Protocol for combined N-of-1 trials to assess cerebellar neurostimulation for movement disorders in children and young adults with dyskinetic cerebral palsy.

BACKGROUND: Movement and tone disorders in children and young adults with cerebral palsy are a great source of disability. Deep brain stimulation (DBS) of basal ganglia targets has a major role in the treatment of isolated dystonias, but its efficacy in dyskinetic cerebral palsy (DCP) is lower, due to structural basal ganglia and thalamic damage and lack of improvement of comorbid choreoathetosis and spasticity. The cerebellum is an attractive target for DBS in DCP since it is frequently spared from hypoxic ischemic damage, it has a significant role in dystonia network models, and small studies have shown promise of dentate stimulation in improving CP-related movement and tone disorders. METHODS: Ten children and young adults with DCP and disabling movement disorders with or without spasticity will undergo bilateral DBS in the dorsal dentate nucleus, with the most distal contact ending in the superior cerebellar peduncle. We will implant Medtronic Percept, a bidirectional neurostimulator that can sense and store brain activity and deliver DBS therapy. The efficacy of cerebellar DBS in improving quality of life and motor outcomes will be tested by a series of N-of-1 clinical trials. Each N-of-1 trial will consist of three blocks, each consisting of one month of effective stimulation and one month of sham stimulation in a random order with weekly motor and quality of life scales as primary and secondary outcomes. In addition, we will characterize abnormal patterns of cerebellar oscillatory activity measured by local field potentials from the intracranial electrodes related to clinical assessments and wearable monitors. Pre- and 12-month postoperative volumetric structural and functional MRI and diffusion tensor imaging will be used to identify candidate imaging markers of baseline disease severity and response to DBS. DISCUSSION: Our goal is to test a cerebellar neuromodulation therapy that produces meaningful changes in function and well-being for people with CP, obtain a mechanistic understanding of the underlying brain network disorder, and identify physiological and imaging-based predictors of outcomes useful in planning further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT06122675, first registered November 7, 2023.

[Pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus: a case report].

Nocardia is a rarely encountered opportunistic gram-positive bacterium that exhibits marked invasiveness and dissemination. Typically, acquired through trauma or inhalation, this pathogen primarily affects immunocompromised individuals and is a potentially life-threatening risk in severe cases. Nocardia otitidiscaviarum is a particularly rare subtype of Nocardia infection, and the occurrence of concurrent Aspergillus infection is extremely rare. In cases where both infections manifest concomitantly, rapid and accurate diagnosis is essential to facilitate the subsequent selection of appropriate anti-infective interventions. This paper reported the diagnostic and therapeutic experience in managing a case of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. The patient presented with an acute onset, rapid progression, and early manifestation of respiratory failure. The diagnostic process included respiratory pathogen culture and bronchoscopy, which was supplemented with targeted next-generation sequencing (tNGS). These comprehensive diagnostic modalities led to the identification of pulmonary co-infection with Nocardia otitidiscaviarum and Aspergillus. After adjustment of the antibiotic regimen, the patient's condition improved rapidly, culminating in a timely discharge.

[Diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery].

Objective: To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). Methods: This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged (M (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). Results: All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms. Conclusions: The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.

[Effects of cognition-related lifestyles on early cognitive decline in community older adults in China].

Objective: To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline. Methods: The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline. Results: In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 (OR=0.683, 95%CI: 0.457-1.019; OR=0.623, 95%CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 (OR=0.491, 95%CI: 0.297-0.812; OR=0.556, 95%CI: 0.332-0.929; trend P=0.024). Conclusion: Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

[Intermediate and long-term outcomes of transcatheter closure of congenital coronary cameral fistulas in 66 children].

