Multicenter Clinical Study Research Articles

Analysis of 25 surgical cases of thymic neuroendocrine tumors and thymic carcinoma

BackgroundThe purpose of this study was to evaluate the clinicopathological characteristics of patients who underwent surgical resection for thymic neuroendocrine tumors (TNET) or thymic carcinoma.MethodsIn this study, we retrospectively evaluated the clinicopathological characteristics of our surgical patients at Fukuoka University Hospital from January 1995 to December 2018.ResultsThere were nine cases of TNET and 16 cases of thymic carcinoma. Regarding the pathological type, the TNET group included three atypical carcinoid cases, two large cell neuroendocrine tumor cases, two small cell carcinoma cases, and two other cases. The thymic carcinoma group included 15 squamous carcinoma cases and one case of adenosquamous carcinoma. Based on the Masaoka-Koga staging system, six TNET cases and 11 thymic carcinoma cases were stage III or IV. The complete resection rate was 77% in the TNET group and 81% in the thymic carcinoma group. Additional chemotherapy and/or radiotherapy was performed in five cases of TNET and 11 cases of thymic carcinoma. The five-year survival rate and five-year disease-free survival rate were 87.5% and 75.0% in the TNET group and 58.9% and 57.1% in the thymic carcinoma group, respectively, with no significant difference between the two groups (P = 0.248 and P = 0.894, respectively). In the univariate analysis, complete resection was a statistically significant prognostic factor (P = 0.017).ConclusionIn this study, no difference in prognosis was observed between TNET and thymic carcinomas. To understand the characteristics of these tumors, further case accumulation and multicenter clinical studies are needed. (243words)

Efficacy and safety of Pranabb® syrup to reduce cough and improve sleep quality in children compared to usual recommended hydration measures

Background: Coughing is crucial for protecting the airways, but associated to unpleasant symptoms that often lead to pediatrician visits. Natural remedies like honey and essentials oils are being increasingly used to effectively relieve symptoms associated with cough. Objectives: Evaluate the efficacy and safety of Pranabb® cough syrup, an organic honey-based natural formulation tailored for pediatric patients, in relieving cough symptoms. Methods: One-week multicenter comparative clinical study of 50 children, 28 in the treatment group and 22 in the control group with supportive measures (increased hydration). Pediatrician appointments were scheduled at the baseline and on day 7, with a progress check call on day 3. Parents kept a daily cough diary. Results: Day 3 results show a significant decrease in daytime cough, night-time cough and global score more pronounced and statistically significant in the study group, although the more severe baseline level in the study group. On day 7, decrease in daytime and overall cough scores was greater in the study group (p<0.05). The frequency of awakenings due to coughing decreased on day 3 only in the study group (p<0.05) and on day 7 for both groups, although it was higher and more significant in the study group (-1.82 p<0.01 vs -1.25 p<0.05). In addition, the safety analysis confirms that the syrup is not toxic to children. Conclusion: Pranabb® Cough Syrup is safe and effective, reducing cough severity and nighttime awakenings in children and improving parents’ ability to sleep. More randomized clinical trials will be interesting to get more homogeneity between the two groups at baseline.

Capacitive biophysical stimulation improves the healing of vertebral fragility fractures: a prospective multicentre randomized controlled trial

