Observation of Skewed Electromagnetic Wakefields in an Asymmetric Structure Driven by Flat Electron Bunches.

Relativistic charged-particle beams that generate intense longitudinal fields in accelerating structures also inherently couple to transverse modes. The effects of this coupling may lead to beam breakup instability and thus must be countered to preserve beam quality in applications such as linear colliders. Beams with highly asymmetric transverse sizes (flat beams) have been shown to suppress the initial instability in slab-symmetric structures. However, as the coupling to transverse modes remains, this solution serves only to delay instability. In order to understand the hazards of transverse coupling in such a case, we describe here an experiment characterizing the transverse effects on a flat beam, traversing near a planar dielectric lined structure. The measurements reveal the emergence of a previously unobserved skew-quadrupolelike interaction when the beam is canted transversely, which is not present when the flat beam travels parallel to the dielectric surface. We deploy a multipole field fitting algorithm to reconstruct the projected transverse wakefields from the data. We generate the effective kick vector map using a simple two-particle theoretical model, with particle-in-cell simulations used to provide further insight for realistic particle distributions.

[A prospective cohort study on the effect of implant restoration following micro crestal flap-alveolar ridge preservation at molar extraction sockets with severe periodontitis].

Objective: To evaluate the survival rate, success rate, soft tissue conditions and marginal bone level changes of implants following micro crestal flap-alveolar ridge preservation at molar extraction sockets with severe periodontitis, compared to natural healing. Methods: From March 2015 to January 2017, patients scheduled for molar extraction as a consequence of severe periodontitis and planned implant-retained prostheses from Department of Periodontology Peking University School and Hospital of Stomatology were selected. A total of 40 molar extraction sockets from 40 patients received implant placement following micro crestal flap-alveolar ridge preservation or natural healing. The front consecutive 20 teeth were assigned to the natural healing group, and the back ones were assigned to the micro crestal flap-alveolar ridge preservation (MCF-ARP) group. The superstructures were placed 6 months later. Within 2 weeks (baseline) and 1, 2 and 3 years after implant crown restoration, modified plaque index, probing depth, modified bleeding index and keratinized tissue width were recorded every six months. Parallel periapical radiographs were taken to evaluate the peri-implant marginal bone level and to calculate marginal bone loss. Independent sample t test or Mann-Whitney U test were used to compare the differences in the above clinical and imaging indicators between the two groups. Results: The implant survival rate and success rate of the two groups were both 100% (20/20). There were no significant differences in the modified plaque index, probing depth, modified bleeding index, buccal keratinized tissue width and marginal bone loss between two groups at 1, 2 and 3 years after implant crown restoration (all P>0.05). Marginal bone loss was 0.22 (0.14, 0.34) mm in the natural healing group and 0.21 (0.12, 0.30) mm in the MCF-ARP group at a 3-year post-loading evaluation. Conclusions: Within the limitations of the present study, implants placed at ridge preserved and naturally healed molar extraction sockets with severe periodontitis demonstrate comparable clinical outcomes at a 3-year post-loading evaluation.

High energy electron diffraction instrument with tunable camera length.

Ultrafast electron diffraction (UED) stands as a powerful technique for real-time observation of structural dynamics at the atomic level. In recent years, the use of MeV electrons from radio frequency guns has been widely adopted to take advantage of the relativistic suppression of the space charge effects that otherwise limit the temporal resolution of the technique. Nevertheless, there is not a clear choice for the optimal energy for a UED instrument. Scaling to beam energies higher than a few MeV does pose significant technical challenges, mainly related to the inherent increase in diffraction camera length associated with the smaller Bragg angles. In this study, we report a solution by using a compact post-sample magnetic optical system to magnify the diffraction pattern from a crystal Au sample illuminated by an 8.2 MeV electron beam. Our method employs, as one of the lenses of the optical system, a triplet of compact, high field gradients (>500 T/m), small-gap (3.5 mm) Halbach permanent magnet quadrupoles. Shifting the relative position of the quadrupoles, we demonstrate tuning the magnification by more than a factor of two, a 6× improvement in camera length, and reciprocal space resolution better than 0.1 Å-1 in agreement with beam transport simulations.

