Acute Phase Research Articles

Analysis of the expression characteristics and clinical value of immune function indicators in patients with human immunodeficiency virus infection

Objective: To explore the expression characteristics and clinical value of immune function indicators in patients with human immunodeficiency virus (HIV) infection. Methods: In this retrospective study, clinical data of 196 patients with HIV infection (observation group) and 196 health examinees (control group) admitted to our hospital from November 2021 to March 2023 were retrospectively analyzed. Patients in the observation group were further classified based on the staging as acute phase (n=53), asymptomatic phase (n=65), and acquired immunodeficiency (AIDS) phase (n=78). Levels of immune function indicators in the observation group and the control group were compared, and the correlation between immune function index levels and disease staging was analyzed. Results: Levels of CD3+, CD4+, CD4+/CD8+, B cells, and NK cells were lower in the observation group (P<0.05), were significantly lower in asymptomatic patients compared with patients in the acute phase (P<0.05), and were significantly lower in patients with AIDS than those in asymptomatic patients (P<0.05). The results for CD8+ were in contrast to the above(P<0.05). Spearman analysis confirmed that levels of CD3+, CD4+, CD4+/CD8+, B cells and NK cells significantly negatively correlated, and levels of CD8+ significantly positively correlated with the stages of HIV (P<0.05). Conclusions: The immune function indicators of patients with HIV infection are markedly abnormal, which is mainly manifested by the decreased levels of CD3+, CD4+, CD4+/CD8+, B cells and NK cells, and the increased levels of CD8+. The profile of the immune function indicators correlates with the progressive severity of the disease. doi: https://doi.org/10.12669/pjms.40.10.9895 How to cite this: Wang N, Zeng T. Analysis of the expression characteristics and clinical value of immune function indicators in patients with human immunodeficiency virus infection. Pak J Med Sci. 2024;40(10):2233-2237. doi: https://doi.org/10.12669/pjms.40.10.9895 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Study protocol: Cerebral autoregulation, brain perfusion, and neurocognitive outcomes after traumatic brain injury -CAPCOG-TBI.

Moderate-severe traumatic brain injury (msTBI) stands as a prominent etiology of adult disability, with increased risk for cognitive impairment and dementia. Although some recovery often occurs within the first year post-injury, predicting long-term cognitive outcomes remains challenging, partly due to the significant pathophysiological heterogeneity of TBI, including acute cerebrovascular injury. The primary aim of our recently funded study, cerebral autoregulation, brain perfusion, and neurocognitive outcomes after traumatic brain injury (CAPCOG-TBI), is to determine if acute cerebrovascular dysfunction after msTBI measured using multimodal non-invasive neuromonitoring is associated with cognitive outcome at 1-year post-injury. This longitudinal observational study will be conducted at two Level 1 trauma centers in Texas, USA, and will include adult patients with msTBI, and/or mild TBI with neuroimaging abnormalities. Multimodal cerebral vascular assessment using transcranial Doppler and cerebral near-infrared spectroscopy (NIRS) will be conducted within 7-days of onset of TBI. Longitudinal outcomes, including cognitive/functional assessments (Glasgow Outcome Scale and Patient-Reported Outcomes Measurement Information System), cerebral vascular assessment, and imaging will be performed at follow-ups 3-, 6-, and 12-months post-injury. We aim to recruit 100 subjects with msTBI along with 30 orthopedic trauma controls (OTC). This study is funded by National Institute of Neurological Disease and Stroke (NINDS) and is registered on Clinicaltrial.org (NCT06480838). We anticipate that msTBI patients will exhibit impaired cerebrovascular function in the acute phase compared to the OTC group. The severity of cerebrovascular dysfunction during this stage is expected to inversely correlate with cognitive and functional outcomes at 1-year post-injury. Additionally, recovery from cerebrovascular dysfunction is expected to be linked to cognitive recovery. The results of this study could help to understand the contribution of cerebrovascular dysfunction to cognitive outcomes after TBI and pave the way for innovative vascular-focused interventions aimed at enhancing cognitive recovery and mitigating neurodegeneration following msTB. In addition, its focus toward personalized medicine to aid in the management and prognosis of TBI patients.