BackgroundCapacitively coupling electric fields (CCEF) is a method of non-invasive biophysical stimulation that enhances fracture repair and spinal fusion. This multicentre randomized controlled trial aimed to further examine the roles of CCEF in (1) the resolution of vertebral bone marrow oedema (VBME) using a follow-up MRI study and (2) pain relief, analgesic drug consumption and quality of life improvement in stimulated patients who were referred with acute vertebral fragility fractures (VFFs) compared to non-stimulated patients.MethodsBetween September 2016 and December 2019, patients who were referred to the spine centres that participated in this multicentre randomized clinical study with acute VFFs of type OF1 or OF2 were included in the present study. All the VFFs were conservatively managed according to Good Clinical Practice. Moreover, the patients were randomized into two groups: the CCEF group received, as an adjunct to the clinical study protocol, biophysical stimulation with a CCEF device (Osteospine, IGEA) for 8 h per day for 60 days, whereas the control group was treated according to the clinical study protocol. At baseline (T0), the 30-day follow-up (T1), the 60-day follow-up (T2), and the 6-month follow-up (T3), each patient underwent clinical evaluation using the Visual Analogue Scale (VAS) for Pain and the Oswestry Disability Index (ODI). Analgesic therapy with paracetamol 1000 mg tablets for 7 days—or longer, depending on the pain intensity—was performed; patients were required to report their paracetamol consumption on a specific sheet between study day 8 to 180 days of follow-up. MRI studies of the thoracolumbar spine were performed at 0 (T0), 30 (T1) and 60 days of follow-up (T2) using a 1.5-T MRI system in all of the centres that took part in the study. For each VBME area examined via MRI, the vertebral body geometry (i.e. anterior wall height/posterior wall height and vertebral kyphosis) were assessed.ResultsA total of 66 patients (male: 9, 13.63%; mean age: 73.15 years old) with 69 VFFs were included in the present study and randomized as follows: 33 patients were included in the control group and the remaining 33 patients were randomized into the CCEF group. In the CCEF group, good compliance with CCEF therapy was observed (adherence = 94%), and no adverse effects were recorded. In the stimulated patients, faster VBME resolution and significantly less vertebral body collapse during follow-up were observed compared to the control patients. Moreover, in the active group, faster pain reduction and improvement in the ODI mean score were observed. Stimulated patients also reported a significantly lower paracetamol consumption rate from the third follow-up after treatment until the 6-month follow-up. In terms of sex-related differences, in the CCEF group, VBME showed a faster resolution in male patients compared with females.ConclusionBiophysical stimulation with CCEF, as an adjunct to traditional conservative treatment, is a useful tool to hasten the VBME resolution process and prevent vertebral body deformation. These MRI findings also correlate with faster back pain resolution and quality of life improvement. From the third follow-up after treatment untilthe 6-month follow-up, stimulated patients reported a significantly lower paracetamol consumption than control patients, even though back pain and quality of life showed no significant differences between the two groups.Level of evidenceII.Trial Registration Register: ClinicalTrials.gov, number: NCT05803681.

'Monkeypox 2.0': Case series on a reconditioned virus causing sexually transmissible disease in urban population.

MPOX (Monkeypox) viral infection, a zoonotic disease previously confined to the African sub-continent, has caught attention worldwide recently due to its resurgence in a new 'avatar' among urban communities. Dermatologists in the U. A. E. started to see patients with fever and a self-limiting pustular necrotic rash that was negative for all other infectious investigations. We performed a prospective observational multicenter clinical study of the demographics, skin manifestations, and outcomes of patients presenting with necrotic pustular lesions and/or fever. 35 cases of PCR confirmed MPOX cases, mostly in the expatriate population, were followed up and found to have high-risk heterosexual contact on an average of 1week prior to disease onset. We found that they have characteristic annular pustular lesions with necrotic center or "Smoke ring pustules' in all cases. Lesion tenderness and predilection for the lower abdomen, pubic area, and genitalia were observed. Most cases were systemically stable, with fever lasting for an average of 4days and elevated CRP levels. Genital lesions were prone to secondary bacterial infections. The disease was severe, with larger annular plaques in one of our patients found to be living with HIV. The overall prognosis in healthy individuals is good, with lesions healing within an average of 2weeks without scarring. 'New world MPOX' should be unclassified from zoonosis to a sexually transmitted infection (STI) capable of transmission in an urban population. Our findings can help in early clinical suspicion and differentiation from other STI's for primary and secondary health care physicians.

Immediate versus delayed implant placement of novel fully tapered tissue-level implants - A retrospective multicenter clinical study.

To compare the clinical and radiological outcomes of novel fully tapered tissue-level implants in immediate implant placement (type 1) versus late implant placement (type 4) for the first time. For this clinical study, 318 fully tapered tissue-level implants in 65 patients were inserted immediately (n = 68 implants) or late (n = 250 implants) in two different centers. Implant survival and success rates and marginal bone levels were analyzed. After a mean follow-up of 12.0 ± 5 months, implant survival rates were 97.8% for all implants. No statistically significant difference in implant survival rates between type 1 and type 4 could be detected (98.5% vs 97.6%, HR 0.70, 95%-CI 0.084-5.81). Neither for implant length (HR 0.53, 95%-CI 0.055-5.08) nor for implant width (HR 0.27, CI 0.028-2.55), a significant influence on implant survival could be detected. Type of used biomaterial for filling the gap and immediate loading showed no effect on implant survival. Mean marginal bone loss was 0.02 ± 0.05 mm for type 1 and 0.04 ± 0.1 for type 4. Within the limitations of this retrospective study and the short follow-up, the results demonstrated comparable high survival and success rates and stable marginal bone levels for type 1 and type 4 placement of this novel tissue-level implant (no clinical trial registration as retrospective study design).

