Levels Of Degradation Products Research Articles

Clinicopathological features and prognosis of IgA vasculitis nephritis with nephrotic-range proteinuria in children.

To investigate the clinical features, kidney pathology, treatment regimens, and clinical outcomes of IgA vasculitis nephritis (IgAVN) with nephrotic-range proteinuria in children. A retrospective review of children diagnosed with IgAVN between January 2019 and December 2022 was conducted. Participants were divided into two groups based on their urine protein/creatinine (UPCR) levels. Biodata, clinical characteristics, laboratory findings, pathologic features, treatment regimens, and outcomes were abstracted from case records and analyzed. A total of 255 children were identified, 94 with nephrotic-range proteinuria (UPCR ≥ 200 mg/mmol) and 161 with non-nephrotic proteinuria (UPCR < 200 mg/mmol). Patients in the nephrotic-range proteinuria group were significantly younger and had worse grades of glomerular and acute tubulointerstitial injury compared to those in the non-nephrotic proteinuria group. Higher levels of blood urea nitrogen (BUN), D-dimer (DD), and fibrin degradation products (FDP), and lower levels of total protein (TP), albumin (ALB), urine creatinine (Cr), prothrombin time (PT), activated partial thromboplastin time (APTT), IgG, CD3 + cells, and CD4 + cells were found in patients in the nephrotic-range proteinuria group. Clinical outcome of patients with nephrotic-range proteinuria was significantly associated with ISKDC grading, proportion of glomerular crescents and severity of acute tubulointerstitial injury. Children with nephrotic-range proteinuria exhibit more severe disordered immunologic function, hypercoagulability, glomerular and tubulointerstitial pathological damage, and have worse outcomes than those with lower proteinuria levels. Clinicians should pay great attention to the kidney injury and more extensive studies are required to identify optimal treatment regimens to improve outcomes in patients.

The effect of perioperative sequential application of multiple doses of tranexamic acid on postoperative blood loss after PLIF: a prospective randomized controlled trial.

Tranexamic acid (TXA) has been utilized in spinal surgery to effectively reduce intraoperative blood loss (IBL) and allogeneic blood transfusion rates. However, the traditional TXA regimen might last the entire duration of hyperfibrinolysis caused by surgical trauma, resulting in its limited ability to reduce postoperative blood loss (PBL). Therefore, the aim of this study was to investigate the effectiveness of perioperative sequential administration of multiple doses of TXA in reducing PBL in patients who underwent posterior lumbar interbody fusion (PLIF). From October 2022 to June 2023, 231 patients who were diagnosed with lumbar degenerative disease and scheduled to undergo PLIF were prospectively enrolled in the present study. The patients were randomly divided into three groups. Moreover, all patients received an intravenous injection of TXA at a dose of 15mg/kg 15min before the surgical skin incision. Patients in Group A received a placebo of normal saline after surgery, while patients in Group B received three additional intravenous injections of TXA at a dose of 15mg/kg every 24h. Patients in Group C received three additional intravenous injections of TXA at a dose of 15mg/kg every 5h. The primary outcome measure was PBL. In addition, this study assessed total blood loss (TBL), IBL, routine blood parameters, liver and kidney function, coagulation parameters, fibrinolysis indexes, inflammatory indicators, drainage tube removal time (DRT), length of hospital stay (LOS), blood transfusion rate, and incidence of complications for all subjects. The PBL, TBL, DRT, and LOS of Group B and Group C were significantly lower than those of Group A ( P <0.05). The level of D-dimer (D-D) in Group C was significantly lower than that in Group A on the first day after the operation ( P =0.002), and that in Group B was significantly lower than that in Group A on the third day after the operation ( P =0.003). The interleukin-6 levels between the three groups from 1 to 5 days after the operation were in the order of Group A > Group B > Group C. No serious complications were observed in any patient. The results of multiple stepwise linear regression analysis revealed that PBL was positively correlated with incision length, IBL, smoking history, history of hypertension, preoperative fibrinogen degradation product level, and blood transfusion. It was negatively correlated with preoperative levels of fibrinogen, red blood cells, blood urea nitrogen, and age. Compared to female patients, male patients had an increased risk of PBL. Finally, the incidence of PBL was predicted. Sequential application of multiple doses of TXA during the perioperative period could safely and effectively reduce PBL and TBL, shorten DRT and LOS, reduce postoperative D-D generation, and reduce the postoperative inflammatory response. In addition, this study provided a novel prediction model for PBL in patients undergoing PLIF.

ADAMTS-13: A Prognostic Biomarker for Portal Vein Thrombosis in Japanese Patients with Liver Cirrhosis.

