Recovery Phase In Patients Research Articles

Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis.

Emergence agitation (EA) is a behavioural disturbance encountered during the recovery phase of patients following general anaesthesia. It is characterised by restlessness, involuntary limb movements, and drainage tube withdrawal and may significantly harm patients and medical staff. The mechanism of EA has not been fully understood and is still a challenging subject for researchers. We extracted relevant publications published between 1 January 2001 and 31 December 2023 on the Web of Science Core Collection platform. VOSviewer software was utilised to analyse the retrieved literature and predict the development trends and hotspots in the field. The results show that the number of publications grew annually, with China contributing the most, followed by the United States and South Korea. The co-occurrence of keywords "children," "propofol," "risk factors" are current research hotspots. Owing to its self-limiting and short-duration characteristics, EA lacks standardised clinical time guidelines and objective assessment tools, which may be the focus of future research in this field. Understanding the research hotspots and the latest progress in this field, this study will help to continuously improve the clinical understanding and management of EA, and help to timely identify environmental risk factors for EA in clinical practice.

Elevated Interleukin-6 (IL-6) Levels with Ig (G & M) Antibodies in the Recovery Phase of Patients with COVID-19: Indication of Cytokine Storm and Re-infection

The innate immune response to coronavirus disease (COVID-19) by inflammatory cytokines, such as interleukin 6 (IL-6), has been described as an early response, followed by an adaptive immune response with the production of antibodies. IL-6 is produced in response to viral infections and is crucial for the activation of T cells and the differentiation of B cells, which produce antibodies. Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are produced during the initial acute period of infection and the recovery period from the period of onset of symptoms. There has been some relationship between the innate response of the cytokine and the adaptive response of the antibodies in patients with COVID-19 infection. There has been a positive correlation between IL-6 levels and the presence of COVID-19 antibodies, suggesting that higher IL-6 levels may be associated with a stronger immune response and studies have confirmed that patients with higher IL-6 levels have a higher antibody response. High IL-6 levels on admission observed within 2 weeks after onset of symptoms were positively correlated with high concentrations of IgG seen 5 weeks after onset of symptoms. We have previously described elevated IL-6 levels in the sera of 68% of COVID-19 convalescent patients (40–93 days) post-onset of symptoms (recovery phase). In this study we decided to investigate whether there was some relationship between the IL-6 levels in patients 40–93 days post-onset of symptom in the recovery phase and their antibody response using a wide range of antibody assays (iCHROMA IgG, GOLD IgG & IgM, Abbott SARS-CoV-2 IgG II Quant-test (Abbott S IgG), Diasorin Liaison SARS-CoV-2 S1/2 (Diasorin S1/2 IgG). The patients were divided into two groups, those with normal IL-6 levels (<7 pg/ml) and those with elevated IL-6 levels (>7 pg/ml). All patients (100%) had positive IgG antibodies, only 8 out the 28 patients (29%) were positive for IgM antibodies. The mean antibodies concentrations of the patients (n = 9) with normal IL-6 levels (<7 pg/ml) for iCHROMA IgG (20.0 Units), GOLD IgG (34.4 AU/mL), Abbott IgG (4175 AU/mL), Diasorin Liaison IgG (75.8 AU/mL) and GOLD IgM (4.7 AU/mL), respectively. The mean antibodies concentrations of the patients (n = 19) with elevated IL-6 levels (>7 pg/ml) for iCHROMA IgG (20.9 Units), GOLD IgG, (34.9 AU/mL), Abbott IgG (2287 AU/mL), Diasorin Liaison IgG (121.7 AU/mL) and GOLD IgM (11.2 AU/mL), respectively. The antibodies of the patients with the elevated IL-6 levels were significantly higher for Diasorin Liaison IgG (p = 0.02) and GOLD IgM (p = 0.003) but lower for Abbott IgG (p = 0.02). In conclusion, this study using a panel of antibody assays highlights that increased levels of IL-6 in the convalescent phase (recovery phase) indicate an active immune response leading to higher concentrations of antibodies especially IgM, suggesting that cytokine storms and re-infection occur in the recovery phase.