Real-World Assessment of Personalized Approach With Voglibose Fixed-Dose Combination in Type 2 Diabetes Mellitus.

Post-prandial hyperglycemia (PPHG) remains a complex aspect in the management of type 2 diabetes mellitus (T2DM) in the Indian population due to uncertainty in the optimal utilization of alpha-glucosidase inhibitors (AGIs) either as standalone therapy or in combination, whether initiated initially or as a sequential therapy. This was a post-approval, observational, multicentric clinical study conducted at 50 centers according to principles of the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use Guideline for Good Clinical Practice (ICH-GCP) and Declaration of Helsinki and local ethics approval. Descriptive and analytical statistics were applied for conclusion and categorical variables using SPSS version 29.0.1.0 (171) (Armonk, NY: IBM Corp.). Protocol analyses of 515 cases revealed baseline demographics as follows: age 57.35±10.04 years, weight 72.86±10.92 kg, and BMI 28.33±6.07 kg/m2. Comorbidities included hypertension (N=169, 32.82%), thyroid disorders (N=99, 19.22%), and heart failure (N=92, 17.86%). Concomitant oral antidiabetics (OADs) prescribed as DPP4i (9.50%), SGLT2i (19.20%), and DPP4i+SGLT2i (7.20%). Study drug reduced glycosylated hemoglobin (HbA1c) by 13.77% (1.25% mean change, p<0.01), fasting blood glucose (FBG) by 23.69% (44.61 mg/dL mean change, p<0.01), post-prandial blood glucose (PPBG) by 24.57% (70.46 mg/dL mean change, p<0.01), and body weight by 4.43% (3.21 kg mean change, p<0.01) over 12 weeks. A total of 161 patients accomplished targeted PPBG of <180 mg/dL (119.13 mg/dL mean change, p<0.01). Regression analysis considering PPBG and HbA1c ≤7.5% showed a weak correlation between them (R-value=0.13, R-squared value=0.02), whereas between PPBG and HbA1c ≤9% yielded moderate positive correlation (R-value=0.53, R-squared value=0.28). There were no adverse events reported or analyzed during the observation period. Voglibose fixed-dose combination (FDC) demonstrates significant effectiveness at the initial dosage when started early in the management of T2DM and high PPBG levels. Moreover, it exhibits good tolerability, thereby contributing to higher compliance among Indian patients who consume a high-carbohydrate diet.

Efficacy and Safety of Lianhua Qingke Tablets in the Treatment of Long Coronavirus Disease (COVID) Cough: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study

Lianhua Qingke tablets, a patented traditional Chinese medicine that has validated clinical efficacy for treating cough caused by severe acute respiratory syndrome coronavirus 2 infection, lack rigorous evidence-based research evaluating their effect on long coronavirus disease (COVID) cough. A randomized, double-blind, placebo-controlled, multicenter clinical study was conducted among patients with long COVID cough from 19 hospitals and 23 community health centers in China. Patients were randomized 1:1 to receive either Lianhua Qingke tablets or placebo orally for 14 days (four tablets, 1.84 g, three times a day). The primary endpoint indicator was the disappearance of cough, with the remission of cough also considered. Among 482 randomized patients, 480 (full analysis set 480; per-protocol set 470; safety set 480) were included in the primary analysis. According to the full analysis, the time until cough disappearance was significantly shorter in the trial group than in the control group, with a significant increase in the 14-day cough disappearance rate. Accordingly, the time to cough remission was significantly shorter in the trial group than in the control group. The change in the total symptom score was significantly greater in the trial group than in the control group on days 7 and 14, consistent with the results indicated by the visual analog scale (VAS) and cough evaluation test (CET) scores. No serious adverse events were recorded during the study. Lianhua Qingke tablets significantly improved the clinical symptoms of patients with long COVID cough.