Portal vein thrombosis (PVT), one of the most prevalent hepatic vascular conditions in patients with liver cirrhosis (LC), is associated with high mortality rates. An imbalance between a disintegrin-like metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) enzyme and von Willebrand factor (VWF) is responsible for hypercoagulability, including spontaneous thrombus formation in blood vessels. Herein, we aimed to identify potential prognostic and diagnostic biomarkers in Japanese patients with LC and PVT. In total, 345 patients were divided into two groups: 40 patients who developed PVT (PVT group) and 305 who did not develop PVT (NPVT group). Among the 345 patients with LC, 81% (279/345) were deemed ineligible due to the presence of preventive comorbidities, active or recent malignancies, and organ dysfunction. The remaining 66 patients were divided into two groups: the PVT group (n = 33) and the NPVT group (n = 33). Plasma ADAMTS-13 activity (ADAMTS-13:AC) and the vWF antigen (VWF:Ag) were measured using enzyme-linked immunosorbent assays. Contrast-enhanced, three-dimensional helical computed tomography (CT) was used to detect and characterize PVT. ADAMTS-13:AC was significantly lower in the PVT group than in the NPVT group. No significant differences in plasma vWF:Ag or liver stiffness were observed between the two groups. ADAMTS-13:AC of <18.8 was an independent risk factor for PVT on multivariate analyses (odds ratio: 1.67, 95% confidence interval: 1.21-3.00, p < 0.002). The receiver operating characteristic analysis of ADAMTS-13:AC revealed an area under the curve of 0.913 in PVT detection. Patients with PVT having ADAMTS-13:AC ≥18.8 (n = 17) had higher albumin levels and better prognoses than those with ADAMTS-13:AC <18.8 (n = 16). No significant correlations of ADAMTS-13:AC levels with either fibrin degradation product or D-dimer levels were observed. ADAMTS-13:AC levels could be potential diagnostic and prognostic biomarkers for PVT in Japanese patients with LC.

Quantitative determination of the components of the mixture – ear drops “Melavet” by the method of high-performance liquid chromatography

The pharmaceutical industry is one of the most regulated industries in the world, and most medicines remain safe and effective. The level of impurity and degradation products in active pharmaceutical ingredients (APIs) must be strictly controlled and meet the specifications required by international bodies. for many years, chromatography has been the method of choice for assessing the chemical purity of medicinal substances and products and has a wide range of applications in the pharmaceutical industry, from research and development to laboratory quality control. The ability to integrate mass spectrometry into the chromatography workflow has been a real breakthrough in the science of separation, finding many inscriptions, especially in the field of pharmaceutical analysis. Therefore, the relevance of the research lies in finding the quantity of the composition of the created mixture – ear drops “Melavet” by the HPLC method with mass detection of the initial components. The purpose of the work is to create analytical methods for determining the active components of the mixture when they are present in the sample and interact with each other. Materials and methods: Chromato-mass-spectrometric studies, high-performance liquid chromatography (HPLC, LCMS). LCMS device: Agilent 1200 Quaternary DAD HPLC System (degasser, binary pump, autosampler, column thermostat, diode-matrix detector; single-quadrupole mass spectrometer Agilent 1100 LCMSD SL instrument; OpenLAB CDS Software. For the new combined veterinary test of ear drops “Melavet” 10 ml, containing various components, it is necessary to develop optimal methods of standardization. For this, 6 solutions of the external standard of each component were prepared. Based on the research, a method was developed for the simultaneous determination of the components in the model mixture ear drops “Melavet” 10 ml by the method of high-performance liquid chromatography using the same mobile and stationary phases, as well as similar chromatographic conditions, which were used during the study of individual samples of the external standard. When analyzing the chromatographic data, the presence of dioxidin in the mixture was fully consistent. In comparison with the external standards of each component, there are separate icons of substances on the chromatogram of the mixture, which contain information about the purity of the components and the interaction between them. During the research, a highly sensitive technique for the simultaneous determination of the components of the model mixture “Melavet” ear drops 10 ml by the method of high-performance liquid chromatography was developed. The optimal conditions for the simultaneous determination of the components of the mixture in one sample are selected. It was established that there is no interaction between the components of the mixture when they are simultaneously in the sample solution.

