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Frontiers in Immunology 2024This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved...
This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
Topics: Humans; Pancreatic Neoplasms; Antigens, Neoplasm; Liquid Biopsy; Precision Medicine; Cancer Vaccines; Liver Neoplasms; Male; Peptides; Middle Aged; Vaccines, Subunit; Immunization; Female; Biomarkers, Tumor
PubMed: 38938562
DOI: 10.3389/fimmu.2024.1414737 -
Journal of Cardiothoracic Surgery Jun 2024Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is...
BACKGROUND
Thoracic endovascular aortic repair (TEVAR) is a minimally invasive technique used to treat type B aortic dissections. Left subclavian artery (LSA) reconstruction is required when treating patients with involvement of LSA. The best antiplatelet therapy after LSA reconstruction is presently uncertain.
METHODS
This study retrospectively analyzed 245 type B aortic dissection patients who underwent left subclavian artery revascularization during TEVAR. Out of 245 patients, 159 (64.9%) were in the single antiplatelet therapy (SAPT) group, receiving only aspirin, and 86 (35.1%) were in the dual antiplatelet therapy (DAPT) group, receiving aspirin combined with clopidogrel. During the 6-month follow-up, primary endpoints included hemorrhagic events (general bleeding and hemorrhagic strokes), while secondary endpoints comprised ischemic events (left upper limb ischemia, ischemic stroke, and thrombotic events), as well as death and leakage events. Both univariate and multivariate Cox regression analyses were performed on hemorrhagic and ischemic events, with the Kaplan-Meier method used to generate the survival curve.
RESULTS
During the six-month follow-up, the incidence of hemorrhagic events in the DAPT group was higher (8.2% vs. 30.2%, P < 0.001). No significant differences were observed in ischemic events, death, or leakage events among the different antiplatelet treatment schemes. Multivariate Cox regression analysis showed that DAPT (HR: 2.22, 95% CI: 1.07-4.60, P = 0.032) and previous chronic conditions (HR:3.88, 95% CI: 1.24-12.14, P = 0.020) significantly affected the occurrence of hemorrhagic events. Chronic conditions in this study encompassed depression, vitiligo, and cholecystolithiasis. Carotid subclavian bypass (CSB) group (HR:0.29, 95% CI: 0.12-0.68, P = 0.004) and single-branched stent graft (SBSG) group (HR:0.26, 95% CI: 0.13-0.50, P < 0.001) had a lower rate of ischemic events than fenestration TEVAR (F-TEVAR). Survival analysis over 6 months revealed a lower risk of bleeding associated with SAPT during hemorrhagic events (P = 0.043).
CONCLUSIONS
In type B aortic dissection patients undergoing LSA blood flow reconstruction after synchronous TEVAR, the bleeding risk significantly decreases with the SAPT regimen, and there is no apparent ischemic compensation within 6 months. Patients with previous chronic conditions have a higher risk of bleeding. The CSB group and SBSG group have less ischemic risk compared to F-TEVAR group.
Topics: Humans; Male; Female; Retrospective Studies; Platelet Aggregation Inhibitors; Subclavian Artery; Middle Aged; Aortic Dissection; Endovascular Procedures; Aortic Aneurysm, Thoracic; Aged; Clopidogrel; Aspirin; Aorta, Thoracic; Treatment Outcome; Blood Vessel Prosthesis Implantation; Postoperative Complications; Endovascular Aneurysm Repair
PubMed: 38937841
DOI: 10.1186/s13019-024-02932-3 -
Journal of Cardiothoracic Surgery Jun 2024Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of different anesthetic regimens on postoperative cognitive function of elderly patients undergoing thoracic surgery: a double-blinded randomized controlled trial.
OBJECTIVE
Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure.
METHODS
A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively.
RESULTS
POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001).
CONCLUSION
For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.
Topics: Humans; Aged; Male; Female; Thoracic Surgical Procedures; Postoperative Cognitive Complications; Double-Blind Method; Sevoflurane; Aged, 80 and over; Dexmedetomidine; Propofol; Anesthetics, Inhalation; Cognition; Incidence; Remifentanil; Anesthetics, Intravenous
PubMed: 38937812
DOI: 10.1186/s13019-024-02939-w -
Trials Jun 2024Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic...
