Tag: pubmed

Vaccine. 2022 Oct 26:S0264-410X(22)01303-2. doi: 10.1016/j.vaccine.2022.10.043. Online ahead of print.

ABSTRACT

The mass vaccination program has been actively promoted since the end of 2020. However, waning immunity, antibody-dependent enhancement (ADE), and increased transmissibility of variants make the herd immunity untenable and the implementation of dynamic zero-COVID policy challenging in China. To explore how long the vaccination program can prevent China at low resurgence risk, and how these factors affect the long-term trajectory of the COVID-19 epidemics, we developed a dynamic transmission model of COVID-19 incorporating vaccination and waning immunity, calibrated using the data of accumulative vaccine doses administered and the COVID-19 epidemic in 2020 in mainland China. The prediction suggests that the vaccination coverage with at least one dose reach 95.87%, and two doses reach 77.92% on 31 August 2021. However, despite the mass vaccination, randomly introducing infected cases in the post-vaccination period causes large outbreaks quickly with waning immunity, particularly for SARS-CoV-2 variants with higher transmissibility. The results showed that with the current vaccination program and 50% of the population wearing masks, mainland China can be protected at low resurgence risk until 8 January 2023. However, ADE and higher transmissibility for variants would significantly shorten the low-risk period by over 1 year. Furthermore, intermittent outbreaks can occur while the peak values of the subsequent outbreaks decrease, indicating that subsequent outbreaks boosted immunity in the population level, further indicating that follow-up vaccination programs can help mitigate or avoid the possible outbreaks. The findings revealed that the integrated effects of multiple factors: waning immunity, ADE, relaxed interventions, and higher variant transmissibility, make controlling COVID-19 challenging. We should prepare for a long struggle with COVID-19, and not entirely rely on the COVID-19 vaccine.

PMID:36328883 | DOI:10.1016/j.vaccine.2022.10.043

Actas Urol Esp (Engl Ed). 2022 Jul 27:S2173-5786(22)00069-5. doi: 10.1016/j.acuroe.2022.07.001. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVE: The most frequently studied factors in patients treated by robotic radical prostatectomy are PSA and pathological features of the biopsy and prostatectomy specimen. Studies on the factors associated with the surgical technique are scarce and with controversial results. The objective is to identify all possible surgical factors and their relationship with disease-free and metastasis-free survival.

PATIENTS AND METHOD: Prospective study approved by the Ethics Committee, including patients who underwent robotic radical prostatectomy since January 2009 with a minimum follow-up of 5 years. Surgeon, surgical time, blood loss, fascial access, continence techniques, preservation of the fascia, neurovascular bundles, bladder neck, urethra, learning curve and surgical complications, were analyzed as possible prognostic factors. We performed univariate and matched comparisons of survival using Kaplan-Meier estimation and long-rank tests. The significance level for multiple comparisons was established with False Discovery Rate-adjustment (adjusted p).

RESULTS: Cohort of 667 patients with a median follow-up of 69 months. In univariate analysis, surgeon (adjp=0.018), preservation of puboprostatic ligaments (adjp=0.02), preservation of endopelvic fascia (adjp=0.001) and performing periurethral suspension (adjp<0.001) are poor prognostic factors for disease-free survival. Fascia preservation also negatively affects metastasis-free survival (adjp=0.04). Previous abdominal surgeries, prostate, surgical time, blood loss, type of residual urethra, middle lobe, fascial access, fascia or bladder neck preservation, have no statistical significance.

CONCLUSIONS: The surgeon and specific aspects of the surgical technique are determining factors in disease-free survival. Preservation of the fascia is the only factor that negatively affects metastasis-free survival.

PMID:36328875 | DOI:10.1016/j.acuroe.2022.07.001

Eur J Intern Med. 2022 Oct 31:S0953-6205(22)00378-8. doi: 10.1016/j.ejim.2022.10.020. Online ahead of print.

ABSTRACT

BACKGROUND: Risk-stratification of patients has a major role in the prevention and treatment of cardiovascular disease. The aim was to find the most informative predictors of cardiovascular events in patients undergoing Coronary CT Angiography.

METHODS: We carried out a secondary analysis of a large registry dataset. The included population comprises adults aged 18 or older who underwent Coronary CT Angiography of 64-detector rows or greater. We clustered patients based on their characteristics and compared the risk for poor clinical outcomes between the two clusters.

RESULTS: There were two clusters of patients having different risks for all-cause death, myocardial infarction, and late revascularization [hazard ratios (95%CI) = 2.28 (2.02, 2.57), 1.63 (1.40, 1.89), and 2.46 (2.1, 2.88), all P < 0.001]. The severity of stenosis in the left main coronary artery adjusted for age and sex was the most significant predictor of the high-risk cluster [adjusted odds ratio (95%CI) = 3.35 (2.98, 3.77), P < 0.001]. The severity of stenosis in the first obtuse marginal branch of the left circumflex, distal left circumflex, distal left anterior descending, posterior descending, the first diagonal branch of the left anterior descending, and proximal right coronary artery were important as well (all adjusted odds ratios ≥ 2.52). Cluster profiling showed a higher performance for CT Angiography features (sensitivity = 97.4%, specificity = 85.7%, C-statistic = 98.7%) than calcium, Framingham, and Duke scores in identifying high-risk patients (C-statistic = 82.1, 77.0, and 88.2%, respectively).

