Late Stage Of Treatment Research Articles

Mixed grafting of small auto- and cryopreserved allo-skin for residual wound repair in severe burn patients: A retrospective study.

The wound repair process for extensively deep burn patients is a recurring and highly challenging endeavor. A prolonged healing time beyond 3 weeks after injury often leads to compromised healing outcomes. The limited availability of autologous skin grafts remains the primary obstacle in achieving timely wound repair. This study aimed to investigate an approach that minimizes the reliance on autologous skin grafts for repairing residual wounds in severe burn patients. This was a retrospective review of 74 burn patients with large residual wounds in the middle- and late-stages of treatment who were admitted to the Burn Center of the First Affiliated Hospital of Naval Medical University between 2012 and 2022. Mixed grafting of small auto- and cryopreserved allo-skin was used in 32 patients with an expansion ratio of 1:9-16. Routine microskin grafting was applied in 17 cases with an expansion ratio of 1:10-15. Meek grafting was employed in 25 patients with an expansion ratio of 1:4-6. The main outcomes of this study were the wound healing rate and scar formation. The wound healing rate in the mixed grafting group was significantly greater than that in the microskin and Meek grafting groups (89 ± 5.8 % vs. 66.5 ± 6.9 % and 75.4 ± 5.1 %, respectively; P < 0.001). Multiple linear regression analysis showed that under the same conditions, the wound healing rate of microskin grafting and Meek grafting decreased by 24.6 % and 16.8 % compared with mixed grafting respectively. Follow-up studies of 43 of total 74 burn patients over 1-2 years revealed that the mean VSS scores for pigmentation, pliability, scar height, and vascularity in the mixed grafting group (n = 23) were significantly lower (total score 4.23 ± 2.17) than those in the microskin grafting group (n = 12; 6.02 ± 2.73, P = 0.03), and not significantly different from those in the Meek grafting group (n = 18; 4.37 ± 2.13, P = 0.74). Mixed grafting of small auto- and allo-skin minimizes the reliance on limited autologous skin resources while achieving superior healing rates and lower scar formation for repairing deep burn wounds. Compared with the microskin and Meek grafting methods, the mixed grafting approach significantly enhances wound healing rates and outcomes in patients with extensive deep burns. Our findings suggest that mixed grafting is a viable and effective strategy for improving wound repair and functional outcomes in severely burned patients.

The Experience of Patients with Endocrine Therapy for Breast Cancer: A Patient Journey Map Based on Qualitative Research.

(1) Background: While there is extensive documentation on the medical experience of breast cancer, a thorough understanding of the various stages of endocrine therapy remains insufficient. The aim of this study was to map the experiences and coping styles of breast cancer patients during endocrine therapy. (2) Methods: Qualitative research was conducted to gather insights into the experiences of breast cancer patients undergoing endocrine therapy. The themes were organized through content analysis and induction. Subsequently, patients were invited for face-to-face interviews at a top-three hospital in Guangzhou to supplement and validate the findings from the literature review. The patient journey was then mapped based on both the literature review and the semi-structured interviews. (3) Results: A total of 24 studies were included that described patients' experiences and behaviors during the early, middle, and late stages of treatment, leading to the formation of a preliminary framework. Interviews were conducted with 20 patients, which confirmed and enriched the findings from the literature review. Based on these results, a stage trajectory for endocrine therapy in breast cancer was established. (4) Conclusions: The patient journey map developed in this study clearly and intuitively illustrates the thought and emotion matrix, as well as the behavior matrix, of breast cancer patients undergoing endocrine therapy. This provides a theoretical foundation for enhancing clinical services tailored to the needs of these patients.

Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience.