Epigenetic trajectory predicts development of clinical rheumatoid arthritis in ACPA+ individuals: Targeting Immune Responses for Prevention of Rheumatoid Arthritis (TIP-RA).

The presence of autoantibodies to citrullinated protein antigens (ACPAs) in the absence of clinically-apparent inflammatory arthritis (IA) identifies individuals "at-risk" for developing future clinical rheumatoid arthritis (RA). However, it is unclear why some ACPA+ individuals convert to clinical RA while others do not. We explored the possibility in the Targeting Immune Responses for Prevention of Rheumatoid Arthritis (TIP-RA) study that epigenetic remodeling is part of the trajectory from an at-risk state to clinical disease and identifies novel biomarkers associated with conversion to clinical RA. ACPA-Controls, ACPA+ At-Risk, and Early RA individuals were followed for up to 5 years, including obtaining blood samples annually and at RA diagnosis. Peripheral blood mononuclear cells (PBMCs) were separated into CD19+ B cells, memory CD4+ T cells, and naïve CD4+ T cells using antibodies and magnetic beads. Genome-wide methylation within each cell lineage was assayed using the Illumina MethylationEPIC v1.0 beadchip. ACPA+ At-Risk participants who did or did not develop RA were designated "Pre-RA" or "Non-converters", respectively.Differentially methylated loci (DML) were selected using the Limma software package. Using the Caret package, we constructed machine learning models in test and validation cohorts and identified the most predictive loci of clinical RA conversion. Cross-sectional differential methylation analysis at baseline revealed DMLs that distinguish the Pre-RA methylome from ACPA+ Non-converters, the latter which closely resembled ACPA-Controls. Genes overlapping these DMLs correspond to aberrant NOTCH signaling and DNA repair pathways in B cells. Longitudinal analysis showed that ACPA-Control and ACPA+ Non-converter methylomes are relatively constant. In contrast, the Pre-RA methylome remodeled along a dynamic "RA methylome trajectory" characterized by epigenetic changes in active regulatory elements. Clinical conversion to RA, defined based on diagnosis, marked an epigenetic inflection point for cell cycle pathways in B cells and adaptive immunity pathways in naïve T cells. Machine learning revealed individual loci associated with RA conversion. This model significantly outperformed autoantibodies plus acute phase reactants as predictors of RA conversion. DNA methylation is a dynamic process in ACPA+ individuals at-risk for developing RA that eventually transition to clinical disease. In contrast, non-converters and controls have stable methylomes. The accumulation of epigenetic marks over time prior to conversion to clinical RA conforms to pathways that are associated with immunity and can be used to identify potential pathogenic pathways for therapeutic targeting and/or use as prognostic biomarkers.

The Relationship between Plasminogen Activator Inhibitors and the Severity of COVID-19

The fibrinolysis process is assisted by plasminogen activators and inhibitors by converting plasminogen into plasmin, which later will promote the fibrinolysis process. Incomplete fibrinolysis increases the risk of thrombosis in patients with COVID-19. Plasminogen Activator Inhibitor (PAI-1) plays an important role as acute phase reactants to be used as a marker to assess the prognosis and mortality of COVID-19 patients. This study aimed to elaborate on whether fibrinolysis shutdown occurs in COVID-19 patients using PAI-1 as a marker of fibrinolysis. This was a cross-sectional analytical study from November 2022 to May 2023. This research consisted of a total of 39 patients with COVID-19, hospitalized at Haji Adam Malik General Hospital, Medan. PAI-test in COVID-19 patients was carried out with the ELISA method using Chemwell Analyzer. The severity of COVID-19 measured by clinical examination was divided into moderate, severe, and critical. The association between the two variables was subjected to a comparative test followed by a correlation test to explore the association between the two variables with an independent T-test. In this study, the median PAI-1 level was 1.77 ng/mL (0.71–11.49 ng/mL). The highest PAI-1 levels were observed in the critical severity group, followed by the severe and moderate group of 8.54 ng/mL (5.76–10.84), 2.45 ng/mL (0.71–11.49), and 1.29 ng/mL (0.73–3.77), respectively. There was a significant relationship between PAI-1 levels and the severity of COVID-19 patients (p=0.003). PAI-1 cut-off value of 1.89 ng/mL may predict the degree of COVID-19 severity with sensitivity of 88.9%, specificity of 90.5%, and accuracy of 89.7%. This study classified the severity of COVID-19 into two categories, which are moderate (n=21) and severe-critical (n=18) to obtain the AUC value of PAI-1. PAI-1 can be used to predict the severity of COVID-19 disease with a moderate level (AUC >70–80%). This phenomenon can be secondary to enhanced platelet aggregation, inflammation micro thrombosis, and impaired fibrinolysis. Fibrinolysis disorders lead to a fibrin buildup and increased levels of PAI-1 in the circulation.

