. Conclusion: Maculopapular skin rash was the most common manifestation during acute febrile phase of chikungunya fever, while cutaneous hyperpigmentation was the most common dermatologic sequelae after resolution of fever.

Ảnh hưởng của bệnh đi kèm trên kết cục đột quỵ thiếu máu não cấp

Background: Comorbidities that help predict poor outcomes in patients with acute ischemic stroke play a part in treatment planning and provide necessary information for patients and their families. Objective: Identify comorbidities that can predict poor outcomes 90 days after the onset of acute ischemic stroke. Subjects and methods: Prospective study including 150 acute ischemic stroke patients at Trieu An Hospital, Ho Chi Minh City. Subjects recruited upon admission were collected NIHSS score and comorbidities. Subjects had modified Rankin scores collected 90 days after disease onset. Univariate analysis and multivariate regression analysis were used to determine the role of variables on stroke outcomes. Results: The mean age was 65, male accounts for 62.0%. There were 8 factors univariately associated with poor outcome after 90 days of acute ischemic stroke onset: NIHSS, age, atrial fibrillation, valvular heart disease, coronary artery disease, heart failure, extracranial atherosclerosis and dementia. Among them, dementia is an independent prognostic factor for poor outcomes through multivariate analysis. The number of comorbidities is closely related to poor outcomes, the number of comorbidities ≥ 3 predicts patients with poor outcomes after 90 days of disease onset with a sensitivity of 96.6%; Specificity was 88.0%; The area under the curve was 96.3%. Conclusion: In acute ischemic stroke patients with comorbidities ≥ 3, the patient's prognosis is poor. In addition, dementia is an independent prognostic factor of poor outcome after 90 days from disease onset.

CLINICAL FEATURES OF COVID-19 INFECTION IN NEWBORNS: A RETROSPECTIVE ANALYSIS

Background. The COVID-19 pandemic has significantly impacted all age groups, including newborns. During the fifth surge, the prevalence of the Omicron variant among infants increased dramatically. While SARS-CoV-2 is generally milder in children than adults, newborns are vulnerable due to their immature immune systems. Clinical manifestations in newborns can range from asymptomatic to severe cases with respiratory distress or multi-organ dysfunction. Purpose of study. Description of clinical manifestations, course and outcomes of coronavirus infection in newborns. Materials and methods of study. A retrospective analysis was conducted on 110 newborns with COVID-19 admitted to the Children’s Clinical Infectious Diseases Hospital of Almaty between 2021 and early 2022. The study used electronic medical records as the source of research data. Demographic data such as age and sex were collected, along with epidemiological data including international or domestic travel within two weeks prior to the onset of the disease, known exposure to a person with positive SARS-CoV-2 infection, and a history of pregnancy. Results. The infants’ mean age was 17 days, with 44 boys (40%) and 66 girls (60%). Four newborns were admitted to the hospital at less than seven days of life. When analyzing the severity of the cases, the following proportions of newborns were observed: (3/110, 2.7%) were asymptomatic, (44/110, 40%) had mild symptoms, (57/110, 51.8%) were moderately severe, (4/110, 3.6%) severe, and (2/110, 1.8%) had very severe illness. The majority (68.4%) were hospitalized within three days of symptom onset. Fever was common, and all infants underwent chest CTs. Despite some severe cases, 99% had favorable outcomes, with only one fatality. Conclusion. This study indicates that most COVID-19 infections in newborns were contracted from household contacts. Clinical symptoms in infants included fever, catarrhal symptoms, and signs of intoxication, with some showing normal temperatures. Laboratory findings varied, with common changes including monocytosis and neutrophilia. Respiratory complications, such as bronchitis and pneumonia, were prevalent. Comorbidities, particularly congenital disorders, increased the risk of severe outcomes and mortality. Most newborns recovered within 1-2 weeks, though viral carriage persisted in many.

The incidence and risk factors of gastrointestinal dysfunction during enteral nutrition in mechanically ventilated critically ill patients.