Objective: To evaluate the intermediate and long-term outcomes and technical aspects of transcatheter closure (TCC) of coronary cameral fistulas (CCF) in pediatric patients. Methods: This was a case-control study. All pediatric patients with CCF who underwent TCC between January 2005 and December 2019 were retrospectively reviewed. Data was collected from medical records, including demographic characteristics, procedural details, intraoperative and postoperative serious adverse events, follow-up results and prognosis. Patients with serious adverse events and without serious adverse events were compared regarding their clinical features and CCF characteristics. Comparisons between groups were performed with independent sample t test, chi-square test or Fisher exact test. Results: A total of 66 CCF patients (34 boys, 32 girls, 3.9 (1.9, 6.2) years old, 15 (11, 20) kg) underwent attempted TCC. All of the CCF were all medium or large fistulas including 55 proximal fistulas (83%) and 11 distal fistulas (17%). The CCF originated more frequently from the right coronary artery (38 cases (58%)), followed by the left coronary artery (28 cases (42%)). The incidence of coronary artery aneurysms (CAA) was 61% (40/66).Procedural treatment was achieved in 64 patients and procedural success was achieved in 59 patients (92%). Six (9%) serious adverse events occurred in 5 patients during the perioperative period. Acute complications included procedure-related death in one patient and acute myocardial infarction in one patient. Periprocedural complications occurred in 3 patients at one day postoperatively including acute myocardial infarction (2 cases), occluder detachment (1 case), and tricuspid chordae tendinae rupture (1 case). Clinical follow-up data were available in 58 of the 62 patients who underwent initial successful TCC with a follow-up period of 9.3 (6.5, 13.4) years. Ten adverse events occurred in 9 patients including 5 complications consisted of aortic valve perforation (1 case), coronary thrombosis (1 case), progressive aneurysmal dilation after reintervention (1 case), and new-onset tricuspid valve prolapse with significant regurgitation (2 cases) and large residual shunts due to fistula recanalization (5 cases). Therefore, the incidence of intermediate and long-term adverse events was 17% (10/58). During the periprocedural and follow-up period, 16 adverse events occurred in 13 patients, whereas no adverse events occurred in 51 patients. Patients with seriovs adverse events presented with larger proportion of large CCF (11/13 vs. 39% (20/51), P=0.005), giant CAA (10/13 vs.14% (7/51), P=0.030), and higher mean pulmonary artery pressure ((20±9) vs.(16±6) mmHg, 1 mmHg=0.133 kPa, t=2.02, P=0.048) compared to patients without serious adverse events. Conclusions: TCC in CCF children appears to be effective with favorable intermediate and long-term outcomes. Strict indication of TCC is mandatory.

Accessible and reliable neurometric testing in humans using a smartphone platform.

Tests of human brain circuit function typically require fixed equipment in lab environments. We have developed a smartphone-based platform for neurometric testing. This platform, which uses AI models like computer vision, is optimized for at-home use and produces reproducible, robust results on a battery of tests, including eyeblink conditioning, prepulse inhibition of acoustic startle response, and startle habituation. This approach provides a scalable, universal resource for quantitative assays of central nervous system function.

[Analysis of the risk factors of persistent inflammation-immunosuppression-catabolism syndrome in patients with extensive burns].

Objective: To investigate the risk factors and treatment outcome of persistent inflammation-immunosuppression-catabolism syndrome (PICS) in patients with extensive burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, 220 patients with extensive burns who were admitted to Guangzhou Red Cross Hospital of Jinan University met the inclusion criteria, including 168 males and 52 females, aged 18-84 (43±14) years. According to the occurrence of PICS, the patients were divided into PICS group (84 patients) and non-PICS group (136 patients). The general data such as sex, age, complication of underlying diseases and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on admission, sepsis-related organ failure evaluation (SOFA) scores on admission and 14 days post admission, and proportion of patients with mechanical ventilation over 48 h during treatment, special conditions such as total burn area, full-thickness burn area, proportion of patients admitted within 48 h post injury, and exposed deep wound area at the 30th day post injury, outcome indicators such as hospitalization day, total cost of hospital stay, number of surgeries, and death of patients in the 2 groups were collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, and chi-square test. The multivariate logistic regression analysis was performed on the indicators with statistically significant differences between the two groups except for outcome indicators, and the independent risk factors influencing secondary PICS in patients with extensive burns were screened. Results: The APACHE Ⅱ and SOFA scores on admission, and proportion of patients with mechanical ventilation over 48 h during treatment of patients in PICS group were significantly higher than those in non-PICS group (t=6.78, Z=-4.75, χ2=4.74, respectively, P<0.05). There were no statistically significant differences in the rest of general data of patients between the two groups (P>0.05). The total burn area, full-thickness burn area, and exposed deep wound area at the 30th day post injury in PICS group were significantly greater than those in non-PICS group (t=6.29, Z=-7.25, Z=-8.73, P<0.05), the exposed deep wound areas at the 30th day post injury in PICS group and non-PICS group were respectively 25% (15%, 35%) total body surface area (TBSA) and 8% (0, 13%) TBSA, while the proportion of patients admitted within 48 h post injury was significantly lower than that in non-PICS group (χ2=6.13, P<0.05). The hospitalization day, total cost of hospital stay, and number of surgeries of patients in PICS group were significantly higher than those in non-PICS group (with Z values of -7.12, -8.48, and -6.87, respectively, P<0.05), while the deaths of patients in the 2 groups were similar (P>0.05). The APACHE Ⅱ score on admission and exposed deep wound area at the 30th day post injury both were the independent risk factors for PICS in patients with extensive burns (with odds ratios of 1.15 and 1.07, 95% confidence intervals of 1.06-1.25 and 1.05-1.10, respectively, P<0.05). Conclusions: The APACHE Ⅱ score on admission and exposed deep wound area at the 30th day post injury are the independent risk factors for PICS in patients with extensive burns. The patients with secondary PICS had good prognosis with more surgical intervention and hospitalization day, and higher total cost of hospital stay.