Characteristics of renal pathology and coagulation function in IgA nephropathy and IgA vasculitis associated nephritis

BackgroundThe objective of this study is to investigate the clinical and pathological differences between patients with IgA nephropathy (IgAN) and IgA vasculitis associated nephritis (IgAVN).MethodsA total of 253 patients with IgAN and 71 patients with IgAVN were retrospectively included in the study, and clinical and laboratory data were collected and analysed.ResultsCompared with IgAVN group, months from onset to kidney biopsy were significantly prolonged in IgAN patients because of the lack of obvious symptoms such as rash, abdominal symptoms, and joint pain (13.5 ± 26.6 vs. 10.2 ± 31.6 months, P = 0.007), and the levels of serum creatinine (92.3 ± 94.7 vs. 68.9 ± 69.2 µmol/L, P = 0.015) was higher and eGFR (99.1 ± 35.2 vs. 123.4 ± 41.8 mL/min/1.73m2, P < 0.001) was lower in IgAN group. The pathological results revealed that patients with IgAN have a greater degree of chronic kidney injury compared to patients with IgAVN. In addition, the levels of plasma D-Dimers (1415.92 ± 1774.69 vs. 496.78 ± 711.91 ng/mL, P < 0.001) and fibrinogen degradation products (FDP) (3.92 ± 4.73 vs. 1.63 ± 2.46 µg/mL, P = 0.001) were significantly higher in IgAVN patients than in IgAN patients. The deposition of fibrinogen in the renal tissues was more severe and the cumulative partial remission rate was higher in patients with IgAVN as compared to those with IgAN (P = 0.001).ConclusionsIn comparison, IgAN patients had poorer renal function, whereas IgAVN patients had more severe coagulation abnormalities. These findings provide a basis for the differentiation of the two diseases at an early stage.

Tumor Lysis Syndrome in a Patient with BRAFV600E Mutated Colon Cancer Treated with Cetuximab and Encorafenib.

Tumor lysis syndrome (TLS) is a fatal complication associated with chemotherapy. We herein report a case of TLS in a 73-year-old woman with metastatic BRAFV600E mutated colon cancer after she received combined treatment with cetuximab and encorafenib. The serum uric acid, urea nitrogen, and creatinine levels were elevated on day four of the first cycle. The fibrin degradation product (FDP) and D-dimer levels were also high. Diuresis and rasburicase were initiated for TLS, and the laboratory data all normalized on day 8. Thus, the possibility of TLS being induced by targeted drugs in patients with solid tumors, including colorectal cancer, must not be overlooked.

Hematological disorders as a complication of COVID-19

Background. Coronavirus disease (COVID-19) can affect the blood and hemostasis systems and lead to complications that require intensive care. The aim is to detect such common complications by studying literary sources and clinical experience. Materials and methods. The search for relevant literature was conducted in PubMed, and in the other databases such as Science Direct, Google Scholar, Scopus and Web of Science. The literature search was done using the keywords “COVID-19”, “SARS-CoV-2” in combination with “coagulation dysfunction”, “coagulopathy”, “hematological manifestations”, “hematological parameters”, “deep vein thrombosis”, “pulmonary embolism”, “arterial thrombosis”, “D-dimer”, “fibrinogen”, “lymphopenia”, “thrombocytopenia”. Results. COVID-19-associated coagulopathy is characterized by high levels of D-dimer and fibrin degradation products in blood plasma, changes in prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count. Endothelial dysfunction caused by coronavirus leads to an increased risk of thrombotic complications, both in venous and arterial systems, additionally to the existing higher risk of thrombosis in the intensive care unit. The venous thromboembolism frequency among unvaccinated hospitalized patients and during ultrasound screening is significantly higher. Coronavirus disease can lead to arterial thrombosis in areas such as the aorta, kidneys, cerebral and peripheral arteries. COVID-19 can cause enhanced-fibrinolytic-type disseminated intravascular coagulation or limited thrombotic microangiopathy. According to research, patients with severe COVID-19 usually had leukocytosis, lymphopenia, and an elevated neutrophil-to-lymphocyte ratio. Thrombocytopenia is observed not only during the acute coronavirus disease, but also in the post-COVID-19 period. Both thrombosis and bleeding can occur in patients undergoing extracorporeal membrane oxygenation. Conclusions. A high level of D-dimer, a prolongation of prothrombin time, an increase or a quick decrease in fibrinogen level, lymphopenia, neutrophilia, and an increase in the neutrophil-to-lymphocyte ratio are considered prognostic factors for the severity of coronavirus disease. Deep vein thrombosis and pulmonary embolism are the most common thrombotic events in patients with COVID-19. Arterial thrombosis occurs more often in the cerebral arteries and arteries of the extremities.