To assess the occurrence and risk factors of gastrointestinal (GI) dysfunction during enteral nutrition (EN) in critically ill patients supported with mechanical ventilation. Prospective observational study. Totally 252 patients admitted at a mixed medical-surgical ICU were enrolled. GI symptoms and the potential risk variables were recorded during the first 14 days of EN. The incidence of GI dysfunction was 65.5%, and the incidence of diarrhoea, constipation, abdominal distension, and upper GI intolerance was 28.2%, 18.3%, 6.7% and 12.3%, respectively. The median onset days of constipation, diarrhoea, abdominal distension and UDI was 3, 5, 5 and 6 days, respectively. Multivariable Cox regression analysis showed a significant relationship between GI dysfunction and age (HR = 2.321, 95% CI: 1.024-5.264, p = 0.004), APACHE-II score at ICU admission (HR = 7.523, 95% CI: 4.734-12.592, p = 0.018), serum albumin level (HR = 0.594, 95% CI: 0.218-0.889, p = 0.041), multidrug-resistant bacteria-positive culture (HR = 6.924, 95% CI: 4.612-10.276, p<0.001), negative fluid balance (HR = 0.725, 95% CI: 0.473-0.926, p = 0.037), use of vasopressor drugs (HR = 1.642, 95% CI: 1.297-3.178, p<0.001), EN way (HR = 6.312, 95% CI: 5.143-11.836, p<0.001), infusion rate (HR = 1.947, 95% CI: 1.135-3.339, p<0.001), and intra-abdominal hypertension (HR = 3.864, 95% CI: 2.360-5.839, p<0.001). Critically ill patients supported with mechanical ventilation are at a high risk of GI dysfunction. Interventions such as the use of laxatives or prokinetic agents, control of EN infusion rate, and maintaining a normal state of hydration, might be beneficial for the prevention of GI dysfunction in critically ill patients. No.

Non-invasive SARS-CoV-2 RNA detection and human transcriptome analysis using skin surface lipids

There have been several reports of skin manifestations in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected on the skin surface, including the sebum, of these patients. In this study, SARS-CoV-2 RNA was detected using real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of skin surface lipids (SSLs) collected using an oil-blotting film from the faces of hospitalized patients with COVID-19. Human transcriptome analysis was also performed using the same samples. In facial SSLs of patients with COVID-19, the RT-PCR positivity rate was 84.6% (11/13 samples) within 5 days and 30.4% (7/23 samples) by 6–10 days of symptom onset. In the transcriptome analysis, the most characteristic SSL-RNA profile was the upregulation of interferon-stimulated gene (ISG)-related genes, such as ISG15, IFITM1, and MX1. This study presents an alternative technique using SSLs for non-invasive SARS-CoV-2 RNA detection and simultaneous analysis of human molecular pathogenesis in patients with COVID-19.

Circadian rhythm in atrial fibrillation detected by implantable loop recorder: a post-hoc analysis of a randomized clinical trial

Abstract Introduction Previous studies suggest the existence of circadian, weekly, and seasonal rhythms in the occurrence of atrial fibrillation (AF), which may be utilized to improve the yield of screening. The heterogeneity of AF natural history also necessitates better phenotyping to overcome the challenges of identifying candidates for screening and treatment. Purpose To explore the potential circadian rhythm in AF occurrence in persons without known arrhythmia but at high risk of AF and stroke. Methods Post-hoc analysis of the LOOP study (Atrial Fibrillation Detected by Continuous Electrocardiogram Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), which randomized 6004 AF naïve participants (≥70 years old with additional stroke risk factors) 1:3 to receive implantable loop recorder screening or usual care. All loop recorder data was extracted to obtain the date and time of AF episode onset, AF duration, mean and max heart rate (HR) during AF, and symptom annotations. New-onset AF episodes lasting ≥6 minutes were adjudicated, and all subsequent episodes were included in the analysis. Results A total of 41,713 AF episodes (median duration 18 (8-64) minutes) were identified among 430 participants (Table 1). The median number of episodes for each participant with AF was 21 (4-82) and the median AF burden was 0.17% (0.04%-0.83%) of time from debut to end of monitoring. The most and least frequent days of AF onset were Sunday (15.3%) and Friday (13.6%), respectively, while AF occurred slightly more often during spring (26%) than in other seasons. The median time of onset was 09:57:15 AM (05:15:30 AM – 03:33:00 PM). The most frequent time of onset was at 09:00 AM (rounded to the nearest hour), which was two times more likely than at 09:00 PM, and 22% of all episodes occurred between 08:00 and 11:00 AM (Figure 1). A total of 25,329 (61%) episodes occurred between midnight and noon (AM). Nocturnal episodes, defined as episodes with onset between 10:00 PM and 07:00 AM, occurred in 368 (86%) AF participants and constituted a median of 40% of all episodes and 37% (14%-63%) of each participant’s episodes. The median duration of nocturnal episodes was 28 (10-104) minutes compared to 14 (8-44) minutes for daytime episodes. The averaged heart rate during AF was 81 (71-96) beats per minute (BPM), while 330 (77%) participants had AF episodes with heart rates equal to or above 100 BPM, and the duration of these episodes was 50 (15-201) minutes compared to 30 (21-85) minutes for slower episodes (below 100 BPM). Conclusion A circadian pattern was observed for screening-detected AF. AF onset occurred predominantly between 08:00 and 11:00 AM, representing more than one in five episodes. Nocturnal AF occurred in most participants with AF and accounted for almost half of all episodes, while these episodes also lasted longer than daytime episodes. This may warrant future studies investigating the timing of AF screening.