Evaluation of coinfection between SARS-CoV-2 and dengue virus in São Luís/MA

The COVID-19 pandemic has become a global public health emergency, especially in subtropical regions endemic for arboviruses. During the acute phase of the disease, Dengue and COVID-19 present similar laboratory profiles and symptomatology, complicating clinical diagnosis. This study analyzed the occurrence of coinfections between dengue virus and SARS-CoV-2 in patients treated at a laboratory in São Luís, Maranhão. A total of 150 random serum samples from patients, collected between April and May 2020, tested positive for IgM/IgA antibodies against SARS-CoV-2. For the detection of dengue virus (DENV), reactions were standardized using specific primers for each serotype (1-4). Subsequently, cDNA amplification was performed by conventional PCR, and the amplicons were analyzed by agarose gel electrophoresis. Through this study, it was possible to identify one sample (0.6%) positive for the DENV-4 serotype. This study validates the possibility of coinfections in dengue-endemic areas.

Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction.

Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion. Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins. We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage. Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.

The Effect of Lower Limb Combined Neuromuscular Electrical Stimulation on Skeletal Muscle Cross-Sectional Area and Inflammatory Signaling.

In individuals with a spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre- and post-intervention. The results suggest a potential preservation of muscle CSA in the Comb-NMES group compared to a control group. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study's findings suggest that early application of Comb-NMES post-SCI may attenuate inflammatory pathways linked to muscle atrophy and promote muscle repair. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.

An investigation on choroidal and retinal thickness alterations in Posner-Schlossman syndrome patients

BackgroundWe aimed to compare choroidal thickness (ChT) and retinal nerve fiber layer (RNFL) thickness in the affected and contralateral eyes of patients with Posner-Schlossman Syndrome (PSS) during acute, remission, and intermittent phases.MethodsThis prospective observational study included 18 patients(36 eyes) diagnosed with PSS. These patients underwent a comprehensive ophthalmologic evaluation including slit lamp examination, visual acuity testing, intraocular pressure (IOP) measurement, and funduscopic examination, and assessment of RNFL thickness, macular thickness, and macular ChT. Patient data collected included gender, age, number of keratic precipitates (KPs), and number of episodes. Optical coherence tomography (OCT) was used to measure RNFL thickness, macular thickness, and macular ChT in both eyes during the acute, remission, and intermittent phases. The affected eye was compared with the unaffected eye at each phase.ResultsIn affected eyes, macular ChT was lower in the acute phase compared to the remission phase at N1500, N1000, N500, and subfoveal locations (allp < 0.05).The central macular recess ChT was also significantly thinner in the acute phase compared to the intermittent and remission phases. Age significantly correlated with ChT in the central recess (p = .024). Macular thickness was thinner during the acute phase in the affected eye (p = .048). The RNFL in the affected eye was thinner in the intermittent phase than in the acute phase at the inferior-temporal (p = .011) and global sectors (p = .044). During the acute phase, RNFL in the affected eye was thinner at the superior-nasal (p = .049), inferior-temporal (p = .003), and global (p = .041) sectors compared to the unaffected eye. In the intermittent phase, the affected eye’s RNFL was thinner at the superior-nasal, inferior-temporal, inferior-nasal, and global sectors compared to the unaffected eye (allp < 0.05), while no difference was observed in both eyes at the nasal, superior-temporal, and temporal sectors. The number of episodes and age were significantly associated with RNFL thickness (p < .05).ConclusionThis study demonstrated that in eyes affected by PSS, RNFL, macular ChT, and macular thickness thinned during the acute phase. The number of episodes and age are significant factors in the development of PSS.

