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At least 73 records · Page 4Linked to original sources
PubMed2004

PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis.

Mutations in the PROP1 gene are the most frequent genetic defects in patients with combined pituitary hormone insufficiency. However, controversy exists about the timing and extent of pituitary insufficiency, and it remains unclear whether adrenal failure is a typical feature of this condition. We performed a retrospective longitudinal analysis of nine patients with PROP1 mutations who were under medical supervision at our clinic for 15.7 +/- 3.4 yr. All patients initially presented with growth failure (height sd score, -3.7 +/- 0.3) at a mean age of 4.9 +/- 0.8 yr. They were first diagnosed with GH and TSH deficiency, and replacement therapy was instituted at 6.1 +/- 1.1 and 6.8 +/- 1.2 yr, respectively. All seven patients who reached pubertal age required sex hormone substitution at 15.0 +/- 0.7 yr. Repeated functional testing of the anterior pituitary axes revealed a progressive decline with age in peak levels of GH, TSH, prolactin, and LH/FSH. All patients developed at least partial adrenal insufficiency, with a gradual decline of the function of the pituitary adrenal axis and eventually required substitution with hydrocortisone at a mean age of 18.4 +/- 3.5 yr. It is concluded that anterior pituitary function in patients with PROP1 mutations deteriorates progressively and includes adrenal insufficiency as a feature of this condition, which has important clinical relevance in childhood and adolescence.

Adolescent↗
PubMed1995

A detailed longitudinal analysis on the use of naltrexone in the treatment of bulimia.

In accord with our auto-addiction opioid model, naltrexone was previously reported to be effective in the treatment of bulimia in a controlled double-blind clinical trial with a randomized cross-over design. This is a detailed longitudinal analysis over a 16 month period of one subject from that study. Attenuation in bulimic symptoms in two-drug as compared to no-drug periods was demonstrated. The duration for which the drug was needed was also addressed. The subject is an illustration of a therapeutic response on multiple parameters including binges, purges, urges to perform both behaviors, eating patterns, scaled feelings and Eating Disorder Inventory questionnaire scores. A rare allergic reaction to the drug is reported. It appeared to be heat and photosensitive, even in the presence of sun screen, occurred after a delay and did not appear immediately on skin testing. Use of naltrexone after desensitization is also reported.

Adult↗
PubMed1983

A longitudinal analysis of torque and its relationship to achievement and educational classification among normal, disturbed, and learning-disabled children.

Torque (clockwise circlings with either hand on a visual-motor task) has been shown to be related to a variety of academic, personal, and adjustment difficulties (Blau, 1977b). A longitudinal analysis was conducted for 948 third-grade students, selected randomly from various special and nonspecial education programs from a large, urban/suburban school system. Current measures of achievement, grade retention, and special education categorization were related to torque data obtained 4 years previously. Only grade retention was found to differ significantly between the torque and no torque groups. While the overall findings indicate no clear relationship between torque and various academic variables, some significant findings and trends in the data warrant further investigation.

Achievement↗
PubMed2000

Calcium accretion in girls and boys during puberty: a longitudinal analysis.

The primary purpose of this study was to estimate the magnitude and variability of peak calcium accretion rates in the skeletons of healthy white adolescents. Total-body bone mineral content (BMC) was measured annually on six occasions by dual-energy X-ray absorptiometry (DXA; Hologic 2000, array mode), a BMC velocity curve was generated for each child by a cubic spline fit, and peak accretion rates were determined. Anthropometric measures were collected every 6 months and a 24-h dietary recall was recorded two to three times per year. Of the 113 boys and 115 girls initially enrolled in the study, 60 boys and 53 girls who had peak height velocity (PHV) and peak BMC velocity values were used in this longitudinal analysis. When the individual BMC velocity curves were aligned on the age of peak bone mineral velocity, the resulting mean peak bone mineral accrual rate was 407 g/year for boys (SD, 92 g/year; range, 226-651 g/year) and 322 g/year for girls (SD, 66 g/year; range, 194-520 g/year). Using 32.2% as the fraction of calcium in bone mineral, as determined by neutron activation analysis (Ellis et al., J Bone Miner Res 1996;11:843-848), these corresponded to peak calcium accretion rates of 359 mg/day for boys (81 mg/day; 199-574 mg/day) and 284 mg/day for girls (58 mg/day; 171-459 mg/day). These longitudinal results are 27-34% higher than our previous cross-sectional analysis in which we reported mean values of 282 mg/day for boys and 212 mg/day for girls (Martin et al., Am J Clin Nutr 1997;66:611-615). Mean age of peak calcium accretion was 14.0 years for the boys (1.0 years; 12.0-15.9 years), and 12.5 years for the girls (0.9 years; 10.5-14.6 years). Dietary calcium intake, determined as the mean of all assessments up to the age of peak accretion was 1140 mg/day (SD, 392 mg/day) for boys and 1113 mg/day (SD, 378 mg/day) for girls. We estimate that 26% of adult calcium is laid down during the 2 adolescent years of peak skeletal growth. This period of rapid growth requires high accretion rates of calcium, achieved in part by increased retention efficiency of dietary calcium.