Respiratory exchange ratio overshoot during exercise recovery: a novel prognostic marker in heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background In recent years considerable new evidence has been added on the analysis of the recovery phase in patients with heart failure. Transient increases (overshoot) in respiratory gas variables have been observed during exercise recovery, but their clinical significance is not clearly understood. Respiratory Exchange Ratio (RER) at peak exercise (RER peak) is an objective index of exercise intensity. The overshoot phenomenon of the RER is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET) but initial studies have found a decreased RER-magnitude in patients with heart failure with reduced ejection fraction (HFrEF). Purpose To characterize the functional and prognostic significance of RER recovery kinetics in individuals with HFrEF. Methods This cross-sectional study included all patients with HFrEF who underwent functional evaluation with maximal CPET for the heart transplant checklist at the Sports and Exercise Medicine Division of the Padova University Hospital between January 2018 and December 2021. The presence of overshoot phenomena of different respiratory gas indices was evaluated during the recovery phase, focusing on the RER. The RER behaviour has been evaluated assessing the maximal value during recovery phase (RER max) and the magnitude of the RER overshoot (RER mag). Results 164 patients with HFrEF and 128 controls were included in the study. RER recovery parameters were significantly lower in patients with HFrEF compared to healthy subjects. The RER overshoot showed significant correlations with prognostically relevant CPET parameters and these RER metrics were significantly higher in patients presenting better ventilatory and Weber classes. 24 patients with HFrEF did not present a RER overshoot showing worse cardiorespiratory fitness and efficiency compared to patients with overshoot. Mean follow-up period was 2.57 years during which there were 55 first major cardiovascular events, 22 deaths, 21 heart transplants, and 9 ventricular assist device implantations. The absence of RER overshoot predicted major adverse cardiac events- and transplant-free survival in univariate and multivariate Cox regression analysis. Conclusions RER overshoot represents a new index to monitor respiratory gas kinetics during the recovery phase, since it is a feasible and reproducible parameter for clinical practice. A reduced overshoot or its absence are significantly associated with functional impairment, cardiorespiratory inefficiency and worse prognosis. Thus, the evaluation of the respiratory gas indices during recovery from maximal CPET should be included in routine test interpretation, particularly for patients with HFrEF.

Roles of Astrocytic Endothelin ETB Receptor in Traumatic Brain Injury.

Traumatic brain injury (TBI) is an intracranial injury caused by accidents, falls, or sports. The production of endothelins (ETs) is increased in the injured brain. ET receptors are classified into distinct types, including ETA receptor (ETA-R) and ETB receptor (ETB-R). ETB-R is highly expressed in reactive astrocytes and upregulated by TBI. Activation of astrocytic ETB-R promotes conversion to reactive astrocytes and the production of astrocyte-derived bioactive factors, including vascular permeability regulators and cytokines, which cause blood-brain barrier (BBB) disruption, brain edema, and neuroinflammation in the acute phase of TBI. ETB-R antagonists alleviate BBB disruption and brain edema in animal models of TBI. The activation of astrocytic ETB receptors also enhances the production of various neurotrophic factors. These astrocyte-derived neurotrophic factors promote the repair of the damaged nervous system in the recovery phase of patients with TBI. Thus, astrocytic ETB-R is expected to be a promising drug target for TBI in both the acute and recovery phases. This article reviews recent observations on the role of astrocytic ETB receptors in TBI.

Effect of Hematologic Values in Determining the Resolution of Subacute Thyroiditis and Long-Term Hypothyroidism Risk

Subacute thyroiditis (SAT), which can be considered a disease with infectious signs and parameters, can affect humans and lead to permanent hypothyroidism. Haematological parameters play an essential role in SAT; these parameters begin to normalise after the thyrotoxic phase; however, there is still a gap in knowledge about how these parameters play a role in SAT prognosis. Therefore, we wanted to investigate haematological parameters and their impact on treatment response and recovery phase in patients with SAT. 51 SAT patients and 44 healthy controls were included in the study. ESR, CRP, NLR and MPV were recorded at the diagnosis and after resolution. The changes in these parameters were compared to determine the resolution phase. The ratio of permanent hypothyroidism after one year was studied, and its relevance with these parameters at the time of diagnosis was explored. 36 of 51 SAT patients were female in the study (70.5%). The mean age was 45.53 ± 11.46 years. In the acute phase, WBC, Neutrophil, platelet, ESR, N/L, and P/L were significantly higher (p<0.05). In the recovery phase, MPV and lymphocyte count were significantly higher (p: 0.002 and p=0.002). WBC, CRP, and ESR had the highest AUC values in ROC analysis (0.990, 0.959, 0.907, p<0.05). P/L and N/L ratios also had higher ratios for the acute phase (0.807, 0.98, p<0.05, respectively). Δ ESR, Δ CRP, Δ N/L, and Δ P/L had the highest AUC for the recovery phase (AUC= 0.990, 0.899, 0889,0.800, p<0.5, respectively). Permanent hypothyroidism after one year was 9/42 (21.4%). In addition to ESR and CRP, NLR, PLR and MPV were also successfully used to estimate SAT activity and response to treatment. Moreover, a decrease in NLR and PLR and an increase in MPV were associated with the treatment response and resolution phase. However, these parameters did not determine the long-term risk of hypothyroidism.