Novel combined pharmacological strategy to alleviate acute phase response following zoledronic acid treatment.

Osteoporosis is a common condition associated with high morbidity rates, often requiring treatment with bisphosphonates such as zoledronic acid. However, the persistence to zoledronic acid infusion is commonly limited by acute phase response (APR). This retrospective study aimed to evaluate the efficacy of a novel combination therapy in preventing APR symptoms. A retrospective case-control study was conducted on 931 patients who received their first zoledronic acid infusion between 2011 and 2021. We evaluated the efficacy of combination therapy comprising a single dose of hydrocortisone prior to the infusion and a 3-d oral regimen of non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone following the infusion. Patients were divided into protocol (receiving combination therapy) and control groups (without treatment). Baseline characteristics, APR incidence, and the efficacy of symptom control were compared between groups using Fisher's exact test and Student's t-test. There was no difference in APR incidence between the protocol (n = 507) and control group (n = 407; p = 0.1442). However, the protocol group exhibited lower intolerable APR levels (3.72% vs. 16.71%; p < 0.0001) and complete symptom relief in 96.28% of cases. The combination therapy protocol effectively reduced intolerable APR and relieved symptoms in most patients following zoledronic acid infusion. This study highlights the importance of proactive management strategies for APR and emphasizes the potential of combination therapy in alleviating APR symptoms and reducing the occurrence of severe APR in patients undergoing osteoporosis management.

Longitudinal investigation of a single variant SARS-CoV-2-outbreak in the immunologically naïve population of Ulvik, Norway

PurposeTo perform an extensive investigation of the clinical features and long-term complications among the n = 134 adults and children with nucleic acid amplification test (NAAT) verified SARS-CoV-2-infection in the immunologically naïve population of Ulvik, Norway, during the single variant B.1.1.7 outbreak in late January through February 2021.MethodsEvery infected person regardless of whether symptoms of COVID-19 were present was invited to answer a web-based questionnaire at two- and seven months after testing positive. The period from initial infection to the first questionnaire was assessed retrospectively, and the time points at two- and seven months were assessed prospectively.ResultsA total of 87 of 134 (65%) NAAT-positive persons answered the first questionnaire, of which 35/87 (40%) were children, and 74 of 87 (85%) answered the second questionnaire. Children experienced symptoms less often than adults during the acute phase of infection (51% (18/35) versus 81% (42/52) (p = .004)). At two-months follow-up 88% (53/60) of participants with symptoms during the acute phase, including all children, reported no longer having symptoms. Among those with persisting symptoms at seven months, fatigue (18/25) and insomnia (16/24) were common.ConclusionIn an immunologically naïve population infected with the SARS-CoV-2 B.1.1.7 variant, the clinical features of acute phase symptoms were similar to previous studies. Children underwent asymptomatic infection more often than adults, and adults more often experienced persisting symptoms. Insomnia and fatigue were common complaints among those with persisting symptoms seven months after infection.

Persistent dysfunctions of brain metabolic connectivity in long-covid with cognitive symptoms.

Our study examines brain metabolic connectivity in SARS-CoV-2 survivors during the acute-subacute and chronic phases, aiming to elucidate the mechanisms underlying the persistence of neurological symptoms in long-COVID patients. We perfomed a cross-sectional study including 44 patients (pts) with neurological symptoms who underwent FDG-PET scans, and classified to timing infection as follows: acute (7 pts), subacute (17 pts), long-term (20 pts) phases. Interregional correlation analysis (IRCA) and ROI-based IRCA were applied on FDG-PET data to extract metabolic connectivity in resting state networks (ADMN, PDMN, EXN, ATTN, LIN, ASN) of neuro-COVID pts in acute/subacute and long-term groups compared with healthy controls (HCs). Univariate approach was used to investigate metabolic alterations from the acute to sub-acute and long-term phase. The acute/subacute phase was characterized by hyperconnectivity in EXN and ATTN networks; the same networks showed hypoconnectivity in the chronic phase. EXN and ATTN hypoconnectivity was consistent with clinical findings in long-COVID patients, e.g. altered performances in neuropsychological tests of executive and attention domains. The ASN and LIN presented hyperconnectivity in acute/subacute phase and normalized in long-term phase. The ADMN and PDMN presented a preseverved connectivity. Univariate analysis showed hypometabolism in fronto-insular cortex in acute phase, which reduced in sub-acute phase and disappeared in long-term phase. A compensatory EXN and ATTN hyperconnectivity was found in the acute/subacute phase and hypoconnectivity in long-term. Hypoconnectivity and absence of hypometabolism suggest that connectivity derangement in frontal networks could be related to protraction of neurological symptoms in long-term COVID patients.