‘Freeze the measles’: how to improve backward tracing with a new digital tool

Abstract Background A measles outbreak occurred in Tuscany, between January and April 2024. There were 37 cases (Incidence: 40,5 per million) with 32 cases (24 confirmed) in the Health District of Pisa. Even if bidirectional tracing showed a better effectiveness in pandemics, there aren’t ready-to-use standardized tools for backward tracing. Methods Pisa Public Health Unit created a digital tool based on a spreadsheet and called “Freeze the measles” which records measles cases and the locations where they passed through (hotspots). These were uploaded on a cloud shared with all the tracers. Hotspots have an expiry date of 21 days. Hotspots and home address case were plotted on a digital map. In a new investigation, tracers could find out if the case visited some hotspots before getting sick and check the distance between home address and hotspots, reducing recall bias. Every case was interviewed about 21 days before rash onset (backward) and plus or minus 4 days of rash onset (forward). The tool matched data to identify contacts and exposure. Results Since the index case wasn’t found, the first 5 unrelated cases were considered index cases for this outbreak. Second and third wave involved 17 cases. The tool allows to find an epidemiological link for 16 of them, while 1 case remained unrelated. A super-spreader was identified with 12 secondary cases occurred at hospital emergency room (7), at a near home minimarket (4) and in a large furniture store (1). In second and third waves, tool was able to link 94% of cases. 2 additional cases were imported. When the last hotspot became frozen without new cases occurring, the outbreak was considered ended. The outbreak lasted 33 days. Conclusions The “Freeze the measles” tool allows to identify transmission chains through an interactive map built on cases and their mobility. Key messages • Contact tracing needs an appropriate backward investigation to be more effective. • New digital tools as ‘Freeze the measles’ could improve preparedness and management of outbreaks.

What is the impact of acute endocrine and metabolic alterations on long-term ischemic stroke prognosis: a prospective study

BackgroundPost-stroke stress can trigger instant survival but its influence on long-term ischemic stroke outcomes remains controversial. Thus, we sought to explore the associations of acute post-stroke stress evidenced by endocrine and metabolic changes, with long-term ischemic stroke outcomes.MethodsAdmissions for acute ischemic stroke within seven days of onset were prospectively recruited to determine acute endocrine and metabolic variations measured by thyroid parameters and the stress hyperglycemia ratio (SHR). Long-term ischemic stroke prognoses were followed up for one year, with the primary outcome being a modified Rankin Scale score of 3 to 6.ResultsA total of 887 patients were enrolled, of which 535 reached the final one-year followed up at a poor prognosis rate of 29.3%. Patients with poor outcomes were observed to have lower levels of free triiodothyronine (fT3) and higher levels of SHR on admission. Medium values (fT3, 4.4 mmol/L; SHR, 8 nmol/L) were used to divide patients into four gradient stress degrees. Larger acute endocrine and metabolic variations (fT3 < 4.4 mmol/L and SHR ≥ 8 nmol/L) were independently associated with a poor one-year prognosis (adjusted OR = 4.231, P = 0.001).ConclusionsHigh degrees of acute post-stroke stress may aggravate long-term ischemic stroke prognosis and timely stress-reduced interventions may help promote post-stroke living quality is equally important as survival.

