Prolonged Treatment Time Research Articles

Deep Learning and GAN-Synthesis for Auto-Segmentation of Pancreatic Cancer by Non-Enhanced CT for Adaptive Radiotherapy

In conventional adaptive radiotherapy (ART) for pancreatic cancer, contrast-enhanced CT (CECT) helps to more precisely delineate primary gross tumor volume (GTV) than non-enhanced CT (NECT). However, frequent use of contrast medium can damage kidneys and prolong treatment time. Moreover, traditional manual delineation is labor-intensive and highly dependent on the experience of oncologists. Currently, automatic delineation based on deep learning with Generative Adversarial Networks (GAN)-based CT synthesis is one of the most feasible solutions to these problems. A dataset of 35 pancreatic cancer patients was retrospectively collected from May 2021 to December 2022. All patients consist of a pair of NECT and CECT. We designed and developed an automatic delineation framework (Proposed) for GTV of pancreatic cancer based on Trans-cycleGAN and a modified 3D U-Net. TranscycleGAN can not only synthesize CECT from NECT, but can also augment the amount of CT images; then all real and synthesized CT images were used to train the modified 3D U-Net for automatic delineation of GTV; finally, our framework was able to automatically delineate GTV by NECT, but not only by CECT. Our framework was evaluated by dice similarity coefficient (DSC), 95% Harsdorff distance (95HD) and average surface distance (ASD) with oncologists' manual delineation ("gold standard"). The evaluation results were summarized in Table 1. The proposed framework achieved the best automatic delineation results by NECT, which was superior to that of CECT: 0.917 & 0.903 of DSC, 2.498mm & 3.029mm of HD95, 0.481mm & 0.534mm of ASD, p < 0.05 for DSC and HD95. Specifically, it is significantly superior to the automatic delineation results using U-Net by CECT 0.917 & 0.818 of DSC, 2.498mm & 13.228mm of HD95, 0.481mm & 3.633mm of ASD, p < 0.05 for DSC. We proposed an automatic delineation framework for contouring GTV in ART of pancreatic cancer based on deep learning and Trans-cycleGAN network. This framework could automatically delineate GTV and achieve better performance with NECT compared to CECT. Our method could not only reduce the use of contrast medium, but also increase the precision and effectiveness of tumor delineation, which could have a positive impact on precision radiotherapy.

Accelerated degradation of micro-pollutant by combined UV and chlorine dioxide: Unexpected inhibition of chlorite formation

UV/chlorine dioxide (ClO2) process can be intentionally or accidently conducted and is potentially effective in micro-pollutants degradation. UV irradiation can promote ClO2 decay and subsequently result in the formation of reactive radicals. Hence, the co-exposure of ClO2 and UV exhibited a synergetic effect on metribuzin (MET) degradation. The MET degradation was promoted by UV/ClO2 with a rate of 0.089 min−1 at pH 7.5, which was around 2.4 folds the total of rates caused by single ClO2 (0.004 min−1) and single UV (0.033 min−1). Reactive radicals mainly HO• and reactive chlorine species were involved in the acceleration effect, and contributed to 59%–67% of the total degradation rate of MET during UV/ClO2 under pHs 5.5–7.5. Among them, HO• was the predominant contributor and the contribution rate gradually rose under higher pH. Chlorite (ClO2−) and chlorate (ClO3−) formation has been the major concern of ClO2 oxidation. However, a comparison of their formation during UV/ClO2 and ClO2 oxidation is rarely reported. Herein, during MET degradation by ClO2, only ClO2− was identified with the highest amount of 1.17 mg L−1. Conversely, during MET degradation by UV/ClO2, only ClO3− was identified with the highest amount of 0.68 mg L−1, showing an upward trend with prolonging treatment time. Furthermore, organic halogenated DBPs formation after 24 h post-chlorination with UV/ClO2 and ClO2 pre-treatments was comparatively evaluated. Organic DBPs formation after post-chlorination was higher with UV/ClO2 pre-treatment compared to ClO2 pre-treatment. The overall concentration of DBPs produced with 30 min UV/ClO2 pre-treatment was about 4.5 times that with 1min UV/ClO2 pre-treatment. This study provided useful reference for the application of UV/ClO2 in micro-pollutants degradation.