Collaborative inference for treatment effect with distributed data-sharing management in multicenter studies.

Data sharing barriers present paramount challenges arising from multicenter clinical studies where multiple data sources are stored and managed in a distributed fashion at different local study sites. Merging such data sources into a common data storage for a centralized statistical analysis requires a data use agreement, which is often time-consuming. Data merging may become more burdensome when propensity score modeling is involved in the analysis because combining many confounding variables, and systematic incorporation of this additional modeling in a meta-analysis has not been thoroughly investigated in the literature. Motivated from a multicenter clinical trial of basal insulin treatment for reducing the risk of post-transplantation diabetes mellitus, we propose a new inference framework that avoids the merging of subject-level raw data from multiple sites at a centralized facility but needs only the sharing of summary statistics. Unlike the architecture of federated learning, the proposed collaborative inference does not need a center site to combine local results and thus enjoys maximal protection of data privacy and minimal sensitivity to unbalanced data distributions across data sources. We show theoretically and numerically that the new distributed inference approach has little loss of statistical power compared to the centralized method that requires merging the entire data. We present large-sample properties and algorithms for the proposed method. We illustrate its performance by simulation experiments and the motivating example on the differential average treatment effect of basal insulin to lower risk of diabetes among kidney-transplant patients compared to the standard-of-care.

Optimal strategies for modeling anatomy in a hybrid intelligence framework for auto-segmentation of organs.

Organ segmentation is a fundamental requirement in medical image analysis. Many methods have been proposed over the past 6 decades for segmentation. A unique feature of medical images is the anatomical information hidden within the image itself. To bring natural intelligence (NI) in the form of anatomical information accumulated over centuries into deep learning (DL) AI methods effectively, we have recently introduced the idea of hybrid intelligence (HI) that combines NI and AI and a system based on HI to perform medical image segmentation. This HI system has shown remarkable robustness to image artifacts, pathology, deformations, etc. in segmenting organs in the Thorax body region in a multicenter clinical study. The HI system utilizes an anatomy modeling strategy to encode NI and to identify a rough container region in the shape of each object via a non-DL-based approach so that DL training and execution are applied only to the fuzzy container region. In this paper, we introduce several advances related to modeling of the NI component so that it becomes substantially more efficient computationally, and at the same time, is well integrated with the DL portion (AI component) of the system. We demonstrate a 9-40 fold computational improvement in the auto-segmentation task for radiation therapy (RT) planning via clinical studies obtained from 4 different RT centers, while retaining state-of-the-art accuracy of the previous system in segmenting 11 objects in the Thorax body region.

Nomogram for predicting difficult total laparoscopic hysterectomy: a multi-institutional, retrospective model development and validation study.

Total laparoscopic hysterectomy (TLH) is the most commonly performed gynaecological surgery. However, the difficulty of the operation varies depending on the patient and surgeon. Subsequently, patient's outcomes and surgical efficiency are affected. The authors aimed to develop and validate a preoperative nomogram to predict the operative difficulty in patients undergoing TLH. This retrospective study included 663 patients with TLH from Southwest Hospital and 102 patients from 958th Hospital in Chongqing, China. A multivariate logistic regression analysis was used to identify the independent predictors of operative difficulty, and a nomogram was constructed. The performance of the nomogram was validated internally and externally. The uterine weight, history of pelvic surgery, presence of adenomyosis, surgeon's years of practice, and annual hysterectomy volume were identified as significant independent predictors of operative difficulty. The nomogram demonstrated good discrimination in the training dataset [area under the receiver operating characteristic curve (AUC), 0.827 (95% CI, 0.783-0.872], internal validation dataset [AUC, 0.793 (95% CI, 0.714-0.872)], and external validation dataset [AUC, 0.756 [95% CI, 0.658-0.854)]. The calibration curves showed good agreement between the predictions and observations for both internal and external validations. The developed nomogram accurately predicted the operative difficulty of TLH, facilitated preoperative planning and patient counselling, and optimized surgical training. Further prospective multicenter clinical studies are required to optimize and validate this model.