Absorptiometry, Photon↗
PubMed2003

[A longitudinal analysis on the association of serum lipids and lipoproteins concentrations with blood polychlorinated biphenyls level in chronic "Yusho" patients].

We examined the association between blood PCB level and the serum concentrations of total cholesterol, high-density lipoprotein cholesterol and triglycerides. The data was retrieved from the dataset of the nationwide health examination for Yusho patients. We longitudinally analyze the laboratory data of the officially identified Yusho patients who underwent the health examination in Fukuoka and Nagasaki prefectures five times or more during the years from 1986 to 2000. For the longitudinal analysis, the generalized estimating equation model was used adjusting for the age as of 1986, the year of taking the health examination, smoking and drinking habits, body mass index and the site of the examination (Fukuoka or Nagasaki). Ten-fold increase in blood PCB level was associated with the elevation in serum concentration of total cholesterol by 18.4 mg/dL (95% CI, 7.8 to 29.0, P < 0.001) in men and 19.7 mg/dL (95% CI, 8.3 to 31.2, P < 0.001) in women, and the elevation of serum concentration of triglycerides by 43.4% (95% CI, 17.5 to 74.9, P < 0.001) in men and 42.8% (95% CI, 25.7 to 62.1, P < 0.001) in women. Association of blood PCB level with serum concentration of high-density lipoprotein cholesterol was not statistically significant in both men and women. Hypercholesterolemia is a well known risk factor of coronary heart disease. It might be suggested that the high blood PCB level in Yusho patients has some possible health effects on the incidence of coronary heart disease.

Adult↗
PubMed1999

Longitudinal analysis of phonemic clustering and switching during word-list generation in Huntington's disease.

Two characteristics of word-list generation performance are forming clusters (i.e., contiguous words from the same subcategory) and switching among them. Patients with frontal lobe pathology show reduced switching on letter-cued word generation tasks, and clustering has been associated with temporal lobe functioning. Letter-cued word generation was examined in 72 patients with Huntington's disease (HD) and 41 healthy participants of equivalent age and education. As predicted, the patients showed reduced switching but normal clustering. In addition, switching but not clustering correlated inversely with disease severity, as measured by both movement and mental status scales. Furthermore, 5-year longitudinal analysis revealed a monotonic decrease in switching over time, whereas clustering performance remained stable. Control participants performed uniformly over time on both measures. These results are consistent with a progressive reduction in cognitive flexibility attributed to disruption of frontal-subcortical circuits secondary to neostriatal pathology in HD.