Characteristics of Musculoskeletal Signs and Symptoms during the Recovery Phase of Patients with Moderate-to-Severe COVID-19 at the Philippine General Hospital

Introduction. Musculoskeletal complaints have been observed in the recovery phase of patients with moderate-to-severe coronavirus disease 2019 (COVID-19). We noted several referrals for physical rehabilitation at the University of the Philippines-Philippine General Hospital (UP-PGH), a designated COVID-19 referral center. These observations resembled the musculoskeletal manifestations associated with poorer outcomes reported in other coronavirus studies.
 Objectives. The study determined the musculoskeletal signs and symptoms of adults in the recovery phase of moderate to severe COVID-19 using the COVID Musculoskeletal Assessment Tool (CMAT).
 Methods. This was a three-phased, prospective, descriptive study of adults admitted for COVID-19 at the UP-PGH. Phase 1 was the development of the CMAT based on a review of related literature and patient charts, and patient interviews. The tool was pretested and validated in Phase 2 before it was used in the evaluation of study participants in Phase 3 of the research. Data was encoded using Microsoft® Excel 2007 and analyzed using STATA, Version 12.0 (Texas, USA). Descriptive statistics were used to summarize the variables collected for the study.
 Results. A cohort of 40 patients admitted at the UP-PGH for moderate-to-severe COVID-19 infection was evaluated using the CMAT. Most of the patients had an average age of 55 years and were males. Majority resided in an urban area, reached high school education, and were ambulatory before their illness. The most common comorbidities were hypertension and diabetes. All patients required oxygen support. Based on the CMAT, majority of the participants complained of muscle pain, generalized weakness, and easy fatigability. Other common findings were neck-shoulder and lower limb pain, dyspnea on exertion, limited mobility in the trunk, hips, and knees, joint pains, and decreased muscle strength. Half of the participants needed a wheelchair or walker to ambulate. These findings may be due to the COVID-19 disease and to prolonged confinement in bed. Only one patient underwent physical therapy through bedside instructions.
 Conclusion. Musculoskeletal signs and symptoms were common in the patients recovering from COVID-19 disease. The COVID-19 Musculoskeletal Assessment Tool facilitated the evaluation of patients and the recording of results. Early referral for medical rehabilitation and timely intervention are strongly recommended.

Efficacy and Safety of Remote Cardiac Rehabilitation in the Recovery Phase of Cardiovascular Diseases: Protocol for a Multicenter, Nonrandomized, Single-Arm, Interventional Trial.

BackgroundConventional group-based outpatient cardiac rehabilitation through monitoring and center-based approaches for patients in the recovery phase has shown strong evidence for the prevention of cardiovascular diseases. However, there are some cases in which maintaining attendance of center-based cardiac rehabilitation is difficult.ObjectiveThis study aims to ascertain the safety and efficacy of remote cardiac rehabilitation (RCR) in the recovery phase in patients with cardiovascular disease.MethodsPatients satisfying the study criteria will be recruited from multiple institutions (approximately 30) across Japan. In total, 75 patients (approximately 2 or 3 patients from each institution) are proposed to be recruited. Patients enrolled in the RCR group will be lent devices necessary for RCR (including calibrated ergometers and tablets). Patients will perform anaerobic exercise at home using ergometer for 30-40 minutes at least 3 times weekly. During exercise, an instructor will monitor the patient in real time (using interactive video tools and monitoring tools for various vital data). Moreover, educational instructions will be given 3 times weekly using e-learning methods.ResultsThe primary endpoint is the peak oxygen uptake 2-3 months from the start of exercise or 6-min walk test. The extracted data will be compared between RCR patients and controls without RCR.ConclusionsThe establishment of the system of RCR proposed in this study will lead to the development of more extensive applications, which have been insufficient through conventional interventions.Trial RegistrationUniversity Hospital Medical Information Network—Clinical Trials Registry UMIN–CTR UMIN000042942; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048983International Registered Report Identifier (IRRID)DERR1-10.2196/30725

Correlation of CD38 expression with the progression of hemorrhagic fever with renal syndrome.