Tocilizumab (TCZ) which is a humanized interleukin (IL)-6 receptor antibody has been increasingly widespread used in rheumatology practice. TCZ-related hypofibrinogenemia is a not well-described side effect, but awareness seems to be incresing as publications on this topic are also becoming more frequent. Our aim in this study was to determine the frequency, timing, and approach to TCZ-related hypofibrinogenemia in rheumatic diseases. We retrospectively screened our patients who received TCZ for inflammatory rheumatic diseases and studied serum fibrinogen at least once before and/or after drug administration. We recorded and analyzed demographic features (age, gender, diagnosis), comorbidities, laboratory parameters, management, and outcome data. 30 patients who received TCZ due to rheumatological diseases and had at least one fibrinogen level were included in this study. 73.3% were female and median age was found to be 65 (42-82) years, with median disease duration of 148 (36-500) months. 90% of the patients received TCZ for RA and 10% for GCA. We examined the fibrogen levels at an average of 24 months (min 1 max 108) following the start of TCZ treatment. The study group was divided into those with normal fibrinogen levels (normal fibrinogen group) and those with low fibrinogen levels (lowfibrinogen group). In total, hypofibrinogenemia was found in 14 (46.6%) patients. Median serum fibrinogen level in the low fibrinogen group after TCZ was calculated to be 151.5mg/dl (min 92 max 171). Most patients were asymptomatic (71.4%). Ecchymoses were in seen 4 (28,6%) patients. No major bleeding were seen. TCZ was discontinued in 5 out of 14 patients (35.7%), while 9 out of 14 patients (64.3%) were closely followed. Outcomes regarding fibrinogen levels (11 out of 14) were as follows: increase in 4 and not checked in one after cessation of the drug, 3 spontaneous increases under the drug, and 3 persistently low levels on TCZ treatment. We found no difference in terms of gender (p = 0.417), platelets (p = 0.343), ESR (p = 0.448), and CRP (p = 0.660) at the time of TCZ initiation between groups. TCZ-related hypofibrinogenemia is more frequent than expected with occurence in both the early and late stages of treatment. Further research is required to determine whether to regularly measure fibrinogen levels in patients using TCZ and how to treat patients with hypofibrinogenemia.

Multicentric retrospective study on the treatment characteristics, efficacy and safety of eribulin in Slovenian patients with breast cancer.

e13123 Background: Eribulin mesylate (eribulin) is a microtubule inhibitor and a synthetic analog of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin was approved based on the randomized Phase 3 EMBRACE clinical trial, which showed an improvement in survival compared to chemotherapy (CT) of the physician's choice. The efficacy and safety of eribulin treatment in real-world settings has been reported in several studies: Korean and Chinese multicenter retrospective studies and a meta-analysis from 2020. Methods: We included all patients treated with eribulin between January 24, 2013 and September 14, 2022 at the Institute of Oncology Ljubljana (85.4% of patients) and University Medical Centre Maribor (14.6%). Clinical data were collected retrospectively from paper and electronic patient records. The primary endpoints were median progression-free survival (PFS), overall survival (OS), response rates and safety. We performed a descriptive statistical analysis and a survival analysis using the Kaplan-Meier method. Results: 205 patients, whose average age was 58.6 (29-88) years, were included in the study. The majority (79%) had a hormone receptor (HR+) positive tumor, 12.2% were HER2 positive and 16.6% were triple negative. 32/205 (15.6%) were primary metastatic. Of the remaining 173 patients, 160/173 (92.4%) received adjuvant therapy, of which 15% received hormone therapy, 23.1% received CT and 61.9% received both. At the start of treatment with eribulin, 84.9% had visceral tumors and 14.6% had tumors in the CNS. The median number of all treatment lines was 6 (range 2–15) and the median number of CT lines was 4 (0–13). The ECOG performance status was: 0 in 4.9%, 1 in 53.2%, 2 in 35.1% and 3 in 4.9% and 4 in 0.5% of patients. The objective response rate was 7.3% and clinical benefit was achieved in 27.3%. The median CT line in which eribulin was used was the fourth (1–10). Eribulin was used as the last CT line in half of the patients. The median PFS was 3.01 months (95% confidence interval 2.56–3.47) and the median OS was 6.68 months (95% confidence interval 5.60–7.77). Patients who received eribulin in the first 3 lines of treatment had a better OS than those who received eribulin in later lines. Adverse events (AEs) occurred in 52.7%. Eribulin therapy was discontinued due to AEs in 18.5% of patients. The most common AE was fatigue (25.9%), followed by neuropathy and neutropenia (22.9% and 18%). Conclusions: In our retrospective analysis, we found significantly worse results of treatment with eribulin than in previous studies. In our population, eribulin was used in the late stages of treatment and in older patients with poorer performance status. The proportion of patients with visceral and CNS tumors was higher. The side effects were comparable.