Clinical observation of Erdheim–Chester disease: diagnostic difficulties, treatment options

As is known, orphan diseases, which include histiocytosis, including Erdheim-Chester disease (ECD), occur under the guise of other diseases, which complicates timely diagnosis and treatment. The presence of various symptoms in patients with an unspecified diagnosis (weight loss, fever, chills, night sweats, malaise, shortness of breath, thirst, polyuria; pain in the muscles and joints, in the long tubular bones of the upper and lower extremities, in the lower back or abdomen due to kidney damage and/or retroperitoneal fibrosis; exophthalmos; rash, xanthomas; frequent infectious diseases; nystagmus, ataxia, dysarthria) requires doctors to be wary of BEC.The variety of symptoms is due to the involvement of many organs and systems (orbits, kidneys, skin, brain, including the pituitary gland; lungs; heart; blood vessels; tubular bones), which requires a thorough examination, including morphological verification of the pathological process. Histological examination of biopsy specimens for BEC is characterized by histiocytic infiltrates (so-called “foamy histiocytosis”) with signs of inflammation and the presence of Touton giant cells; Immunohistochemistry reveals positive staining of these giant cells for CD68 antigen and factor XIIIa. Bone scintigraphy reveals a pronounced symmetrical accumulation of radiopharmaceuticals in the affected bones; with radiography in places of ossalgia — significant symmetrical bilateral osteosclerosis of the periosteum; according to CT data - “hairy” kidneys, “lined” aorta as a result of infiltration with histiocytes. The BRAF V-600E gene mutation, detected in half of the cases, in combination with one or more clinical and morphological signs allows a correct diagnosis to be made. The treatment of this disease is quite complex due to the lack of multicenter international clinical studies due to the rare occurrence of this pathology. However, clinical studies are currently being conducted on the use of drugs of various groups in the treatment of BEC. There is no doubt that due to the rarity of the disease and the low awareness of doctors, our own clinical experience in managing such patients is of great interest.

Is Robotic Surgery the Future for Resectable Esophageal Cancer?: A Systematic Literature Review of Oncological and Clinical Outcomes

BackgroundRadical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy.MethodsA systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies.ResultsA total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases.ConclusionsThere are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

(281) Low-Intensity Shockwave Therapy Combined with Tadalafil 5mg Daily has Better Efficacy for Mild and Moderate Erectile Dysfunction: The Preliminary Results of a Multicenter Clinical Study in China

Abstract Introduction Most clinical studies have demonstrated that low-intensity extracorporeal shockwave therapy (Li-ESWT) can improved erectile function in patients with erectile dysfunction (ED). The EAU guideline recommended to use Li-ESWT for mild vasculogenic ED patients. However, the therapeutic advantages of Li-ESWT combined with phosphodiesterase type 5 inhibitors (PDE5i) have not been explored clearly in clinical practice for mild and moderate ED patients. Objective To compare the therapeutic effects of Li-ESWT and Li-ESWT combined with PDE5i in mild and moderate ED patients with 8≤IIEF-5≤16 from a multicenter clinical study in China. Methods Patients with ED which IIEF-5 score is less than 22 and aged 18–60 years old were enrolled from three clinical centers from Jun. 2019 to Mar. 2023. The demographic data, International Index of Erectile Function-5 (IIEF-5), erectile hardness score (EHS) and self-reported symptom questions were collected. Patients were treated by a linear low-energy shock waves generator (Renova). Low-intensity shock wave (energy density of 0.09mJ/mm2) treatments were applied (once a week, 4 weeks in total, 5000 shocks each time). Patients in Li-ESWT combined with PDE5i group took 5mg of tadalafil once a day for one continuous month during ESWT. Comparative analyses of pre- and post-treatment and intergroup were used for statistics. Results In total, 42 ED cases (37.43±11.86 years) in Li-ESWT group and 116 cases (37.41±10.14 years) in combined group were enrolled for analysis. The IIEF-5 score and EHS in both groups were significantly improved after 1 month treatment (p&amp;lt;0.01). Compared with Li-ESWT group, patients in combined group significantly had higher self-reported efficiency (61.2% vs. 47.6%, p=0.013), IIEF-5 scores (15.34±7.15 vs. 13.96±7.71, p=0.039) and EHS (2.85±0.82 vs. 2.69±0.89, p=0.050). In the mild and moderate ED (with 8≤IIEF-5≤16) sub-group, 30 ED cases (36.81±10.99 years) in Li-ESWT group and 96 cases (36.80±10.69 years) in combined group were enrolled for analysis. The combined regimen showed better therapeutic advantages, including effective parameters IIEF-5(14.50±6.74 vs. 12.87±8.54, p=0.040), EHS (2.85±0.75 vs. 2.81±0.67, p=0.046) and self-reported efficiency (64.2% vs. 54.1%, p=0.001). Conclusions Li-ESWT can effectively improve erectile function in this multicenter clinical study in China, and the combination of Li-ESWT with daily use PDE5i had a better therapeutic effect on Chinese ED patients, especially on mild and moderate ED. Long-term follow-up with large sample study need to be developed for exploring the optimal therapeutic regimen. Disclosure No.