Associations between psychosocial work environment factors and first-time and recurrent treatment for depression: a prospective cohort study of 24,226 employees.

AIMS: Adverse factors in the psychosocial work environment are associated with the onset of depression among those without a personal history of depression. However, the evidence is sparse regarding whether adverse work factors can also play a role in depression recurrence. This study aimed to prospectively examine whether factors in the psychosocial work environment are associated with first-time and recurrent treatment for depression. METHODS: The study included 24,226 participants from the Danish Well-being in Hospital Employees study. We measured ten individual psychosocial work factors and three theoretical constructs (effort-reward imbalance, job strain and workplace social capital). We ascertained treatment for depression through registrations of hospital contacts for depression (International Statistical Classification of Diseases and Related Health Problems version 10 [ICD-10]: F32 and F33) and redeemed prescriptions of antidepressant medication (Anatomical Therapeutic Chemical [ATC]: N06A) in Danish national registries. We estimated the associations between work factors and treatment for depression for up to 2 years after baseline among those without (first-time treatment) and with (recurrent treatment) a personal history of treatment for depression before baseline. We excluded participants registered with treatment within 6 months before baseline. In supplementary analyses, we extended this washout period to up to 2 years. We applied logistic regression analyses with adjustment for confounding. RESULTS: Among 21,156 (87%) participants without a history of treatment for depression, 350 (1.7%) had first-time treatment during follow-up. Among the 3070 (13%) participants with treatment history, 353 (11%) had recurrent treatment during follow-up. Those with a history of depression generally reported a more adverse work environment than those without such a history. Baseline exposure to bullying (odds ratio [OR] = 1.72, 95% confidence interval [95% CI]: 1.30-2.32), and to some extent also low influence on work schedule (OR = 1.27, 95% CI: 0.97-1.66) and job strain (OR = 1.24, 95% CI: 0.97-1.57), was associated with first-time treatment for depression during follow-up. Baseline exposure to bullying (OR = 1.40, 95% CI: 1.04-1.88), lack of collaboration (OR = 1.31, 95% CI: 1.03-1.67) and low job control (OR = 1.27, 95% CI: 1.00-1.62) were associated with recurrent treatment for depression during follow-up. However, most work factors were not associated with treatment for depression. Using a 2-year washout period resulted in similar or stronger associations. CONCLUSIONS: Depression constitutes a substantial morbidity burden in the working-age population. Specific adverse working conditions were associated with first-time and recurrent treatment for depression and improving these may contribute to reducing the onset and recurrence of depression.

[Characteristics and changes of cardiac injury with age in children of Duchenne muscular dystrophy: a prospective cohort study].