Elevated markers of early fibrinolysis disorder as predictors of poor 90-day prognosis in patients with aneurysmal subarachnoid hemorrhage: A large prospective cohort study

ObjectivesEarly fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with poor 90-day prognosis in patients with aSAH. Materials and MethodsA total of 693 consecutive aSAH patients from April 2020 to December 2022 were selected from the Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage (LongTEAM) trial. Poor 90-day prognosis was defined as a modified Rankin Scale 3-6 at 90 days after discharge. D-dimer (DD) and Fibrin degradation product (FDP) levels on admission were used to assess fibrinolysis disorder and patients were classified according to their quartiles. Multivariable logistic regression analysis was used to determine the association. ResultsOf 693 patients included, 131 (18.9%) had poor 90-day prognosis. Patients in the highest quartile of DD and FDP levels had higher risk of poor 90-day prognosis than those in the first quartile (DD: adjusted odds ratio [aOR]=2.22, 95% confidence interval [CI], 1.13-4.36, p = 0.021; FDP: aOR=2.87, 95% CI, 1.48-5.58, p = 0.002), after adjusting for potential risk factors. Meanwhile, a linear dose-response relationship between DD and FDP and poor 90-day prognosis was found. Subgroup analysis showed that DD and FDP were consistently associated with poor 90-day prognosis across subgroups, and no intergroup interaction was found. Interestingly, the associations of DD and FDP with poor 90-day prognosis were more significant in low-grade aSAH patients. ConclusionsElevated markers of early fibrinolysis disorder, including DD and FDP on admission, were associated with poor 90-day prognosis in aSAH patients.

Early identification of lung cancer patients with venous thromboembolism: development and validation of a risk prediction model

IntroductionVenous thromboembolism(VTE) is a leading cause of death in patients with lung cancer. Furthermore, hospitalization of patients with advanced lung cancer for VTE treatment represents a major economic burden on the national public health resources. Therefore, we performed this prospective study to identify clinical biomarkers for the early identification of VTE in lung cancer patients.MethodsThis prospective study enrolled 158 patients with confirmed lung cancer, including 27 who were diagnosed with VTE within six months of the follow-up after lung cancer diagnosis. Multivariate logistic regression analysis was used to evaluate the diagnostic performancese of all the relevant clinical features and laboratory indicators in identifying lung cancer patients with a higher risk of VTE. A novel risk prediction model was constructed consisting of five clinical variables with the best diagnostic performances and was validated using the receiver operation characteristic(ROC) curves. The diagnostic performances of the new risk prediction model was also compared with the Khorana risk score (KRS) and the Padua risk score (PRS).ResultsThe VTE group of lung cancer patients (n = 27) showed significantly higher serum levels of fibrin degradation products (FDP), D-dimer, thrombomodulin (TM), thrombin-antithrombin-complex (TAT), α2-plasmin inhibitor-plasmin Complex (PIC), and tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC) compared to those in the non-VTE group (n = 131). ROC curve analyses showed that the diagnostic efficacy of the new VTE risk prediction model with TM ≥ 9.75 TU/ml, TAT ≥ 2.25ng/ml, t-PAIC ≥ 7.35ng/ml, history of VTE, and ECOG PS score ≥ 2 was superior than the KRS and the PRS in the early identification of lung cancer patients with a higher risk of VTE.ConclusionsThe new risk prediction model showed significantly high diagnostic efficacy in the early identification of lung cancer patients with a high risk of VTE. The diagnostic efficacy of the new risk prediction model was higher than the KRS and the PRS in this cohort of lung cancer patients.

Increased D-dimer and fibrin degradation product levels as potential indicators for evaluating infection-related acute urticaria: a case-case-control study.

About 20% of world population suffer from acute urticaria at some stage in their lives. Recent studies showed coagulation dysfunction in chronic urticaria. The involvement of coagulation changes in acute urticaria remains unclear. Fifty-eight acute urticaria patients were enrolled in this study and divided into two groups (referred to throughout as infection-related and infection-unrelated acute urticaria). The routine laboratory parameters including coagulation tests between the two groups were compared. The correlation between coagulation tests and CRP at acute phase was also assessed. Dynamic change of routine coagulation test results at acute phase and resolving phase was compared. The potential performance of coagulation for infection indication was tested. We found D-dimer, fibrin degradation product (FDP), and fibrinogen (Fg) increased in the acute phase of infection-related acute urticaria patients. D-dimer, FDP, Fg, and APTT are positively correlated with CRP in the acute phase. D-dimer and FDP decreased in the resolving phase of infection-related acute urticaria patients. Higher D-dimer (> 0.48mg/L) and FDP (> 3.84mg/L) may indicate infection-related acute urticaria. In conclusion, in acute urticaria with low venous thromboembolism risk, D-dimer level and dynamic change can be potentially used for the infection-related clinical practice management.

Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate.

Variable fibrinogen content within cryoprecipitate makes accurate dosing challenging in patients with coagulopathic bleeding, in addition to pathogen transmission risks associated with its administration. Purified and standardized human fibrinogen concentrates (HFCs) represent reliable alternatives. Full cryoprecipitate characterization is required to inform selection of an appropriate fibrinogen source for supplementation therapy. Extended biochemical comparison of pooled cryoprecipitate and HFC (Fibryga, Octapharma) was performed using commercially available assays to determine levels of variability in cryoprecipitate and HFC. In addition to standard procoagulant factors, measurements included activities of platelet-derived microparticles (PMPs) and plasminogen, and levels of fibrin degradation products. Cryoprecipitate contains lower fibrinogen levels than HFC (4.83 vs.19.73 g/L; p<0.001), translating to approximately half the amount of fibrinogen per standard cryoprecipitate dose (two pools, pre-pooled from five donations each) vs. HFC (2.14 vs. 3.95 g; p<0.001). Factor XIII (FXIII) levels were also lower in cryoprecipitate vs. HFC (192.17 vs. 328.33 IU/dL; p = 0.002). Levels of procoagulants in cryoprecipitate, such as von Willebrand Factor (VWF) and factor VIII (FVIII), were highly variable, as was PMP activity. A standard cryoprecipitate dose contains significantly higher levels of measured plasminogen and D-dimer fragments than a standard HFC dose. The tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels.

Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression

Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by central nervous (CNS) demyelination resulting in axonal injury and neurological deficits. Essentially, MS is driven by an auto-amplifying mechanism of inflammation and cell death. Current therapies mainly focus on disease modification by immunosuppression, while no treatment specifically focuses on controlling cell death injury. Here, we report that ferroptosis, an iron-catalyzed mode of regulated cell death (RCD), contributes to MS disease progression. Active and chronic MS lesions and cerebrospinal fluid (CSF) of MS patients revealed several signs of ferroptosis, reflected by the presence of elevated levels of (labile) iron, peroxidized phospholipids and lipid degradation products. Treatment with our candidate lead ferroptosis inhibitor, UAMC-3203, strongly delays relapse and ameliorates disease progression in a preclinical model of relapsing-remitting MS. In conclusion, the results identify ferroptosis as a detrimental and targetable factor in MS. These findings create novel treatment options for MS patients, along with current immunosuppressive strategies.

An Observational Study on Levels of Serum Fibrin Degradation Product (FDP), D-Dimer and Procalcitonin in Burn Sepsis

Background: Despite improvements in burn management, infection is still the biggest challenge in major burn cases globally. Burn causes extensive tissue destruction, immune dysfunction, increases the risk of infection and septicemia with high morbidity and mortality. The aim of this study was to observe the levels of serum fibrin degradation product (FDP), D-dimer and procalcitonin in patients with burn sepsis treated in intensive care unit (ICU). Materials &amp; Methods: This observational study was carried out in Department of Burn and Plastic Surgery, Dhaka Medical College Hospital, Dhaka from February 2018 to January 2019. Forty (40) patients with major burns, from (15% to 50% total body surface area burn) with burn sepsis, were recruited for the study. In all cases, plasma level of fibrin degradation product (FDP), D-dimer and procalcitonin were measured and recorded. Result: Male predominance (57.5%) was observed in our study. Eighty five percent (85%) patients had total body surface area burn (TBSA) 20% to 50%. Sixteen patients (40%) suffered from flame burn, 13 (32.5%) patients from scalds and 11 (27.5%) patients had high voltage electric burn. The value of FDP was raised in 62.5% patients, D- dimer in 67.5% patients. Serum procalcitonin level was high (&gt; 2ng/ml), indicating burn sepsis in 47.5% cases but it was not significant (2 sample t – test reveals no significant relationship between rise of serum level of procalcitonin and presence of burn sepsis) Conclusion: Fibrin degradation product (FDP) and D- dimer were raised in two-thirds of burn cases while procalcitonin in two-fifths cases. Measurement of serum level of FDP, Ddimer and procalcitonin may give an idea regarding early onset of bacterial infection and burn sepsis and can serve as an indicator for burn sepsis. J Bangladesh Coll Phys Surg 2023; 41: 193-197

Associations of neutral pH, low-GDP peritoneal dialysis solutions with patient survival, transfer to haemodialysis and peritonitis.

