Observation Period Research Articles

National trends in patterns of under-vaccination in early childhood: National Immunization Survey-Child, United States, 2011–2021

ABSTRACT Background The study's objective was to examine national trends in patterns of under-vaccination in the United States. Research design and methods The National Immunization Survey-Child (NIS-Child) is an annual cross-sectional survey that collects provider-verified vaccination records from a large national probability sample of children. Records from the 2011–2021 NIS-Child were used to assess receipt of the combined 7-vaccine series by age 24 months. Based on prior work, patterns indicative of hesitancy included zero vaccines, not starting ≥1 series, and consistent vaccine-limiting. Patterns indicative of practical issues included starting all series but missing doses. Up-to-date (UTD) was defined as receiving all doses in the combined 7-vaccine series. Results The study population comprised 127,257 children. Over the observation period, patterns indicative of hesitancy significantly decreased (p-trend < 0.0001), patterns indicative of practical issues significantly decreased (p-trend < 0.0001), and UTD significantly increased (p-trend < 0.0001). In 2021, the weighted percentage in each category was as follows: probable hesitancy 6.3% (95% confidence interval [CI] 5.4%, 7.2%), probable practical issues 26.0% (95% CI 24.4%, 27.6%), and UTD 67.7% (95% CI 66.0%, 69.4%). Conclusion Over an 11-year period, vaccination coverage in the United States for the combined 7-vaccine series has improved, with patterns suggestive of practical issues or hesitancy declining.

Surgery for hepatoblastoma in children with trisomy 18: a monocentric study.

Recently, children with trisomy 18 have been receiving more active treatment for malignancies. We report herein seven cases complete resection was achieved, and discuss multidisciplinary treatment for hepatoblastoma in patients with trisomy 18. The medical records of children with trisomy 18 who were treated at the study center between 2010 and 2023 were reviewed. Six of 69 patients had hepatoblastoma development, and three of these underwent multidisciplinary treatment. In addition, 6 patients had been referred by another hospital for treatment, and four of these underwent multidisciplinary treatment. Among the seven patients who underwent multidisciplinary treatment, three, two, and two were categorized in Pre-treatment Extent of Disease (PRETEXT) classification group I, II, and III, respectively. Neoadjuvant chemotherapy resulting in tumor reduction was performed in three cases. In all the cases, complete resection was achieved with pathologically safe margins. Perioperative complications included circulatory failure in one case and bile leakage in two cases. Adjuvant chemotherapy was administered in four cases. The postoperative observation period ranged from 3months to 11years, and all the patients are recurrence-free. Children with trisomy 18 complicated with hepatoblastoma whose cardiopulmonary conditions are stable may be good candidates for chemotherapy and surgery.

Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata

Baricitinib has demonstrated efficacy for treating severe alopecia areata in adults. There is currently limited information about the need for continuous therapy after achieving scalp hair regrowth. To report results from the randomized withdrawal period of the BRAVE-AA1 trial. BRAVE-AA1 was a randomized, placebo-controlled, phase 3 randomized clinical trial with a treatment withdrawal substudy that was conducted at 70 centers in 3 countries beginning in March 2019. It included 654 adults with severe alopecia areata (AA) (Severity of Alopecia Tool [SALT] score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Data were analyzed in August 2023. At week 52, 154 patients who were responders (SALT score ≤20) were rerandomized 3:1 to continue to take their current dose of baricitinib or transition to placebo (randomized withdrawal). Responders randomized to placebo who experienced a loss of treatment benefit (>20-point worsening in SALT score) at any time after week 52 were retreated with their original baricitinib dose. The proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment. The last observation carried forward was used to impute missing or censored data. Of 654 patients who received treatment, the mean (SD) age was 37.1 (13.0) years, and there were 383 women (58.6%). At week 52, 10 of 39 responders taking baricitinib, 2 mg, and 30 of 115 responders taking baricitinib, 4 mg, were rerandomized to placebo. At 4 and 8 weeks of treatment withdrawal, 0% and 10% to 11% of patients, respectively, lost treatment benefit regardless of dose. At week 152, 80% of patients had lost benefit compared with 7% for those who continued baricitinib therapy for both dose groups. Within the follow-up observation periods, 5 of 8 patients taking 2 mg (63%) and 21 of 24 patients taking 4 mg (87.5%) recaptured a SALT score of 20 or less response after retreatment. Severe AA is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe AA who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth. ClinicalTrials.gov Identifier: NCT03570749.