Objective: To explore the characteristics and changes of cardiac injury with age in Duchenne muscular dystrophy (DMD) and its clinical significance. Methods: A prospective cohort study was conducted. The 215 patients diagnosed with DMD in West China Second Hospital from January 2019 to November 2022 and aged from 6 to 18 years were enrolled. Their clinical data, myocardial injury markers, routine electrocardiogram, cardiac magnetic resonance (CMR) and echocardiography were collected. The patients were divided into five age groups: 6-<8, 8-<10, 10-<12, 12-<14 and 14-18 years of age, and matched with healthy boys respectively. Independent sample t test or Mann-Whitney U test was used to compare the clinical data and CMR indexes between DMD patients and controls in all age subgroups, and to compare the value of left ventricular ejection fraction (LVEF) measured by echocardiography and CMR in each subgroup of DMD patitents. Pearson correlation analysis or Spearman correlation analysis was used to explore the relation between the CMR indexes and age in DMD patients. Results: A total of 215 patients with DMD (all male) and 122 healthy boys were included in the study. There were 75 DMD patients and 23 controls in 6-<8 years of age group, 77 DMD and 28 controls in 8-<10 years of age group, 39 DMD and 23 controls in 10-<12 years of age group, 10 DMD and 31 controls in the 12-<14 years of age group, and 14 DMD and 17 controls in 14-18 years of age group. In the DMD patients, the older the age, the lower the levels of creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). In the 6-<8 years of age group, the CK level was 10 760 (7 800, 15 757) U/L, while in the group of 14-18 years of age, it was 2 369 (1 480, 6 944) U/L. As for CK-MB, it was (189±17) µg/L in the 6-<8 years of age group and (62±16) µg/L in the 14-18 years of age group. Cardiac troponin I remained unchanged in <12 years of age groups, but significantly increased in 12-<14 years of age group, reaching the highest value of 0.112 (0.006, 0.085) µg/L. In the DMD patients, the older the age, the higher the proportion of abnormal electrocardiogram (ECG). In the 6-<8 years of age group, the proportion is 29.3% (22/75), while in the 14-18 years of age group, it was 10/14. Correlation analysis showed that the left ventricular end-diastolic volume index was positively related with age (r=0.18, P=0.015), and the left ventricular stroke volume index and cardiac output index were negatively related with age (r=-0.34 and -0.31, respectively, both P<0.001). In the DMD patients, the older the age, the lower LVEF, with the LVEF decreasing to (49.3±3.1)% in the 14-18 years of age group. The LVEF of DMD cases was significantly lower than that of controls in the age subgroups of 8-<10, 10-<12, 12-<14 and 14-18 years of age groups ((57.9±5.2) % vs. (63.6±0.8)%, 60.7% (55.9%, 61.9%) vs. 63.7% (60.2%, 66.0%), 57.1% (51.8%, 63.4%) vs. 62.1 % (59.5%, 64.5)%, (49.3±3.1) % vs. (61.6±1.3)%, respectively; all P<0.01). In the DMD patients, the older the age, the higher the proportion of positive late gadolinium enhancement (LGE). In the 6-<8 years of age group, it was 22% (11/51), in the 12-<14 years of age group, it was 13/14, and in the 14-18 years of age group, all DMD showed positive LGE. The value of LVEF of DMD cases measured by echocardiography was significantly higher than that measured by CMR in 6-<8 years of age group and 8-<10 years of age group (63.2% (60.1%, 66.4%) vs. 59.1 % (55.4%, 62.9%), and (62.8±5.2) % vs. (57.9±5.2)%, all P<0.001). Conclusion: DMD patients develop cardiac injury in the early stage of the disease, and the incidence of cardiac damage gradually increases with both age and the progression of disease.

[Echocardiographic two-dimensional strain evaluation of right ventricular function in healthy adults].

Objective: To explore the feasibility of using two-dimensional speckle tracking echocardiography for measuring right ventricular strain and function in healthy adults, and to analyze the impact of age and gender. Methods: This study is a cross-sectional study. Healthy adults who underwent physical examination in the Physical Examination Center of Beijing Hospital from January 1, 2020 to January 1, 2021 were included. Two researchers independently measured various right ventricular longitudinal strain indices using the Echopac software, including (global longitudinal strain (GLS), apical longitudinal strain (ALS), midventricle longitudinal strain (MLS), basal longitudinal strain (BLS), free wall GLS (FWGLS), free wall ALS (FWALS), free wall MLS (FWMLS) and free wall BLS (FWBLS)) as well as tricuspid annular plane systolic excursion (TAPSE) and right ventricle-fraction of area change (RVFAC). The above indicators were taken as the average of two physicians. The consistency of the measurements by two physicians was evaluated by the within-group correlation coefficient (ICC). Results: A total of 233 subjects were included, including 137 males, aged (58.5±14.2) years. ICC values was all above 0.8 with excellent agreement. The values of FWGLS and GLS in healthy adults were -26.63% and -21.89%, respectively. There was no statistically significant difference in TAPSE ((2.06±0.41)cm vs. (2.10±0.39)cm, P=0.510) and RVFAC ((51.17±9.91)% vs. (50.89±8.65)%, P=0.826) between males and females. The values of various right ventricular long axis strain indicators (GLS, ALS, MLS, BLS, FWGLS, FWMLS, FWMLS, FWBLS) in females aged 18 to 40 and 41 to 65 years were higher than those in males of the same age (all P<0.05), while there was no statistically significant difference in the values of various right ventricular long axis strain indicators between the sexes in subjects aged 65 years and above (all P>0.05). In females, the right ventricular GLS, ALS, MLS, FWGLS, FWALS, FWMLS, and FWBLS values in the groups aged 18 to 40 and 41 to 65 years were significantly higher than those in the group aged 65 years and above (all P<0.05). In contrast, no significant differences were found in these indices among different age groups in males (all P>0.05). Conclusions: Using two-dimensional speckle tracking technology in echocardiography to measure right ventricular strain indicators is feasible and highly reproducible. Gender and age have an impact on right ventricular strain indicators.