Effect of Sarcopenia on Functional Recovery in Acute Stroke Patients Admitted for Standard Rehabilitation Program.

Background and Objectives: Sarcopenia is a significant concern in stroke rehabilitation, with a high prevalence reported in acute stroke patients. This study examines the effect of sarcopenia on rehabilitation outcomes in acute stroke patients. Materials and Methods: This study was conducted with acute stroke patients admitted within 90 days of onset to the rehabilitation hospital. Participants were divided into a stroke with sarcopenia group and a stroke without sarcopenia group. Evaluations were conducted at baseline, 4 weeks, and 8 weeks, including the following assessments: manual muscle testing (MMT), Berg Balance Scale (BBS), functional ambulation category (FAC), and Modified Barthel Index (MBI). Both groups received an identical rehabilitation program for 8 weeks. Results: Significant within-group improvements were observed in both groups across all measures (p < 0.05). However, the stroke with sarcopenia group showed significantly less improvement in MMT, BBS, FAC, and MBI compared to the stroke without sarcopenia group at both 4 and 8 weeks (p < 0.05). Conclusions: These results underscore the significant impact of sarcopenia on functional recovery in stroke patients, despite both groups receiving identical rehabilitation programs. The presence of sarcopenia was a critical predictor of poorer outcomes in muscle strength, balance, ambulation, and activities of daily living. Given these findings, specific rehabilitation strategies targeting sarcopenia are needed to improve recovery in stroke patients. Future research should include larger sample sizes, longer follow-ups, and sarcopenic patient-specific rehabilitation programs.

A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of Tongmai Yangxin pill on ventricular remodeling in acute anterior STEMI patients after primary PCI

BackgroundAcute ST-segment elevation myocardial infarction (STEMI) is a severe form of coronary heart disease and a leading cause of mortality and morbidity. This can mainly be ascribed to adverse ventricular remodeling (VR). However, the efficacy of existing treatment strategies for STEMI is not entirely satisfactory. Tongmai Yangxin Pill (TMYX), a patented traditional Chinese medicine (TCM), has been approved for treating various cardiovascular diseases. PurposeThe purpose was to assess the effect of TMYX on VR in acute STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Study DesignA multicenter, randomized, double-blinded, and placebo-controlled trial conducted across 11 hospitals in China. MethodA total of 270 patients with acute anterior STEMI, undergoing PPCI within 10 days of symptom onset were enrolled and randomly assigned to receive either a placebo or TMYX, in addition to guideline-directed treatments for STEMI. The primary endpoint was a change in left ventricular end-diastolic volume index (LVEDVI) at 12 weeks. ResultAmong the 270 randomized patients, 218 (TMYX: 109 and placebo: 109) were included in the per-protocol analysis. At 4 and 12 weeks, TXMY significantly improved LVEDVI than the placebo group ([-2.17(-9.24, 8.28) vs. 3.76(-2.38, 11.48), p < 0.05] and [-1.17 (-12.19, 12.88) vs. 4.46 (-2.89, 11.99), p < 0.05]). Changes in left ventricular end-diastolic volume (LVEDV) at 4 weeks were superior in the TMYX group than the placebo group (-4.37 (-17, 13.99) vs. 7.41 (-4.56, 21.79), p < 0.05). Cardiac magnetic resonance imaging (CMRI) showed that left ventricular ejection fraction (LVEF) was significantly greater in the TMYX group than in the placebo group at 4 weeks. There were no statistically significant differences between groups for left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), 6 min walking distance (6MWD), and major adverse cardiac and cerebrovascular events (MACCEs) (p > 0.05). ConclusionTMYX, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly delayed VR in patients with acute anterior STEMI undergoing PPCI within 10 days of symptom onset.