Different shape-controlled synthesis and catalytic property studies on bismuth nanomaterials

Bi with four different morphologies (zero-dimensional (0D) nanoparticles, one-dimensional (1D) nanowires, two-dimensional (2D) nanoplates, and three-dimensional (3D) shuttle like structures) was successfully synthesized by changing the synthetic conditions. The Bi nanostructures were characterized in terms of structure, morphology, surface characteristics, optical properties and catalytic activity using X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR), Brunauer-Emmett-Teller (BET), photoluminescence (PL), UV–vis absorption spectroscopy (UV–Vis) and total organic carbon (TOC) analyzer techniques, respectively. The PL spectra is shown that the reduction of the size of Bi nanomaterials can reduce the recombination rate of photoelectrons and holes, which leads to the effective separation of photocharge carriers and the lowest photoelectron and hole recombination rates. The band gap values of Bi nanoparticles, nanowires, nanoplates and shuttle like structures are 2.71 eV, 2.76 eV, 2.92 eV and 3.22 eV respectively, favouring the harvesting of visible-light. The experimental results of the degradation performance of Bi with different morphologies exhibited that 99.9%, 97.9%, 96.2% and 74.4% degradations of the Rhodamine B (Rh B) was observed for Bi nanoparticles, nanowires, nanoplates and shuttle like structures, respectively. During the degradation of RhB, with the prolongation of treatment time to 90 min, the highest removal rates of chemical oxygen demand (COD) and TOC was 73.5% and 68.4%, respectively. According to TOC analysis, more than 68% of the carbon in the dyes will produce CO2 products. The removal efficiency is attributed to the production of ·O2−, ·OH and h+ and their mineralization to RhB. At the same time, the achieved results also reveal that Bi2O3 and BiOCl was found in Bi surfaces before and after catalytic degradation, which was confirmed by XPS and FTIR technology. In addition, Bi with the same morphology performed different catalytic activities in Rh B solution with different pH values. It was found that the degradation efficiency increased evidently when the pH value decreased. The mechanism of Bi photocatalytic activity was proposed based on the results of product analysis, radical capture and XPS analysis.

Intervention effect of electroacupuncture therapy on drug reducing and discontinuation of insomnia patients with long-term excessive use of zolpidem

ObjectiveTo explore therapeutic interventions after drug withdrawal reduction for insomnia patients who used zolpidem excessively for a long time. MethodsA total of 86 patients with simple insomnia were randomly rolled into treatment (Tre) group (electroacupuncture therapy under low-dose zolpidem+relaxation treatment intervention, n=40) and control (Ctrl) group (low-dose zolpidem+relaxation treatment intervention, n=40), all of which received treatment and intervention for four weeks. ResultsAs a result, after the dosage of zolpidem was gradually reduced, the deep sleep time of patients in the two groups was reduced in the first stage. However, with the prolongation of treatment time, the reduction trend of the two groups was gradually alleviated, but no great difference was found between groups (P>0.05). In the second stage of treatment, the deep sleep time of patients in the two groups gradually recovered and increased, and that in Tre group was greater than that in Ctrl group, and the upward trend was significant but differed slightly between groups (P>0.05). After treatment, the insomnia severity index (ISI) scores of the two groups gradually decreased, and that in Tre group was drastically inferior to those of Ctrl group on days 14 and 28 after treatment (both Ps<0.05). ConclusionsIn summary, electroacupuncture therapy can effectively alleviate the effect of zolpidem on sleep quality in patients with insomnia after drug discontinuation and promote the recovery of deep sleep time in patients, thereby alleviating the side effects and drug dependence of patients.

Factores de tratamiento terapéutico en identidad de recuperación en personas con trastorno por consumo de sustancias: análisis de contenido

Introduction: Various studies have shown that some components located within the treatment are important in building a new recovery identity and in addressing substance use disorders. Objective: the present study aims to explore the impact that the interaction of some treatment-related factors has on the internalization of a long-term recovery identity and the internal logic that follows the maturation of this process from the Opinion of people with substance use disorder who have been abstinent for more than a year. Method: a deductive content analysis was used that was operationalized on the basis of prior knowledge with semi-structured interviews with 9 participants diagnosed with a substance use disorder who were in a state of abstinence for more than one year, selected through intentionality and snowball. Results: the main categories explored that were relevant were: prolonged treatment time and continuous care, motivation to change, and quality of treatment received. Discussion and conclusions: the findings showed the importance of continuing and active treatment to achieve a stable recovery identity, the need for catharsis as an aid for the transition to sobriety and the conscious acceptance of the chronic nature of the disease. Also, the need and voluntary search for help was highlighted after having experienced critical and cumulative experiences of suffering associated with “hitting rock bottom”, the quality of treatment to consolidate a fortuitous rehabilitation, and the support of peers to increase self-efficacy and motivation towards change.