Asociación entre la velocidad estimada de onda de pulso y la muerte por todas las causas en pacientes con insuficiencia cardiaca / Association between estimated pulse wave velocity and all-cause death in patients with heart failure

Antecedentes La arteriosclerosis ha demostrado ser un factor de riesgo para el desarrollo de insuficiencia cardiaca y readmisión. ePWV es un indicador novedoso, no invasivo y simple de la rigidez arterial, y este estudio tiene como objetivo investigar su relación con la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Métodos Este estudio es un estudio de cohorte que incluyó a 1.272 pacientes con insuficiencia cardiaca de los datos de NHANES de 1999 a 2018. El ePWV se dividió en tres grupos y se calculó la tasa de mortalidad acumulada de pacientes con insuficiencia cardiaca utilizando curvas de supervivencia de KM. La relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca se representó mediante un ajuste de curva suavizado. Se utilizó análisis de regresión de COX para evaluar la asociación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Resultados La edad promedio de la población del estudio fue de 67,8±12,6 años, con 862 hombres y 650 mujeres. Durante el período de seguimiento de 12 meses, hubo 790 casos de mortalidad por todas las causas. Se utilizó un análisis de regresión de Cox para validar la relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Los pacientes con niveles más altos de ePWV tendían a tener una tasa de mortalidad por todas las causas más alta. Después del ajuste de múltiples factores, un aumento en ePWV se asoció positivamente con la tasa de mortalidad por todas las causas (HR=1,17, intervalo de confianza [IC] del 95%: 1,12-1,22). En comparación con el tercil más bajo, la HR ajustada por múltiples variables y el IC del 95% para el tercil más alto de ePWV fueron 1,81 (IC del 95%: 1,45-2,27)... (AU)

Background Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. Methods This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. Results The average age of the study population was 67.8±12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR=1.17, 95% confidence interval [CI]: 1.12-1.22). Compared to the lowest tertile, the multivariable-adjusted HR and 95%CI for the highest tertile of ePWV were 1.81 (95%CI: 1.45-2.27). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate... (AU)

Asociación entre la velocidad estimada de onda de pulso y la muerte por todas las causas en pacientes con insuficiencia cardiaca / Association between estimated pulse wave velocity and all-cause death in patients with heart failure