How is political trust associated with economic and environmental policy prioritization? A longitudinal analysis between 2017 and 2022.

In this article, we examine the longitudinal development of economy-over-environment policy priorities in Finland during a period marked by several significant adverse societal events. In addition, we explore the influence of political trust on these priorities over time. We utilize a five-round panel dataset comprising 2155 observations (N = 431) to examine both within-individual and between-individual variations from late 2017 to early 2023. Our findings reveal a significant increase in the prioritization of the economy in each observation period following the COVID-19 outbreak. However, this trend is not observed among individuals with high levels of political trust. The within-individual analysis indicates that high political trust moderates, rather than causes, higher economy-over-environment prioritization. Our study highlights the significance of political trust as a preventing factor against the deprioritization of environmental policies, particularly when societies confront significant and intersecting adverse events.

Evaluation of the efficiency of rehabilitation interventions in patients after unilateral biportal endoscopic discectomy

Background. Unilateral bi-portal endoscopic discectomy (UBED), as other surgical methods of treatment, may require the use of additional rehabilitation interventions in the recovery process of patients. Unfortunately, studies on the effectiveness of nonpharmacological methods in the postoperative period for these patients are insufficient. The study purposed to evaluate the effectiveness of a rehabilitation intervention program in the patients who have undergone UBED. Materials and methods. The study was conducted at the Department of Neurosurgery of the Spine and Spinal Cord of the Ivano-Frankivsk Regional Clinical Hospital in 2022–2023. The sample consisted of the main group (MG, n = 74) — patients who underwent removal of the hernia of the intervertebral disc used UBED and complex rehabilitation and control group (CG, n = 68) — UBED was performed without a rehabilitation course. Study methods: we used visual-analogue scale (VAS) and Oswestry questionnaire before surgery and after it (in 1 day and 1, 6 and 12 months). Results. In the preoperative period, the back pain index was 5.3 ± 1.4 and 5.6 ± 1.1 cm in MG and CG, respectively. In the postoperative period the back pain index according to the VAS decreased to 1.5 ± 0.4 cm in one day after surgery in the MG with its positive dynamics during the year of observation. In CG this index also decreased to 1.4 ± 0.9 cm with a gradual improvement to 0.3 ± 0.1 cm in 12 months. At the 12 months after the surgery the Oswestry index demonstrated that quality of life was better in the subjects of MG compared to the CG (5.4 ± 3.2 and 17.4 ± 3.3 %, respectively). Conclusions. The use of physical ­exercises in combination with massage and hardware physiotherapy in patients who have UBED improved the quality of life of the patients in the long-term observation period, but did not affect the reduction of pain after the surgery in both short-term and long-term observation

Evidence of spontaneous cardiac-locomotor coupling during daily activities in healthy adults.

One way to improve exercise performance and protect heart health is the extended synchronization of the stepping with the diastolic phase of the cardiac cycle. Cardiac-locomotor coupling (CLC) happens when the step rate (SR) equals the heart rate (HR). The extent of CLC in daily life is unknown. This study aims to analyze spontaneous occurrences of CLC during daily activities. A retrospective analysis of daily life recordings from a wrist-worn sensor was undertaken (PMData, N = 16, 5months duration). The deviation between HR and SR was used to define CLC (deviation ≤ 1%) and weak CLC (1%< deviation ≤ 10%). The occurrence and the probability of CLC during everyday life were computed from the recordings. The CLC occurrences were stratified depending on the duration and intensity of the physical activity. Finally, a Monte Carlo simulation was run to evaluate the probability of random occurrences of CLC vs. the observed recordings. Participants couple for 5% and weakly couple for 35% of the observational period. The ratio of 1:1 between HR and SR is the dominating occurrence across the study population and this overrepresentation is significant. CLC occurs mostly for long activities. The extent of CLC for various intensities of activity is subject-dependent. The results suggest that CLC is feasible for most people. CLC occurs spontaneously during unsupervised daily activity in everyone in our cohort, which suggests a mechanistic interaction between the cardiac and the locomotor systems. This interaction should be investigated for medical rehabilitation and sports applications in the future.