Simultaneous object detection and segmentation for patient-specific markerless lung tumor tracking in simulated radiographs with deep learning.

Real-time tumor tracking is one motion management method to address motion-induced uncertainty. To date, fiducial markers are often required to reliably track lung tumors with X-ray imaging, which carries risks of complications and leads to prolonged treatment time. A markerless tracking approach is thus desirable. Deep learning-based approaches have shown promise for markerless tracking, but systematic evaluation and procedures to investigate applicability in individual cases are missing. Moreover, few efforts have been made to provide bounding box prediction and mask segmentation simultaneously, which could allow either rigid or deformable multi-leaf collimatortracking. The purpose of this study was to implement a deep learning-based markerless lung tumor tracking model exploiting patient-specific training which outputs both a bounding box and a mask segmentation simultaneously. We also aimed to compare the two kinds of predictions and to implement a specific procedure to understand the feasibility of markerless tracking on individualcases. We first trained a Retina U-Net baseline model on digitally reconstructed radiographs (DRRs) generated from a public dataset containing 875 CT scans and corresponding lung nodule annotations. Afterwards, we used an independent cohort of 97 lung patients to develop a patient-specific refinement procedure. In order to determine the optimal hyperparameters for automatic patient-specific training, we selected 13 patients for validation where the baseline model predicted a bounding box on planning CT (PCT)-DRR with intersection over union (IoU) with the ground-truth higher than 0.7. The final test set contained the remaining 84 patients with varying PCT-DRR IoU. For each testing patient, the baseline model was refined on the PCT-DRR to generate a patient-specific model, which was then tested on a separate 10-phase 4DCT-DRR to mimic the intrafraction motion during treatment. A template matching algorithm served as benchmark model. The testing results were evaluated by four metrics: the center of mass (COM) error and the Dice similarity coefficient (DSC) for segmentation masks, and the center of box (COB) error and the DSC for bounding box detections. Performance was compared to the benchmark model including statistical testing forsignificance. A PCT-DRR IoU value of 0.2 was shown to be the threshold dividing inconsistent (68%) and consistent (100%) success (defined as mean bounding box DSC > 0.6) of PS models on 4DCT-DRRs. Thirty-seven out of the eighty-four testing cases had a PCT-DRR IoU above 0.2. For these 37 cases, the mean COM error was 2.6 mm, the mean segmentation DSC was 0.78, the mean COB error was 2.7 mm, and the mean box DSC was 0.83. Including the validation cases, the model was applicable to 50 out of 97 patients when using the PCT-DRR IoU threshold of 0.2. The inference time per frame was 170 ms. The model outperformed the benchmark model on all metrics, and the comparison was significant (p < 0.001) over the 37 PCT-DRR IoU > 0.2 cases, but not over the undifferentiated 84 testingcases. The implemented patient-specific refinement approach based on a pre-trained baseline model was shown to be applicable to markerless tumor tracking in simulated radiographs for lungcases.

Chinese clinical practice guidelines for the prevention and treatment of radiation‐induced dermatitis

AbstractRadiation‐induced dermatitis is one of the most prevalent complications in patients undergoing cancer radiotherapy and poses a significant challenge to cancer therapy. The symptoms include erythema, dry desquamation, and moist desquamation, which are frequently observed in patients with breast, head and neck, anal, and vulvar cancers. Early skin reactions typically manifest within 2–4 weeks following the initiation of radiotherapy. In severe cases, acute dermatitis can cause radiotherapy interruptions, prolong treatment time, and ultimately affect patient outcomes and quality of life. Currently, there are numerous guidelines on radiation dermatitis, including the Multinational Association of Supportive Care in Cancer (MASCC), British Columbia Cancer Agency (BCCA), Oncology Nursing Society (ONS), and UK Society of Radiographers (SCoR) guidelines. In China, dermatology experts have drafted a consensus. However, due to the differing backgrounds of experts, recommendations among guidelines vary. These guidelines were first developed by Chinese radiation oncologists. The evidence‐based guideline in this paper fully considers and adopts China's national conditions; hence, it can be easily applied in daily practice.