Antecedentes La arteriosclerosis ha demostrado ser un factor de riesgo para el desarrollo de insuficiencia cardiaca y readmisión. ePWV es un indicador novedoso, no invasivo y simple de la rigidez arterial, y este estudio tiene como objetivo investigar su relación con la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Métodos Este estudio es un estudio de cohorte que incluyó a 1.272 pacientes con insuficiencia cardiaca de los datos de NHANES de 1999 a 2018. El ePWV se dividió en tres grupos y se calculó la tasa de mortalidad acumulada de pacientes con insuficiencia cardiaca utilizando curvas de supervivencia de KM. La relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca se representó mediante un ajuste de curva suavizado. Se utilizó análisis de regresión de COX para evaluar la asociación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Resultados La edad promedio de la población del estudio fue de 67,8±12,6 años, con 862 hombres y 650 mujeres. Durante el período de seguimiento de 12 meses, hubo 790 casos de mortalidad por todas las causas. Se utilizó un análisis de regresión de Cox para validar la relación entre ePWV y la tasa de mortalidad por todas las causas en pacientes con insuficiencia cardiaca. Los pacientes con niveles más altos de ePWV tendían a tener una tasa de mortalidad por todas las causas más alta. Después del ajuste de múltiples factores, un aumento en ePWV se asoció positivamente con la tasa de mortalidad por todas las causas (HR=1,17, intervalo de confianza [IC] del 95%: 1,12-1,22). En comparación con el tercil más bajo, la HR ajustada por múltiples variables y el IC del 95% para el tercil más alto de ePWV fueron 1,81 (IC del 95%: 1,45-2,27)... (AU)

Background Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. Methods This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. Results The average age of the study population was 67.8±12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR=1.17, 95% confidence interval [CI]: 1.12-1.22). Compared to the lowest tertile, the multivariable-adjusted HR and 95%CI for the highest tertile of ePWV were 1.81 (95%CI: 1.45-2.27). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate... (AU)

[Serum glycocalyx markers in patients after cardiac arrest: association with outcomes].

Objective: To assess the levels of serum glycocalyx markers in the first 24 hours after cardiac arrest (CA) and investigate their relationship with 30-day outcomes. Methods: A retrospective cohort study was conducted on prospectively collected data from CA patients, who were admitted to the intensive care units of the Affiliated Hospital of Xuzhou Medical University and obtained return of spontaneous circulation for more than 24 hours between September 2021 and October 2022. Serum samples obtained at the 24-hour after CA were utilized to measure the levels of glycocalyx markers, including heparan sulfate (HS), hyaluronic acid (HA), and syndecan-1 (Sdc-1). Patients were allocated into good function (CPC1-2) and poor function (CPC3-5) groups on the basis of cerebral performance category (CPC) at 30 days post-CA. Logistic regression analysis was used to determine the association between serum glycocalyx markers and neurological outcomes. Patients were regrouped in light of 30-d mortality and Cox regression analysis was used to determine the association between serum glycocalyx markers and 30-d mortality. Results: A total of 71 patients were included in the study, including 31 (43.7%) females and 40 (56.3%) males, with an average age of (59.0±17.0) years. The poor function group (n=49) demonstrated significantly elevated levels of HS and HA when compared to the good function group (n=22) [HS: 2 461.0(1 623.0, 5 492.0) µg/L vs 1 492.0 (914.0, 2 550.0) µg/L, P=0.008; HA: 124.0(97.0, 365.0)µg/L vs 337.0(135.0, 1 421.0) µg/L, P=0.033]. Adjusted logistic regression analysis revealed that HS was independently associated with poor neurological outcome [odds ratio (OR)=0.389, 95% confidence interval (CI): 0.182-0.828, P=0.014]. In the 30-day mortality analysis, the death group (n=32) exhibited significantly higher levels of HS and HA when compared to the survival group (n=39) [HS: 1 880.0(1 011.0, 3 554.0) µg/L vs 2 500.0(1 726.0, 6 276.0) µg/L, P=0.027; HA: 162.0(99.0, 537.0) µg/L vs 813.0(148.0, 1 531.0) µg/L, P=0.025]. Adjusted Cox regression analysis indicated that elevated levels of HS and HA were independent risk factors (HS: HR=1.697, 95%CI: 1.126-2.557, P=0.011; HA: HR=1.336, 95%CI: 1.047-1.705, P=0.020) for 30-day mortality. Conclusions: High level of serum HS in 24 hours after CA may serve as a potential predictive marker for both neurological function and 30-day mortality. However, high level of serum HA appears to primarily predict 30-day mortality. Sdc-1 does not seem to contribute to outcome prediction.