To assess the relationship between the expression of CD38 and the progression of hemorrhagic fever with renal syndrome (HFRS), we determined the levels of CD38 during different phases of HFRS and evaluated the relationship between changes in CD38 expression and the progression of HFRS. The expression of CD38 in 68 patients with HFRS was analyzed by flow cytometry, and this method was also used to determine the levels of CD4+T, CD8+T, and B lymphocytes and NK cells. Furthermore, creatinine (Cr), uric acid (UA), and urea in serum at each stage of HFRS were measured using commercial kits. The basic clinical reference values for leukocytes, platelets (PLT), and red blood cells were determined by conventional methods. The colloidal gold method was used to measure HFRS antibody levels in the patients. A significant change in CD38 expression was observed from the fever phase to the recovery phase in patients with HFRS. Moreover, the expression of CD38 was proportionally correlated with the levels of Cr, UA, and urea in serum. In contrast, there was an inverse correlation between CD38 and PLT. Interestingly, an increase in CD38 expression correlated with an increase in CD8+T lymphocytes, B cells, and NK cells, but with a decrease in CD4+T lymphocytes. The expression of CD38 is associated with the progression of HFRS, suggesting that it may be a potent indicator of the stages of this disorder.

Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study.

Patients with COVID-19 have been reported to experience gastrointestinal symptoms as well as respiratory symptoms, but the effects of COVID-19 on the gut microbiota are poorly understood. We explored gut microbiome profiles associated with the respiratory infection of SARS-CoV-2 during the recovery phase in patients with asymptomatic or mild COVID-19. A longitudinal analysis was performed using the same patients to determine whether the gut microbiota changed after recovery from COVID-19. We applied 16S rRNA amplicon sequencing to analyze two paired fecal samples from 12 patients with asymptomatic or mild COVID-19. Fecal samples were selected at two time points: during SARS-CoV-2 infection (infected state) and after negative conversion of the viral RNA (recovered state). We also compared the microbiome data with those from 36 healthy controls. Microbial evenness of the recovered state was significantly increased compared with the infected state. SARS-CoV-2 infection induced the depletion of Bacteroidetes, while an abundance was observed with a tendency to rapidly reverse in the recovered state. The Firmicutes/Bacteroidetes ratio in the infected state was markedly higher than that in the recovered state. Gut dysbiosis was observed after infection even in patients with asymptomatic or mild COVID-19, while the composition of the gut microbiota was recovered after negative conversion of SARS-CoV-2 RNA. Modifying intestinal microbes in response to COVID-19 might be a useful therapeutic alternative.

Kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19: a descriptive study

BackgroundTo explore the kinetic changes in virology, specific antibody response and imaging during the clinical course of COVID-19.MethodsThis observational study enrolled 20 patients with COVID-19, who were hospitalized between January 20–April 6, 2020, in the two COVID-19 designated hospitals of Zhoushan, Zhejiang and Rushan, Shandong, China, The laboratory findings, imaging, serum response to viral infection, and viral RNA level in the throat and stool samples were assessed from onset to recovery phase in patients with COVID-19.ResultsSARS-COV-2 RNA was positive as early as day four. It remained positive until day 55 post-onset in the sputum-throat swabs and became negative in most cases (55%) within 14 days after onset. Lymphocytopenia occurred in 40% (8/20) of patients during the peak infection period and returned to normal at week five. The most severe inflammation in the lungs appeared in week 2 or 3 after onset, and this was completely absorbed between week 6 and 8 in 85.7% of patients. All patients had detectable antibodies to the receptor binding domain (RBD), and 95% of these patients had IgG to viral N proteins. The antibody titer peaked at week four. Anti-S IgM was positive in 7 of 20 patients after week three.ConclusionsAll COVID-19 patients in this study were self-limiting and recovered well though it may take as long as 6–8 weeks. Our findings on the kinetic changes in imaging, serum response to viral infection and viral RNA level may help understand pathogenesis and define clinical course of COVID-19.