Tissue Plasminogen Activator or Perfluoropropane for Submacular Hemorrhage in Age-Related Macular Degeneration

Evidence is limited to support therapies to treat submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD) as an adjunct to anti-vascular endothelial growth factor therapy (anti-VEGF). To determine if intravitreal tissue plasminogen activator (TPA) or gas improves visual acuity or promotes resolution of SMH secondary to neovascular AMD in eyes treated with ranibizumab. This was a double-masked, sham-controlled, factorial randomized clinical trial and feasibility study that recruited participants from June 2014 to March 2019, with 12 months' follow-up. Included in the trial were patients from 4 UK vitreoretinal units who had fovea-involving SMH of at least 1 disc area secondary to neovascular AMD and were evaluated within 14 days of onset. Study eyes received baseline ranibizumab and were then randomized 2:1:1:1 to 1 of 4 intravitreal treatments: sham injection, perfluoropropane (C3F8), TPA, or combined C3F8 and TPA (C3F8 + TPA). All eyes received monthly pro re nata ranibizumab therapy over 12 months. Outcome assessors were masked to intervention assignment. Best-corrected visual acuity (BCVA) at month 3. Fifty-three of 56 participants (95%; mean [SD] age, 81.5 [8.1] years; 33 female [59%]) reached the primary end point. Study eyes were randomized to the following intravitreal treatments: sham injection (n = 23), C3F8 (n = 11), TPA (n = 11), or C3F8 + TPA (n = 11). On factorial analysis, the combined TPA groups had significantly better month 3 mean logMAR BCVA than those not receiving TPA: 0.66 vs 0.98 (μd = -0.32; 95% CI, -0.58 to -0.07; P = .02). There was no statistically significant difference comparing groups that did vs did not receive C3F8: 0.80 vs 0.90 (μd = -0.11; 95% CI, -0.37 to 0.16; P = .43). The combined TPA groups were less likely to have SMH present at month 1 (10 of 18 [55.6%] vs 21 of 24 [87.5%]; P = .03), a benefit not evident in the combined gas groups. The mean logMAR BCVA at 3 months was not significantly different between the groups: monotherapy control, 0.99; C3F8, 0.97 (vs control μd = -0.02; 95% CI, -0.48 to 0.44); TPA, 0.70 (vs control μd = -0.29; 95% CI, -0.79 to 0.21); combined C3F8 and TPA, 0.71 (vs control μd = -0.36; 95% CI, -0.82 to 0.11); P = .11. No safety differences were identified across the treatment groups. Results of this randomized clinical trial suggest that TPA may increase the chance of visual acuity gain when added to ranibizumab therapy for neovascular AMD in eyes with SMH, warranting consideration of additional clinical trials. ClinicalTrials.gov Identifier: NCT01835067.

Bloodletting for Acute Stroke Recovery: A Systematic Review and Meta-Analysis.

Bloodletting is a non-pharmacological treatment commonly used for acute stroke in traditional East Asian medicine. This study evaluated the efficacy and safety of bloodletting in acute stroke recovery. We conducted a comprehensive search of eight electronic databases up to 4 June 2024 to identify relevant randomized controlled trials (RCTs). Review Manager 5.4 was used for the meta-analysis, with methodological quality assessed using the Cochrane Risk of Bias 2 tool and the GRADE approach. Seventeen RCTs were included in this meta-analysis. The bloodletting group showed statistically significant improvements in neurological deficits compared to the non-bloodletting group, as measured using the National Institutes of Health Stroke Scale (mean difference [MD]: -2.08, 95% confidence interval [CI]: -3.13 to -1.02) and the treatment effective rate (risk ratio: 1.17, 95% CI: 1.11 to 1.22). Motor function also improved significantly in both upper (Fugl-Meyer Assessment, MD: 12.20, 95% CI: 9.67 to 14.73) and lower extremities (MD: 3.86, 95% CI: 2.16 to 5.56). The effect on daily living activities was not significant overall, but benefits were observed in patients treated within three days of stroke onset (Barthel Index, standardized MD: 0.85, 95% CI: 0.01 to 1.69). No significant differences in the frequency of adverse events were observed between the groups. Bloodletting may be an effective and safe adjunctive therapy for patients with acute stroke receiving conventional Western medical treatment. However, further research is necessary because of the small sample sizes and low quality of the included studies.