Age-specific characteristics of head and neck second primary malignancies in patients treated for nasopharyngeal carcinoma: a retrospective study.

This study was performed to analyse the age-specific characteristics of head and neck second primary malignancies (SPMs) in patients treated for nasopharyngeal carcinoma (NPC). The medical records of 56 NPC patients diagnosed with head and neck SPMs were reviewed retrospectively. Patients < 45 years old at NPC diagnosis were assigned to the younger group and those ≥ 45 years of age were assigned to the older group. The treatment of the index NPC, latency period, pathological TNM stage, survival status, and SPM subsite were analysed. Patients in the older group were found to have a shorter median latency period than those in the younger group: 8.5 years (range 3-20 years) versus 11 years (range 1-30 years) (P = 0.015). The proportion of SPMs in the jaw was significantly higher in the younger group (P = 0.002). Patients in the younger group receiving radiotherapy with chemotherapy had a shorter latency period (P = 0.003) and higher risk of developing SPMs in the jaw (P = 0.036) than those receiving radiotherapy alone. A long-term and age-dependent regular customised follow-up strategy for NPC is necessary for the prevention and early detection of head and neck second primary malignancies.

Deep learning-based facial analysis for predicting difficult videolaryngoscopy: a feasibility study.

While videolaryngoscopy has resulted in better overall success rates of tracheal intubation, airway assessment is still an important prerequisite for safe airway management. This study aimed to create an artificial intelligence model to identify difficult videolaryngoscopy using a neural network. Baseline characteristics, medical history, bedside examination and seven facial images were included as predictor variables. ResNet-18 was introduced to recognise images and extract features. Different machine learning algorithms were utilised to develop predictive models. A videolaryngoscopy view of Cormack-Lehane grade of 1 or 2 was classified as 'non-difficult', while grade 3 or 4 was classified as 'difficult'. A total of 5849 patients were included, of whom 5335 had non-difficult and 514 had difficult videolaryngoscopy. The facial model (only including facial images) using the Light Gradient Boosting Machine algorithm showed the highest area under the curve (95%CI) of 0.779 (0.733-0.825) with a sensitivity (95%CI) of 0.757 (0.650-0.845) and specificity (95%CI) of 0.721 (0.626-0.794) in the test set. Compared with bedside examination and multivariate scores (El-Ganzouri and Wilson), the facial model had significantly higher predictive performance (p < 0.001). Artificial intelligence-based facial analysis is a feasible technique for predicting difficulty during videolaryngoscopy, and the model developed using neural networks has higher predictive performance than traditional methods.

Rationale and Design of a Phase II Trial of Combined Serplulimab and Chemotherapy in Patients with Histologically Transformed Small Cell Lung Cancer: a Prospective, Single-arm and Multicentre Study.

AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

[Relationship between coagulation status, autoantibodies, and conception method with subchorionic hematoma].

Objective: To investigate the relationship between subchorionic hematoma (SCH) and coagulation status, autoantibodies, and conception method. Methods: A total of 100 pregnant women diagnosed with SCH from June 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University were included in the SCH group, while 100 healthy pregnant women during the same period were selected as the control group. The coagulation status (including platelet, prothrombin time, thrombin time, activated partial thromboplastin time, fibrinogen, antithrombin Ⅲ, fibrin degradation products, D-dimer, homocysteine, protein S activity, protein C activity), the positive rate of autoantibodies [including antiphospholipid antibodies (anticardiolipin antibody and anti-ß2 glycoprotein Ⅰ antibody), antinuclear antibody] and the mode of conception of the two groups were analyzed. Results: Compared to the control group, the SCH group had higher levels of platelet [(240±45)×109/L vs (227±37)×109/L], fibrinogen [(4.0±0.8) vs (3.6±0.7) g/L], D-dimer [(0.42±0.18) vs (0.31±0.15) mg/L], blood homocysteine [(8.9±4.2) vs (6.9±2.3) µmol/L], and lower level of protein S activity [(55±14)% vs (68±20)%], and there were significant differences between the two groups (all P<0.05). The SCH group had higher positive rates of autoantibodies [24.0% (24/100) vs 8.0% (8/100)], antiphospholipid antibodies [15.0% (15/100) vs 6.0% (6/100)], anti-ß2 glycoprotein Ⅰ antibody [10.0% (10/100) vs 3.0% (3/100)], antinuclear antibody [11.0% (11/100) vs 2.0% (2/100)] and assisted reproduction rate [10.0% (10/100) vs 2.0% (2/100)] than those of the control group (all P<0.05). Conclusion: The occurrence of SCH is related to blood hypercoagulability, positive autoantibodies, and assisted reproduction.