PATIENTS' CHRONOTYPE INFLUENCE IN TREATMENT EFFICIENCY OF PLACENTA CRYERXTRACT CHANGES IN MAXILLOFACIAL PHLEGMONS

Among acute odontogenic inflammatory diseases, a significant subset comprises purulent processes in soft tissues, including abscesses and phlegmons. Methods. The study encompassed 90 patients (both male and female) diagnosed with maxillofacial phlegmons, aged between 35 and 60 years. These patients were divided into three clinical groups, each comprising 30 individuals, further categorized into two subgroups based on circadian rhythms. Analyzing the obtained data, it can be asserted that the most significant changes in markers of lipid peroxidation in patients with superficial phlegmons of maxillofacial localization were experienced in both experimental groups when used against the background of treatment according to standard protocols of intravenous injections of the cryopreserved placenta without and in combination with local injection of the cryopreserved placenta as part of "Levomekol" ointment, in contrast to the control group. It was proved that the markers of lipid peroxidation underwent the most significant changes in both clinical groups compared to the control group, but the largest changes were visualized in the second clinical group. On the 5th day of treatment, SOD activity reliably increases by 15.7% in patients with the morning chronotype and 14.9% - with the evening chronotype. A significant decrease in erythrocyte catalase activity by 51.5% was noted in patients with the evening chronotype and 56.1% - with the morning chronotype. In the control group, significant changes were noted only in the late stages of treatment. The dependence of lipid peroxidation markers on the timing of surgical intervention on the patient's circadian rhythm was established, which is most clearly observed in the 2nd clinical group. Optimal healing of a purulent wound helps to reduce the duration of treatment, accelerate the rehabilitation of patients, and improve the formation of a postoperative scar. Conclusion. Thus, aligning the timing of surgical intervention for maxillofacial phlegmons with the patient's circadian rhythm, particularly when combined with intravenous injections and local application of placenta cryoextract alongside standard treatment, contributes to an optimal modulation of lipid peroxidation markers.

Anthracycline-based hepatic arterial infusion chemotherapy achieved 17months of disease regression in a patient with breast cancer liver metastases resistant to multiple systemic chemotherapies.

Hepatic arterial infusion chemotherapy (HAIC) for liver metastases (LMs) from breast cancer is not a standard of care, but its effectiveness in patients with extensive LMs who cannot tolerate systemic therapy has been reported. Herein, we report a case of breast cancer LMs that were controlled by anthracycline-based HAIC. A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38months; letrozole, nivolumab/fulvestrant, eribulin, gemcitabine/vinorelbine, high-dose toremifene/abemaciclib, and capecitabine for 21months in total). However, owing to its adverse effects and the continued progression of the LMs, systemic therapy was switched to HAIC (40mg/body epirubicin on day 1, 4mg/body mitomycin C on days 1 and 15, and 500mg/body 5-fluorouracil on days 1, 8, and 15; 28-day courses). In response to HAIC, the LMs remarkably regressed and were controlled for 17months without severe adverse effects. HAIC was stopped when multiple brain metastases arose, and the patient died 2months later. This case suggests that HAIC is a reasonable option for patients with extensive LMs, even in the late stage of treatment. HAIC recipients should be carefully selected through multidisciplinary discussions as the survival benefits of HAIC over systemic treatment remain unclear. Our findings identify a potential window for the use of traditional chemotherapeutic agents such as anthracyclines. Novel strategies to improve drug delivery are warranted in the future.

Rare, late onset of immune checkpoint inhibitor-induced type 1 diabetes mellitus in a patient with small-cell lung cancer treated with serplulimab: a case report and review of the literature

BackgroundAs a newly approved immune checkpoint inhibitor in China, serplulimab has been widely used in the immunotherapy of tumors. However, the immune-related adverse events of immune checkpoint inhibitors should not be ignored. Although immune checkpoint inhibitor-induced type 1 diabetes mellitus is a rare complication, it may cause diabetic ketoacidosis and endanger the lives of patients.Case presentationThis case report describes a 55-year-old male of Han nationality from China diagnosed with small-cell lung cancer with multiple metastases who experienced an adverse event of type 1 diabetes mellitus 68 weeks after receiving serplulimab therapy. The patient presented with typical symptoms of diabetic ketoacidosis, including severe thirst, nausea, vomiting, deep respirations, and stupor. Despite the absence of diabetes-related autoantibodies, the patient had extremely low levels of insulin and C-peptide release. Other potential causes of diabetes were ruled out, confirming the condition as serplulimab-induced immune checkpoint inhibitor-induced type 1 diabetes mellitus. After aggressive treatment to correct diabetic ketoacidosis, the patient’s blood glucose levels stabilized and symptoms of diabetes improved significantly, although long-term insulin maintenance therapy was necessary.ConclusionThis case highlights a rare, late-onset adverse event of immune checkpoint inhibitor-induced type 1 diabetes mellitus that may be overlooked during treatment with serplulimab. The monitoring of blood glucose levels and early signs and symptoms of diabetes cannot be relaxed at the late stage of treatment, even if patients do not have elevated blood glucose levels before and during the middle stage of treatment.

Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH2(Fe).

It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.

Eutrophic water remediation efficiency of algicidal bacteria, Cellvibrio sp. G1 and Chitinimonas sp. G2, and their influence on microbial community structure

Algal blooms that occur periodically in rivers, lakes, and reservoirs are associated with the cumulative effects of excess nutrients from industrial and agricultural development. Algicidal bacteria can be used as environmentally friendly biocontrol agents to manage harmful algal blooms in eutrophic water. However, there is still a dearth of studies on the effects of mixed algicidal agents, the persistence of algae removal efficiency, and the impacts on native aquatic microbial communities. Two strains of algicidal bacteria, Cellvibrio sp. G1 and Chitinimonas sp. G2, were previously isolated and purified from reservoir sediment. Herein, G1 and G2 broth cultures, alone and in combination (1:1, V/V), were added to eutrophic water collected from a park at the volume ratio of 5 %. Eutrophic water remediation efficiency under different treatments was monitored for 30 days, and microbial community dynamics in water were analyzed by full-length sequencing of the 16S rRNA genes. The best algae removal efficiency was observed in the water treated with G1 alone, as indicated by the highest algae removal rate of 41.3 %. The total nitrogen removal rates of G1, G2, and their combination were 33.47 %, 23.65 %, and 28.88 %, respectively; ammonia‑nitrogen removal rates were 24.11 %, 25.02 %, and 19.63 %, respectively; total phosphorus removal rates were 24.11 %, 25.02 %, and 19.63 %, respectively; and orthophosphate removal rates were 46.11 %, 44.37 %, and 27.92 %, respectively. In the water treated with G1 and/or G2, the major genera with algicidal capacity (i.e., Cellvibrio and Chitinimonas) were outcompeted by the well adapted genera (e.g., Pseudomonas). At the late stages of treatment, the algicidal genera decreased in relative abundance, leading to decline in algae removal efficiency and increase in chlorophyll concentration. Based on both eutrophic water remediation efficiency and environmental adaptability, G1 alone was superior to G2 alone or in combination with G1, thus having potential practical implications.

Clinical Advances in Implant Transmucosal Contouring for Single Implant Sites: Prosthetic and Biologic Considerations.

Current evidence suggests that proper implant transmucosal contouring can significantly impact supracrestal soft tissue development and crestal bone response both in early and late stages of treatment. The macrodesign and composition of the anatomical healing abutment or temporary prosthesis used during transmucosal contouring are crucial elements for establishing biologic and prosthetic conditions that minimize early bone remodeling, improve esthetic outcomes, and reduce the possibility for future peri-implant inflammation. This article presents clinical directions on the design and fabrication processes of anatomical healing abutments or temporary prostheses for single implant sites under the interpretation of currently available scientific data.