Early Maintenance Treatment Initiation and Relapse Risk Mitigation After a First Event of MOGAD in Adults: The MOGADOR2 Study.

Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes. Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method. We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%. The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk. This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Zirconia full-arch implant prostheses: Survival, complications, and prosthetic space dimensions with 115 edentulous jaws.

To assess the survival and complication rates of 115 monolithic zirconia implant-supported fixed complete dental prostheses (IFCDPs) with an up to 6-year follow-up. One hundred fifteen edentulous jaws (71 patients) underwent complete-arch implant treatment with a digital workflow and were rehabilitated with monolithic zirconia IFCDPs. The primary outcome was to assess survival and complication rates while the secondary outcome was to measure the cross-sectional dimensions (prosthetic space) of those 115 monolithic zirconia IFCDPs and to correlate potential technical complications with the prosthetic space dimensions. Out of the 115 zirconia IFCDPs, 2 fractured, yielding a 98.6% survival rate up to a 6-year follow-up. The most commom minor technical complications were loss of screw access channel filling and porcelain chipping for the modified monolithic IFCDPs. There was no significant association between the count and type of complications and jaw location (maxilla vs. mandible) or prosthesis type (FP1 vs. FP3), according to Fisher's exact test. For maxillary zirconia IFCDPs, the mean square surface for the at the posterior abutment cross-sectional area was 25.18mm2 at the lingual side of the abutment and 34.19mm2 at the buccal side, respectively. The anterior abutment cross-sectional area was 33.92mm2 at the lingual side of the abutment and 29.49mm2 at the buccal side, respectively. For mandibular zirconia IFCDPs, the mean square surface at the posterior abutment cross-sectional area was 29.89 mm2 at the lingual side of the abutment and 39.05mm2 at the buccal side, respectively. The anterior abutment cross-sectional area was 27.07mm2 at the lingual side of the abutment and 56.50mm2 at the buccal side, respectively. At the connector cross-sectional area, the mean square surface for the maxillary zirconia IFCDPs was 64.33 and 90.56mm2 for the mandibular zirconia IFCDPs. The two fractures occurred in the midline (anterior area) for both maxillary FP1 prosthesis and mandibular FP3 prosthesis. The mean surface area at the connector for the maxillary FP1 prosthesis was 28.50 and 82.11mm2 for the mandibular FP3 prosthesis, and was within the range of IFCDP connector square surface area. There was no significant association between the thickness of the zirconia prosthesis and the encountered prosthesis fractures. Monolithic zirconia IFCDPs yielded a 98.6% survival rate, after a mean observation period of 62 months with an SE of 3.1. The connector mean surface area in the two fractured IFCDPs was within the square surface range (minimum-maximum) as for the remaining 113 complication-free IFCDPs.

Correlation analysis of functional relationships between morphological indicators of small intestine mersis during the supply process

