ABSTRACT
BACKGROUND: Different degrees of malnutrition are seen in patients with hematological malignancies. None of the approaches used to determine malnutrition risk have general acceptance. The use of the GLIM criteria developed by the Global Leadership Initiative on Malnutrition has promising results. MATERIALS AND METHODS: A total of 67 patients with leukemia, lymphoma, and multiple myeloma were included in the study. NRS-2002 (Nutritional Risk Screening-2002) was used to screen the nutritional status of the patients, and malnutrition was diagnosed and graded using the GLIM criteria in patients who were found to be at risk of malnutrition in this test. The parameters followed in the groups with and without malnutrition were compared. The Kolmogorov-Smirnov, Mann-Whitney U, and Chi-square test were used for statistical analysis. RESULTS: Patients were analyzed by dividing them into two groups as those with and without malnutrition. The presence of infection, duration of fever, antibiotic, and antifungal use were significantly higher in malnourished than in nonmalnourished patients. Platelet counts and sodium levels were significantly lower in the malnourished arm. CONCLUSION: Early nutritional support can increase the immunological status of patients with malignant disorders as well as their tolerability to treatment. Minimizing the risk of malnutrition and providing timely calorie and vitamin support are factors that may directly affect febrile neutropenia, duration of fever, and antifungal use, which will consequently lead to a decrease in the length of hospitalization.
Subject(s)
Hematologic Neoplasms , Malnutrition , Humans , Antifungal Agents , Hematologic Neoplasms/complications , Malnutrition/etiology , Nutritional Status , Anti-Bacterial Agents , Fever , Nutrition AssessmentABSTRACT
BACKGROUND: Aim to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR) at the time of diagnosis, which is an inexpensive and easily accessible parameter, compared to factors known as prognostic value (such as R-IPI and NCCN-IPI) in patients with diffuse large B-cell lymphoma (DLBCL). AIM: Prognostic value of NLR at diagnosis in DLBCL. METHODS: A hundred (100) newly diagnosed DLBCL patients were included. The correlations between the NLR with clinical characteristics, treatment response, and survival were analyzed. The NLR cut-off value was taken at 3.5 according to the receiver operating characteristic curve. RESULTS: There were 53 patients with an NLR of 3.5 and 47 patients with an NLR < 3.5. Patients with NLR ≥ 3.5 had a complete response (CR) rate of 66.0% (n = 31/47), and patients with NLR < 3.5 had a CR rate of 98.1% (n = 51/52). The median progression-free survival (PFS) was 132.5 months (95%CI 103.1-162.0). PFS in the NLR ≥ 3.5 group (36 months) was significantly (P < 0.000) shorter than in the NLR < 3.5 group (185 months). The median overall survival (OS) for NLR ≥ 3.5 and NLR < 3.5 was 79.2 months (95% CI 51.6-106.8) and 197.8 months (95% CI 173.2-222.5), respectively. NLR ≥ 3.5 was associated with worse OS than NLR < 3.5 (P = 0.000). The high value of NLR (≥3.5) had lower treatment response rates, higher relapse, and death rates. CONCLUSION: High NLR was associated with poor treatment response, PFS, and OS. NLR can be used as a cost-effective and easy-to-interpret prognostic marker in DLBCL patients.
Subject(s)
Lymphocytes , Lymphoma, Large B-Cell, Diffuse , Neutrophils , Humans , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/blood , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Female , Male , Middle Aged , Prognosis , Lymphocytes/pathology , Aged , Adult , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged, 80 and over , Lymphocyte Count , Young Adult , Adolescent , Leukocyte Count , ROC CurveABSTRACT
Gender-based violence is a global phenomenon threatening women irrespective of race, nationality, education or socio-economic status. Evidence shows that domestic violence help calls have been increasing in many countries during the Covid-19 pandemic, but the effect on female homicides, this extreme form of violence, is not clear. In this study, we analyze the effects of social distancing measures and in particular the impact of curfews on female homicides in Turkey where domestic violence and female homicides are on the rise, causing public uproar. We find that the probability that a woman is killed by an intimate partner declined by about 57 percent during the period of strict social distancing measures, and by 83.8 percent during curfews in comparison to the same period between 2014 and 2019. We do not find any impact on female homicides by other perpetrator types. We argue that the decline in female homicides is driven by physical difficulties faced by ex-partners to reach victims, especially during curfews and fewer women leaving current partners due to economic hardships and fear of infection. Increased probability of getting caught might have also played a role in deterring deadly crimes against women.