[Association analysis between sex hormone levels and all-cause mortality in Hainan female centenarians].

Objective: To investigate the distribution characteristics of sex hormones and their relationship with all-cause mortality in Hainan female centenarians. Methods: All the subjects were from China Hainan Centenarian Cohort Study. A total of 717 female centenarians were included in the final analysis. Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazard regression was used to analyze the relationship between sex hormones and survival time. Results: The M(Q1, Q3) of estradiol and progesterone among female centenarians was 32.60 (18.40, 58.70) pmol/L and 0.62 (0.32, 1.01) nmol/L. The estradiol (pmol/L) and progesterone (nmol/L) in the survival and death groups were 26.65 vs.37.80, 0.54 vs.0.69, respectively, with statistical differences (P<0.05). Cox multivariate analysis showed that estradiol and progesterone were significantly associated with death (P<0.05), the hazard ratio (HR) of estradiol Q4 was 1.58 (95%CI: 1.17-2.15), and the HR of progesterone Q3 was 1.53 (95%CI: 1.10-2.12), HR for Q4 was 1.63 (95%CI: 1.15-2.32). Subgroup and cross-analysis showed that estradiol was statistically significant with hypertension, diabetes, and low high-density lipoprotein cholesterol (P<0.05), and progesterone interacted with diabetes (P=0.016), while testosterone interacted with low high-density lipoprotein cholesterol (P=0.034). Conclusion: It is suggested that the estrogen levels of female centenarians in Hainan were associated with a higher mortality risk and an increased risk of cardiovascular metabolic disease (such as diabetes, hypertension, and abnormal lipid metabolism).

[Association between smoking status and mortality risk among elderly people aged 60 and above in Beijing City].

Objective: To examine the association between smoking status and related mortality among elderly people aged 60 and above in urban and rural areas of Beijing City. Methods: Based on Beijing City Elderly Comprehensive Health Cohort Study from 2009 to 2014, a total of 4 499 eligible older adults included in the baseline survey were followed up and investigated to collect information on survival and death. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs), and the dose-response relationship was estimated between the smoking index, the years of quitting and mortality. Results: The median (IQR) age of 4 499 subjects was 70.00 (10.00) years old, including 1 814 (40.32%) males. The proportion of non-smokers, former smokers and current smokers was 69.50% (3 127/4 499), 13.20% (594/4 499) and 17.30% (778/4 499), respectively. After adjusting for confounding factors such as demographic and sociological characteristics, lifestyle, etc., the results of multivariate Cox regression analysis showed that, compared to non-smokers, former smokers had a 30.6% increased risk of all-cause mortality [HR (95%CI): 1.306 (1.043-1.636)] and the HR (95%CI) of all-cause, malignant tumor and lung cancer mortality among current smokers has increased by 50.0% [HR (95%CI): 1.500 (1.199-1.877)], 80.3% [HR (95%CI): 1.803 (1.226-2.652)] and 212.6% [HR (95%CI): 3.126 (1.626-6.012)], respectively. The smoking index was positively associated with the increased risk of all-cause, malignant tumor and lung cancer mortality, while the years of smoking cessation were negatively associated with that risk (P<0.05). Conclusion: Smoking is associated with tobacco-related mortality among elderly people in Beijing City.