Characteristics of intestinal microbiota in the acute phase of Kawasaki disease in infants and children

To study the composition, abundance, and functional profiles of the intestinal microbiota in infants and young children with Kawasaki disease (KD) during the acute phase, and to explore the potential role of intestinal microbiota in the pathogenesis of KD. Six children aged 0-3 years with acute KD admitted to the Department of Cardiology, Children's Hospital Affiliated to Capital Institute of Pediatrics from July to October 2021 were prospectively included as the KD group. Six age- and sex-matched healthy children who underwent physical examinations at the hospital during the same period were selected as the healthy control group. Metagenomics sequencing was used to detect and compare the differences in the microflora structure and functional profiles of fecal samples between the two groups. There were significant differences in the structural composition and diversity of intestinal microbiota between the two groups (P<0.05). Compared with the healthy control group, the abundance of Listeria_monocytogenes (family Listeriaceae and genus Listeria), Bifidobacterium_rousetti, Enterococcus_avium, and Enterococcus_hirae was significantly higher in the intestinal microbiota in the KD group (|LDA|>2.0, P<0.05). The steroid degradation and apoptosis pathways were significantly upregulated in the KD group compared with the healthy control group, while the Bacterial_secretion_system, Sulfur_metabolism, Butanoate_metabolism, Benzoate_degradation, β-alanine metabolism, and α-linolenic acid pathways were significantly downregulated (|LDA|>2, P<0.05). There are significant differences in the structure and diversity of intestinal microbiota between children aged 0-3 years with acute KD and healthy children, suggesting that disturbances in intestinal microbiota occur during the acute phase of KD. In particular, Listeria_monocytogenes, Enterococcus_avium, and Enterococcus_hirae may be involved in the pathogenesis of KD through steroid degradation and apoptosis pathways.

A rare presentation of stress cardiomyopathy in a patient with ulcerative colitis

Stress cardiomyopathy is a reversible cause of acute left ventricular dysfunction that can cause disease-related complications in the acute phase. Due to overlapping symptoms and investigation findings, stress cardiomyopathy can be misdiagnosed as an acute myocardial infarction. Hence correct identification of the condition is of great importance. It is increasingly being described with several medical conditions, which are associated with increased catecholamine surge like inflammatory bowel disease. Although the disease is reversible, due to the disease-related severe complications it is important to promptly identify and treat accordingly to prevent morbidity and mortality.

A Recent Advance in the Diagnosis, Treatment, and Vaccine Development for Human Schistosomiasis.

Schistosomiasis, which affects a large number of people worldwide, is among the most overlooked parasitic diseases. The disease is mainly prevalent in sub-Saharan Africa, southeast Asian countries, and South America due to the lack of adequate sanitation. The disease is mainly associated with poor hygiene, sanitation, and contaminated water, so it is also known as a disease of poverty. Three Schistosoma species (S. mansoni, S. japonicum, and S. haematobium) cause significant human infections. Co-infections with Schistosoma and other parasites are widely common. All these parasites may cause intestinal or urogenital schistosomiasis, where the disease may be categorized into the acute, sensitized, and chronic phases. The disease is more prevalent among school children, which may cause anemia and reduce development. Chronic infections frequently cause significant liver, intestinal, and bladder damage. Women exposed to contaminated water while performing normal duties like washing clothes might acquire urogenital schistosomiasis (UGS), which can cause tissue damage and raise the risk of blood-borne disease transmission, including human immunodeficiency virus (HIV) transmission. Praziquantel (PZQ) is the World Health Organization (WHO)-prescribed treatment for individuals who are known to be infected, but it does not prevent further re-infections with larval worms. Vaccine development and new molecular-based diagnosis techniques have promised to be a reliable approach to the diagnosis and prevention of schistosomiasis. The current review emphasizes the recent advancement in the diagnosis of schistosomiasis by molecular techniques and the treatment of schistosomiasis by combined and alternative regimes of drugs. Moreover, this review has also focused on the recent outbreak of schistosomiasis, the development of vaccines, and their clinical trials.