Adult↗
PubMed2026

Longitudinal analysis of genomic and immune differences between primary and metastatic nasopharyngeal carcinoma for precision oncology.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a common malignancy with a high incidence in Southern China and Southeast Asia. Distant metastasis remains a major cause of poor prognosis. This study aims to explore the genomic and immune microenvironmental changes in primary and metastatic NPC through longitudinal analysis, to provide insights for guiding precision treatment strategies. METHODS: We analyzed tumor samples from 11 male NPC patients with distant metastasis. Paired primary and metastatic samples underwent targeted whole-exome sequencing (551 genes) and RNA sequencing (289 genes). Multiplex immunohistochemistry was performed to assess immune cell composition and immune response markers. Genomic alterations and immune features were compared between primary and metastatic tumors, and their associations with clinical outcomes were evaluated. RESULTS: Metastatic tumors exhibited distinct chromosomal changes, including frequent 1q gain, while 6p gain showed a trend toward prolonged survival. Primary tumors showed stronger immune suppression characterized by increased B-cell and Treg infiltration and elevated CTLA4 and IDO1 expression, whereas metastatic lesions displayed more active immune responses. Liver metastases presented a distinct immune landscape with lower CD8+ T-cell density compared to non-liver metastases. In locoregionally advanced NPC, high expression of oncogenic genes such as EGFR and MYC correlated with shorter disease-free survival, while elevated PANCK expression and enhanced cytotoxicity were linked to better outcomes. These results delineate the molecular and immune evolution of NPC and provide a foundation for developing precision therapeutic strategies. CONCLUSION: This study identifies key molecular and immune features associated with NPC survival. Primary tumors show an immunosuppressive phenotype, suggesting potential benefits from combining CTLA4 or IDO1 inhibitors with PD-1 blockade. Liver metastases exhibit distinct immune features, supporting the need for site-specific precision therapies. These findings contribute to personalized management strategies in NPC, guiding treatment based on molecular and immune profiles.

distant metastasis↗
PubMed2005

Longitudinal analysis of B cell repertoire and antibody gene rearrangements during early HIV infection.

In chronically HIV infected individuals, a number of functional B cell abnormalities have been described. However, the immediate changes that occur in the B cell compartment following viral exposure and how they affect the long-term course of infection are not well understood. We report the longitudinal analysis of B cell repertoires during early infection in untreated and treated individuals receiving highly active antiretroviral therapy (HAART). Analysis was based on IgG heavy chain gene utilization and CDR3 length measurement and relationship with CD4/CD8 counts, viral load, and total serum IgG, and anti-HIV antibodies levels. Repertoires were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. The findings indicate a stable peripheral B cell repertoire during the first 72 weeks following infection, particularly in the HAART treated patients. A modest association between B cell repertoire integrity and viremia levels as well as treatment was detected.

Adult↗
PubMed1995

Longitudinal analysis of cytomegalovirus load in renal transplant recipients using a quantitative polymerase chain reaction: correlation with disease.

Serial surveillance samples of urine collected from 103 renal transplant recipients were analysed by polymerase chain reaction (PCR) for the presence of human cytomegalovirus (HCMV) DNA. The PCR results were consistently negative in 70 patients, none of whom developed HCMV disease, and PCR positive in 33 patients of whom 10 developed HCMV disease (P < 0.001). In 12 patients, PCR results were positive in three or more consecutive samples indicating extensive HCMV replication. HCMV load in 104 samples from these patients was analysed using a quantitative co-amplification PCR system. The maximal viral burden in the symptomatic patients ranged from 10(5.9) to 10(7.12) genomes/ml urine (median 10(6.5)) and in the asymptomatic patients from 10(4) to 10(5.7) genomes/ml urine (median 10(5.2)). The 10(1.3) difference between these median values was significant (P < 0.01). Individual kinetic profiles of viral burden showed that high levels of HCMV correlated with clinically apparent disease. In the majority of the asymptomatic individuals HCMV load remained between 10(4) and 10(5.1) genomes/ml urine; however, in two patients fluctuations in viral load were observed involving higher viral levels (up to 10(5.7) genomes/ml urine) suggesting that immune responses able to modulate viral replication could be studied in individual patients. Analysis of the temporal appearance and quantity of HCMV in the urine with alterations in white cell numbers showed that leukopenia occurred following the appearance of HCMV in the urine of symptomatic patients but preceded HCMV in the urine of asymptomatic patients (P = 0.01). Overall, these results show that longitudinal analysis using fully quantitative PCR methods for HCMV can provide insight into the natural history of HCMV disease in renal transplant recipients.

Adolescent↗
PubMed2006

Longitudinal analysis of simian immunodeficiency virus (SIV) replication in the lungs: compartmentalized regulation of SIV.