Evidence map of clinical research on Chinese patent medicines for post-acute myocardial infarction heart failure

An evidence map was established to comprehensively sort out the clinical research in the treatment of post-acute myocardial infarction heart failure(P-AMI-HF) with Chinese patent medicines, so as to reveal the distribution of evidence in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and EMbase were searched for the randomized controlled trial(RCT), systematic reviews/Meta-analysis, and guidelines/consensus in this field. The evidence was analyzed and displayed in the form of a combination of text, charts, bubble charts, and bar charts, and the quality of RCT, systematic reviews/Meta-analysis, and guidelines/consensus were evaluated by RoB 1.0, AMSTAR2, and AGREE Ⅱ, respectively. A total of 163 RCTs, 4 systematic reviews/Meta-analysis, 1 network Meta-analysis, 2 observational studies, and 5 guidelines/consensus were included. In recent years, the total number of publications in this field has shown an upward trend. There were a variety of Chinese patent medicines in the treatment of P-AMI-HF, among which Shenfu Injection received the most attention. The clinical RCT and systematic reviews/Meta-analysis generally had poor quality, and the RCT mostly had a small size, a single center, and a short cycle. The outcome indicators mainly included cardiac function indicators, myocardial injury markers, total response rate, hemodynamic indicators, and safety indicators, while the characteristic efficacy indicators of TCM received insufficient attention. The development processes of some guidelines/consensus lack standardization, which compromised their authority and rationality. Chinese patent medicines have advantages in the treatment of P-AMI-HF, while there are also problems, which remain to be solved by more high-quality evidence. That is, more large-sample and multi-center clinical studies should be carried out in the future, and the formulation process of relevant systematic reviews/Meta-analysis and guideline/consensus should be standardized and the quality of evidence should be improved. In this way, the effectiveness and safety of Chinese patent medicines in the treatment of P-AMI-HF can be explored.

The acoustic trap theory and its application to lung ultrasound

In this lecture, the acoustic trap theory, as first introduced in 2016 in the context of lung ultrasound (DOI: 10.7863/ultra.15.08023), will be illustrated. Recent publications focusing on the design and validation of lung mimicking phantoms (DOI: 10.1038/s41598-017-13078-9, 10.1121/10.0001797, 10.1121/10.0007482) will be reviewed in the light of this theory. Moreover, its relevance to the monitoring and diagnosis of lung diseases by means of quantitative lung ultrasound spectroscopy will be discussed. To this end, results obtained within published (DOI: 10.1109/TUFFC.2020.3012289, 10.1121/10.0001723) and ongoing multicenter clinical studies, performed with dedicated multi-frequency imaging modalities implemented on open research scanners, will be presented and looked at through the lens of this theory.

Comprehensive functional outcome analysis and importance of bone remodelling on personalized cranioplasty treatment using Poly(methyl methacrylate) bone flaps.