аdhesion disease has become a widespread disease, which for years has maintained a tendency to constant growth, and remains one of the most complex and unsolved topical problems of the functional state of the abdominal cavity. At the moment, most changes in the functioning of the gastrointestinal tract are associated with a violation of the tissue barrier during the penetration of pathogenic types of microorganisms and absorption of toxic substances, which is one of the effects of biological factors on the intestine. Understanding the structure of the body, its morphological and functional features, the ability to understand the patterns of vital and pathological processes in various organs, tissues and the whole body. At the moment, the functional connections between the immune, nervous and endocrine links in the functioning of the tissues of the peritoneum and its components during the progressive adhesion process remain incompletely investigated. At the same time, it is also important to pay attention to the behavioral characteristics of the organism. Purpose of our investigation was to investigate the correlational relationships between the morphological indicators of the mesentery of the small intestine during the experimental adhesion process. The analysis of the relationship between the body weight and BMI of the animals of the experimental group with the morphological parameters of the adhesion formations (quantity and thickness) showed a high level of correlation, and confirms the influence of intensive processes of fibrin formation on the morphometric indicators of the experimental animals. Correlation analysis between the number of detected milk spots, the thickness of detected adhesions and the total number of lymphocytes, as well as PNA+-immunologically immature and SBA+B-lymphocytes at each observation period in the animals of the experimental group during the adhesion process showed the dependence of the thickness of fibrin formations and the number of immunocompetent cells, which can be characterized as a local immune response that determines the intensity of collagen formation by the serous membranes and affects the degree of adhesion formation. The revealed correlations between antigen-presenting cells, the area of ​​collagen fibers of the 1st and 3rd types, and the total number of lymphocytes, as well as PNA+-immunologically immature and SBA+-B-lymphocytes at each observation period in the animals of the experimental group during the adhesion process, indicate the morphogenetic function of lymphocytes against the background of the growth of the protein-synthesizing function of fibroblasts, which leads to an increase in the synthesis of collagen and other components of the connective tissue matrix. On the 14th and 21st days of the study, correlations were established between the number of antigen-presenting cells and the area of ​​collagen fibers of the 1st and 3rd types at each observation period in the animals of the experimental group during the adhesion process. The presence of these correlations indicates that the morpho-functional state of the SALC lymphoid tissue associated with the serous membranes of the peritoneum is determined by the activation of one or another link of immunity. After an antigenic impact on the body, there are shifts in the direction of activation of the population of B1-lymphocytes of the mesentery of the small intestine and B2-lymphocytes, which changes the structure of the tissue barrier of the peritoneum and affects the general state of the body.

Research on the coupling measurement of medical education and health resource allocation under the background of healthy China

Objective To analyze the coupling and coordination level of medical education and health resource allocation in China, and to provide scientific basis for promoting the high-quality development of medical education and the efficient allocation of health resources.MethodsBased on the panel data from 2011 to 2021, the coupling coordination degree model was used to measure the coupling coordination index of medical education and health resources in China. The spatial auto-correlation model was used to analyze the development status and distribution characteristics of the coupling coordination degree of the two systems. The kernel density estimation method was used to analyze the dynamic evolution trend of the coupling coordination of the two systems. The QR quantile regression model was used to explore the key factors affecting the coupling coordination degree of the two systems.ResultsDuring the observation period, the coupling coordination degree of the two systems increased from 0.393 to 0.465, with a growth rate of 18.3%. The coupling coordination degree between regions gradually decreased in the eastern-central and eastern-western regions, and there were still large differences between the central and western regions. The coupling coordination degree of the two systems in the region was significantly different in the eastern and western regions, and the central region was relatively similar. There is a positive spatial correlation between the provinces, and 25.81% of the provinces have transitions. Finally, the number of points in the first and third quadrants is higher than that in the second and fourth quadrants. In the process of dynamic distribution, the degree of polarization of the coupling coordination degree curve of the two systems is gradually weakened. Per capita GDP, residents ' income difference and population size are the positive and significant factors driving the coupling and coordinated development of the two systems.ConclusionThe coupling and coordination degree of the two systems of medical education and health resource allocation showed a stable upward trend during the observation period, and the global spatial positive correlation also gradually increased, showing the spatial agglomeration characteristics of ' high-high agglomeration ' and ' low-low agglomeration '. The spatial difference of coupling coordination degree shows a shrinking trend and develops towards equalization. The coupling coordination degree of the two systems is affected by social, economic and demographic factors to varying degrees. Therefore, it is necessary to innovate the coordinated development mechanism of the two systems, promote the two-way flow of medical education and health resource allocation in talents, technology and other elements, and then promote the coupling and coordinated development of the two systems.

A Real-World Data Observational Analysis of the Impact of Liposomal Amphotericin B on Renal Function Using Machine Learning in Critically Ill Patients.