A Prospective Randomized Study to Assess the Quality of Life in Post-Operative Recovery Phase in Patients Undergoing Surgery for Isolated Vertically Undisplaced Mandibular Parasymphysis Fracture Using Twin Mix Solution.

Trauma is a major cause for facial fractures commonly encountered by maxillofacial surgeons. Mandible is commonly involved in facial trauma resulting in an isolated fracture or associated with other facial bones due to its prominent location in the facial skeleton. This study was undertaken to investigate the quality of life (QoL) post-operatively in patients diagnosed with undisplaced parasymphysis fracture who underwent open reduction and internal fixation (ORIF) under local anesthesia (LA) using the twin mix (TM) solution. A prospective randomized clinical study was conducted among 40 patients aged between 20-55years requiring ORIF for unilateral vertically undisplaced parasymphysis fracture under LA. Group A patients (n = 20) received conventional LA solution with adrenaline, and Group B patients (n = 20) received freshly prepared TM solution for their surgical intervention as a day care procedure. Various parameters such as jaw function, ability to masticate and labialis activity (lower lip pout) were assessed. The data were collected and analyzed applying student's t test, Shapiro-Wilk test using SPSS software. All the 20 patients in Group B who received TM solution exhibited better jaw function and mouth opening with a mean score of (±SD) of 4.55 (±0.944). They also exhibited reduced difficulty in mastication and ability to purse the lower lip on third post-operative day as compared to the patients in Group A. No complications were observed among the patients post-operatively in both the groups of this study. TM solution proves to be superior as compared to the conventional LA solution as the former offers an improved clinical outcomes enhancing the QoL post-operatively in patients undergoing ORIF for undisplaced parasymphysis mandibular fracture.

Direct Anterior Approach in Total Hip Arthroplasty Leads to Superior Outcomes at 3-Month Follow-up When Compared With the Posterior Approach: A Matched Study Using Propensity Score Analysis.

Objective:The purpose of this study was to report and compare early outcomes during the first 3 months of the recovery phase in patients who underwent primary total hip arthroplasty (THA) with direct anterior approach (DAA) and posterior approach (PA).Background:The DAA for primary THA has gained popularity within the past few years. Although controversy exists regarding the long-term benefit when compared with the PA, several authors have reported markedly better outcomes in the early recovery weeks, when using DAA.Methods:For this study, data were prospectively collected and retrospectively reviewed for all primary THAs from March 2014 to October 2017. Included patients underwent primary THA through DAA or PA and had minimum 3-month postoperative measures for the Harris Hip Score, Forgotten Joint Score-12, Veterans RAND 12 Mental (VR-12 Mental), Veterans RAND 12 Physical (VR-12 Physical), 12-Item Short-Form (SF) Survey Mental, 12-Item SF Survey Physical (SF-12 Physical), Visual Analog Scale, and patient satisfaction. An analysis using propensity score matching was done to establish the DAA and PA groups. Matching (1:1 ratio) was conducted based on the following covariates: age, sex, body mass index, and laterality.Results:Twenty-four DAA THA patients were successfully matched using propensity scoring to 24 PA THA patients. The DAA group demonstrated significantly higher scores for the following patient-reported outcome scores: Harris Hip Score, VR-12 Mental, VR-12 Physical, and SF-12 Physical (P = 0.0090, P = 0.0388, P = 0.0063, and P = 0.0132, respectively).Conclusion:At 3-month follow-up, both the DAA and PA groups reported favorable outcomes after THA. However, the DAA group scored markedly higher regarding quality-of-life outcomes when compared with a propensity score–matched group of PA patients.

Growth Hormone Improves Cognitive Function After Experimental Stroke.