BACKGROUND: Before the onset of AIDS, replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) in the lungs is considered to be latent. When and how virus replication is controlled in the lungs is unclear. In the present study, we examine virus replication in the lungs and in cells recovered from bronchoalveolar lavage (BAL) samples in a comprehensive, longitudinal analysis of an SIV/macaque model. METHODS: Gene-specific RNA and DNA were quantitated by polymerase chain reaction (PCR) and by real-time reverse-transcription PCR (RT-PCR). Alveolar macrophages were isolated using Dynabeads CD14 (Invitrogen). Expression of CCAAT/enhancer-binding protein beta (C/EBP beta ) isoforms was examined by Western blot analysis. RESULTS: SIV replication occurred in the lungs during acute infection and correlated with plasma viral load. Innate immune responses involving interferon- beta and the dominant-negative isoform of C/EBP beta were induced at this time. SIV RNA expression was suppressed in the lungs during asymptomatic infection, when no correlation existed with plasma viral load until SIV RNA levels rebounded again during late-stage disease. Modulation of viral RNA levels in BAL cells reflected RNA levels in lung tissue throughout each phase of infection. CONCLUSION: Quantitation of SIV RNA in BAL cells provides a consistent surrogate assessment of virus replication in lung tissue. Innate immune responses contribute to compartmentalized suppression of acute SIV replication in the lungs.

Animals↗
PubMed1997

Longitudinal analysis of CD4 T cell counts, T cell reactivity, and human immunodeficiency virus type 1 RNA levels in persons remaining AIDS-free despite CD4 cell counts <200 for >5 years.

CD4 cell count, T cell reactivity, and human immunodeficiency virus type 1 (HIV-1) RNA load were examined in 10 persons remaining free of AIDS while CD4 cell counts were <200/mm3 for >5 years, so-called low CD4 cell count long-term survivors (low CD4 LTS), and 10 matched rapid and 10 matched intermediate progressors (AIDS within 1 and 1-3 years). Longitudinal analysis of CD4 cell count and T cell reactivity revealed slower declines in low CD4 LTS. HIV-1 RNA load was 1 log/mL lower in the low CD4 LTS compared with the rapid progressors, with a similar linear increase over time in low CD4 LTS and progressors of 0.1 log/year. There was considerable overlap between groups. The constant difference between low CD4 LTS and progressors probably reflects HIV RNA load early after infection, but low CD4 LTS and progressors show similar slopes of HIV-1 RNA load rise.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

A 13-year longitudinal analysis of risk factors and clinic visitation patterns of patients with repeated gonorrhea.

A retrospective study of 2498 patients who made multiple visits to a sexually transmitted disease clinic over a 13-year period analyzed risk factors, default patterns, and repeated infections associated with gonococcal urethritis. An analysis of visitation patterns found that being young, black, and male and having a history of gonococcal urethritis before visiting the clinic was positively related to the total time a patient remained involved with the clinic. Default rates for all patients increased with successive clinic visits. A focused analysis was carried out on the records of 146 patients who returned to the clinic within 12 months with a second diagnosis of gonococcal urethritis. It was found that this group of "repeaters," who comprised 15% of the total population with gonococcal urethritis, accounted for approximately 29% of all diagnoses of this infection over the 13-year study period. Repeaters were found to be more frequently male, black, single, and to be less likely to return for a test-of-cure culture. Longitudinal analysis found that the median time repeaters remained involved with the clinic was approximately 130 days. The relatively brief clinic "half-life" and rapid rates of removal of repeaters are discussed in terms of the development of strain-specific immunity to Neisseria gonorrhoeae in a closed population of patients.

Adult↗
PubMed1994

Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire.