[Advances in clinical studies of chronic cough].

Chronic cough is a common complaint in respiratory specialist clinics, with a significant impact on cough-specific quality of life and psychophysiological health. The diagnosis, treatment and management of chronic cough remains a major challenge. We summarized a series of recent advances from clinical studies in the epidemiology, diagnosis and management of chronic cough over the past year.

[Comparison of two child growth standards in assessing the nutritional status of children under 6 years of age].

Objective: To compare the application of China growth standard for children under 7 years of age (China standards) and World Health Organization child growth standards (WHO standards) in evaluating the prevalence of malnutrition in children aged 0-<6 years in China. Methods: The research data came from the national special program for science & technology basic resources investigation of China, named "2019-2021 survey and application of China's nutrition and health system for children aged 0-18 years". Multi-stage stratified random sampling was used to recruit 28 districts (regions) in 14 provinces, autonomous regions or municipalities across the country. Children (n=38 848) were physically measured and questionnaires were conducted in the guardians of the children. The indicators of stunting, underweight, wasting, overweight and obesity were evaluated by China standards and WHO standards respectively. Chi-square test was used to comparing the prevalence of each nutritional status between the two standards, as well as the comparison between the two standards by gender and age. Results: Among the 38 848 children, 19 650 were boys (50.6%) and 19 198 were girls (49.4%), 19 480 urban children (50.1%) and 19 368 rural children (49.9%). The stunting, underweight and wasting cases in the study population were 2 090 children (5.4%), 1 354 children (3.5%) and 1 276 children (3.3%) according to the China standards, and 1 474 children (3.8%), 701 children (1.8%) and 824 children (2.1%) according to the WHO standards, respectively; the above rates according to the China standards were slightly higher than those to the WHO standards (χ2=111.59, 213.14, and 99.99, all P<0.001). The overweight and obesity cases in the study population were 2 186 children (5.6%) and 1 153 children (3.0%) according to the China standards, and 2 210 children (5.7%) and 1 186 children (3.1%) according to the WHO standards, with no statistically significant differences (χ2=0.14 and 0.48, P=0.709 and 0.488, respectively). Compared to the results based on WHO standards, the China standards showed a lower prevalence of overweight and obesity in boys (χ2=14.95 and 5.85, P<0.001 and =0.016, respectively), and higher prevalence of overweight in girls (χ2=12.60, P<0.001); but there was no statistically significant differences in girls' obesity prevalence between the two standards (χ2=2.62, P=0.106). Conclusions: In general, the prevalence of malnutrition among children aged 0-<6 years based on China standards is slightly higher than that on WHO standards. To evaluate the nutritional status of children, it is advisable to select appropriate child growth standards based on work requirements, norms or research objectives.

[Second allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and donor changes in relapsed hematological malignancies after the first allogeneic transplant].