Studies Point to Benefits of Early Treatment With Long-Acting Antipsychotics

Back to table of contents Previous article Next article Clinical & ResearchFull AccessStudies Point to Benefits of Early Treatment With Long-Acting AntipsychoticsNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:23 Nov 2022https://doi.org/10.1176/appi.pn.2022.12.10.39AbstractPatients with schizophrenia who were prescribed oral antipsychotics for less than three years saw greater symptom improvements when switching to long-acting injectable formulations than those who had been taking the oral medications longer.iStock/Rawf8Numerous studies have pointed to the benefits of long-acting injectable antipsychotics (LAIs) at reducing the risk of symptom relapse, hospitalizations, and other adverse outcomes in patients with schizophrenia. A pair of recent studies provide evidence that switching from oral antipsychotics to LAIs within the first two to three years of a diagnosis may provide the greatest benefit.One study involved data collected from Taiwan’s national health insurance on over 19,000 people aged 16 to 65 who had a schizophrenia diagnosis, were taking oral antipsychotics, and were hospitalized for acute psychosis between 2002 and 2005. Among this group, Joni Yu-Hsuan Shao, Ph.D., a professor of biomedical informatics at Taipei Medical University in Taiwan, and colleagues identified 678 patients who were switched from oral antipsychotics to an LAI during hospitalization and who continued to receive the LAI at least 12 months after discharge; 312 received LAIs within three years of their first oral antipsychotic prescription (early stage of treatment), while 366 transitioned following three or more years of oral medication use (late stage of treatment).As described in the Journal of Clinical Psychiatry, each of these patients was matched to a patient of similar age, sex, hospitalization date, and psychiatric comorbidities who continued taking oral antipsychotics following discharge from the hospital. All patients were followed up from their date of hospitalization until the end of the study period (December 31, 2015) or death, whichever came first. During this period the researchers recorded all instances of rehospitalizations (psychiatric or other medical), psychiatric emergency room (ER) visits, or death.Early LAI switchers had the following:37% reduced risk of psychiatric hospitalization.44% reduced risk of any hospitalization.42% reduced risk of a psychiatric ER visit.51% reduced risk of death by any cause.The reductions in adverse health outcomes were not seen in patients who were switched during the late stage of illness; in fact, patients who switched to LAIs in the late stage of treatment had a 34% increased risk of psychiatric rehospitalization during the follow-up period compared with patients who stayed on oral antipsychotics.“These real-world data demonstrated that LAIs in the early stage of treatment of hospitalized patients increased disease control and had long-term benefits,” Shao and colleagues wrote.The other study was published in JAMA Network Open and conducted by Yue Wei, M.P.H., of the University of Hong Kong and colleagues. The investigators used health records data to identify 23,719 individuals diagnosed with schizophrenia between 1993 and 2019 who were prescribed at least one oral and LAI antipsychotic during this time. They compared the health outcomes of these patients during periods while taking oral antipsychotics with periods while taking LAIs.As expected, patients had lower rates of emergency department visits, hospitalizations, and suicide attempts while taking an LAI antipsychotic relative to their time taking an oral antipsychotic. The benefits were more pronounced for those who began taking LAI antipsychotics within two years of a schizophrenia diagnosis; compared with periods they were taking the oral medication, these patients had the following:76% reduced risk of a psychiatric hospitalization.65% reduced risk of any hospitalization.33% reduced risk of an emergency department visit.72% reduced risk of a suicide attempt while on an LAI.Shao said these findings support the critical period hypothesis, which posits that schizophrenia-related deterioration is particularly aggressive in the two to five years after the first episode of psychosis.The Shao study was supported by the Bali Psychiatric Center, Taiwan. The Wei study was supported by The Excellent Young Scientists Fund of the National Natural Science Foundation of China. ■Resources“Long-term Outcomes of Early Use of Long-Acting Injectable Antipsychotics in Schizophrenia”“Association of Long-Acting Injectable Antipsychotics and Oral Antipsychotics With Disease Relapse, Health Care Use, and Adverse Events Among People With Schizophrenia” ISSUES NewArchived

The potential effects and mechanisms of Gegen Qinlian Decoction in oxaliplatin-resistant colorectal cancer based on network pharmacology

BackgroundResistance to chemotherapeutic drugs, such as oxaliplatin (OXA), can lead to unsatisfactory chemotherapy results during the treatment of advanced colorectal cancer (CRC). Therefore, we investigated the potential targets and mechanisms of Gegen Qinlian Decoction (GQD) against OXA-resistant CRC through network pharmacology and performed molecular docking and experimental verification. MethodsWe collected potential compounds, targets, and related disease genes from public databases. The pharmacology model of the compound-target-pathway network and protein-protein interaction (PPI) network were established. The potential active components and mechanisms underlying GQD reversing OXA-resistant CRC were systematically predicted, and the key targets were verified by performing molecular docking and in vitro and in vivo experiments. ResultsA total of 160 active ingredients, 407 potential targets, and 406 CRC drug resistance genes were collected. 16 intersecting genes, which included ABCG2 and belonged to 139 active compounds including baicalin and wogonin. They were enriched in 12 signaling pathways, including ABC transport and metabolism. Along with network topology analysis, ABCB1 and ABCC2 were identified as key targets and proved that various active components of GQD combined well with them. GQD alone and synergized with OXA could inhibit the protein and mRNA of ABC transporters in vivo and in vitro, decrease the IC50 of OXA-resistant CRC to OXA with a good synergistic index at different treatment times and concentrations, improve the sensitivity of OXA-resistant CRC to OXA, inhibit drug efflux, decrease tumor volume, and increase the weight of nude mice at the late stage of treatment. ConclusionsGQD can target ATP-binding proteins, inhibit ABC transporters, reverse OXA resistance, increase the sensitivity of OXA-resistant CRC cells to OXA, decrease tumor volume, alleviate toxic side effects, improve prognosis, and have good synergistic therapeutic effects. These results provide an effective research tool to elucidate ethnomedicine for modernizing refractory diseases.