Human immunodeficiency virus 1 (HIV-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using freshly isolated peripheral blood mononuclear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-1-specific CTL have been defined, the effector cells mediating this vigorous response have been characterized less well. Specifically, no studies have addressed the breadth and duration of response to a defined epitope. In the present study, a longitudinal analysis of T cell receptor (TCR) gene usage by CTL clones was performed in a seropositive person using TCR gene sequences as a means of tracking responses to a well-defined epitope in the glycoprotein 41 transmembrane protein. 10 CTL clones specific for this human histocompatibility leukocyte antigen-B14-restricted epitope were isolated at multiple time points over a 31-mo period. All clones were derived from a single asymptomatic HIV-1-infected individual with a vigorous response to this epitope that was detectable using unstimulated PBMC. Polymerase chain reaction amplification using V alpha and V beta family-specific primers was performed on each clone, followed by DNA sequencing of the V-D-J regions. All 10 clones utilized V alpha 14 and V beta 4 genes. Sequence analysis of the TCR revealed the first nine clones isolated to also be identical at the nucleotide level. The TCR-alpha junctional region sequence of the tenth clone was identical to the junctional region sequences of the other nine, but this clone utilized distinct D beta and J beta gene segments. This study provides evidence that the observed high degree of HIV-1-specific CTL activity may be due to monoclonal or oligoclonal expansion of specific effector cells, and that progeny of a particular CTL clone may persist for prolonged periods in vivo in the presence of a chronic productive viral infection. The observed limited TCR diversity against an immunodominant epitope may limit recognition of virus variants with mutations in regions interacting with the TCR, thereby facilitating immune escape.

Amino Acid Sequence↗
PubMed1985

Longitudinal analysis of three intrathecally produced immunoglobulin subpopulations in an MS patient.

Four murine anti-idiotypic (a-Id) hybridoma antibodies were produced against immunoglobulins (Ig) present in the cerebrospinal fluid (CSF) obtained from an MS patient 2 mo after the onset of disease. The four a-Id antibodies were shown to delineate idiotopes present on three distinct Ig subpopulations designated ID-19, ID-40, and ID-97. All three Ig subpopulations were produced in part by intrathecally localized B cells, together making up approximately 5% of the total CSF-Ig 2 mo after the onset of disease. Longitudinal analysis of the concentration of these Ig subpopulations in CSF showed that two subpopulations, ID-40 and ID-97, exhibited a regular relation to the clinical course of the disease, i.e., were decreased (ID-40) or increased (ID-97) in the first CSF sample obtained after two consecutive exacerbations. Screening of sera from 52 optic neuritis patients and 51 heterologous MS patients revealed that one MS patient's serum contained an Ig subpopulation that was idiotypically cross-reactive with ID-97. So far, screening of these Ig subpopulations for reaction with several viruses (measles, parainfluenza type 1, influenza type A, cytomegalovirus, herpes simplex virus, rubella virus, poliovirus, murine encephalomyelitis viruses, and reovirus) and myelin basic protein has failed to reveal their antigen specificities.

Adult↗
PubMed2004

Cross-sectional and longitudinal analysis of myelin-reactive T cells in patients with multiple sclerosis.

Activated myelin-specific T cells are thought to mediate inflammatory tissue damage in multiple sclerosis (MS). Applying a large panel of myelin antigens, we demonstrate the direct ex vivo detection of viable IFN-gamma/TNF-alpha producing CD4+/CD69+ T cells 6 hours after antigenic challenge, by intracellular flow cytometry in 3/33 MS patients and 2/26 healthy controls with calculated frequencies of (mean +/- SEM): 0.031% +/- 0.002% versus 0.037% +/- 0.029%. By comparison, the recently developed IL-7 modified proliferation assay revealed i) a higher number of individuals showing myelin reactivity (17/37 MS patients and 12/24 healthy individuals) and ii) a significant difference in the response to myelin basic protein (MBP) between the two groups in a longitudinal analysis, indicating a higher activity of myelin-specific T cells in MS patients. Our data provide new perspectives in detecting pathogenetically relevant T cells, but clearly demonstrate the different conclusions which must be drawn from various approaches concerning the quantification of autoreactive T cells.

Adult↗
PubMed2005

In-depth, longitudinal analysis of viral quasispecies from an individual triply infected with late-stage human immunodeficiency virus type 1, using a multiple PCR primer approach.