A bi-directional beam-line energy ramping for efficient patient treatment with scanned proton therapy

Objective. The treatment of mobile tumours using Pencil Beam Scanning (PBS) has become more prevalent in the last decade. However, to achieve the same beam delivery quality as for static tumours, treatments have to be combined with motion mitigation techniques, not limited but including, breath hold, gating and re-scanning, which typically prolong treatment time. In this article we present a novel method of bi-directional energy modulation and demonstrate our initial experience in improvement of treatment efficiency. Approach. At Paul Scherrer Institute Gantry 2 mobile tumours are treated by combining PBS with gating and volumetric re-scanning (VR), where the target volume is irradiated multiple times. Initial implementation of VR used only descending beam energies, creating a substantial dead time due to the beam-line initialization (ramping) before each re-scan. In 2019 we commissioned an energy meandering strategy that allows us to avoid beam line ramping in-between energy series while maintaining beam delivery quality. Main results. The measured beam parameters difference for both energy sequence are in the order of the typical daily variations: 0.2 mm in beam position and 0.2 mm in range. Using machine log files, we performed point-to-point dose difference calculations between original and new applications where we observed dose differences of less than 2%. After three years of operation employing bi-directional energy modulation, we have analysed the individual beam delivery time for 181 patients and have compared this to simulations of the timing behaviour assuming uni-directional energy sequence application. Depending on treatment complexity, we obtained plan delivery time reductions of up to 55%, with a median time gain of 17% for all types of treatments. Significance. Bi-directional energy modulation can help improving patient treatment efficiency by reducing delivery times especially for complex and specialised irradiations. It could be implemented in many existing facilities without significant additional hardware upgrades.

Enhancement of sludge dewaterability by repeated inoculation of acidified sludge: Extracellular polymeric substances molecular structure and microbial community succession

Improving the dewatering performance of sewage sludge is of great scientific and engineering significance in the context of accelerated urbanization and increasingly strict environmental regulations. Acidified sludge (AS) can improve sludge dewatering performance, but the dewatering effect of repeated inoculation is unclear. The effects of long-term repeated inoculation of AS on the sludge dewaterability were investigated. The molecular structure and microbial community succession of extracellular polymeric substances (EPS) are emphasized. The results revealed that increasing the inoculation ratio of AS reduced the pH, absolute value of sludge zeta potential, and sludge particle size, and the decreasing trend was more evident with prolonging treatment time. Under the conditions of 30% and 50% AS inoculation, the dewatering performance of the sludge was significantly improved (p < 0.05). Compared with the raw sludge, the specific resistance of filtration (SRF) and capillary suction time of 30% inoculation were reduced by 64.3% and 50.1% after 30 cycles, respectively. Excluding loosely bound (LB)-EPS, soluble (S)-EPS and tightly bound (TB)-EPS exhibited a visible decrease, the protein in TB-EPS was significantly related to sludge dewaterability (p < 0.05). The fluorescent components of aromatic protein and fulvic acid-like substances in TB-EPS were significantly associated with SRF, with a correlation coefficient 0.99 (p < 0.05). Both the increase in the percentages of random coil and decrease in α-helix in TB-EPS contributed to improving dewaterability. Increasing Firmicutes and decreasing Chloroflexi levels improved the sludge dewatering capacity. Repeated inoculation did not disrupt the dewatering effect of AS rather increased the feasibility of the engineering application of AS. Considering the dewatering performance and cost synthetically, 30% AS inoculated ratio is feasible for practical applications.

Efficacy and safety profile of dupilumab for the treatment of atopic dermatitis in children and adolescents: A systematic review and meta-analysis.

Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis (AD) in children and adolescents. Previous systematic reviews explored the effectiveness and safety of dupilumab in adults with AD. However, the underlying mechanisms of AD can vary among different age groups, emphasizing the need for separate investigation into the use of dupilumab in children and adolescents with AD. To evaluate the efficacy and safety of dupilumab in children and adolescents with AD based on evidence from clinical trials and observational studies. The process of meta-analysis was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines. Seven clinical trials and 11 observational studies involving 1275 children and adolescents with AD were eligible for quantitative analysis. Overall, the pooled percentages of eczema area and severity index (EASI) 50, EASI 75, EASI 90, EASI 100, and investigator's global assessment (IGA) 0/1 were 72.9% (95% CI: 61.6%-81.9%), 57.4% (48.1%-66.2%), 31.3% (24.0%-39.7%), 29.7% (23.3%-37.0%), and 35.2% (29.3%-41.5%). With prolonged treatment time, an increase was seen in the pooled rate of EASI response, indicating that dupilumab may provide sustained benefits for children and adolescents over the long term. The reported adverse events were primarily mild and manageable, with an overall incidence rate of 7.2% across clinical trials and 7.6% across observational studies. Dupilumab was an effective and safe treatment option for children and adolescents with AD, with positive results observed from long-term use and an acceptable safety profile. More long-term, high-quality, controlled studies in different regions are needed for further verification.