CONCLUSION: Coronary CT Angiography can accurately risk-stratify patients concerning poor clinical outcomes.

PMID:36328870 | DOI:10.1016/j.ejim.2022.10.020

Br J Oral Maxillofac Surg. 2022 Sep 16:S0266-4356(22)00244-3. doi: 10.1016/j.bjoms.2022.07.016. Online ahead of print.

ABSTRACT

The commonest cause of microvascular free flap failure is thrombosis at the anastomosis. Pharmacological antithrombotic therapies have been used to mitigate this risk, but they carry the risk of bleeding and haematoma formation. To justify any intervention, it is necessary to evaluate the benefits and balance of risks. This meta-analysis aims to quantify the value of systemic anticoagulation during head and neck free tissue reconstruction. We performed a systematic review on the impact of additional prophylactic antithrombotic therapy on head and neck (H&N) free tissue transfer (on top and above the use of low molecular weight heparin to prevent deep vein thrombosis). We carried a PRISMA-guided literature review, following registration with PROSPERO. All studies analysing the possible impact of prophylactic anticoagulants on free flap surgery in the head and neck were eligible. The primary outcome was perioperative free flap complications (perioperative thrombosis, partial or total free flap failure, thrombo-embolic events, or re-exploration of anastomosis). Secondary outcomes included haematoma formation or bleeding complications requiring further intervention. We identified eight eligible studies out of 454. These included 3531 free flaps for H&N reconstruction. None of the assessed interventions demonstrated a statistically significant improvement in free flap outcomes. Accumulative analysis of all anti-coagulated groups demonstrated an increased relative risk of free flap complications [RR 1.54 (0.73-3.23)] compared to control albeit not statistically significant (p = 0.25). Pooled analysis from the included studies showed that the prophylactic use of therapeutic doses of anticoagulants significantly (p = 0.003) increased the risk of haematoma and bleeding requiring intervention [RR 2.98 (1.47-6.07)], without reducing the risk of free flap failure. Additional anticoagulation does not reduce the incidence of free flap thrombosis and failure. Unfractionated heparin (UFH) consistently increased the risk of free flap complications. The use of additional anticoagulation as ‘prophylaxis’ in the perioperative setting, increases the risk of haematoma and bleeding.

PMID:36328862 | DOI:10.1016/j.bjoms.2022.07.016

Ann Emerg Med. 2022 Oct 31:S0196-0644(22)00585-6. doi: 10.1016/j.annemergmed.2022.08.011. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision.

METHODS: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration.

RESULTS: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort.

CONCLUSION: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.

PMID:36328855 | DOI:10.1016/j.annemergmed.2022.08.011

Ann Emerg Med. 2022 Oct 31:S0196-0644(22)00578-9. doi: 10.1016/j.annemergmed.2022.08.014. Online ahead of print.

ABSTRACT

Causal diagrams are used in biomedical research to develop and portray conceptual models that accurately and concisely convey assumptions about putative causal relations. Specifically, causal diagrams can be used for both observational studies and clinical trials to provide a scientific basis for some aspects of multivariable model selection. This methodology also provides an explicit framework for classifying potential sources of bias and enabling the identification of confounder, collider, and mediator variables for statistical analyses. We illustrate the potential serious miscalculation of effect estimates resulting from incorrect selection of variables for multivariable modeling without regard to their type and causal ordering as demonstrated by causal diagrams. Our objective is to improve researchers’ understanding of the critical variable selection process to enhance their communication with collaborating statisticians regarding the scientific basis for intended study designs and multivariable statistical analyses. We introduce the concept of causal diagrams and their development as directed acyclic graphs to illustrate the usefulness of this methodology. We present numeric examples of effect estimate calculations and miscalculations based on analyses of the well-known Framingham Heart Study. Clinical researchers can use causal diagrams to improve their understanding of complex causation relations to determine accurate and valid multivariable models for statistical analyses. The Framingham Heart Study dataset and software codes for our analyses are provided in Appendix E1 (available online at http://www.annemergmed.com) to allow readers the opportunity to conduct their analyses.

PMID:36328854 | DOI:10.1016/j.annemergmed.2022.08.014

J Clin Oncol. 2022 Nov 3:JCO2200975. doi: 10.1200/JCO.22.00975. Online ahead of print.

ABSTRACT

PURPOSE: The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non-small-cell lung cancer (mNSCLC).

METHODS: Patients (n = 1,013) with EGFR/ALK wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT.