Cognitive impairment is a common outcome for stroke survivors. Growth hormone (GH) could represent a potential therapeutic option as this peptide hormone has been shown to improve cognition in various clinical conditions. In this study, we evaluated the effects of peripheral administration of GH at 48 hours poststroke for 28 days on cognitive function and the underlying mechanisms. Experimental stroke was induced by photothrombotic occlusion in young adult mice. We assessed the associative memory cognitive domain using mouse touchscreen platform for paired-associate learning task. We also evaluated neural tissue loss, neurotrophic factors, and markers of neuroplasticity and cerebrovascular remodeling using biochemical and histology analyses. Our results show that GH-treated stroked mice made a significant improvement on the paired-associate learning task relative to non-GH-treated mice at the end of the study. Furthermore, we observed reduction of neural tissue loss in GH-treated stroked mice. We identified that GH treatment resulted in significantly higher levels of neurotrophic factors (IGF-1 [insulin-like growth factor-1] and VEGF [vascular endothelial growth factor]) in both the circulatory and peri-infarct regions. GH treatment in stroked mice not only promoted protein levels and density of presynaptic marker (SYN-1 [synapsin-1]) and marker of myelination (MBP [myelin basic protein]) but also increased the density and area coverage of 2 major vasculature markers (CD31 and collagen-IV), within the peri-infarct region. These findings provide compelling preclinical evidence for the usage of GH as a potential therapeutic tool in the recovery phase of patients after stroke.

The measurement of drug-induced interferon γ-releasing cells and lymphocyte proliferation in severe cutaneous adverse reactions.

The lymphocyte transformation test (LTT) is a standard laboratory method to identify culprit drugs in patients with a history of drug-induced non-immediate hypersensitivity and is mainly performed during the recovery phase. The measurement of drug-specific interferon γ (IFN-γ)-releasing cells has been introduced to confirm culprit drugs, even during the acute phase of drug allergy. This study aimed to evaluate the capability of the enzyme-linked immunospot assay (ELISpot) to detect drug-specific IFN-γ-releasing cells during the acute phase and the capability of LTT to identify culprit drugs during the recovery phase in patients presenting with severe cutaneous adverse reactions (SCARs). Peripheral blood mononuclear cells (PBMCs) from 23 SCAR patients were collected during the acute and recovery phases and assayed for drug-specific IFN-γ-releasing cells and lymphocyte proliferation, respectively. Drug-specific IFN-γ-releasing cells were detectable in 73.9% of SCAR subjects (55.6% and 85.7% in patients who were and were not taking systemic steroids, respectively), whereas LTT results were positive in 52.2% of SCAR subjects. The frequencies of drug-specific IFN-γ-releasing cells were significantly higher in patients with positive LTT than in those with negative LTT (260.1 ± 110.0 and 46.6 ± 20.7 cells/106 PBMCs, P = 0.01). A significant correlation between the results of the IFN-γ ELISpot assay and LTT was demonstrated (r = 0.65, P value <0.01). The IFN-γ ELISpot assay could be a useful tool to identify culprit drugs in SCAR patients when culprit drug identification is urgently needed during the acute phase of drug allergy.

VIRUS-SPECIFIC HUMORAL IMMUNE RESPONSE ISOTYPIC STRUCTURE IN ADULT PATIENTS HOSPITALIZED WITH INFLUENZA A

The aim of this investigation was a comparative analysis of isotypic structure of specific antiviral systemic humoral immune response in hospitalized patients with influenza caused by virus A(H3N2) or A(H1N1), including the A(H1N1)pdm09. Paired acute and convalescent phase sera from 109 adult patients aged 18 to 67 years with laboratoryconfirmed influenza A were analyzed by ELISA. Purified surface glycoproteins of influenza A viruses of different subtypes containing the hemagglutinin and neuraminidase were used as antigen for sensitization of plates in ELISA.The absence of type-specific conserved internal proteins in antigenic material allowed to carry out a subtype-specific differentiation of antibodies against influenza viruses in ELISA. Regardless of the subtype of influenza A viruses caused the disease, the most pronounced response was observed by subtype-specific IgG1 (70–90% of seroconversions). It has been shown for the first time that low activity of virus-induced IgG2 (6–9% of seroconversions) is a peculiarity of the immune response both to primary or recurrent infections with A(H1N1)pdm09. In patients repeatedly suffered by «seasonal» influenza A(H1N1) in 2007/2008 or influenza A(H3N2) in 2012–2014 IgG2 seroconversion’s rates were 40–59% (р 0,05). Reaction virusspecific IgG3 was also weaker in patients with influenza A(H1N1)pdm09 (29–44% of seroconversions) than in subjects with influenza A(H1N1) or A(H3N2) (65% and 56% of seroconversions, respectively). Geometric mean titers of virus neutralizing antibodies identified during recovery phase in patients with primary and secondary influenza A(H1N1)pdm09 (1/28 and 1/103, respectively) were significantly lower than in patients recovered from influenza A(H1N1) or A(H3N2) (GMT were 1/594 and 1/378, respectively). It was shown that the surface glycoproteins of influenza A viruses may be an allergens. Virus-specific IgE seroconversion rates were comparable in all groups reaching 25–45%. The high activity of virus-induced serum IgA was detected in patients with influenza A(H3N2) or A(H1N1)pdm09 (60–79% of seroconversions). Thus, study of virus-specific activity of various immunoglobulin isotypes provides important information about the formation of adaptive antiviral immune response to influenza A viruses, and also estimate the contribution of its protective and immunopathogenic components to pathogenesis of the disease.