Possible sitafloxacin-induced dysglycemia: Case report

A 93-year-old diabetic patient was prescribed sitafloxacin (100 mg, bid, po) for 8 days to treat a pulmonary infection. Prior to the treatment with sitafloxacin, his blood sugar was well controlled, but during treatment, his blood sugar showed abnormal biphasic dysregulation, with a downward trend in the early stages of treatment (d1-3) and an upward trend in the late stages of treatment (d4-8), and the dysglycemia persisted for about 20 days after treatment. Sitafloxacin, like other fluoroquinolones, may be strongly linked to glucose homeostasis abnormalities in this case, necessitating clinical medical staff vigilance, particularly in patients with high-risk diabetes.

Evaluation of MRD-status in post-induction period in pediatric patients with acute lymphoblastic leukemia.

The need to study the significance of minimal residual disease (MRD) at the induction therapy in patients with acute lymphoblastic leukemia (ALL) is beyond doubt. This has been confirmed by many years of work by many research groups. The role of MRD in the late stages of treatment and the impact of these values on patients survival requires research and discussion. To evaluate the influence of MRD-status in post-induction period on survival in patients with acute lymphoblastic leukemia. From 2010 to 2022, 135 patients with primary B-ALL enrolled in ALL-IC BFM 2009 protocol. Median age was 5.4 year (range 1-17). Male was 62 (49,5%) and female 73 (54,1%). The diagnosis was based on WHO 2016 criteria. Stratification on prognostic risk groups was carried out according to protocol criteria. Prednisone response evaluated at day 8 of treatment. The 15th, 33th, and 78th (as post-induction) day response was assessed by bone marrow cytology and level of MRD by flow cytometry. 5y-overall survival (OS) for patients with MRD-negative status on day 15 was 94,4±5,4% and 87,0±3,4% for MRD-positive (p=0,5). On day 33 patients with MRD-negative status achieved 5y-OS in 86,7±5,8% and 89,6±3,5% for MRD-positive (p=0,6).5y-OS for patients with MRD-negative status on day 78 was 90.8±4.0%, MRD-positive - 90,4+6.5%. DFS for MRD-negative status was 88.5±4.5%, for MRD-positive - 66.3±11.8% (p=0,1). EFS for MRD-negative patients was 87.2±4,6% and for MRD-positive 66.3±11.8% (p=0,09). We have found a tendency between MRD status on day 78 and the frequency of relapses in patients. At the moment, there are no reliable data on the effect of post-induction MRD status on survival. The assessment of MRD in the post-induction period has prognostic prospects and requires further study.

Morphological and Physiological Responses of Melia azedarach Seedlings of Different Provenances to Drought Stress

Melia azedarach Linn. is a deciduous tree of the Melia genus in the Meliaceae family that is native to China. To study the mechanism of drought resistance in Melia azedarach and evaluate the drought resistance capacity of each provenance, we selected eight provenances (Shandong Kenli, Jiangsu Pizhou, Hubei Shayang, Jiangsu Xuanwu, Jiangxi Xihu, Jiangsu Jurong, Guangdong Luogang, and Henan Shihe) as the research subjects and set four levels of drought stress treatment (CK: 75% of field capacity, mild drought: 60% of field capacity, moderate drought: 45% of field capacity, and severe drought: 30% of field capacity). The results showed that the growth in the seedling height and the ground diameter, the leaf relative water content, transpiration rate (Tr), net photosynthetic rate (Pn), stomatal conductance (Gs), and the content of chlorophyll (Chl) decreased with the increasing stress levels, while the root–shoot ratio, water saturation deficit, and the contents of malondialdehyde (MDA) increased. The SOD in most provenances initially increased and then decreased, reaching a peak during moderate drought. At the late stage of treatment, the magnitude of the changes in the photosynthetic indicators was more pronounced than in the physiological indicators. Principal component analysis showed that the contribution of all four principal components under the three drought stresses was above 85%, which represented the majority of the original data. Combined with the affiliation function method and weights, the comprehensive evaluation value (D value) of the drought resistance was calculated for the eight provenances. Then, we obtained the order of drought resistance of the test materials under the three drought stresses, respectively. The combined results revealed that the drought resistance of Henan Shihe and Jiangxi Xihu was stronger, while the drought resistance of Guangdong Luogang and Hubei Shayang was weaker. Based on the above findings, we can select provenances with strong and weak drought resistance for transcriptome sequencing to screen drought-resistant genes for an in-depth study at the molecular level.