RESULTS: PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P = .0009; median, 5.5 v 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758; median, 13.3 v 11.7 months; 24-month OS, 29.6% v 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003; median, 6.2 v 4.8 months) and OS (HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) were significantly improved with T + D + CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events.

CONCLUSION: D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.

PMID:36327426 | DOI:10.1200/JCO.22.00975

Acta Cir Bras. 2022 Oct 28;37(7):e370705. doi: 10.1590/acb370705. eCollection 2022.

ABSTRACT

PURPOSE: To explore the mechanism of jatrorrhizine on apoptosis and fibrosis induced by myocardial infarction (MI) in an animal model.

METHODS: The left anterior descending branch of coronary artery was surgically ligated to duplicate the mouse model of MI. The sham and infarcted mice were treated with normal saline once a day, while mice in experimental groups received low-dose (LD) and high-dose (HD) jatrorrhizine once a day respectively. Two weeks later, cardiac function was detected by echocardiography, and histopathological examination was performed using hematoxylin and eosin (H&E) and Masson staining. The expressions of p53, TGF-β1, Smad/2/3, Bax, Bcl-2, collagen I and collagen III were quantified using qRT-PCR and western blot assays.

RESULTS: Jatrorrhizine significantly improved left ventricular ejection fraction (LVEF) and left ventricle end-systolic (LVES) in mice. Histopathological, administration of jatrorrhizine weakened infiltration of inflammatory cells and cardiac fibrosis in myocardium of mice caused by MI. Additionally, jatrorrhizine suppressed cardiomyocyte apoptosis exhibited as its capability to reverse changes of Bax and Bcl-2 levels in myocardium caused by MI. Jatrorrhizine statistically significantly downregulated expression of collagen I and collagen III, as well as TGF-β1, Smad2/3 and p53.

CONCLUSIONS: Jatrorrhizine reduce cardiomyocyte apoptosis and fibrosis through inhibiting p53/Bax/Bcl-2 and TGF-β1/Smad2/3 signaling pathways.

PMID:36327404 | DOI:10.1590/acb370705

Acta Cir Bras. 2022 Oct 28;37(8):e370804. doi: 10.1590/acb370804. eCollection 2022.

ABSTRACT

PURPOSE: Various postoperative protocols have been proposed to improve outcomes and accelerate nerve regeneration. Recently, the use of physical exercise in a post-surgical neurorraphy procedure has shown good results when started early. We experimentally investigated the hypothesis that post-operative exercise speeds up results and improves clinical and morphologic parameters.

METHODS: Isogenic rats were randomly divided into four groups: 1 SHAM; 2 SHAM submitted to the exercise protocol (EP); 3 Grafting of the sciatic nerve; and 4 Grafting of the sciatic nerve associated with the EP. The EP was based on aerobic activities with a treadmill, with a progressive increase in time and intensity during 6 weeks. The results were evaluated by the sciatic functional index (SFI), morphometric and morphologic analysis of nerve distal to the lesion, and the number of spinal cord motor neurons, positive to the marker Fluoro-Gold (FG), captured retrogradely through neurorraphy.

RESULTS: Functional analysis (SFI) did not show a statistical difference between the group grafted with (-50.94) and without exercise (-65.79) after 90 days. The motoneurons count (Spinal cord histology) also showed no diference between these groups (834.5 × 833 respectively). Although functionally there is no difference between these groups, morphometric study showed a greater density (53.62) and larger fibers (7.762) in GRAFT group. When comparing both operated groups with both SHAM groups, all values were much lower.

CONCLUSIONS: The experimental model that this aerobic treadmill exercises protocol did not modify nerve regeneration after sciatic nerve injury and repair with nerve graft.

PMID:36327398 | DOI:10.1590/acb370804

Acta Cir Bras. 2022 Oct 28;37(8):e370803. doi: 10.1590/acb370803. eCollection 2022.

ABSTRACT

PURPOSE: To describe the microsurgical anatomical aspects of the extratemporal facial nerve of Wistar rats under a high-definition video system.

METHODS: Ten male Wistar rats (12-15 weeks old), without veterinary diseases, weighing 220-280 g, were used in this study. All animals in this study were submitted to the same protocol and by the same surgeon. A 10-mm incision was made below the bony prominence of the right or left ear, and extended towards the angle of the mandible. The dissection was performed and the main branches of the facial nerve were dissected.

RESULTS: The main trunk of the facial nerve has a length of 0.88 ± 0.10 mm and a length of 3.81 ± 1.03 mm, measured from its emergence from the stylomastoid foramen to its bifurcation. Seven branches originating from the facial nerve were identified: posterior auricular, posterior cervical, cervical, mandibular, buccal, temporal, and zygomatic.

CONCLUSIONS: The anatomy of the facial nerve is comparable to that of humans, with some variations. The most observed anatomical division was the distribution in posterior auricular, posterior cervical, cervical, mandibular, buccal, temporal, and zygomatic branches. There is no statistical difference between the thickness and distance of the structures compared to the contralateral side.

PMID:36327397 | DOI:10.1590/acb370803