A Comparative Prospective Study Between Conventional Chemo-Radiotherapy and Pure Accelerated Radiotherapy With Concurrent Chemotherapy for the Treatment of Locally Advanced Head and Neck Cancer.

The established standard treatment for locally advanced head and neck squamous cell carcinoma is concurrent chemoradiotherapy, but the optimum radiotherapy schedule for best disease control and acceptable toxicity is still evolving. Tumor control probability decreases with each day's prolongation of treatment time. Shorteningthe overall treatment time of radiation by pure accelerated radiotherapy may be a good option. One hundred and sixty-five patients with histopathologically proven squamous cell carcinoma of the head and neck were included in the study and were assigned into two groups from January 2017 to June 2019. The total dose of 70 Gy was given, 2 Gy/fraction/day. Treatment was given five days a week (conventional radiotherapy) and six days a week (pure accelerated radiotherapy). Both groups received weekly concurrent injections of cisplatin. The stage (p=0.006)and fractionation of radiation (p=0.018) were the independent factors affecting disease-free survival (DFS). There was a statistically significant difference (p=0.019) in the recurrence of patients in different fractionation schedules. The median DFS was 39 months with a 95% CI of 31.44 - 46.55. One- and three-yearDFS was 51% and 8.5% respectively in the five fractions/week schedule arm while 54.5% and 9.5% respectively in the six fractions/week schedule group. Pure accelerated radiotherapy is more efficacious in terms of disease control with comparable mildly increased acute side effects.

Fibrillation of whey protein isolate by radio frequency heating for process efficiency: Assembly behavior, structural characteristics, and in-vitro digestion

In this study, a novel technology involving radio frequency heating (RF) was applied to promote the production of whey protein isolate (WPI) nanofibrils. As the prolonged treatment time, gradual increases were observed in the conversion rate (>16 h with the conventional processes), fluorescence intensity, and free amino acid content of WPI. During the fibrillation process, WPI was hydrolyzed into small molecular weight peptides that self-assembled into fibrils, resulting in a significant increase in the ζ-potential and surface hydrophobicity. Conformational and structural changes that favored an increased content of β-sheets were confirmed by Fourier transform infrared and circular dichroism spectroscopy. A linear fibril structure with a proper aspect ratio (length/diameter, 35.50 ± 0.39) formed at 7 h. Moreover, the good resistance to proteolytic digestion (especially gastric stage) of certain fibrils makes them suitable for application as nutraceutical delivery vehicles. Our findings move a step forward for WPI fibrillation by RF heating.

Pretreatment information-aided automatic segmentation for online magnetic resonance imaging-guided prostate radiotherapy.

It is necessary to contour regions of interest (ROIs) for online magnetic resonance imaging (MRI)-guided adaptive radiotherapy (MRIgART). These updated contours are used for online replanning to obtain maximum dosimetric benefits. Contouring can be accomplished using deformable image registration (DIR) and deep learning (DL)-based autosegmentation methods. However, these methods may require considerable manual editing and thus prolong treatment time. The present study aimed to improve autosegmentation performance by integrating patients' pretreatment information in a DL-based segmentation algorithm. It is expected to improve the efficiency of current MRIgART process. Forty patients with prostate cancer were enrolled retrospectively. The online adaptive MR images, patient-specific planning computed tomography (CT), and contours in CT were used for segmentation. The deformable registration of planning CT and MR images was performed first to obtain a deformable CT and corresponding contours. A novel DL network, which can integrate such patient-specific information (deformable CT and corresponding contours) into the segmentation task of MR images was designed. We performed a four-fold cross-validation for the DL models. The proposed method was compared with DIR and DL methods on segmentation of prostate cancer. The ROIs included the clinical target volume (CTV), bladder, rectum, left femur head, and right femur head. Dosimetric parameters of automatically generated ROIs were evaluated using a clinical treatment planning system. The proposed method enhanced the segmentation accuracy of conventional procedures. Its mean value of the dice similarity coefficient (93.5%) over the five ROIs was higher than both DIR (87.5%) and DL (87.2%). The number of patients (n=40) that required major editing using DIR, DL, and our method were 12, 18, and 7 (CTV); 17, 4, and 1 (bladder); 8, 11, and 5 (rectum); 2, 4, and 1 (left femur head); and 3, 7, and 1 (right femur head), respectively. The Spearman rank correlation coefficient of dosimetry parameters between the proposed method and ground truth was 0.972±0.040, higher than that of DIR (0.897±0.098) and DL (0.871±0.134). This study proposed a novel method that integrates patient-specific pretreatment information into DL-based segmentation algorithm. It outperformed baseline methods, thereby improving the efficiency and segmentation accuracy in adaptive radiotherapy.

Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma

The majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model. We showed that cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines with AMO1 being the most sensitive cell line (IC50 = 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6 µM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells that was associated with significant downregulation of STAT3, AKT, and ERK1/2. Cell cycle analysis showed that cynaropicrin treatment arrested AMO1 cells in the G2M phase along with an increase in the sub-G0G1 phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G0G1 phase, implying cell death. Using confocal microscopy, we revealed that cynaropicrin disrupted the microtubule network in U2OS cells stably expressing α-tubulin-GFP. Furthermore, we revealed that cynaropicrin promoted DNA damage in AMO1 cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently to a novel form of cell death, parthanatos. Finally, we demonstrated that cynaropicrin (5, 10 µM) significantly reduced tumor growth in a T-cell acute lymphoblastic leukemia (T-ALL) xenograft zebrafish model. Taken together, these results demonstrate that cynaropicrin causes potent inhibition of hematopoietic tumor cells in vitro and in vivo.

Comparison of Efficacy of Baricitinib and Dupilumab in the Treatment of Chinese Moderate-To-Severe Atopic Dermatitis: A Retrospective Study

Introduction: The treatment of atopic dermatitis (AD) patients with insufficient response or intolerance to topical medication remains clinical challenges, and there is a paucity of head-to-head trials comparing the efficacy of novel biological agents such as JAK inhibitor and antibody. Methods: To compare the efficacy of selective JAK1/JAK2 inhibitor baricitinib and interleukin-4 monoclonal antibody dupilumab in the treatment of patients with moderate-to-severe AD, a retrospective cohort study method was adopted. Clinical data from June 2020 to April 2022 were systematically reviewed. Eligible patients who received baricitinib or dupilumab were screened according to the following inclusion criteria: (1) age ≥ 18 years; (2) moderate-to-severe AD: baseline investigator global assessment (IGA) score ≥ 3, baseline eczema area and severity index (EASI) score ≥ 16; (3) poor response or intolerance to at least one topical drug in the past 6 months; (4) no topical glucocorticoids were used in the past 2 weeks and no systematic treatment was given in the past 4 weeks. Patients of the baricitinib group were treated with oral baricitinib in doses of 2 mg per day for 16 weeks, and patients of the dupilumab group were treated with standardized use of dupilumab for 16 weeks, with the initial 600 mg subcutaneous injection and the following 300 mg subcutaneous injection every 2 weeks. The clinical efficacy score indexes including the IGA score, EASI score, and Itch Numeric Rating Scale (NRS) score. These scores at 0, 2, 4, 8, 12, and 16 weeks after the start of treatment were collected. Results: A total of 54/45 patients treated with baricitinib/dupilumab were included. There was no significant difference in the decrease of all scores between the two groups at the 4th week (p > 0.05). There was no difference in the EASI score and Itch NRS score (p > 0.05), but the IGA score of the baricitinib group was lower at the 16th week (Z = 4.284, p < 0.001). Within the first 4 weeks, the Itch NRS score of the baricitinib group decreased rapidly, but with the prolongation of treatment time, there was no significant difference between the two groups at the 16th week (Z = 1.721, p = 0.085). Conclusions: The efficacy of baricitinib at a dose of 2 mg daily was similar to dupilumab, and the improvement in pruritus was significantly faster in the early stage of treatment (the first 4 weeks) than that of dupilumab.