Long-term Outcomes of Early Use of Long-Acting Injectable Antipsychotics in Schizophrenia.

Background: Long-acting injectable antipsychotics (LAIs) may potentially benefit patients requiring psychiatric hospitalization during the early stages of schizophrenia. However, few studies have compared the long-term effectiveness between patients who switched to LAIs and those who remained on oral antipsychotics (OAPs).Methods: Using the Taiwan National Health Insurance Research Database, we constructed a population-based cohort with 19,813 new OAP users with ICD-9-CM-defined schizophrenia who were hospitalized from 2002 to 2005. Within this cohort, 678 patients who switched to LAIs during their hospitalization were identified. The LAI group was matched to patients who remained on OAPs (n = 678). The LAI cohort was further subdivided for analysis into patients who switched to LAIs within 3 years of OAP initiation ("an early stage") and those who switched after 3 years ("a late stage"). Conditional Cox regressions and conditional negative binomial regressions were used to estimate the risk of death and the number of hospital visits between the two groups.Results: During the 13-year study period, 312 patients switched to LAIs within the first 3 years of OAP initiation. All- and natural-cause mortalities in these patients were significantly lower than in those who remained on OAPs. The hazard ratios (HRs) for all- and natural-cause mortalities were 0.49 (95% confidence interval [CI], 0.27-0.87) and 0.30 (95% CI, 0.15-0.60), respectively. No significant decrease associated with LAIs was observed in unnatural-cause mortality. Patients receiving LAIs had lower risks of rehospitalization (incidence rate ratio [IRR] = 0.56, 95% CI, 0.45-0.69), psychiatric hospitalization (IRR = 0.63, 95% CI, 0.50-0.81), and psychiatric emergency room visits (IRR = 0.58, 95% CI, 0.45-0.75) compared to patients who remained on OAPs. Use of LAIs in the late stage of treatment did not decrease the risk of relapse or mortality.Conclusions: Switching to LAIs during the first 3 years of treatment improved antipsychotic adherence, decreased relapses, and reduced long-term mortality. Our results provide evidence to support the benefits of early LAI treatment in schizophrenia.

Screening and identification of key enzyme genes for steroidal saponin biosynthesis in Dioscorea zingiberensis under low phosphorus stress

To investigate the responses of key enzymes involved in steroidal saponin biosynthesis of Dioscorea zingiberensis to low phosphorus stress, we designed three treatments of severe phosphorus stress, moderate phosphorus stress, and normal phosphorus level. The D. zingiberensis plants were collected at the early, middle, and late stages of treatment. The content of total steroidal saponins in different tissues of D. zingiberensis was determined by spectrophotometry for the identification of the critical stage in response to low phosphorus stress. BGI 500 sequencing platform was employed to obtain the transcript information of D. zingiberensis samples at the critical stage of low phosphorus stress, and then a transcriptome library was constructed. The correlation between the expression of genes involved in steroidal saponin biosynthesis and the content of total steroidal saponins was analyzed for the screening of the key enzyme genes in response to low phosphorus stress. Further, the expression patterns of these genes were analyzed by real-time fluorescence PCR(qRT-PCR). The content of total steroidal saponins in D. zingiberensis had obvious tissue specificity under low phosphorus stress, and the early stage of stress was particularly important for D. zingiberensis to respond to low phosphorus stress. A total of 101 593 unigenes were obtained by transcriptome sequencing, of which 77.35% were annotated in NT, NR, SwissProt, KOG, GO, and KEGG. A total of 256 transcripts of known key enzyme genes in the biosynthetic pathway of steroidal saponins were identified. The expression levels of 69 transcripts encoding 18 catalytic enzymes were significantly correlated with the content of total steroidal saponins. The qRT-PCR results showed that several key enzyme genes presented different expression patterns in four tissues under low phosphorus stress. The results indicated that the content of total steroidal saponins and the expression of key enzyme genes regulating steroidal saponin biosynthesis in D. zingensis changed under low phosphorus stress. This study provides the biological information for elucidating the molecular mechanism of steroidal saponin biosynthesis in D. zingensis exposed to low phosphorus stress.