Cranioplasty involves the surgical reconstruction of cranial defects arising as a result of various factors, including decompressive craniectomy, cranial malformations, and brain injury due to road traffic accidents. Most of the modern decompressive craniectomies (DC) warrant a future cranioplasty surgery within 6-36months. The conventional process of capturing the defect impression and polymethyl methacrylate (PMMA) flap fabrication results in a misfit or misalignment at the site of implantation. Equally, the intra-operative graft preparation is arduous and can result in a longer surgical time, which may compromise the functional and aesthetic outcomes. As part of a multicentric pilot clinical study, we recently conducted a cohort study on ten human subjects during 2019-2022, following the human ethics committee approvals from the participating institutes. In the current study, an important aspect of measuring the extent of bone remodelling during the time gap between decompressive craniectomy and cranioplasty was successfully evaluated. The sterilised PMMA bone flaps were implanted at the defect area during the cranioplasty surgery using titanium mini plates and screws. The mean surgery time was 90 ± 20min, comparable to the other clinical studies on cranioplasty. No signs of intra-operative and post-operative complications, such as cerebrospinal fluid leakage, hematoma, or local and systemic infection, were clinically recorded. Importantly, aesthetic outcomes were excellent for all the patients, except in a few clinical cases, wherein the PMMA bone flap was to be carefully customized due to the remodelling of the native skull bone. The extent of physiological remodelling was evaluated by superimposing the pre-operative and post-operative CT scan data after converting the defect morphology into a 3D model. This study further establishes the safety and efficacy of a technologically better approach to fabricate patient-specific acrylic bone flaps with improved surgical outcomes. More importantly, the study outcome further demonstrates the strategy to address bone remodelling during the patient-specific implant design.

Evaluation of the impact of diagnostic blood loss and red blood cell transfusion in very-low-birth-weight anaemic neonates during hospitalization: A multi-centre retrospective clinical study.

Diagnostic blood loss is a significant factor in the development of anaemia in neonates with very low birth weight. This study aimed to assess the clinical efficacy of intervention approaches involving varying diagnostic blood loss and red blood cell transfusion volumes in neonates with very low birth weights experiencing anaemia during hospitalization. A total of 785 newborns with anaemia weighing less than 1500 g were enrolled from 32 hospitals in China. The study involved monitoring diagnostic blood loss and red blood cell transfusion and evaluating relevant interventions such as red blood cell transfusion and clinical outcomes. Three intervention approaches were established based on the difference between blood loss and transfusion (Intervention Approaches 0, 1 and 2). The primary outcomes measured were unsatisfactory weight gain during hospitalization and neonatal mortality. The secondary outcomes included related complications. In the non-hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.081-8.431, p = 0.035). Multivariate analysis revealed that Intervention Approach 1 had a protective effect on weight gain. In the hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (OR: 3.335, 95% CI: 1.785-6.234, p = 0.000) and mortality (OR: 5.341, 95% CI: 2.449-11.645, p = 0.000), while Intervention Approach 1 had the lowest incidence of intraventricular haemorrhage. Intervention Approach 1 demonstrated favourable outcomes in both anaemia groups. Intervention Approach 1 improved weight gain and reduced mortality and complications in both the non-hospital-acquired and hospital-acquired anaemia groups.

Meta‑analysis of the efficacy of venetoclax and azacitidine combination therapy and azacitidine monotherapy for treating acute myeloid leukemia.

The present study aimed to compare the efficacy of combination therapy with venetoclax and azacitidine with that of azacytidine monotherapy in the treatment of acute myeloid leukemia (AML). The Web of Science, PubMed, Embase, The Cochrane Library, Weipu Database, Wanfang Digital Periodicals, Sinomed, China National Knowledge Infrastructure, ProQuest Dissertations and Theses and Cumulative Index to Nursing and Allied Health Literature were searched for publications on the treatment of AML with venetoclax combined with azacitidine or with azacitidine monotherapy. A total of 5,271 relevant studies were retrieved, of which 10 were included. Literature quality was evaluated according to the Cochrane systematic review methodology, and data were extracted for meta-analysis using Review Manager 5.4. The combination of venetoclax and azacitidine demonstrated greater overall efficacy than azacitidine monotherapy for AML treatment. Notably, combination therapy resulted in a higher frequency of complete remission. By contrast, combined treatment and monotherapy showed no significant differences in partial remission, whereas there was a statistically significant decrease in the frequency of no remission in the combination therapy group compared with in the monotherapy group. The results also revealed a significantly higher incidence of adverse reactions when venetoclax and azacitidine were combined in the treatment of AML compared with the observed rates in response to azacitidine monotherapy. Moreover, subgroup analyses showed that no statistically significant differences were observed between the two groups regarding adverse events, including hypokalemia and liver insufficiency. In conclusion, the combination of venetoclax and azacitidine was more effective than azacitidine alone, and had a good clinical application value in the treatment of AML. Although some adverse reactions occurred in response to the combination therapy, they did not significantly affect the prognosis of AML. To better evaluate the efficacy and safety of this treatment regimen, multicenter clinical studies with larger sample sizes are required.