Liposomal amphotericin B (L-AmB) has become the mainstay of treatment for severe invasive fungal infections. However, the potential for renal toxicity must be considered. To evaluate the incidence of acute kidney injury (AKI) in critically ill patients receiving L-AmB for more than 48 h. Retrospective, observational, single-center study. Clinical, demographic and laboratory variables were obtained automatically from the electronic medical record. AKI incidence was analyzed in the entire population and in patients with a "low" or "high" risk of AKI based on their creatinine levels at the outset of the study. Factors associated with the development of AKI were studied using random forest models. Finally, 67 patients with a median age of 61 (53-71) years, 67% male, a median SOFA of 4 (3-6.5) and a crude mortality of 34.3% were included. No variations in serum creatinine were observed during the observation period, except for a decrease in the high-risk subgroup. A total of 26.8% (total population), 25% (low risk) and 13% (high risk) of patients developed AKI. Norepinephrine, the SOFA score, furosemide (general model), potassium, C-reactive protein and procalcitonin (low-risk subgroup) were the variables identified by the random forest models as important contributing factors to the development of AKI other than L-AmB administration. The development of AKI is multifactorial and the administration of L-AmB appears to be safe in this group of patients.

Endoscopic Surveillance after (Procto)Colectomy with Gastrointestinal Reconstruction in Patients with Familial Adenomatous Polyposis (FAP)-Principles, Goals and Practical Aspects Based on 12 Years of Observation.

(1) Background: Familial adenomatous polyposis (FAP) is a hereditary condition characterized by the development of numerous adenomas in the large intestine, often necessitating colectomy due to an elevated risk of colorectal cancer. Despite surgical intervention, adenomas frequently recur, underscoring the importance of ongoing surveillance. This study evaluates the outcomes of a 12-year endoscopic follow-up after colectomy and gastrointestinal reconstruction for FAP. (2) Methods: A retrospective analysis was conducted on 41 FAP patients who underwent at least one postoperative endoscopic examination. Assessments of the pouch or rectum were performed every 12-18 months following ileorectal anastomosis and every 18-24 months after ileal pouch-anal anastomosis. Follow-up biopsies were assessed using the adopted Spigelman classification. (3) Results: Postoperative pathology revealed invasive colorectal cancer in three patients. Abdominoperineal resection was performed in two cases due to secondary invasive carcinoma, and one T1 tumor was radically removed with ESD. One patient underwent radical pouch excision following a nodal pelvic recurrence of rectal cancer. Over a 12-year observation period, the mean Spigelman score increased by 2 points, and the proportion of patients with low-grade polypoid lesions decreased. The quantity or size of polyps increased in 24 patients, decreased in 8 patients, and remained stable in 9 patients. In four patients, granular, laterally spreading tumors were discovered in the rectal stump. (4) Conclusions: Regular endoscopic surveillance in FAP patients facilitates early identification of neoplastic and inflammatory changes. The downstaging potential highlights the effectiveness of early interventions. While the Spigelman classification assessed polyps well, it did not predict cancer occurrence. A notable number of patients had invasive cancer at the time of surgery, underscoring the importance of early surgical qualification, which is particularly crucial for identifying upstaging or secondary cancer.

The impact of board characteristics on executive compensation: evidence from Jakarta Islamic Index Company

Purpose – This study aims to examine the effect of board characteristics on CEO compensation. The board characteristics examined in this study include board independence and gender diversity consisting of woman on board and independent woman board on CEO compensation.Design/methodology/approach – The population in this study is a company belonging to the Jakara Islamic Index (JII) at the Indonesian Stock Exchange for the period 2012 - 2016. The sample in this research was determined by purposive sampling method with a total sample of 75 annual reports.Findings – The results show that independent board gender diversity consisting of female boards and independent female boards has no effect on CEO compensation.Research limitations/implications – The sample of this study is a company with shares included in the Jakarta Islamic Index on the Indonesian Stock Exchange (IDX) with an observation period of 2012-2016. Hypothesis testing in this study using multiple linear regression analysis.Practical implications – Boards to oversee and control the actions of opportunists manager, and define the most important decisions of companies, one of which compensation for the CEO, so that corporate objectives can be achieved. With the larger board size will increase oversight function of the board to act opportunistically manager so control oversight of CEO compensation more stringent design and can be defined more precisely.Originality/value – Research on the role of women in board composition is gaining attention, but not much has been explored in a country with a strong patriarchal culture like Indonesia.