Postoperative Hyperuricemia—A Risk Factor in Elective Cardiosurgical Patients

Hyperuricemia is a well-known cardiovascular risk factor. The aim of our study was to investigate the connection between postoperative hyperuricemia and poor outcomes after elective cardiac surgery compared to patients without postoperative hyperuricemia. In this retrospective study, a total of 227 patients after elective cardiac surgery were divided into two groups: 42 patients with postoperative hyperuricemia (mean age 65.14 ± 8.9 years) and a second group of 185 patients without it (mean age 62.67 ± 7.45 years). The time spent on mechanical ventilation (hours) and in the intensive care unit (days) were taken as the primary outcome measures while the secondary measure comprised postoperative complications. The preoperative patient characteristics were similar. Most of the patients were men. The EuroSCORE value of assessing the risk was not different between the groups nor the comorbidities. Among the most common comorbidities was hypertension, seen in 66% of all patients (69% in patients with postoperative hyperuricemia and 63.7% in those without it). A group of patients with postoperative hyperuricemia had a prolonged time of treatment in the intensive care unit (p = 0.03), as well as a prolonged duration of mechanical ventilation (p < 0.01) and a significantly higher incidence of the following postoperative complications: circulatory instability and/or low cardiac output syndrome (LCOS) (χ2 = 4486, p < 0.01), renal failure and/or continuous venovenous hemodiafiltration (CVVHDF's) (χ2 = 10,241, p < 0.001), and mortality (χ2 = 5.22, p < 0.01). Compared to patients without postoperative hyperuricemia, elective cardiac patients with postoperative hyperuricemia have prolonged postoperative treatment in intensive care units, extended durations of mechanically assisted ventilation, and a higher incidence of postoperative circulatory instability, renal failure, and death.

The combination of a prolonged treatment time window and alpha-fetoprotein benefits the tumor response of hepatocellular carcinoma patients as evaluated by the imRECIST: a single-center, retrospective study.

The combined immunotargeting therapy of hepatocellular carcinoma (HCC) have brought remarkable results. There are still some drawbacks to the application of the immune-modified Response Evaluation Criteria in Solid Tumors to Immunotherapy (imRECIST). How many weeks does it take to confirm the true disease progression for HCC patients who had reported disease progression for the first time based on imRECIST. Whether alpha-fetoprotein (AFP), an important indicator in the progression and prognosis of liver cancer, has the same value in immunotherapy. This prompted more clinical data to gather evidence that the immunotherapy time window issue contradicts the potential benefit of therapy. This study retrospectively analyzed the clinical data of 32 patients who had undergone immunotherapy plus targeted therapy at the First Affiliated Hospital of Chongqing Medical University from June 2019 to June 2022. ImRECIST was used to evaluate the therapeutic efficacy among the patients. Before initial treatment and each immunotherapy cycle, each patient underwent standard abdominal computed tomography (CT) imaging and some biochemical indicators to assess physical condition and tumor response. All patients included will be divided into 8 groups. The differences in the survival outcomes of each treatment group were analysed. Among the 32 advanced HCC patients, 9 patients achieved stable disease (SD), 12 patients showed progressive disease (PD), 3 patients showed a complete response (CR), and 8 patients showed a partial response (PR). There is no difference in baseline characteristics between subgroups. In relation to patients with PD, a prolonged therapeutic time window and the provision of continuous medication may lead to a PR, prolonging their overall survival (P=0.5864). Compared to the patients with continuous PD, there was no significant difference in the survival of patients with increased AFP concentrations after treatment who achieved PR or SD and ultimately showed PD (P=0.6600). In our study, the time window for treatment may need to be extended in the process of immunotherapy for HCC patients. An analysis of AFP may assist the imRECIST by providing a more accurate evaluation of tumor progression.

In Vitro and In Vivo Efficacy of NITD-916 against Mycobacterium fortuitum.

Mycobacterium fortuitum represents one of the most clinically relevant rapid-growing mycobacterial species. Treatments are complex due to antibiotic resistance and to severe side effects of effective drugs, prolonged time of treatment, and co-infection with other pathogens. Herein, we explored the activity of NITD-916, a direct inhibitor of the enoyl-ACP reductase InhA of the type II fatty acid synthase in Mycobacterium tuberculosis. We found that this compound displayed very low MIC values against a panel of M. fortuitum clinical strains and exerted potent antimicrobial activity against M. fortuitum in macrophages. Remarkably, the compound was also highly efficacious in a zebrafish model of infection. Short duration treatments were sufficient to significantly protect the infected larvae from M. fortuitum-induced killing, which correlated with reduced bacterial burdens and abscesses. Biochemical analyses demonstrated an inhibition of de novo synthesis of mycolic acids. Resolving the crystal structure of the InhAMFO in complex with NAD and NITD-916 confirmed that NITD-916 is a direct inhibitor of InhAMFO. Importantly, single nucleotide polymorphism leading to a G96S substitution in InhAMFO conferred high resistance levels to NITD-916, thus resolving its target in M. fortuitum. Overall, these findings indicate that NITD-916 is highly active against M. fortuitum both in vitro and in vivo and should be considered in future preclinical evaluations for the treatment of M. fortuitum pulmonary diseases.