Proteomic Profiles of Human Arterioles Isolated From Fresh Adipose Tissue or Following Overnight Storage

Arterioles are key determinants of the total peripheral vascular resistance, which, in turn, is a key determinant of arterial blood pressure. However, the amount of protein available from one isolated human arteriole may be less than 5 μg, making proteomic analysis challenging. In addition, obtaining human arterioles requires manual dissection of unfrozen clinical specimens. This limits its feasibility, especially for powerful multicenter clinical studies in which clinical specimens need to be shipped overnight to a research laboratory for arteriole isolation. We performed a study to address low-input, test overnight tissue storage and develop a reference human arteriolar proteomic profile. In tandem mass tag proteomics, use of a booster channel consisting of human induced pluripotent stem cell–derived endothelial and vascular smooth muscle cells (1:5 ratio) increased the number of proteins detected in a human arteriole segment with a false discovery rate of <0.01 from 1051 to more than 3000. The correlation coefficient of proteomic profile was similar between replicate arterioles isolated freshly, following cold storage, or before and after the cold storage (1-way analysis of variance; P = .60). We built a human arteriolar proteomic profile consisting of 3832 proteins based on the analysis of 12 arteriole samples from 3 subjects. Of 1945 blood pressure–relevant proteins that we curated, 476 (12.5%) were detected in the arteriolar proteome, which was a significant overrepresentation (χ2 test; P < .05). These findings demonstrate that proteomic analysis is feasible with arterioles isolated from human adipose tissue following cold overnight storage and provide a reference human arteriolar proteome profile highly valuable for studies of arteriole-related traits.

Approaches to the Treatment of Patients with Myelofibrosis and Polycythemia Vera with Constitutional Symptoms in Real-World Clinical Practice in the Russian Federation: Intermediate Results of a Multi-Center Observational Prospective Clinical Study

Aim. To describe the methods of drug therapy implemented for the disease control in patients with polycythemia vera (PV) and myelofibrosis (MF) as well as to analyze manifestations and severity of the disease symptoms in real-world clinical practice.&#x0D; Materials &amp; Methods. The analysis focused on the data of 1229 patients. In 629 (51.18 %) patients, PV was diagnosed, MF was identified in 521 (42.39 %) patients. The diagnosis of 79 (6.43 %) patients was not reported. Early stage of primary MF (PMF) was detected in 182 (34.93 %) patients, PMF fibrosis stage was identified in 251 (48.18 %) patients, post-polycythemic MF was registered in 61 (11.71 %) patients, and 13 (2.5 %) patients showed post-thrombocythemic MF. In 14 (2.69 %) patients, MF type was not reported. By the time of diagnosis, the median age of PV patients was 56 years (range 17–86 years), and that of MF patients was 55 years (range 16–83 years) (p = 0.022). The proportion of women among PV patients was 57 %, among MF patients it was 65 % (p = 0.0065).&#x0D; Results. The assessment of thrombotic complication risk in PV showed that 51.01 % (n = 302) of patients belong to the low-risk, 39.86 % (n = 236) belong to the intermediate-risk, and only 9.12 % (n = 54) of patients belong to the high-risk groups. Distribution of MF patients between risk groups demonstrates favorable prognosis for most patients. The group of low and intermediate-1 risks includes 56.43 % (n = 294) patients according to the prognostic scoring system IPSS and 68.52 % (n = 357) according to the prognostic scoring system DIPSS. In the vast majority of cases, patients received hydroxycarbamide therapy: 81.81 % (n = 832) in the total cohort, 83.33 % (n = 465) in the PV group, and 79.96 % (n = 367) in the MF group. Interferon-α was administered to 19.71 % (n = 110) of PV patients and 29.85 % (n = 137) of MF patients. Ruxolitinib was assigned to 3.14 % (n = 19) of PV patients and 21.35 % (n = 98) of MF patients.&#x0D; Conclusion. Regular monitoring of the PV and MF course and treatment efficacy can provide recommendations for adequate change of therapy in case of the failure of previous treatment. It should be emphasized that the timely switch to the second-line therapy results in reduced disability and mortality among PV and MF patients with myeloproliferative neoplasms.