Value of Functional Protein S Activity Assays for Detection of Type II Protein S Deficiency

Abstract Background Protein S deficiency is a hereditary thrombophilia which occurs in three forms: Type I (quantitative), type II (qualitative) and type III (qualitative due to a gain of function). Literature suggests that of these, type II is the rarest and most difficult to diagnose. Type II protein S deficiency is only detectable by assaying protein S activity with a functional, clot-based test. However, this test is susceptible to interference and has a lower specificity when compared to antigen assays used to detect free and total protein S levels. Subsequently, the Choosing Wisely Guidelines released by the ABIM Foundation recommends against using protein S activity assays entirely. Instead, they suggest using only free protein S antigen assays. Although the rationale is to avoid false positive results from the protein S activity assay, it ultimately may result in a failure to detect type II protein S deficiency. Objective This study, performed at a tertiary medical center in the Midwestern region of the United States, aims to determine the proportion of false positives in functional assays as well as the percent of true type II protein S deficiency cases within this testing population. Methods All cases with abnormal protein S function within the institution were evaluated from July 2018 through July 2023 and classified as acquired or hereditary deficiencies. Cases were classified as acquired if there was evidence of liver disease, vitamin K deficiency, ongoing thrombosis, consumption, disseminated intravascular coagulopathy, or pregnancy. Possible hereditary deficiency cases were classified as type I, type II and type III: Type I if all assays were low, type III if both active and free protein S assays were low with normal total protein S, and type II if only protein S activity was low. The cutoff defined for normal total and free protein S levels was greater than 70% activity, and the low protein S activity cutoff was defined as less than 50%. Patients with low protein S activity but normal immunologic protein S and an elevated factor VIII were considered falsely low values. Chart review will be performed for remaining cases with low protein S activity to rule out confounders such as vitamin K deficiency, warfarin use, acute phase reaction, or pregnancy. Results From a total of 8805 panels performed to assess for possible thrombophilia, 1580 (18%) were found to have decreased protein S activity. Of these cases, 599 (38%) were considered falsely decreased due to elevated factor VIII levels. 322 cases (3.7%) were considered possible hereditary deficiencies: 217 type III (2.5%), 27 type II (0.3%), and 80 type I (0.9%). Discussion Our data indicates the prevalence of subtypes may be differently distributed than previously believed, which may call for current guidelines to be reevaluated.

Association of COVID-19 with acute and post-acute risk of multiple different complications and mortality in patients infected with omicron variant stratified by initial disease severity: a cohort study in Hong Kong