Recurrent Pulmonary Tuberculosis in China, 2005 to 2021

Despite posing a significant challenge to global tuberculosis (TB) elimination efforts, recurrent TB remains understudied due to the challenges of long-term observation. To investigate the burden of recurrent TB using data from patients with pulmonary TB (PTB) in China. This retrospective cohort study included all bacteriologically confirmed or clinically diagnosed PTB cases reported to the Tuberculosis Information Management System with completed or successful treatment outcomes from January 1, 2005, to December 31, 2021. Data were analyzed from July 15, 2022, to October 28, 2023. Newly diagnosed PTB was classified into primary, hematogenous disseminated, or secondary PTB. The primary outcome was the annual recurrence rate, stratified by disease classification, over the 17-year observation period. The recurrence rate for year n was calculated by dividing the number of patients with recurrent TB in year n by observed person-years in year n. The secondary outcome was the annual proportion of recurrent TB among reported cases and associated risk factors. Of 13 833 249 patients with TB reported to the Tuberculosis Information Management System, 10 482 271 with PTB met the inclusion criteria. Of these, 68.9% were male, 22.3% were 65 years or older, 89.6% were of Han ethnicity, and 68.4% were agricultural workers. A total of 413 936 patients experienced a recurrent TB episode after successful treatment, resulting in an overall recurrence rate of 0.47 (95% CI, 0.47-0.48) per 100 person-years. The recurrence rate for patients with primary PTB was 0.24 (95% CI, 0.22-0.26) per 100 person-years; for hematogenous disseminated PTB, 0.37 (95% CI, 0.36-0.38) per 100 person-years; and for secondary PTB, 0.48 (95% CI, 0.47-0.48) per 100 person-years. The cumulative proportion of recurrences within the first 2 years accounted for 48.9% of all recurrent cases. The proportion of recurrent cases among notified incident cases increased 1.9-fold from 4.7% in 2015 to 8.8% in 2021. Among other factors, ages 45 to 64 years (adjusted hazard ratio, 1.77 [95% CI, 1.65-1.89]) and having completed treatment (adjusted hazard ratio, 1.16 [95% CI, 1.14-1.18]) were identified as associated with recurrence. In this retrospective cohort study, the PTB recurrence rate was substantially higher than the incidence, and the proportion of recurrent cases increased. Almost half of the recurrence occurred within the first 2 years, suggesting that routine posttreatment follow-up may represent an important strategy for accelerating TB elimination.

Transfusion of allogenic cord blood to patients with multiple myeloma: safety analysis and influence on the immunophenotype of blood lymphocytes in the early period

Severe immune dysfunction occurs in the majority of cancer patients. One of the methods for overcoming immune disorders is transplantation of peripheral blood hematopoietic stem cells, both autologous and allogeneic, and transfusion of allogeneic natural killer cells (NK cells). Umbilical cord blood is a known source of not only hematopoietic stem cells (HSCs) but also NK cells, characterized by the rapid availability of blood samples from public cord blood banks. Purpose of the study: to analyze the safety of simultaneous transfusion of three allogeneic cord blood to patients with relapsed/refractory multiple myeloma in the early period (7 days after administration), and also to study the response of subpopulations of peripheral blood lymphocytes of patients to this intervention. The pilot study included 10 patients (7 men and 3 women) with relapsed/refractory multiple myeloma who had previously received more than 3 lines of therapy. The age of the patients was 59.4±3.4 years; all of them received a single transfusion of three allogeneic samples of umbilical cord blood with an average dose of leukocytes of 60.50±8.2 × 108 (NK cells – 4.36±1.2 × 108) per one patient. A total of 30 samples of umbilical cord blood, alloreactive for KIR receptors of the receptor-ligand type, were transfused. The selection of HSCs concentrates was carried out in the umbilical cord blood bank of the Dynasty Medical Center. Before transfusion of umbilical cord blood, patients received cyclophosphamide 5 mg/kg. After transfusion, patients received five subcutaneous injections of IL-2 (roncoleukin) in the amount of 1 million units per day. Observation at the time of assessment of preliminary results: 7 days after transfusion. Analysis of the immunophenotype of patient lymphocytes was studied twice: on the day of transfusion before the start of the protocol and 7 days after transfusion of umbilical cord blood. No early adverse reactions to transfusions were observed. Simultaneous transfusion of three allogeneic cord blood to patients with relapsed/refractory multiple myeloma is a safe procedure. There are no adverse reactions, serious adverse events, or significant reactions/changes in the immunophenotype of patient lymphocytes in the early observation period within 7 days after the intervention.