[Treatment strategies for patients with resistant advanced breast cancer to CDK4/6 inhibitors].

CDK4/6 inhibitors have become the standard of care for HR-positive, HER2-negative advanced breast cancer. However, there is still a lack of standard recommendations for the subsequent treatment of patients with CDK4/6 inhibitor resistance, especially those with primary resistance or rapid progression. Currently, appropriate treatment strategies included re-challenge of CDK4/6 inhibitors, combination with PI3K/AKT/mTOR inhibitors, new antibody drug conjugate (ADC), novel endocrine therapy drugs, and chemotherapy. In addition, many new targeted drugs and new combination treatment strategies are also being explored. In the future, precise treatment strategies based on biomarkers should be established, as well as the optimal sequence of use of different therapies.

[Effect of compound chamomile and lidocaine hydrochloride gel on oropharyngeal complications after the use of laryngeal mask airway with positive pressure ventilation].

Objective: To evaluate the effect of compound chamomile and lidocaine hydrochloride gel on oropharyngeal complications after the use of laryngeal mask airway with positive pressure ventilation. Methods: A total of 64 patients undergoing elective surgery under general anesthesia using laryngeal mask airway (LMA) with positive pressure ventilation in Beijing Tongren Hospital Affiliated to Capital Medical University From January to March 2023 were prospectively selected and divided into two groups by the random number table method: normal saline group (n=32), with 18 males and 14 females, aged 28-64 (48.4±10.6) years, and the compound chamomile and lidocaine hydrochloride gel group (chamomile gel group, n=32), with 18 males and 14 females, aged 24-64 (46.3±10.8) years. Patients in both groups received total intravenous anesthesia. Before LMA placement, the front, shoulder and back of LMA were lubricated with normal saline and compound chamomile and lidocaine hydrochloride gel in the normal saline group and the chamomile gel group, respectively. The main outcome measure was the incidence of postoperative oropharyngeal mucosal inflammation at different time points after the removal of the laryngeal mask. Secondary outcome measures included oropharyngeal mucositis score, sore throat score, hoarse voice score, cough score and throat dryness score at different time points after LMA removal, the number of LMA insertion times, time of successful insertion and leakage pressure, as well as stress reactions such as cough and agitation before and after LMA removal, and adverse reactions such as tongue numbness and protective pharyngeal reflex limitation during recovery. Results: The incidence of oropharyngeal mucositis in the chamomile gel group was 25.0% (8/32), 31.3% (10/32), 28.1% (9/32) and 3.1% (1/32) at 0.5, 3, 6 and 24 h after LMA removal, respectively, which were lower than those of normal saline group [53.1% (17/32), 59.4% (19/32), 59.4% (19/32) and 21.9% (7/32)] (all P<0.05). The oropharyngeal mucositis scores of patients in the chamomile gel group were 0 (0, 0.8), 0 (0, 1.0), 0 (0, 1.0) and 0 (0, 0) respectively at 0.5, 3, 6 and 24 h after LMA removal, which were lower than those in the saline group [1.0 (1.0, 1.8), 1.0 (0, 2.0), 1.0 (0, 2.0) and 0 (0, 0)] (all P<0.05). The cough score of the patients in the chamomile gel group was 0 (0, 0) and 0 (0, 0) at 3, 6 h after LMA removal, which were lower than those of the normal saline group [(0, 0) and 0 (0, 0)] (both P<0.05). The throat dryness score of the patients in the chamomile gel group was 0 (0, 1.0) at 3 h after LMA removal, which was lower than that of the normal saline group [1.0 (0.3, 1.0)] (P=0.019). The time of successful LMA insertion in the chamomile gel group was 25.0 (20.3, 29.8) s, which was shorter than that in the saline group [29.0 (25.0, 32.0) s] (P=0.016). There were no significant differences in the number of LMA insertion, leakage pressure, postoperative sore throat and hoarse voice scores between the two groups (all P>0.05). Likewise, there were no stress reactions such as cough and agitation before and after LMA removal, and no adverse reactions such as tongue numbness and limited protective pharyngeal reflex during recovery. Conclusion: Compound chamomile and hydrochloride lidocaine gel can reduce the incidence of postoperative oropharyngeal mucositis, relieve the symptoms of postoperative oropharyngeal mucositis, pharyngeal dryness and cough, and improve the postoperative comfort of patients using the laryngeal mask airway with positive pressure ventilation.