A novel mouse strain optimized for chronic human antibody administration

Therapeutic human IgG antibodies are routinely tested in mouse models of oncologic, infectious, and autoimmune diseases. However, assessing the efficacy and safety of long-term administration of these agents has been limited by endogenous anti-human IgG immune responses that act to clear human IgG from serum and relevant tissues, thereby reducing their efficacy and contributing to immune complex–mediated pathologies, confounding evaluation of potential toxicity. For this reason, human antibody treatment in mice is generally limited in duration and dosing, thus failing to recapitulate the potential clinical applications of these therapeutics. Here, we report the development of a mouse model that is tolerant of chronic human antibody administration. This model combines both a human IgG1 heavy chain knock-in and a full recapitulation of human Fc receptor (FcγR) expression, providing a unique platform for in vivo testing of human monoclonal antibodies with relevant receptors beyond the short term. Compared to controls, hIgG1 knock-in mice mount minimal anti-human IgG responses, allowing for the persistence of therapeutically active circulating human IgG even in the late stages of treatment in chronic models of immune thrombocytopenic purpura and metastatic melanoma.

Thyroid functions as a parameter in monitoring of antiepileptic drugs

ABSTRACT Introduction Epilepsy is a chronic neurological disorder that is treated with multiple medications that can have significant side effects. This study investigated the potential effects of antiepileptic drugs on thyroid function. Methods The participants in this study were epileptic adults who had been consistently monitored in follow-up care. The effects of antiepileptic drugs on the serum levels of the thyroid stimulating hormone (TSH), free T3 (fT3), and free T4 (fT4) of these patients were investigated retrospectively by comparing laboratory recordings in three defined periods: prior to antiepileptic drug treatment, between 6 months and 1 year of treatment (early stage), and after 1 year of treatment (late stage). Results A total of 300 epileptic patients (F/M: 175/125) were included in the study. Significant differences in TSH and fT4 serum levels in the late stage compared to the pre-treatment stage (p = 0.006 and p = 0.0005, respectively) were found. TSH values in the late stage of treatment were abnormally high in one case and low in five cases; all six of these cases had normal pre-treatment and early-stage TSH values. Patients who received monotherapy with valproic acid, levetiracetam or carbamazepine were evaluated separately and there was no statistically significant difference in TSH and fT3 levels, while fT4 levels were significantly increased during treatment in each treatment group. Conclusions A significant increase in TSH levels was found in epileptic patients on polytherapy. Our results give us the opportunity to highlight the potential unique or cumulative effect of antiepileptic drugs on thyroid hormone levels.

An Aerobic Degradation Model for Landfilled Municipal Solid Waste

Municipalities output large amounts of solid waste into landfills, but degradation slows during the middle and late stages of treatment. Therefore, accelerating the treatment of degradable substances to achieve rapid stabilization, excavation, screening, and reuse would increase landfill utility and reduce economic costs. This article provides an aerobic degradation model for landfilled municipal solid waste that includes two types of biochemical reactions. Using degradable solid-phase organic matter and ammonia nitrogen as limiting substrates, an equation describing degradation over time was obtained. Both aerobic organic matter hydrolysis and the synchronous nitrification and denitrification reaction followed a kinetic, first-order equation. The influences of temperature, water content, oxygen concentration, and carbon to nitrogen ratio on the kinetic reactions were considered. Similarly, the exothermic reaction characteristics were considered. The model was applied to two previously conducted experiments. The results showed that the model can accurately reflect the degradation laws of various substances under aerobic degradation conditions. SDC and ammonia nitrogen were rapidly degraded and reached very low levels in a short time under aerobic conditions. This indicated that aeration has a significant effect on the degradation of aged waste, which can be used in the accelerated stabilization of aged landfills in the future.