Objective: The purpose of this study was to assess the safety and efficacy of a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced-intensity conditioning (RIC) in patients with hematological malignancies who had relapsed after the first allo-HSCT. Methods: Between April 2018 and June 2021, 44 patients with hematological malignancies (B-ALL 23, T-ALL/T-LBL 4, AML15, and MDS 2) were enrolled and retrospectively examined. Unrelated donors (n=12) or haploidentical donors (n=32) were used. Donors were replaced in all patients for the second allo-HSCT. Hematological and immunological germline predisposition genes and hematopoietic and immune function tests were used to select the best-related donor. Total body irradiation (TBI) /fludarabine (FLU) -based (n=38), busulfan (BU) /FLU-based (n=4), total marrow irradiation (TMI) /FLU-based (n=1), and BU/cladribine-based (n=1) were the RIC regimens used. For graft versus host disease (GVHD) prevention, cyclosporine, mycophenolate mofetil, short-term methotrexate, and ATG were used. Eighteen (40.9%) of 44 patients with gene variations for which targeted medications are available underwent post-transplant maintenance therapy. Results: The median age was 25 years old (range: 7-55). The median interval between the first and second HSCT was 19.5 months (range: 6-77). Before the second allo-HSCT, 33 (75%) of the patients were in complete remission (CR), whereas 11 (25%) were not. All patients had long-term engraftment. The grade Ⅱ-Ⅳ GVHD and severe acute GVHD rates were 20.5% and 9.1%, respectively. Chronic GVHD was found in 20.5% of limited patterns and 22.7% of severe patterns. CMV and EBV reactivation rates were 29.5% and 6.8%, respectively. Hemorrhage cystitis occurred in 15.9% of cases, grade Ⅰ or Ⅱ. The 1-yr disease-free survival (DFS), overall survival (OS), and cumulative recurrence incidence (RI) rates of all patients were 72.5% (95% CI, 54.5%-84.3%), 80.6% (95% CI, 63.4%-90.3%), and 25.1% (95% CI, 13.7%-43.2%), respectively, with a median follow-up of 14 (2-39) months. There were eight deaths (seven relapses and one infection). The rate of non-relapse mortality (NRM) was only 2.3%. The CR patients' 1-yr RI rate was significantly lower than the NR patients (16.8% vs 48.1%, P=0.026). The DFS rate in CR patients was greater than in NR patients, although there was no statistical difference (79.9% vs 51.9%, P=0.072). Univariate analysis revealed that CR before the second allo-HSCT was an important prognostic factor. Conclusion: With our RIC regimens, donor change, and post-transplant maintenance therapy, the second allo-HSCT in relapsed hematological malignancies after the first allo-HSCT is a safe and effective treatment with high OS and DFS and low NRM and relapse rate. The most important factor influencing the prognosis of the second allo-HSCT is the patient's illness condition before the transplant.

Assessing the feasibility of SUVindex (a metric derived from FDG PET/CT) for the diagnosis of polymyalgia rheumatica.

AIM: To evaluate the feasibility of standard uptake value (SUV) index (ratio lesional maximum SUV [SUVmax] to liver mean SUV [SUVmean]) as a metabolic parameter for diagnosing polymyalgia rheumatica (PMR). MATERIALS AND METHODS: A retrospective group of patients with PMR and controls with symptoms similar to PMR but diagnosed with other diseases. Semiquantitative and qualitative analysis of 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake at 18 sites was undertaken for all patients. The diagnostic value of positron-emission tomography/computed tomography (PET/CT) for PMR was assessed by R software using logistic regression and a generalised additive model (GAM). All images were examined independently by two nuclear medicine physicians with extensive work experience. RESULTS: The characteristic sites of PMR were the ischial tuberosity, interspinous bursa, periarticular hip, and symphysis pubis enthesis. The area under the curve (AUC) of the characteristic site SUV index was 0.930, and the best cut-off value was 1.685 with a sensitivity of 84.6% and a specificity of 92.6%. After adjusting for potential confounders, the probability of PMR diagnosis increased as the characteristic site SUV index increased and there was a nonlinear correlation between the two. When the characteristic site SUV index was ≥2.56, the probability of PMR gradually reached the threshold effect, which was as high as 90% or more. CONCLUSION: The characteristic site SUV index is an independent factor for diagnosing PMR, and PMR should be highly suspected when it is ≥ 1.685. Nonetheless, it is important to note that these findings are based on an initial retrospective single-centre study and require external validation and further prospective evaluation before being translated into clinical practice.