[The effect of modified nasopharynx airway with spontaneous breathing under general anesthesia on the postoperative recovery quality of patients undergoing hysteroscopic daytime surgery].

Objective: To explore the impact of a new type of modified nasopharynx airway preserving spontaneous breathing under general anesthesia on the postoperative recovery quality of patients undergoing hysteroscopic daytime surgery. Methods: A total of 80 patients undergoing hysteroscopic daytime surgery at Beijing Tongren Hospital from August to December 2022 was prospectively selected. The patients were randomly divided into two groups using a random number table method: patients in the laryngeal mask mechanical ventilation general anesthesia group (laryngeal mask group, n=40) aged (46.8±10.1) years (20-65 years), while patients in the modified nasopharyngeal airway preserving spontaneous breathing general anesthesia group (nasopharyngeal airway group, n=40) aged (45.5±12.1) years (26-65 years). The main outcome measures were the clinical recovery score (CRS) and modified alertness and sedation score (MOAA/S) of patients at different postoperative time points. Secondary observation indicators included anesthesia induction time, awakening time, and extubation time, changes of hemodynamic indicators between preoperative and intraoperative period, and incidence of adverse reactions during and after surgery. Results: The CRS scores [M (Q1, Q3)] of patients in the nasopharyngeal airway group were 8 (8, 9), 8 (8, 9), 8 (8, 9), 9 (9, 9) and 10 (10, 11) at postoperative awakening, immediately after extubation, 5 minutes after extubation, 15 minutes after extubation, and 30 minutes after extubation, respectively, which were higher than those in the laryngeal mask group [7 (6, 8), 7 (7, 8), 7 (7, 8), 8 (8, 8) and 9 (8, 9)] (all P<0.001). The MOAA/S scores of the nasopharyngeal airway group were 5 (5, 5), 5 (5, 5), 5 (5, 5) and 5 (5, 5) at postoperative awakening, immediately after extubation, 5 minutes after extubation, and 15 minutes after extubation, respectively, which were higher than those in the laryngeal mask group [4 (3, 5), 4 (4, 5), 5 (5, 5) and 5 (5, 5)] (all P<0.05). The anesthesia induction time, awakening time, and extubation time of the nasopharyngeal airway group were (47.8±4.3) s, (4.1±1.7) min and (4.5±1.7) min, respectively, which were shorter than those of laryngeal mask group [(138.8±4.2) s, (7.2±2.9) min and (8.1±2.7) min] (all P<0.05). The mean arterial pressure (MAP) of patients in the nasopharynx airway group during extubation was (84.9±10.2) mmHg (1 mmHg=0.133 kPa), which was lower than that of the laryngeal mask group [(93.2±7.5) mmHg] (P<0.05). The partial pressure of end-tidal carbon dioxide (PetCO2) during cervical dilation was (22.0±5.9) mmHg, which was lower than those of the laryngeal mask group [(37.2±2.2) mmHg] (P<0.05). The PetCO2 during intrauterine operation and extubation were (45.5±6.7) and (41.6±4.5) mmHg, which were higher than those of the laryngeal mask group [(39.2±4.1) mmHg and (38.6±3.6) mmHg] (both P<0.05). The incidence of respiratory depression and body movement during surgery in the nasopharyngeal airway group were 27.5% (11/40) and 17.5% (7/40), respectively, which were higher than those in the laryngeal mask group [0 and 0] (both P<0.05). The incidence of postoperative drowsiness was 2.5% (1/40), which was lower than that of the laryngeal mask group [17.5% (7/40)] (P<0.05). There was no severe physical activity or intraoperative awareness in the two groups. Conclusion: The new modified general anesthesia method of preserving spontaneous breathing through the nasopharynx airway can improve the postoperative recovery quality of patients, and reduce the occurrence of adverse reactions, which facilitates rapid recovery after hysteroscopic daytime surgery.