Peritoneal dialysis (PD) solutions containing low levels of glucose degradation products (GDPs) are associated with attenuation of peritoneal membrane injury and vascular complications. However, clinical benefits associated with neutral-pH, low-GDP (N-pH/L-GDP) solutions remain unclear. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the associations between N-pH/L-GDP solutions and all-cause mortality, cause-specific mortality, transfer to haemodialysis (HD) for ≥30days and PD peritonitis in adult incident PD patients in Australia and New Zealand between 1 January 2005 and 31 December 2020 using adjusted Cox regression analyses. Of 12814 incident PD patients, 2282 (18%) were on N-pH/L-GDP solutions. The proportion of patients on N-pH/L-GDP solutions each year increased from 11% in 2005 to 33% in 2017. During the study period, 5330 (42%) patients died, 4977 (39%) experienced transfer to HD and 5502 (43%) experienced PD peritonitis. Compared with the use of conventional solutions only, the use of any form of N-pH/L-GDP solution was associated with reduced risks of all-cause mortality {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]}, cardiovascular mortality [aHR 0.65 (95% CI 0.56-0.77)], infection-related mortality [aHR 0.62 (95% CI 0.47-0.83)] and transfer to HD [aHR 0.79 (95% CI 0.72-0.86)] but an increased risk of PD peritonitis [aHR 1.16 (95% CI 1.07-1.26)]. Patients who received N-pH/L-GDP solutions had decreased risks of all-cause and cause-specific mortality despite an increased risk of PD peritonitis. Studies assessing the causal relationships are warranted to determine the clinical benefits of N-pH/L-GDP solutions.

The Renin-Angiotensin System in COVID-19: Can Long COVID Be Predicted?

(1) Background: Co-morbidities such as hypertension and cardiovascular disease are major risk factors for severe COVID-19. The renin-angiotensin system (RAS) is critically involved in their pathophysiology and is counter-balanced by both angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and the kallikrein-kinin system (KKS). Considerable research interest with respect to COVID-19 treatment is currently being directed towards the components of these systems. In earlier studies, we noticed significantly reduced carboxypeptidase N (CPN, KKS member) activity and excessive angiotensin-converting enzyme (ACE, RAS member) activity in the sera of both hospitalized COVID-19 patients and a subgroup of convalescent patients. The data had been obtained using labeled bradykinin (BK) as a reporter peptide, which is a target of both CPN and ACE. The data were supplemented with mass-spectrometry-based serum proteomic analysis. Here, we hypothesize that the degree of BK serum degradation could be indicative of Long COVID. (2) Review and Discussion: The recent literature is briefly reviewed. The fact that the levels of the BK serum degradation products did not reach normal concentrations in almost half of the patients during convalescences could have been partially due to a dysregulated RAS. (3) Conclusions: Standard tests for routine patient care in Long COVID come often back normal. We suggest that the measurement of selected members of the RAS such as ACE and angiotensin II or the use of our BK degradation assay could identify Long COVID candidates. Clinical studies are required to test this hypothesis.

Relationship between the postoperative lactate dynamic levels, the acute gastrointestinal injury and the prognosis among patients who undergo surgical treatment for acute type A aortic dissection

IntroductionThis study aimed to determine the relationship between the postoperative lactate dynamic levels, the postoperative acute gastrointestinal injury (AGI), and the prognosis among the patients who underwent surgical treatment for an acute Stanford type-A aortic dissection (aTAAD). MethodsA total of 271 aTAAD patients were recruited and monitored. Of the 271 aTAAD patients, 29.2% developed an AGI and were designated as the AGI group (n = 79); the other patients (n = 192) were designated as the non-AGI group. According to the 2-year follow up, the aTAAD patients were also divided into the alive and death subgroups for further analysis. ResultsBinary logistic regression analysis revealed that the postoperative 4-h lactate (P4L) level, time-to-return to the normal blood lactate level (TRNL), postoperative 16-h lactate (P16L) level, and neutrophil granulocyte (NEU) count had a good predictive value for an AGI after aTAAD. The 8-week and 2-year mortality rates were higher in the AGI group than the non-AGI group (P < 0.05). Basic data and clinical characteristics were significantly different between the alive and death groups (P < 0.05). A higher AGI rate and mortality occurred in the P4L level ≥10.15 mmol/L subgroup, TRNL ≥21-h subgroup, P16L level ≥2.95 mmol/L subgroup, NEU count ≥10.9 × 109/L subgroup, PaO2 < 77.7 mmHg subgroup, WBC count ≥9.58 × 109/L subgroup, and the operative time ≥427 min subgroup than the corresponding comparison subgroups (P < 0.05). The postoperative 0-h lactate (P0L) level, TRNL, postoperative 24-h lactate (P24L) level, D-dimer level, fibrinogen degradation products (FDP) level, duration of mechanical ventilation, and length of hospitalization were independent factors influencing the 30-day mortality rate in patients who underwent surgery for an aTAAD (P < 0.05). Cox regression multivariate analysis after univariate analysis of all-cause mortality showed the TRNL, postoperative 12-h lactate (P12L) level, P16L level, P24L level, D-dimer level, FDP level, and length of hospitalization were independently associated with the 2-year mortality rate in patients who underwent surgery for an aTAAD (P < 0.05). ConclusionThe postoperative lactate changes and TRNL effectively predicted postoperative AGI and the mortality rate in patients with who underwent surgery for an aTAAD. The TRNL and P24L level were independent risk factors for the 30-day and 2-year mortality rates in patients who underwent surgery for an aTAAD.