Incidence and risk factors of post-stroke seizure among ischemic stroke patients

BackgroundPost-stroke seizure (PSS) increases morbidity and mortality after ischemic stroke, but a comprehensive understanding of its incidence and risk factors is lacking. We report the rate and risk factors of PSS at a single institution. MethodsA retrospective cohort study of adult acute ischemic stroke patients between 2018 and 2022 at a comprehensive stroke center was conducted. Patients with a history of seizures, additional stroke during index admission, or death within 7 days of stroke onset were excluded. Early PSS was defined as a new seizure occurring ≤7 days after stroke onset, while late PSS occurred >7 days after stroke onset. Multivariable logistic regression and cox proportional hazard analysis was conducted. Results1211 participants met inclusion criteria. Patients were a mean age of 67.82 and were primarily male (58.7 %), white (72.6 %), and non-Hispanic (91.9 %). Incidence of PSS was 8.8 % (n = 106), of which 53.8 % (n = 57) were early and 46.2 % (n = 49) were late. Bivariate analysis identified younger age, diabetes, baseline National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early Computed Tomography Score ≤5, cortical involvement, and hemorrhagic transformation as significant in the development of PSS. Multivariable cox proportional hazard analysis identified cortical involvement (hazard ratio [HR]: 2.31, 95 % confidence interval [CI] [1,29, 4.14]), NIHSS ≥ 21 (HR: 1.82, 95 % CI [1.02, 3.22]),and younger age (HR: 0.97, 95 % CI [0.96, 0.98]) as significant PSS predictors. ConclusionPSS occurred in 8.8 % of patients presenting with ischemic stroke. Hemorrhagic transformation, cortical involvement, high NIHSS, and younger age were significant predictors of PSS.

Outcomes and Healthcare Resource Utilization in Patients with COVID-19 Treated with Nirmatrelvir-Ritonavir: Real-World Data Analysis.

Background: Nirmatrelvir-ritonavir was granted emergency use authorization in Israel in January 2022 to treat high-risk patients with mild-to-moderate COVID-19. The aim of the study was to assess the association between nirmatrelvir-ritonavir treatment and COVID-19-related hospitalization and healthcare resource utilization (HCRU) in a country with a high level of vaccinations compared to patients who were offered treatment and declined. Methods: The Maccabi Healthcare Services dataset was used to identify high-risk SARS-CoV-2-positive adults from January to February 2022 who received nirmatrelvir-ritonavir within 5 days of symptom onset (treatment group) or who were offered nirmatrelvir-ritonavir treatment and declined it (reference group). COVID-19-related hospitalizations and all-cause mortality and HCRU within 30 days were compared between treatment and reference groups using inverse probability of treatment weighting. Results: Treatment and reference groups included 3460 (median age, 68.4 years) and 1654 (70.2 years) patients, respectively. Patients with ≥1 dose of COVID-19 vaccine accounted for 89.5% (treatment group) and 72.1% (reference group) of the total. Treatment was associated with a lower risk of COVID-19-related hospitalization (adjusted OR, 0.59 [95% CI, 0.41,0.83]). Results were similar by age group (18-64/≥65 years) and among patients with/without vaccination in the prior 180 days. There were 11 (0.3%) versus 11 (0.7%) deaths in the treatment and reference groups, respectively. Treated patients had lower inpatient HCRU and greater less intensive outpatient HCRU (e.g., telemedicine and emergency room visits). Conclusions: Nirmatrelvir-ritonavir treatment was associated with a reduced risk of COVID-19-related hospitalization and a shift to less intensive outpatient HCRU. Comparison with a reference group of nirmatrelvir-ritonavir-eligible patients who declined treatment enabled an unbiased outcome assessment. Real-world data gathered during the Omicron BA.1 variant wave of COVID-19 in Israel support the continued use of nirmatrelvir-ritonavir for high-risk adults of all ages, regardless of previous vaccinations.

Epidemiological study of the relationship between meteorological factors and onset of acute aortic dissection in Japan.