[Efficacy and safety of new systemic therapies in moderate-to-severe atopic dermatitis in the elderly: meta-analysis].

Objective: To systematically evaluate the efficacy and safety of new systemic therapies (biological agents and JAK inhibitors) in moderate-to-severe elderly atopic dermatitis. Methods: The database of Embase, PubMed, Web of Science,Cochrane, the Global Resource of Eczema Trials database, ClinicalTrials. Gov, CNKI, Wanfang, VIP were used to search for literatures of randomized controlled trials (RCTs) and real-world studies of the treatment of moderate-to-severe AD with the new systemic therapies from January 2014 to February 2023. Two reviewers independently screened the literature, extracted the data and evaluated the risk of bias included in the study. Data were analyzed by Review Manager 5.3 software for meta-analysis and odds ratio (OR) and 95% confidence interval were used as the effect statistics. The heterogeneity and publication bias were assessed. Results: A total of five studies (523 elderly patients and 802 young patients) using dupilumab were included for meta-analysis. Dupilumab showed good efficacy in elderly AD, with 74.6%(390/523) of patients whose EASI reached 75, which there was no significant difference with young patients (OR=0.79, 95%CI:0.58-1.07, P=0.122); the proportion of elderly patients with NRS improvement≥4 was 68.7%(244/355), and there was no significant difference with young patients (OR=0.79, 95%CI:0.55-1.14, P=0.213). The most common adverse reactions were conjunctivitis, facial and neck erythema and injection site reactions, and there are no serious adverse events in both groups. The incidence of adverse events in elderly patients was 24.3%(65/267), which was not significantly different from that in young patients (OR=1.07, 95%CI:0.65-1.77, P=0.789). There are few studies on other biological agents and JAK inhibitors in elderly AD patients. We only found 4 studies of elderly AD patients using JAK inhibitors (2 studies on abrocitinib and 2 studies on upadacitinib). The clinical efficacy of abrocitinib in the elderly was not significantly different from that in the young. The incidence of serious adverse events of abrocitinib and upadacitinib increased in the elderly and was dose-related. Conclusion: The efficacy and safety of dupilumab in elderly AD patients were similar to those in the young patients, and the JAK inhibitor needs to be further studied and verified.

[Preventive effect of atropine premedication on vagal reflex in patients undergoing suspension laryngoscopy during anesthesia induction].

Objective: To evaluate the preventive effect of atropine premedication during anesthesia induction on vagal reflex in patients undergoing suspension laryngoscopy. Methods: A total of 342 patients (202 males and 140 females) scheduled for suspension laryngoscopy under general anesthesia in Beijing Tongren Hospital from October 2021 to March 2022 were prospectively enrolled, with a mean age of (48.1±11.9) years. The patients were randomly divided into two groups using the random number table method: the treatment group (n=171) and the control group (n=171). Patients in the treatment group were administrated with 0.5 mg atropine intravenously guttae (ivgtt) while patients in the control group were given equivalent volume of normal saline. For all patients, if heart rate (HR)<50 beats/min happened during the insertion of the suspension laryngoscope, the operation should be stopped and the laryngoscope should be removed. Patients without HR recovery after the removal of the laryngoscope should be given 0.5 mg atropine, and the operation should be continued after the HR recovered. The primary outcome was the incidence of HR fluctuation over 20% (ΔHR>20%) before and immediately after suspension laryngoscope fixation, and the secondary outcomes included HR, mean arterial pressure (MAP) of the two groups recorded before and after anesthesia induction, before and immediately after suspension laryngoscope fixation, and the incidences of sinus bradycardia, laryngoscope removal and atropine treatment during operation. Results: The incidences of ΔHR>20% and bradycardia immediately after the suspension laryngoscope fixation were 14.6% (25/171) and 12.9% (22/171) in the treatment group, which were significantly lower than those in the control group [28.1% (48/171) and 29.8% (51/171)] (both P<0.05). The HR immediately after the suspension laryngoscope fixation in the treatment group [(66.4±13.5) beats/min] and in the control group [(60.8±15.7) beats/min] was significantly lower than those before the suspension laryngoscope fixation [(74.7±11.1) beats/min and (67.6±12.8) beats/min, respectively] (both P<0.05). There were no significant differences in MAP between the two groups at each time point (all P>0.05). The incidence of laryngoscope removal once plus 0.5 mg atropine administration, laryngoscope removal twice plus 0.5 mg atropine administration and laryngoscope removal twice plus 1.0 mg atropine administration was 9.9% (17/171), 1.8% (3/171) and 0 (0) in the treatment group, respectively, which was significantly lower than those in the control group [24.0% (41/171), 5.8% (10/171) and 2.3% (4/171), respectively] (all P<0.05). Conclusion: Atropine premedication during anesthesia induction can effectively reduce the occurrence of vagal reflex in patients undergoing suspension laryngoscopy.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.