Effect of ultrasound-guided injection of botulinum toxin type A into shoulder joint cavity on shoulder pain in poststroke patients: study protocol for a randomized controlled trial.
BACKGROUND
Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem.
METHODS
This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score.
DISCUSSION
Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function.
TRIAL REGISTRATION
Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 .
Topics: Humans; Shoulder Pain; Ultrasonography, Interventional; Stroke; Botulinum Toxins, Type A; Randomized Controlled Trials as Topic; Injections, Intra-Articular; Treatment Outcome; Pain Measurement; Shoulder Joint; Time Factors; Hemiplegia; Recovery of Function; Range of Motion, Articular; China; Neuromuscular Agents; Double-Blind Method; Biomechanical Phenomena
PubMed: 38937804
DOI: 10.1186/s13063-024-08258-8 -
Parasites & Vectors Jun 2024Indoor residual spraying (IRS) has been implemented to prevent malaria in Zambia for several decades, but its effectiveness has not been evaluated long term and in Vubwi...
BACKGROUND
Indoor residual spraying (IRS) has been implemented to prevent malaria in Zambia for several decades, but its effectiveness has not been evaluated long term and in Vubwi District yet. This study aimed to assess the association between IRS and the malaria burden in Zambia and Vubwi District and to explore the factors associated with refusing IRS.
METHODS
A retrospective study was used to analyze the association between IRS and malaria incidence in Zambia in 2001-2020 and in Vubwi District in 2014-2020 by Spearman correlation analysis. A case-control study was used to explore the factors associated with IRS refusals by households in Vubwi District in 2021. A logistic regression model was performed to identify factors associated with IRS refusals.
RESULTS
The malaria incidence reached its peak (391/1000) in 2001 and dropped to the lowest (154/1000) in 2019. The annual percentage change in 2001-2003, 2003-2008, 2008-2014, 2014-2018 and 2018-2020 was - 6.54%, - 13.24%, 5.04%, - 10.28% and 18.61%, respectively. A significantly negative correlation between the percentage of population protected by the IRS against the total population in Zambia (coverage) and the average malaria incidence in the whole population was observed in 2005-2020 (r = - 0.685, P = 0.003) and 2005-2019 (r = - 0.818, P < 0.001). Among 264 participants (59 in the refuser group and 205 in the acceptor group), participants with specific occupations (self-employed: OR 0.089, 95% CI 0.022-0.364; gold panning: OR 0.113, 95% CI 0.022-0.574; housewives: OR 0.129, 95% CI 0.026-0.628 and farmers: OR 0.135, 95% CI 0.030-0.608 compared to employees) and no malaria case among household members (OR 0.167; 95% CI 0.071-0.394) had a lower risk of refusing IRS implementation, while those with a secondary education level (OR 3.690, 95% CI 1.245-10.989) had a higher risk of refusing IRS implementation compared to those who had never been to school.
CONCLUSIONS
Increasing coverage with IRS was associated with decreasing incidence of malaria in Zambia, though this was not observed in Vubwi District, possibly because of the special geographical location of Vubwi District. Interpersonal communication and targeted health education should be implemented at full scale to ensure household awareness and gain community trust.
Topics: Zambia; Humans; Case-Control Studies; Malaria; Mosquito Control; Incidence; Retrospective Studies; Insecticides; Female; Male; Animals; Adult; Child, Preschool; Child; Adolescent
PubMed: 38937791
DOI: 10.1186/s13071-024-06328-z -
Journal of Orthopaedic Surgery and... Jun 2024The incidence of cervical spinal brucellosis is low, only a few case reports have been published, and case series are not widely reported in the medical literature....
BACKGROUND
The incidence of cervical spinal brucellosis is low, only a few case reports have been published, and case series are not widely reported in the medical literature. Therefore, clinical features, management, and outcomes of cervical spinal brucellosis are relatively unknown. In this series, the authors report 15 cases of patients with cervical spinal brucellosis, including clinical characteristic, imaging findings, management plans, the institution's experience, and outcomes at 1 year postoperatively.