BackgroundFew studies have attempted to use clinical and laboratory parameters to stratify COVID-19 patients with severe versus non-severe initial disease and evaluate age-specific differences in developing multiple different COVID-19-associated disease outcomes.MethodsA retrospective cohort included patients from the electronic health database of Hong Kong Hospital Authority between 1 January 2022 and 15 August 2022 until 15 November 2022. The cohort was divided into three cohorts by age (≤ 40, 41–64, and ≥ 65 years old). Each age cohort was stratified into four groups: (1) COVID-19 critically exposed group (ICU admission, mechanical ventilation support, CRP > 80 mg/L, or D-dimer > 2 g/mL), (2) severely exposed group (CRP 30–80 mg/L, D-dimer 0.5–2 g/mL, or CT value < 20), (3) mildly–moderately exposed group (COVID-19 positive-tested but not fulfilling the criteria for the aforementioned critically and severely exposed groups), and (4) unexposed group (without COVID-19). The characteristics between groups were adjusted with propensity score-based marginal mean weighting through stratification. Cox regression was conducted to determine the association of COVID-19 disease severity with disease outcomes and mortality in the acute and post-acute phase (< 30 and ≥ 30 days from COVID-19 infection) in each age group.ResultsA total of 286,114, 320,304 and 194,227 patients with mild–moderate COVID-19 infection; 18,419, 23,678 and 31,505 patients with severe COVID-19 infection; 1,168, 2,261 and 10,178 patients with critical COVID-19 infection, and 1,143,510, 1,369,365 and 1,012,177 uninfected people were identified in aged ≤ 40, 40–64, and ≥ 65 groups, respectively. Compared to the unexposed group, a general trend tending towards an increase in risks of multiple different disease outcomes as COVID-19 disease severity increases, with advancing age, was identified in both the acute and post-acute phases. Notably, the mildly–moderately exposed group were associated with either insignificant risks (aged ≤ 40) or the lowest risks (aged > 40) for the disease outcomes in the acute phase of infection (e.g., mortality risk HR (aged ≤ 40): 1.0 (95%CI: 0.5,2.0), HR (aged 41–64): 2.1 (95%CI: 1.8, 2.6), HR (aged > 65): 4.8 (95%CI: 4.6, 5.1)); while in the post-acute phase, these risks were largely insignificant in those aged < 65, remaining significant only in the elderly (age ≥ 65) (e.g., mortality risk HR (aged ≤ 40): 0.8 (95%CI: (0.5, 1.0)), HR (aged 41–64): 1.1 (95%CI: 1.0,1.2), HR (aged > 65): 1.5 (95%CI: 1.5,1.6)). Fully vaccinated patients were associated with lower risks of disease outcomes than those receiving less than two doses of vaccination.ConclusionsThe risk of multiple different disease outcomes in both acute and post-acute phases increased significantly with the increasing severity of acute COVID-19 illness, specifically among the elderly. Moreover, future studies could improve by risk-stratifying patients based on universally accepted thresholds for clinical parameters, particularly biomarkers, using biological evidence from immunological studies.

Clinical Implication of Time of Ischaemic Stroke Among Post-Stroke Survivors from Eastern India: A Circadian Perspective.

The circadian variation in stroke occurrence is a well-documented phenomenon. However, the circadian effect on stroke outcome, particularly on post-stroke cognition, has not yet been fully elucidated. We aim to evaluate the influence of diurnal variation of stroke onset upon post-stroke cognition and development of post-stroke depression. Based on 4-hourly time period of stroke occurrence, 249 recruited cohorts were categorized into 6 groups. Several clinical and cognitive parameters were compared among the groups. Then, the mRNA expression of core clock genes in Peripheral Blood Mononuclear Cells were quantified and correlated with post-stroke outcomes among 24 acute phase cases with day-time or night-time stroke occurrence. Furthermore, the genetic susceptibility towards a higher number of cases in the morning was examined by genotyping CLOCK (rs1801260T/C, rs4580704G/C) and CRY2 (rs2292912C/G) genes variants in cases and 292 controls. In our study, the peak for highest incidence although observed during the early morning from 4 to 8 am, the nocturnal-onset stroke cases showed more severity (12.2 ± 5.67) at the time of admission irrespective of arterial territory involved. The night onset cases were also found to be more susceptible to develop language impairment and post-stroke depression in due course of time. Upon transcript analysis, circadian genes (BMAL1 and CRY1) were found to be downregulated in night-time cases than day-time ones during the acute phase of onset. In addition, those mRNA levels also showed a correlation with raw scores for language and depression. However, the difference in incidence frequency along a day did not reveal any genetic correlation. Therefore, we suggest night-time stroke to be positively associated with higher immediate severity and poor cognitive outcome than day-time injury and propose downregulation of circadian genes during the acute phase could be the underlying molecular mechanism for this.