ABSTRACT
Metal silicide-based thermocouples were fabricated by screen printing thick films of the powder compositions onto alumina tapes followed by lamination and sintering processes. The legs of the embedded thermocouples were composed of composite compositions consisting of MoSi2, WSi2, ZrSi2, or TaSi2 with an additional 10 vol % Al2O3 to form a silicideâ»oxide composite. The structural and high-temperature thermoelectric properties of the composite thermocouples were examined using X-ray diffraction, scanning electron microscopy and a typical hotâ»cold junction measurement technique. MoSi2-Al2O3 and WSi2-Al2O3 composites exhibited higher intrinsic Seebeck coefficients (22.2â»30.0 µV/K) at high-temperature gradients, which were calculated from the thermoelectric data of composite//Pt thermocouples. The composite thermocouples generated a thermoelectric voltage up to 16.0 mV at high-temperature gradients. The MoSi2-Al2O3//TaSi2-Al2O3 thermocouple displayed a better performance at high temperatures. The Seebeck coefficients of composite thermocouples were found to range between 20.9 and 73.0 µV/K at a temperature gradient of 1000 °C. There was a significant difference between the calculated and measured Seebeck coefficients of these thermocouples, which indicated the significant influence of secondary silicide phases (e.g., Mo5Si3, Ta5Si3) and possible local compositional changes on the overall thermoelectric response. The thermoelectric performance, high sensitivity, and cost efficiency of metal silicideâ»alumina ceramic composite thermocouples showed promise for high-temperature and harsh-environment sensing applications.
ABSTRACT
The physical properties of particle-reinforced composite materials are highly affected by the distribution of particles within a matrix material. In this study, a microstructural image analysis method with a new distribution index for quantifying the degree of distribution in composite materials was developed. The free-path spacing between particles was measured to calculate the distribution (D) index based on the coefficient of variation. The proposed method was applied to six digitally created reference patterns as representative binary composite microstructures and three actual ceramic-matrix composites, respectively. It is found that the D index increased from 0.00 to 0.67 depending on the degree of distribution or homogeneity level based on the reference patterns. The homogeneity levels for the binary composites are then classified from a perfect (maximum) to very low level (minimum) based on increasing D index values, where a high D index presents a poorer distribution. The results obtained for reference patterns and metal silicide-refractory oxide composite microstructures indicate that the proposed method is a useful tool to quantify the degree of distribution with high accuracy, and can be efficiently used for different types of composite microstructures.
ABSTRACT
OBJECTIVE: Hydrocarbon pneumonia is distinct among the types of childhood pneumonia in that it has a different pathogenesis and treatment and is preventable. In this study, the cases of 54 children with hydrocarbon pneumonia admitted to the Dicle University Medical Faculty Pediatric Chest Diseases Unit between the years 2006 and 2010 were analyzed retrospectively. PATIENTS AND METHODS: The medical records of 54 patients diagnosed with pneumonia after ingesting/inhaling hydrocarbons were analyzed retrospectively. Age, sex, presenting symptoms, clinical status, radiological and laboratory findings and response to treatment and prognosis were noted. RESULTS: 35 (64.8%) of the patients were male, 19 (35.2%) were female and the ages of the patients ranged from 1 to 5 with an average of 2.49 ± 0.80. The etiologies of the pneumonia were thinner (33%), naphta (3.7%) and kerosene. In 49 of the patients (90.7%), the symptoms started to occur the day the patient was exposed to hydrocarbons. The average length of hospital stay was 4.0 ± 2.3 days. Six patients were treated in the intensive care unit (ICU), and one patient with hydrocarbon pneumonia due to kerosene ingestion died. Inhaled corticosteroids were administered to 18 patients who were progressively deteriorating and inhaled salbutamol was given to 16 patients with bronchospasm. Patients with radiological findings on their chest X-rays and auscultatory findings were found to have longer hospital stays (p < 0.05). CONCLUSIONS: To prevent chemical pneumonia, precautions must be taken to stop children under 5 years of age from using/abusing chemical substances. Although some cases of chemical pneumonia lead to death, with diligent care and treatment, the outcomes are promising. The patients in this study group responded well to treatment with inhaled corticosteroids and salbutamol.