METHODS
The study reviewed the clinical and radiographic records of 15 patients who received antimicrobial pharmacotherapy, and anterior cervical debridement and fusion for cervical spinal brucellosis. The data collected included patient demographic characteristics, spinal level affected, abscess, neurology, pathological reports, duration and type of antimicrobial regimens, details of orthopedic management, and complications incurred during the procedure.
RESULTS
Neck pain (100%) and limb paralysis (86.7%) were the most common clinical presentations, and the disease had a rapid progression. The C6-7 segment was the most commonly affected segment, followed by C4-5 and C5-6. Imaging commonly revealed epidural or paravertebral abscesses (80%). There was a significant improvement in the VAS, JOA, and NDI scores three months after surgery, and the scores continued to improve until the final follow-up. There was a statistically significant difference between the pre- and postoperative scores (P < 0.05). The ESR and CRP levels returned to normal within three months postoperatively, being 7.7 ± 4.5 mm/h and 7.55 ± 3.48 mg/L, respectively. There were statistically significant differences between the pre- and postoperative levels (P < 0.05). The positive rate of bacterial culture testing of pus or lesion tissues was only 40%, but blood cultures revealed an even lower positivity rate (33.3%). The average antimicrobial pharmacotherapy regimen duration was 6.1 ± 1.9 months. All patients achieved intervertebral bone fusion within 8 months (4.8 ± 1.4 months) after surgery and were cured with non-recurrence.
CONCLUSIONS
Spinal brucellosis rarely affects the cervical region, but its impact is more dangerous due to potential complications such as paraplegia or tetraplegia arising from epidural abscesses that compress the spinal cord. Surgical debridement, along with essential antimicrobial therapy, is an effective strategy and can lead to satisfactory prognosis in managing cervical spinal brucellosis.
Topics: Humans; Male; Brucellosis; Retrospective Studies; Female; Middle Aged; Adult; Cervical Vertebrae; Follow-Up Studies; Treatment Outcome; Aged; Spinal Fusion; Debridement; Cohort Studies; Anti-Bacterial Agents; Time Factors
PubMed: 38937747
DOI: 10.1186/s13018-024-04868-9 -
BMC Infectious Diseases Jun 2024Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Refractory Helicobacter pylori (H. pylori) infection inevitably increase the difficulty of drug selection. Here, we described our experience with the use of a novel tetravalent IgY against H. pylori for the treatment of patients with refractory H. pylori infection.
METHODS
Patients were randomly assigned to receive the standard quadruple therapy (amoxicillin, clarithromycin, omeprazole and bismuth potassium citrate ) for 2 weeks or 250 mg of avian polyclonal IgY orally twice a day for 4 weeks. The binding efficacy of IgY to H. pylori antigens was detected by western blotting. C-urea breath test was performed to evaluate the eradication therap's efficacy. The side effects of IgY were evaluated via various routine tests. The questionnaire was used to gather clinical symptoms and adverse reactions.
RESULTS
Western blot analysis showed that tetravalent IgY simultaneously bind to VacA, HpaA, CagA and UreB of H. pylori. Tetravalent IgY had an eradication rate of 50.74% in patients with refractory H. pylori and an inhibition rate of 50.04% against DOB (delta over baseline) of C-urea. The symptom relief rate was 61.76% in thirty-four patients with clinical symptoms, and no adverse reactions were observed during tetravalent IgY treatment period.
CONCLUSIONS
Polyclonal avian tetravalent IgY reduced H. pylori infection, and showed good efficacy and safety in the treatment of refractory H. pylori infection patients, which represented an effective therapeutic option of choice for patients with refractory H. pylori infection.
Topics: Humans; Helicobacter Infections; Male; Female; Helicobacter pylori; Middle Aged; Immunoglobulins; Adult; Anti-Bacterial Agents; Treatment Outcome; Aged; Drug Therapy, Combination; Clarithromycin; Amoxicillin; Young Adult; Antibodies, Bacterial
PubMed: 38937679
DOI: 10.1186/s12879-024-09498-4 -
Scientific Reports Jun 2024The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum...