Factors Associated With Prolonged Ventilation in Patients Receiving Prone Positioning Protocol With Muscle Relaxants for Severe COVID-19 Pneumonia.

Prone positioning and neuromuscular blocking agents (NMBAs) are frequently used to treat severe respiratory failure from COVID-19 pneumonia. Prone positioning has shown to improve mortality, whereas NMBAs are used to prevent ventilator asynchrony and reduce patient self-inflicted lung injury. However, despite the use of lung-protective strategies, high death rates in this patient population have been reported. We retrospectively examined the factors affecting prolonged mechanical ventilation in subjects receiving prone positioning plus muscle relaxants. The medical records of 170 patients were reviewed. Subjects were divided into 2 groups according to ventilator-free days (VFDs) at day 28. Whereas subjects with VFDs < 18 d were defined as prolonged mechanical ventilation, subjects with VFDs ≥18 d were defined as short-term mechanical ventilation. Subjects' baseline status, status at ICU admission, therapy before ICU admission, and treatment in the ICU were studied. Under the proning protocol for COVID-19, the mortality rate in our facility was 11.2%. The prognosis may be improved by avoiding lung injury in the early stages of mechanical ventilation. According to multifactorial logistic regression analysis, persistent SARS-CoV-2 viral shedding in blood (P = .03), higher daily corticosteroid use before ICU admission (P = .007), delayed recovery of lymphocyte count (P < .001), and higher maximal fibrinogen degradation products (P = .039) were associated with prolonged mechanical ventilation. A significant relationship was found between daily corticosteroid use before admission and VFDs by squared regression analysis (y = -0.00008522x2 + 0.01338x + 12.8; x: daily corticosteroids dosage before admission [prednisolone mg/d]; y: VFDs/28 d, R2 = 0.047, P = .02). The peak point of the regression curve was 13.4 d at 78.5 mg/d of the equivalent prednisolone dose, which corresponded to the longest VFDs. Persistent SARS-CoV-2 viral shedding in blood, high corticosteroid dose from the onset of symptoms to ICU admission, slow recovery of lymphocyte counts, and high levels of fibrinogen degradation products after admission were associated with prolonged mechanical ventilation in subjects with severe COVID-19 pneumonia.

Retinochoroidal Manifestation of Toxoplasmosis in a Young Patient

We report the case of a 15-year-old young girl, with retinochoroidal manifestation of toxoplasmosis, without vitritis. Serology for Toxoplasma gondii was positive (IgG positive /IgM negative), but PCR for Toxoplasma gondii in peripheral blood samples was negative. Blood tests including complete hemogram (total leukocyte, red blood cell and platelet count) except for hemoglobin, coagulogram (APTT, INR, and fibrin degradation product level) and routine blood biochemistry (serum urea, creatinine, and random blood sugar) were within normal limits. The serum levels of triglycerides, low density lipoproteins, high-density lipoproteins and calcium were within normal limits. Direct ophthalmoscopy of the right eye revealed a well-demarcated circular atrophic pigmented scar of about four disc diameters involving the macula. We did not initiate any therapy, because the process appeared to be active anymore. In our case demonstrate of retinochoroidal manifestation of toxoplasmosis by routine fundus examination in a young patient with uncharacteristic complaints.