Relevance of Non-Contrast Computed Tomography (NCCT) Based Alberta Stroke Program Early CT Score (ASPECTS) in Predicting Severity of Acute Ischemic Stroke at Presentation and Its Functional and Cognitive Outcome at 90 Days

Introduction: ASPECTS is a NCCT based topographic scoring system that provides quantitative measure of early ischemic changes. The score was initially developed for evaluating candidacy for stroke thrombolysis but currently also predicts functional and cognitive outcomes of stroke. Methods: 35 patients with acute ischemic stroke presenting within 48 hours of onset were included in the study. NIHSS score was ascertained at presentation and ASPECTS score was calculated (less than 6 and 6 or greater). On presentation NIHSS score and length of hospital stay were considered to be markers of early severity and mRS and MOCA scores were assessed at 90 days. Patients with MoCA less than 26 were considered to be having post stroke cognitive impairment. Results: Correlation between ASPECTS and NIHSS, stay length, 90-day mRS and MoCA were -0.452, -0.632, -0.778, 0.618 respectively. ASPECTS of less than 6 by univariate analysis was seen to be a risk factor for more severe strokes in acute setting with greater morbidity and cognitive decline at 90 days. Cardioembolic strokes also tended to have greater post stroke cognitive decline. Discussion: Poorer ASPECTS score at admission had greater stroke severity in acute phase and has worse long-term outcomes both in terms of functional and cognitive impairment and a cut off of less than 6 can be considered for the same. Conclusion: ASPECTS score is a surrogate marker of early and long-term stroke severity and its impacts.

Relationship between soft tissue envelope thickness of the lower extremity and acute periprosthetic joint infection of the knee.

The prevalence of obesity is increasing worldwide and it is known to be associated with many postoperative complications, including infection. Patients' body fat distribution may vary and body mass index (BMI) does not provide sufficient information about adipose tissue thickness of the lower extremities. The aim of this study is to investigate the relationship between thigh diameters and early postoperative prosthesis-related joint infections (PJI) in patients who underwent arthroplasty. The study included 76 patients and 114 knees who were operated on by a single surgeon and underwent total knee arthroplasty (TKA) due to primary knee osteoarthritis between May 2022 and September 2023 in a tertiary reference hospital. Circumference of the thickest part of the operated thigh (cm), preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, height, weight, BMI and the presence of early postoperative prosthesis-related joint infections were evaluated. The mean BMI was 32.6 ± 4.2 (kg/m2). Two (2.6%) were normal weight, 14 (18.5%) were overweight, 58 (76.3%) were obese and 2 (2.6%) were morbidly obese. The mean circumference of the thickest part of the thigh was 57.56 ± 6.38 (cm). 6 patients were diagnosed with PJI in the acute phase. The mean circumference of the thickest part of the thigh was statistically significantly greater in the group with acute PJI compared to the group without PJI (p = 0.048). The incidence of acute PJI was found to be significantly higher in patients with larger thigh diameters, whereas no such relationship was observed for BMI. The incorporation of preoperative soft tissue envelope measurements into routine clinical examination may prove beneficial in reducing the risk of PJI.

Simultaneous Genotyping of Three SNVs, rs5471, rs5472, and rs2000999 Involved in Serum Haptoglobin Levels by Fluorescent Probe-Based Melting Curve Analysis.

Haptoglobin (Hp) is a hemoglobin-binding acute-phase serum protein. Several single nucleotide variations (SNVs) within the Hp gene (HP) or Hp-related protein gene (HPR), such as rs5471 (A>C) and rs5472 (A>G) in HP promoter region and rs2000999 (G>A) in intron 2 of HRP, are suggested to correlate with the serum Hp levels. To determine these three SNVs simultaneously, a genotyping assay based on duplex dual-labeled fluorescent probes was developed. The method was then validated by analyzing genomic DNA from 121 Ghanaian and two Japanese subjects who had been previously genotyped for rs5471, rs5472, and rs2000999. Both rs5471 and rs5472 could be determined as haplotypes with a single FAM-labeled fluorescent probe, and rs2000999 could be genotyped with a HEX-labeled fluorescent probe. The results obtained with the present method were consistent with the previous results except for those of three Ghanaian subjects. All three subjects appear to have multiple HPR copy number variants characteristic of African populations, which may have led to incorrect results during previous genotyping. This method allows us to genotype these three SNVs in a relatively large number of samples, especially in African populations where rs5471 is uniquely distributed.