The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum norepinephrine (NE) dosage (MND) and mortality in neonates with septic shock. This retrospective cohort study included neonates with evidence of septic shock and those who received NE infusion. The study included 123 neonates, with 106 in the survival group and 17 in the death group. The death group exhibited significantly lower birth weight (p = 0.022), 1-min Apgar score (p = 0.005), serum albumin (p < 0.001), and base excess (BE) (p = 0.001) levels, but higher lactate (LAC) levels (p = 0.009) compared to the survival group. MND demonstrated an ROC area under the curve of 0.775 (95% CI 0.63-0.92, p < 0.001) for predicting mortality, with an optimal threshold of 0.3 µg/(kg·min), a sensitivity of 82.4%, and a specificity of 75.5%. Multivariate logistic regression indicated that an MND > 0.3 µg/(kg·min) (OR, 12.08, 95% CI 2.28-64.01) was associated with a significantly higher mortality risk. Spearman rank correlation showed a positive correlation between MND and LAC (r = 0.252, p = 0.005), vasoactive-inotropic score (VIS) (r = 0.836, p < 0.001), and a negative correlation with BE (r = - 0.311, p = 0.001). MND > 0.3 µg/(kg min) is a useful predictive marker of mortality in neonatal septic shock.
Topics: Humans; Shock, Septic; Infant, Newborn; Norepinephrine; Male; Female; Retrospective Studies; ROC Curve; Apgar Score
PubMed: 38937631
DOI: 10.1038/s41598-024-65744-4 -
Scientific Reports Jun 2024This article investigated the kinetic studies of thorium adsorption from an aqueous solution with graphene oxide functionalized with aminomethyl phosphonic acid (AMPA)...
This article investigated the kinetic studies of thorium adsorption from an aqueous solution with graphene oxide functionalized with aminomethyl phosphonic acid (AMPA) as an adsorbent. First, the AMPA-GO adsorbent was characterized using TEM, XRD, and FTIR methods. Experiments were performed in two batch and continuous modes. In batch mode, adsorption kinetics were studied in different pH (1-4), temperature (298-328 K), initial concentration (50-500 mg L), and dosages (0.1-2 g L). The results showed that thorium adsorption kinetic follows pseudo-first-order kinetic model and that the adsorption reaction is endothermic. The maximum experimental adsorption capacity of thorium ions was observed 138.84 mg g at a pH of 3, adsorbent dosage of 0.5 g L, and a temperature of 328 K. The results showed that AMPA-GO adsorbent can be used seven times with an acceptable change in adsorption capacity. In continuous conditions, the effect of feed flow rate (2-8 mL min), initial concentration (50-500 mg L), and column bed height (2-8 cm) was investigated. The continuous data was analyzed using the Thomas, Yoon-Nelson, and Bohart-Adams models. The experimental data of the column were well matched with the Thomas, and Yoon-Nelson models. The research results showed that the use of functionalized graphene oxide adsorbents has a great ability to remove thorium from aqueous solutions.
PubMed: 38937613
DOI: 10.1038/s41598-024-65709-7 -
Scientific Reports Jun 2024Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both...
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both prophylactic and curative interventions. This retrospective before-after study investigates the effects of a management strategy integrating perfusion computed tomography (CTP), vigilant clinical monitoring and standardized systemic administration of milrinone on the occurrence of delayed cerebral infarction (DCIn). The period included 277 patients, and the one 453. There was a higher prevalence of Modified Fisher score III/IV and more frequent diagnosis of vasospasm in the period. Conversely, the occurrence of DCIn was reduced with the management strategy (adjusted OR 0.48, 95% CI [0.26; 0.84]). Notably, delayed ischemic neurologic deficits were less prevalent at the time of vasospasm diagnosis (24 vs 11%, ), suggesting that CTP facilitated early detection. In patients diagnosed with vasospasm, intravenous milrinone was more frequently administered (80 vs 54%, ) and associated with superior hemodynamics. The present study from a large cohort of aSAH patients suggests, for one part, the interest of CTP in early diagnosis of vasospasm and DCI, and for the other the efficacy of CT perfusion-guided systemic administration of milrinone in both preventing and treating DCIn.
Topics: Humans; Subarachnoid Hemorrhage; Milrinone; Male; Female; Middle Aged; Cerebral Infarction; Retrospective Studies; Tomography, X-Ray Computed; Aged; Vasospasm, Intracranial; Adult; Administration, Intravenous
PubMed: 38937568
DOI: 10.1038/s41598-024-65706-w