Social stigma of people with mental disorders and attitude to psychiatric treatment in Polish society

Introduction People with mental disorders (MD) may experience social stigma in various spheres of their lives. This phenomenon is based on negative social beliefs and hostile perceptions about mental disorders. Stigma may lead to social exclusion and discrimination (unjust treatment compared to people without MD). It may also result in resistance to using professional medical help (psychiatrist, psychotherapist) by people who experience symptoms of MD. Objectives The study aims to analyze the attitude of Polish society toward people with mental disorders and the attitude toward psychiatric treatment. The study investigates the correlation between the abovementioned attitudes and socioeconomic parameters of the respondents. Methods The study was conducted on a group of 1,230 respondents with the anonymous, authorial questionnaire disseminated by the CAWI technique. The questionnaire consisted of 10 single-choice questions concerned with the socioeconomic parameters of the respondents (age, place of residence, education, gender) and their attitudes toward mental health problems. The chi-square test and Kendall’s tau-b correlation coefficient (τb) were used to analyze the correlations between the above parameters (with p&lt;0,05). Results Over 33% of respondents believes that people with MD are more aggressive than people who do not present this type of disorder. In turn, 16.4% of respondents admitted that they would feel uncomfortable in the presence of a person with mental disorders. There was no statistically significant correlation between the above beliefs and any socioeconomic parameter. Every tenth respondent would not hire a person with MD. Resistance to employment increased with the respondents’ age and level of education, whereas it decreased with the population of respondents’ domiciles. More than 17% of respondents would feel resistance to contacting with psychiatrist, and 4.1% of them already hide the fact of treatment from their family. The resistance to using psychiatric help was higher in villages and smaller towns than in bigger centers. Conclusions The study shows negative attitudes towards people with MD are still relatively frequent in Polish society. The stereotypical perception of this group of entities is generally not dependent on any analyzed socioeconomic parameter. Such correlations exist only in some areas (employment). Because of the negative perception of MD, some people who struggle with these problems do not use a psychiatrist’s professional help. In effect, these entities remain undiagnosed and untreated. Treatment delay may lead to exacerbating symptoms, prolong treatment time (including the necessity of hospitalization), and increase its cost. Reducing the stigma is necessary for counteracting discrimination against people with mental disorders and improving the mental health condition of Polish society. It requires educational activities and appropriate legal regulations. Disclosure of Interest None Declared

Orthodontic urgencies and their management during COVID-19 pandemic-A web-based survey.

This investigation aimed to evaluate the most common orthodontic urgencies, their management, and changes in routine biosafety measures and the total income of the dental office in South India during the COVID-19 pandemic. A questionnaire was drafted using Google Forms with questions in four domains pertaining to orthodontic urgencies, biosafety measures, treatment duration, and income. After validation, this questionnairewas sent to 750 orthodontists via WhatsApp messenger (WhatsApp Inc, Menlo Park, Calif) over a period of 14 days.Descriptive statistics and comparisons were performed using independent t- and Chi-square tests. Majority of the orthodontists (62.3%) had closed their clinics only during the first lockdown. Many (63%) had scheduled urgent appointments along with routine limited patients per day. The most frequent urgencies were related to the breakage of brackets, archwires, molar tubes, bands, and temporary anchorage devices. Aligners were the least problematic. The treatment time was also prolonged. Telephonic advice and virtual assistance via WhatsApp messages/videos were found to be successful in the management of urgencies.Most orthodontists had strengthened their routine biosafety measures.The financial impact of this pandemic was considerable, with nearly 50% reduction in total income. Urgencies linked to preadjusted edgewise appliances, such as breakage of brackets and tubes, and archwire-related injuries were the most common. Prolongation of treatment time and negative financial impact were the other problems encountered during this pandemic. Drastic changes had occurred in routine biosafety measures, which prevented the spread of infection among orthodontists and patients.