Several factors influence the onset of acute aortic dissection (AAD). However, few studies have examined AAD onset, weather conditions, and meteorological factors in Japan. This study aimed to identify meteorological factors associated with the onset of AAD in Japan. In this self-controlled study, patients diagnosed with AAD onset from May 1, 2012, to April 30, 2021, at Shizuoka City Shizuoka Hospital (Shizuoka, Japan) were included. Meteorological data from the Shizuoka District Meteorological Office were used. Control days were randomly selected from a 29-day period centered on the day of onset. Conditional logistic regression models were used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for the onset of AAD relative to the control day due to changes in meteorological factors. In total, 538 patients were included. The meteorological factors associated with the onset of AAD were identified as the daily mean temperature (OR = 1.10; 95% CI = 1.04-1.16), daily minimum temperature (OR = 1.09; 95% CI = 1.03-1.14), daily maximum temperature (OR = 1.05; 95% CI = 1.00-1.10), and the mean of the daily mean temperatures for the previous 7 days (OR = 1.17; 95% CI = 1.07-1.28) with a 1°C decrease in the temperature. The results of this study are expected to help raise awareness in clinical practice and among the general public about the increased risk of AAD associated with a drop in temperature.

Effectiveness of remdesivir in patients with COVID-19 and severe renal insufficiency: a nationwide cohort study in Japan

Background The effectiveness of remdesivir in patients with coronavirus disease 2019 (COVID-19) and severe renal insufficiency remains underexplored. Objectives To evaluate whether remdesivir reduces the risk of mortality or invasive mechanical ventilation/extracorporeal membrane oxygenation (IMV/ECMO) in this population. Methods This retrospective observational study utilising the COVID-19 Registry Japan (COVIREGI-JP) included noncritical patients with COVID-19 and severe renal insufficiency (defined as serum creatinine levels ≥3 mg/dL, on maintenance dialysis, or kidney transplant recipients) admitted to Japanese hospitals within 7 days of symptom onset between January 1, 2020 and May 8, 2023. Patients were classified into the remdesivir group if remdesivir was initiated within the first 2 days of admission. We estimated the multivariable-adjusted hazard ratio (HR) for mortality and initiation of IMV/ECMO using landmark analysis to address immortal time bias. Results Among the 1,449 patients included in the landmark analysis (median age, 74 years [interquartile range 62–84 years]; 992 [68.5%] were male), 272 initiated remdesivir within the first 2 days of admission. During the 28 days from the landmark timepoint, 19 (7.0%) and 136 (11.6%) patients in the remdesivir and control groups, respectively, had an outcome. The remdesivir group had a lower risk of mortality or IMV/ECMO initiation than the control group (adjusted HR, 0.44; 95% confidence interval, 0.23–0.83). Conclusions In noncritical patients with COVID-19 and severe renal insufficiency at admission, initiating remdesivir early after disease onset, within the first 2 days of admission, led to a lower risk of mortality or IMV/ECMO initiation, compared with non-initiation of remdesivir.

Expression of microRNA-21 in acute ischemic stroke: relationship with inflammatory cytokines, clinical severity, and clinical outcome

Background When the brain is deprived of oxygen and nutrients due to stenosis or arterial rupture, neurons in the affected area suffer irreversible damage and cellular death. MicroRNA has been shown to regulate target genes implicated in arterial hypertension, atherosclerosis, and diabetes mellitus, all of which influence the risk of ischemic stroke through inflammation, oxidative stress, cell proliferation, and apoptosis. The study aims to determine the changes in miRNA expression, namely miRNA-21, between acute ischemic stroke patients and controls and their relationship to proinflammatory cytokines, clinical severity, and outcome. Methods Serum samples from tertiary hospitals and controls were used to evaluate miRNA-21 expression as well as cytokines TNF-α, IL-10, ICAM-1, and CCL5 levels within 7 days of stroke onset. The 30-day clinical severity and outcome were assessed using the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), respectively. Result A total of 64 acute ischemic stroke patients and 22 age-matched controls were recruited, with median ages of 56 and 55.5 years old, respectively. There were more male subjects than females (35 to 29). A statistically significant difference was observed in miRNA-21 expression between patients and controls (p&lt;0.001). This finding implies that miRNA-21 expression may have a contribution in acute stroke patients. This was followed by an increase in proinflammatory markers TNF-α, IL-10, ICAM-1, and CCL5. However, no association was found between miRNA-21 and any pro-inflammatory cytokine. There was no significant correlation between miRNA-21 or cytokines markers with clinical severity or prognosis. Conclusion Our study demonstrated increased miRNA-21 expression and proinflammatory cytokine expression in acute ischemic stroke patients relative to controls. However, this was not related to clinical severity or clinical outcomes.