The Fate of Injured Corticospinal Tracts in Patients with Intracerebral Hemorrhage: Diffusion Tensor Imaging Study

Little is known about the fate of the injured CST for a large number of patients with ICH. Using DTT, we investigated the longitudinal changes of injured CSTs in patients with an ICH. We recruited 45 patients with CST injury by an ICH in the supratentorial subcortical area. Two longitudinal DTTs were acquired: 1 within 30 days and the other after 3 months from onset. DTTs for the CST were classified into 3 types: type A, the CST was preserved around the hematoma; type B, the CST was interrupted around the hematoma; and type C, the CST did not reach the hematoma. At the first DTT, the motor functions of type C were worse than those of types A and B (P < .01), and motor functions of type A were better than those of type C at the second DTT (P < .01). Of 14 type A, 2 changed to type B (14.3%) and 12 did not change (85.7%); of 12 type B, 11 changed to type A (91.7%) and 1 changed to type C (8.3%); of 19 type C, 3 changed to type A (15.8%) and 16 did not change (84.2%). We found that the injured CST could change from the early stage to the chronic stage during the motor recovery phase in patients with an ICH. These results would be helpful in prediction of longitudinal DTT changes from the early stage to the chronic stage following ICH.

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation.

Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.

Plasma Endotoxin and Serum Cytokine Levels in Patients With Alcoholic Hepatitis: Relation to Severity of Liver Disturbance

Endotoxin plays an important role in the initiation and aggravation of alcoholic liver disease. In this study, we evaluated plasma endotoxin levels and serum concentrations of cytokines and lipopolysaccharide binding protein (LBP) during the acute and recovery phase of patients with alcoholic hepatitis; we also explored the prognostic factors associated with a fatal outcome. Fourteen patients, consisting of eight patients with alcoholic hepatitis (AH), five cirrhotics with superimposed AH (LC+AH), and one patient with severe alcoholic hepatitis (SAH), were studied. Among these, two with LC+AH died of hepatic failure. Plasma endotoxin levels in the acute phase were higher in patients with AH (184.4 +/- 159.4 pg/ml) and LC+AH (206.9 +/- 174.9 pg/ml) than in healthy subjects (10.4 +/- 5.5 pg/ml, p < 0.001). In particular, in one patient with SAH and one of two nonsurvivors, plasma endotoxin levels were markedly high relative to the other cases. In most survivors, plasma endotoxin levels decreased in the recovery phase, whereas they further increased at the terminal stage in one of two nonsurvivors. Serum interleukin (IL)-6 and IL-8 levels in the acute phase were significantly higher in patients with AH and LC+AH as compared with healthy subjects. These levels were especially high in nonsurvivors and in one patient with SAH. IL-10 increased in two nonsurvivors, one patient with SAH, and one with LC+AH. In the recovery phase, these cytokine levels in survivors tended to decrease, but in nonsurvivors, IL-6 remained high, and IL-8 and IL-10 further increased. Tumor necrosis factor-alpha levels were below the detection limit throughout the course in all patients. Serum lipopolysaccharide binding protein (LBP) generally was elevated in the acute phase and decreased in the recovery phase in all survivors, but in one of the nonsurvivors, LBP was elevated markedly at the terminal stage. In the acute phase, plasma endotoxin levels were correlated positively with white blood cell counts, neutrophil counts, and serum IL-8. IL-8 was correlated positively with neutrophil counts and negatively with serum cholinesterase, hepaplastin test, and serum albumin levels. IL-6 was correlated positively with white blood cell and neutrophil counts, C-reactive protein, and serum total bilirubin and negatively with hepaplastin test and serum total protein levels. Serum LBP was correlated positively with white blood cell and neutrophil counts. Endotoxemia and related elevation of IL-8 may play an important role in the activation and migration of neutrophils in patients with alcoholic hepatitis. Marked elevation of inflammatory cytokines, IL-6 and IL-8, are related to severity and poor prognosis of alcoholic hepatitis. Serum LBP may serve as an index of inflammatory reaction in alcoholics.