Subject(s)
Hydrocarbons/adverse effects , Pneumonia/chemically induced , Adrenal Cortex Hormones/therapeutic use , Age Factors , Bronchoconstriction/drug effects , Bronchodilator Agents/therapeutic use , Chi-Square Distribution , Child, Preschool , Female , Humans , Infant , Intensive Care Units , Length of Stay , Male , Pneumonia/diagnosis , Pneumonia/mortality , Pneumonia/physiopathology , Pneumonia/prevention & control , Pneumonia/therapy , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , TurkeyABSTRACT
AIM: Urinary tract infections (UTIs) are common infections affecting children. The aim of our study is to determine microorganisms that cause community-acquired urinary tract infections and their antibiotic susceptibility in children. MATERIALS AND METHODS: Our investigation includes 150 cases which has positive urine culture. The cases are detected at Pediatric Polyclinics of Dicle University between June 2010 and June 2011. RESULTS: The study included 118 (78.7%) female and 32 (21.3%) male children. Urinary tract infections were seen in autumn 10.7% (n = 16), summer 35.3% (n = 53), winter 30.7% (n = 46) and spring 23.3% (n = 35). The culture results indicated 75.3% (n = 113) Escherichia coli; 20.7% (n = 31) Klebsiella; 2.7% (n = 4) Proteus and % 1.3 (n = 2) Pseudomonas. The antibiotic resistance against Escherichia coli was found out is amikacin (3%), ertapenem (7%), imipenem (0%), meropenem (0%), nitrofurantoin (9%), trimethoprim/sulfamethoxazole (58%), piperacillin (83%), amoxicillin/clavulanate (50%), ampicillin/sulbactam (65%), cefazolin (54%), cefotaxime (51%), cefuroxime sodium (51% ) and tetracycline (68%). The resistance ratios of Klebsiella are amikacin (0%), imipenem (0%), levofloxacin (0%), meropenem (0%), amoxicillin/clavulanate (57%), ampicillin/sulbactam (79%), ceftriaxone (68%), cefuroxime sodium (74%) and trimethoprim/sulfamethoxazole (61%). CONCLUSIONS: The results represent the increasing antibiotic resistance against microorganisms among the community-acquired UTI patients in a developing country such as Turkey. So, the physicians should consider resistance status of the infectious agent and choose effective antibiotics which are nitrofurantoin and cefoxitin for their empirical antibiotic treatment. Furthermore, they should be trained about selection of more effective antibiotics and check the regional studies regularly.
Subject(s)
Community-Acquired Infections/drug therapy , Urinary Tract Infections/drug therapy , Adolescent , Child , Child, Preschool , Community-Acquired Infections/microbiology , Drug Resistance, Bacterial , Female , Humans , Infant , Male , Microbial Sensitivity Tests , Seasons , Urinary Tract Infections/microbiologyABSTRACT
OBJECTIVES: Familial mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent and self-limiting fever, peritonitis, arthritis, synovitis, pleuritis, carditis, and erysipelas-like lesions. The aim of this study was to investigate the frequency of the MEFV gene mutation in patients who admitted to hospital with preliminary diagnosis FMF and who had undergone a prior appendectomy. PATIENTS AND METHODS: We retrospectively reviewed the files of 52 patients between the ages of 7-18 who admitted to hospital with preliminary diagnosis of FMF and who had undergone a prior appendectomy. Age, gender and the MEFV gene mutations were included in the data. The 12 known, common MEFV gene mutations [E148Q, P369S, F479L, M6801 (G/C), M6801 (G/A), 1692del, M694V, M6941, K695R, V726A, A744S, R761H] were investigated in the patients. RESULTS: Of these 52 cases, 29 (55.8%) were female and 23 (44.2%) were male. Their mean age was 12.1 +/- 3.1 years (range 7-18 yr). MEFV gene mutation was detected in 31/52 cases (59.6%). In this study was found an high frequency of the MEFV gene mutation in patients admitted to hospital with a preliminary diagnosis FMF who had undergone a prior appendectomy. MEFV gene mutations were M694V 16/41 (39%), E148Q 13/41 (31%), M6801 6/41 (15%), V726A 4/41 (10%) and R761H 2/41 (5%). Other genes mutations were F479L, M6801 (G/A), 1692del, M6941, K695R and A744S. CONCLUSION: There are too much indications of unnecessary appendectomy in MEFV gene mutation carriers. In MEFV gene mutation carriers the frequency of appendicitis can be higher than the normal population. A more detailed and extensive study should be done about it.