The Effect of Renin-Angiotensin-Aldosterone System Inhibitors on Outcomes of Patients Treated with Immune Checkpoint Inhibitors: a Retrospective Cohort Study.

AIMS: Renin-angiotensin-aldosterone system inhibitors (RAASi) are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the data on the response to treatment and tumour-based endpoints across different tumour types are unknown. MATERIALS AND METHODS: We carried out a retrospective study at two tertiary referral centres in Taiwan. All adult patients treated with ICIs between January 2015 and December 2021 were included. The primary outcome was overall survival and the secondary outcomes were progression-free survival (PFS) and clinical benefit rates. RESULTS: In total, 734 patients were enrolled in our study, of which 171 were RAASi users and 563 were non-users. Compared with non-users, RAASi users had a longer median overall survival [26.8 (interquartile range 11.3-not reached) versus 15.2 (interquartile range 5.1-58.4) months, P < 0.001] and PFS [12.2 (interquartile range 3.9-34.5) versus 5.0 (interquartile range 2.2-15.2) months, P < 0.001]. In univariate Cox proportional hazard analyses, the use of RAASi was associated with a 40% reduction in the risk of mortality [hazard ratio 0.58 (95% confidence interval 0.44-0.76), P < 0.001] and disease progression [hazard ratio 0.62 (95% confidence interval 0.50-0.77), P < 0.001]. The association remained significant after adjusting for underlying comorbidities and cancer therapy in multivariate Cox analyses. A similar trend was observed for PFS. Furthermore, RAASi users experienced a greater clinical benefit rate than non-users (69% versus 57%, P = 0.006). Importantly, the use of RAASi before ICI initiation was not associated with improved overall survival and PFS. RAASi were not associated with an increased risk of adverse events. CONCLUSION: The use of RAASi is associated with improved survival outcomes, treatment response and tumour-based endpoints in patients undergoing immunotherapy.

[A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer].

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

[Hsp90 participates in the necroptosis of mouse neural cells induced by aluminum through the RIP1/RIP3/MLKL pathway].

Objective: To investigate whether heat shock protein 90 (HSP90) participates in the necroptosis of C57BL/6 mouse neurons and spatial memory impairment induced by Aluminum maltol [Al (mal) (3)] through RIP1/RIP3/MLKL pathway. Methods: In March 2022, Thirty-two C57 mice were randomly divided into control group, Low dose group, a medium dose group, and a high-dose group, with 8 mice in each group, and injected intraperitoneally with physiological saline, 20, 40, and 80, respectivelyµmol/kgAl (mal) (3) was administered, it was injected 5 days a week and discontinued 2 days for 60 days. Morris water maze test was used to test the spatial learning and memory ability of mice. Nissl staining was used to observe the pathological changes of brain tissue. The protein expression levels of RIP1, RIP3, MLKL and HSP90 in hippocampus were determined by Western blotting. Results: In the water maze experiment, compared with the control group, the number of mice crossing the platform decreased in each dose group, the difference was statistically significant (H=9.50, P=0.023), and the number of mice crossing the platform was statistically significant among each dose group (P <0.05). Compared with the control group, the number of hippocampal nerve cells in each dose group decreased, the arrangement was disordered, and the Nissellite bodies decreased. Western blotting results showed that compared with the control group, the expression level of RIP1 protein in the hippocampus of mice in high-dose group was higher, and the difference was statistically significant (P <0.05). The expression levels of RIP3, MLKL and HSP90 in hippocampal tissue of mice in medium and high dose groups were increased, and the differences were statistically significant (P<0.05). After siRNA intervention decreased the expression of HSP90 protein, the expressions of HSP90, RIP1, RIP3 and MLKL in Al (mal) (3) groups were increased, and the differences were statistically significant (P<0.05) . Conclusion: Through RIP1/RIP3/MLKL pathway, HSP90 is involved in neuronal programmed necrosis and spatial memory impairment induced by maltol aluminum in C57 mice.