Co-infections with more than one human immunodeficiency virus type 1 (HIV-1) subtype appear to be the source of new recombinant strains and may be commonplace in high-risk cohorts exposed to multiple subtypes. Many potential dual infections have been identified during the HIV Superinfection Study in Mbeya, Tanzania, where 600 female bar workers who are highly exposed to subtypes A, C, and D have been evaluated every 3 months for over 3 years by use of the MHAacd HIV-1 genotyping assay. Here we describe an in-depth, longitudinal analysis of the viral quasispecies in a woman who was triply infected with HIV-1 and who developed AIDS and passed away 15 months after enrollment. The MHA results obtained at 0, 3, 6, 9, and 12 months revealed dual-probe reactivities and shifts in subtype over time, indicating a potential dual infection and prompting further investigation. The multiple infection was confirmed by PCR amplification of three genome regions by a multiple primer approach, followed by molecular cloning and sequencing. A highly complex viral quasispecies was found, including several recombinant forms, with vpu/gp120 being the most diverse region. A significant fluctuation in molecular forms over time was observed, showing that the serial sample format is highly desirable, if not essential, for the identification of multiple infections. In a separate experiment, we confirmed that the detection of co-infections is more efficient with the use of multiple amplification primers to overcome the primer bias that results from the enormous diversity in the HIV-1 genome.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Longitudinal analysis of T cells responding to tetanus toxoid in healthy subjects as well as in pediatric patients after bone marrow transplantation: the identification of identical TCR-CDR3 regions in time suggests long-term stability of at least part of the antigen-specific TCR repertoire.

To understand the nature of long-term Th immune responses, we investigated in the present study the TCRBV gene repertoire of CD4(+) T cells specific for the recall antigen tetanus toxoid (TT) in recipients of an allogeneic bone marrow transplantation (allo-BMT) at several time points after transplantation and in their BM donors. We observed that the TCR repertoire of TT-specific CD4(+) Th cells was heterogeneous, and differed between allo-BMT recipients and their respective donors. Some individuals, however, used similar TCR-complementarity-determining region (CDR) 3 motifs that could reflect recognition of and selection by similar promiscuous epitopes of TT. Longitudinal analysis of this TT-specific T cell response revealed that T cells with completely identical TCR were present at several time points after the first analysis in allo-BMT recipients, most probably reflecting long-term stability of at least part of the antigen-specific TCR repertoire. Similar stability of the TT-specific TCR repertoire in time was also noted in the allo-BMT donors. These observations reveal that within a given individual the dominant antigen-specific T cell clones persist in time in an otherwise diverse TT-specific CD4(+) T cell immune response.

Bone Marrow Transplantation↗
PubMed1998

A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response.

The composition of high-density lipoprotein (HDL) changes during inflammation; however, potential changes of HDL function during inflammation and the effects of acute phase proteins that are either on the HDL particles or in the serum have not been clarified. The concentrations of C-reactive protein (CRP), serum amyloid A protein (apoSAA) isoforms, lipids and apolipoproteins, and the activities of lecithin-cholesterol acyltransferase (LCAT) and paraoxonase (PON) were measured before and after laparoscopic cholecystectomy, in 12 patients with cholecystolithiasis to clarify the function of acute-phase HDL and the relationship between acute-phase proteins and HDL functions. Both acute-phase apoSAA (A-apoSAA) and CRP increased, reached their maximum levels 3-6 days after the operation, and then returned to preoperative levels after 2 weeks. In contrast, apolipoproteins and LCAT decreased reciprocally, reached their minimum levels 3-6 days after the operation, and returned to preoperative levels after 2 weeks. However, PON decreased 3-6 days after the operation, and remained low even after 2 weeks. At the nadir the mean activities of LCAT and PON were 56 and 76% of the preoperative levels, respectively. HDL-cholesterol or constitutive apoSAA did not change significantly. LCAT has been reported to be involved in reverse-cholesterol transport and PON to be preventive for lipid peroxidation of low-density lipoprotein in vitro. Thus, during the acute phase of inflammation, HDL may be altered to an atherogenic state due to a decrease in LCAT and PON activities. Therefore, this longitudinal analysis was carried out to determine whether HDL function is modified in a single episode of inflammation and thus may contribute to the occurrence of atherosclerotic disease in patients with chronic or recurrent acute inflammation.

Acute-Phase Reaction↗