Evaluation of Gentamicin Release of PMMA Cements Using Different Methods: HPLC, Elution and Inhibition Zone Testing.

(1) Background: There is an ongoing discussion on the elution efficacy of antibiotic-impregnated cements. Our experiments were intended to clarify if there are differences in the antibiotic elution of HPLC compared with inhibition zone testing using eluates or PMMA discs. (2) Materials and Methods: Two cement brands with different concentrations of the active ingredient were tested in antimicrobial Kirby-Bauer (disc diffusion) assays. Cement platelets were directly applied on the agar plates and their zone of inhibition was measured. In parallel, the platelets were incubated in phosphate buffered saline (PBS) and at distinct points of time transferred into new buffer. At these time points, 50 µL of the bone cement eluates was used for zone of inhibition testing. Standard gentamicin sulfate solutions served as a control in the same test setup. To verify the microbiological investigations, the antibiotic content of the eluates was also measured via high-performance liquid chromatography (HPLC). (3) Results: The experiments with cement eluates showed better differentiable results than the direct application of the cement discs. The results were also comparable to investigations with HPLC and gentamicin sulfate standard solutions. (4) Conclusions: The results of elution rates are influenced by the test system and the period of observation chosen. The microbial test systems reflect the results of HPLC to the same degree and give evidence of the efficacy of the antibiotics. The HPLC tests on eluates were more suitable in representing differences in release characteristics.

An observational study on the relationship between tyrosine kinase inhibitor treatment-free remission and cytotoxic T-lymphocytes in patients with chronic phase chronic myeloid leukemia.

171 Background: Since the introduction of tyrosine kinase inhibitors (TKIs), the effectiveness of treating chronic phase chronic myeloid leukemia has seen remarkable improvement. A current challenge in TKI therapy is achieving treatment-free remission (TFR) safely. Numerous TKI-stop trials and translational studies have investigated factors influencing TFR, including TKI treatment duration, duration of deep molecular response (DMR), cellular immunity activation, and bcr::abl1 transcript type. However, identifying reliable markers for achieving TFR safely remains uncertain. In this multicenter study, we focused on examining the association between TFR and cytotoxic T-lymphocytes (CTLs). Methods: Between June 2020 and March 2022, a total of 45 patients were enrolled: 38 patients with DMR for at least 1 year on TKIs (on TKI group) and 7 patients with DMR for at least 1 year after discontinuing TKIs (off TKI group). The study included 30 males, with a median age of 59 years (range: 29–87). Median TKI treatment duration was 7.7 years (range: 1.5–18.3), and median TKI cessation duration in the off TKI group was 4.9 years (range: 1.7–7.1). Molecular response and cellular immunity were monitored over 12 months post-consent for patients in the off TKI group and after TKI discontinuation for patients in the on TKI group. Results: During the observation period, 25 patients (65.8%) in the on TKI group maintained DMR, while 13 patients (34.2%) lost DMR. Conversely, all patients in the off TKI group sustained DMR. The median TKI treatment duration in the group maintaining DMR (9.45 years, range: 3.3–18.3, N = 32) significantly exceeded that in the group losing DMR (4.9 years, range: 1.5–11.9, N = 13) (P = 0.0048). Patients taking TKIs for over 7 years with a higher percentage of total memory CTLs than total effector CTLs maintained DMR. Conversely, patients losing DMR despite over 10 years of TKI treatment had a higher percentage of total effector CTLs than total memory CTLs. Among the 32 patients maintaining DMR, 19 exhibited a higher percentage of total effector CTLs than total memory CTLs, with 15 (78.9%) maintaining MR5 throughout the study. Furthermore, of the six patients maintaining DMR with relatively short TKI administration (median 5.5 years, range: 3.3–6.4), three displayed a higher percentage of total memory CTLs than total effector CTLs. Among the remaining three patients, two showed strong CTL activation, with one patient having an effector CTL clone over 30% and the other having a memory CTL clone over 30%. Conclusions: This study indicates that a sufficiently prolonged TKI treatment duration (&gt;7 years) and maintaining deeper DMR (≥ MR4.5, preferably MR5) are conducive to safely achieving TFR. Furthermore, a high percentage of total memory CTLs and intense CTL activation may serve as meaningful markers for TFR.