Cerebellum-dependent associative learning is not impaired in a mouse model of neurofibromatosis type 1.

Individuals with Neurofibromatosis type 1 (NF1) experience a high degree of motor problems. The cerebellum plays a pivotal role in motor functioning and the NF1 gene is highly expressed in cerebellar Purkinje cells. However, it is not well understood to what extent NF1 affects cerebellar functioning and how this relates to NF1 motor functioning. Therefore, we subjected global Nf1+/- mice to a cerebellum-dependent associative learning task, called Pavlovian eyeblink conditioning. Additionally, we assessed general motor function and muscle strength in Nf1+/- mice. To our surprise, we found that Nf1+/- mice showed a moderately increased learning rate of conditioned eyeblink responses, as well as improved accuracy in the adaptive timing of the eyeblink responses. Locomotion, balance, general motor function, and muscle strength were not affected in Nf1+/- mice. Together, our results support the view that cerebellar function in Nf1+/- mice is unimpaired.

[Analysis on the concept and clinical practice of patient-controlled analgesia in the treatment of cancer pain by Chinese medical providers].

Objective: To investigated the concept and clinical practice of patient-controlled analgesia (PCA) in the treatment of cancer pain. Methods: Doctors, nurses, pharmacists from the oncology department, pain department, or hospice department were investigated using an electronic questionnaire from December 1 to December 31, 2021. In addition to the basic information, there were 26 questions were collected, including the current situation of cancer pain treatment, the concept of medical staff on PCA treatment of cancer pain and the clinical practice of PCA. Results: Questionnaires from 2 872 medical staff were collected from 993 hospitals in 30 provincial administrative units. Only 34.8% (955/2 748) of medical staff considered that the satisfaction rate of cancer pain control was over 75%, and 27.9% (548/1 968) of medical staff convinced that the satisfaction rate of breakthrough pain control was less than 50%. 97.1% (2 439/2 513) of medical staff considered that PCA could be effectively used for cancer pain treatment. The proportion of medical staff in secondary and tertiary hospitals who thought that PCA was applicable to cancer pain that could not be effectively alleviated by standardized non-invasive drug administration was 64.6% (319/494) and 69.1% (1 262/1 826) respectively, which was higher than that in primary hospitals [57.0% (110/193)] (P=0.002). In different occupations, the proportion of nurses who convinced PCA treatment of cancer pain increased the risk of addiction and drug overdose was 62.8% (431/686) and 76.1% (522/686), respectively, which was higher than doctors [39.2% (670/1709) and 58.2% (995/1709), respectively] and pharmacists [49.2% (58/118) and 65.3% (77/118), respectively] (all P<0.001). There was no significant difference in type of pump, route of administration, mode of infusion, protocol for PCA administration and selection of common medication in PCA treatment of cancer pain among different hospitals (all P>0.05). The calculation of continuous infusion dose and rescue dose of PCA was not uniform among different hospitals. After initiation of PCA, 71.7% (1 226/1 709) of hospitals had insufficient analgesia and most of them needed to be adjusted for 1-3 times to achieve satisfactory analgesia. Conclusion: Medical staff have insufficient cognition of PCA treatment of cancer pain and there is a lack of unified guidance in clinical practice. Therefore, it is an urgent need to develop an expert consensus on PCA treatment of cancer pain.