Mechanism of increase in anaerobic threshold during recovery phase in patients with acute myocardial infarction.

The contribution of venous return to the increase in anaerobic threshold (AT) in patients with acute myocardial infarction (AMI) was investigated. Twenty-seven patients with uncomplicated AMI underwent supine and sitting cardiopulmonary exercise testing, and 10 out of these 27 patients performed constant-workload tests in which cardiac output before and after a phase II program was measured. Data from 8 patients were eliminated because of restenosis after direct percutaneous transluminal coronary angioplasty. The increase in AT was significantly greater in the sitting position than in the supine position, 15.0+/-9.9% and 6.3+/-6.0% respectively. Average O2 pulse at AT changed non-significantly from 8.6+/-1.5 to 8.7+/-1.2 ml min(-1) beat(-1) in the supine position, but it showed a significant increase from 8.1+/-1.3 to 9.2+/-1.3 ml min(-1) beat(-1) when measured in the sitting position. In the constant-workload studies, stroke index showed a significant increase during both supine and sitting exercise. Percent increase in the stroke index from rest to exercise did not differ significantly in the supine position, but did differ significantly in the sitting position. These results strongly suggest that increased venous return as well as improvement in cardiac pump function play a major role in the mechanism of AT increase in an upright position throughout the recovery phase in AMI patients.

Elevated immunosuppressive acidic protein in patients with subacute thyroiditis

Immunosuppressive acidic protein (IAP) has been reported to be found in the sera of not only cancer patients but also collagen diseases such as SLE and rheumatoid arthritis and certain inflammatory diseases such as liver abcess and pyothorax. IAP is proved to be one of the heterogeneity of human serum α1 -acid glycoprotein and to suppress both phytohemagglutinin-induced lymphocyte blast formation and mixed-lymphocyte reaction in vitro (Cancer Research, 41 : 3244, 1981).In the present study, we measured IAP by the single radial immunodiffusion methods in patients with various thyroid diseases.The IAP concentration in patients with subacute thyroiditis was 956 ± 256μg/ml (mean ± S.D., n=32), which is significantly higher than that in hyperthyroidism (267 ± 64μg/ml, n=10), hypothyroidism (328 ± 81μg/ml, n=9), chronic thyroiditis (366 ± 120 μg/ml, n=24) and destructive thyroiditis (352 ± 34μg/ml, n=4), respectively. The normal value of IAP concentration is below 500μg/ml.After therapeutic administration of prednisolone or salicylate to patients with subacute thyroiditis, IAP rapidly decreased to normal levels in association with the recovery of elevated erythrocyte sedimentation rate (ESR) and serum thyroxine (T4) and triiodothyronine (T3).In the densitometric tracing of IAP separated by thin-layer isoelectric focusing at a pH range of 2.5 to 5, the major acidic protein had an isoelectric point (pI) of 3.0 in patients with subacute thyroiditis during the active phase as well as in one patient with gastric cancer. Furthermore, the acidic protein at pI 3.0 decreased and the one at pI 3.1, which is the major protein observed in normal serum, became prominent during the recovery phase in patients with subacute thyroiditis. The major acidic protein also had a pI of 3.1 in the sera of patients with hyperthyroidism, hypothyroidism and chronic thyroiditis.IAP remained within the normal range in a patient with destructive thyroiditis who showed thyrotoxic symptoms and then became hypothyroid.It is suggested that the determination of IAP is useful in the clinical diagnosis of subacute thyroiditis. Further analysis of IAP might be helpful for the clarification of the pathogenesis of subacute thyroiditis.