Experimental Analysis of Chemically Degraded Lubricant’s Impact on Spur Gear Wear

The impact of lubricating oil degradation, which can happen during both storage and use, on spur gear wear is thoroughly examined in this paper at all scales, from macro to nano. A thorough structure was created by combining the results of testing performed at the macroscale on a test rig and at the nanoscale using tools such as FESEM analysis. Using a single-stage spur transmission under two different working conditions (‘40 Nm, 1200 rpm, 198 h’ and ‘50 Nm, 500 rpm, 90 min’), macroscale experiments were carried out using both conventional and artificially degraded lubricant oils. Aqueous hydrochloric acid (36.46% v/v concentration) was added to the lubricating lubricant to induce artificial degradation. Wear development and oil degradation were monitored in real time using tools such as metallic wear detritus sensors and oil sensor suites. Offline methods, such as total acid number (TAN) and pH value readings, were used with periodic lubricant oil samples. It was discovered through both online and offline monitoring methods that the spur gear experienced substantial wear in lubricant-degraded conditions. By demonstrating elevated levels of oxidative degradation products and the formation of new oxidative compounds, such as sulphates and aromatic groups, the attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis of the oil degradation at the nanoscale verified this. In addition, water creation was noted. It is interesting to note that the pH meter has become a viable option for detecting oil degradation and offers a useful way to keep track of lubricant quality. Overall, this study shows that there is a strong connection between macroscale and nanoscale phenomena in the complete method created for assessing the tribological performance of gear lubricants.

Clinical analysis of 11 cases of pregnancy with aortic dissection

Objective: To investigate the treatment and maternal and fetal outcomes of pregnant women with aortic dissection (AD). Methods: The clinical data of 11 pregnant women with AD treated at the First Affiliated Hospital of Air Force Military Medical University from January 1st, 2011 to August 1st, 2022 were collected, and their clinical characteristics, treatment plans and maternal and fetal outcomes were analyzed retrospectively. Results: (1) Clinical characteristics: the age of onset of 11 pregnant women with AD was (30±5) years old, and the week of pregnancy of onset was (31.4±8.0) weeks. Clinical manifestations: the main symptoms were sudden onset of chest and back pain or low back pain. Type of AD: 8 cases of Stanford type A, and 3 cases of type B. The aortic width was (42±11) mm. Diagnostic methods: the diagnosis of AD was confirmed by transthoracic echocardiography (TTE), computed tomography angiography (CTA) or enhanced CT examination, among which 4 cases were confirmed by CTA examination, 4 cases by TTE examination, and 3 cases by enhanced CT examination. Laboratory results: white blood cell count was (15.4±8.7) ×109/L, neutrophil count was (13.5±8.5) ×109/L, the median D-dimer level was 2.7 mg/L (2.1-9.2 mg/L), and the median fibrin degradation products level was 12.0 mg/L (5.4-36.1 mg/L). (2) Treatments: all 11 patients were admitted to hospital in emergency. Before operation, the departments of cardiac surgery, obstetrics, pediatrics and anesthesiology cooperated to develop individualized treatment plan. Aortic surgery was performed in 11 pregnant women with AD. In 6 of them, pregnancy termination was performed at the same time as aortic surgery, and aortic surgery was performed after cesarean section. Four cases of pregnancy termination and aortic operation were performed by stages, including aortic operation after cesarean section in 2 cases, and cesarean section after aortic operation in 2 cases. One case (12+6 weeks of gestation) had spontaneous abortion on the day after aortic surgery. The gestational age of the 11 patients on pregnancy termination was (32.9±7.4) weeks. Aorta surgical methods: 7 patients received under extracorporeal circulation ascending aorta replacement ± aortic valve replacement ± coronary artery transplantation (or coronary artery bypass transplantation)± left and right coronary Cabrol + total arch replacement (or aortic arch replacement)± stent implantation, 1 patient received under extracorporeal circulation aortic root replacement, and 3 patients underwent aortic endoluminal isolation. (3) Maternal and fetal outcomes: among the 11 pregnant women with AD, 9 (9/11) survived, 2 (2/11) died with lower limb ischemia before the onset of the disease. A total of 10 newborns were born in 9 pregnant women after delivery (1 of them was twins), and the 2 cases were spontaneous abortion after aortic surgery in the first trimester (12+6 weeks) and fetal death after hysterotomy in the second trimester (26+3 weeks), respectively. Among the 10 surviving neonates, 3 were full-term infants and 7 were premature infants. The birth weight of newborn was (2 651±784) g. Respiratory distress syndrome was found in 6 cases. The newborns were followed up for (5.6±3.6) years after birth, and the infants developed well during the follow-up period. Conclusions: Pregnancy complicated with AD is dangerous, and chest and back pain is the main clinical manifestation of this disease. With early identification and selection of appropriate diagnostic methods, multidisciplinary diagnosis and treatment, mother and children could obtain good outcomes.