Evaluation of Pepper (Capsicum spp.) Germplasm Collection for Bacterial Wilt (Ralstonia solanacearum) Resistance

This study was conducted to identify resistant pepper accessions against the destructive disease bacterial wilt (BW) caused by Ralstonia solanacearum. A total of 338 pepper (Capsicum species) germplasms collected from different countries and deposited in the National Agrobiodiversity Genebank, Rural Development Administration (RDA), Republic of Korea, were evaluated. The evaluated accessions comprise samples from five distinct species: Capsicum annuum (213), Capsicum baccatum (47), Capsicum chinense (45), Capsicum frutescens (31), and Capsicum chacoense (2). Disease severity scores were recorded over four consecutive weeks and showed an increase in severity from initial inoculation to the end of the evaluation period. A strong correlation was observed between week 1 and 2, as well as between week 3 and 4. Ten resistant pepper accessions were identified. All selected accessions consistently exhibited low disease scores ranging from 0 to 1 throughout the observation period. These accessions belong to C. chinense (2), C. annuum (6), C. chacoense (1), and C. frutescens (1). Accessions such as IT236738 (C. chinense) and IT283498 (C. chinense) were demonstrated to have high resistance, showing no symptoms over all four weeks. Other accessions belonging to C. annuum (IT247232 and IT236340) and C. chacoense (IT158713) maintained a disease score of 0 (no symptoms) for the first three consecutive weeks; however, they developed symptoms with a score of 1 in the fourth week. Other important characteristics of the resistant materials were evaluated, including carotenoids and fruit characteristics. These accessions have important traits beyond resistance to the destructive pepper disease. They will serve as promising resources for breeding resistant pepper varieties against BW to enhance productivity.

Proposals for revised International Working Group–European LeukemiaNet criteria for anemia response in myelofibrosis

AbstractWith emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate interstudy comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group–European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to (1) account for gender-specific differences in determining hemoglobin levels for eligibility criteria; (2) revise the definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices; and (3) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks before study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs non-TDA) and graded (major vs minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.

ESG Risk and Firm’s Performance

This study aims to explore the link between market, financial, and operational performance and environmental, social, and governance (ESG) risk. This quantitative study is based on data analysis from up to 100 observations collected between 2019 and 2023. Companies listed on the Indonesia Stock Exchange IDX LQ45 throughout the observation period serve as the study's samples. Purposive sampling was used to choose the sample, and it was done so based on particular research-relevant criteria. The performance of the company is examined in relation to ESG risks using the robust standard errors model. Stakeholder theory, which highlights the significance of corporate management taking into account the interests of all stakeholders, serves as the foundation for the theoretical model of this work. The dependent variables in the practical model are ROA, ROE, and Tobin's Q, whereas the independent variable is the ESG risk rating. The conclusions drawn from the empirical data demonstrate that market and financial performance are significantly harmed by ESG risk. Nonetheless, operational performance is not significantly impacted by ESG risk. This research adds to the limited body of knowledge about the risk associated with sustainability reporting and how it affects a company's capacity to perform financially and on the market. Organizations that effectively handle environmental, social, and governance (ESG) risks can reap enduring advantages such as enhanced standing and stable finances. A crucial first step toward ensuring sustainability and competitiveness in the future is the incorporation of ESG into company strategy.