Subject(s)
Appendectomy , Cytoskeletal Proteins/genetics , Familial Mediterranean Fever/genetics , Mutation , Adolescent , Appendectomy/statistics & numerical data , Child , Familial Mediterranean Fever/diagnosis , Female , Gene Frequency , Genetic Predisposition to Disease , Hospitalization , Humans , Male , Pedigree , Phenotype , Pyrin , Retrospective Studies , Turkey , Unnecessary ProceduresABSTRACT
The purpose of the Fifth International Hydrocephalus Workshop was to allow clinicians and basic science researchers to educate each other in the advances that have been and are being made in the understanding and treatment of hydrocephalus and related disorders. This vision of the meeting was the work of Dr. Anthony Marmarou, who died a few months before the meeting was held. The presentations on all aspects of the study of hydrocephalus can be roughly grouped into seven basic themes. These themes are a summary of the important lifelong work of Professor Marmarou himself, including mathematical modeling, clinical selection of patients for the treatment of normal pressure hydrocephalus, and the development of international guidelines for the management of this condition. Other themes included the gathering of data, and in particular, randomized controlled trials; the use of magnetic resonance imaging for basic research in hydrocephalus, basic science and in particular the role of aquaporins; reports on clinical studies; and the late outcomes for patients treated in infancy. Finally, a report on the development of a consensus on the definition and classification of hydrocephalus based on the point of obstruction to flow of cerebrospinal fluid was presented.
Subject(s)
Hydrocephalus , Aquaporins , Humans , Hydrocephalus/diagnosis , Hydrocephalus/etiology , Hydrocephalus/therapy , International Cooperation , Magnetic Resonance Imaging , Randomized Controlled Trials as Topic , VentriculostomyABSTRACT
Information on male potency in testicular cancer (TC) patients treated with chemotherapy is insufficient. We aimed to assess the levels of depression and anxiety symptoms, sexual function and gonodotrophins. Participants (n = 27) were identified and recruited from the genitourinary services of two medical centres, one in Inonu University and the other in the Firat University. All patients are TC patients treated with chemotherapy after unilateral orchiectomy. Participants completed follow-up assessments after the completion of the chemotherapy regimen. Serum luteinising hormone, follicle-stimulating hormone and testosterone levels were determined after blood samples had been taken in the morning after an overnight fast. International Index of Erectile Function (IIEF-15) was also used to evaluate erectile dysfunction (ED) score. Beck Depression and Beck Anxiety Scale were used to assess psychological symptoms. The findings indicated that men treated with chemotherapy had significantly different IIEF-15 and Beck Anxiety scores compared with men who did not receive chemotherapy. But no statistically significant difference was determined in the serum gonodotrophin levels and depression score between the two groups. It is concluded that patients with TC undergoing chemotherapy have greater risk than normal men for ED, independently of the gonodotrophin's level.
Subject(s)
Antineoplastic Agents/therapeutic use , Erectile Dysfunction/etiology , Testicular Neoplasms/drug therapy , Adult , Gonadal Steroid Hormones/blood , Humans , Male , Testicular Neoplasms/physiopathologyABSTRACT
We present the case of the childhood ALL that was identified by the translocation of the ABL1 gene to the q21 band of chromosome 2 without t(9;22)(q34;q11) translocation. The observation of a poor clinical course of the case may contribute to explanation of the action of t(9;22)(q34;q11) translocation, of which poor prognostic action is known on ALL's, in terms of ABL1 gene, independent of the BCR gene. On the other hand, the prognostic significance of this variant ABL1 translocation detection, which is very rarely observed, will cast a light on future cases (Tab. 1, Fig. 1, Ref. 11).
Subject(s)
Genes, abl/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Translocation, Genetic , Child, Preschool , Female , Humans , PrognosisABSTRACT
PURPOSE: To evaluate the ocular surface, eyelid changes, meibomian gland morphology, corneal endothelial morphology, and corneal topographic measurements in patients with obstructive sleep apnea syndrome (OSAS). METHODS: There were 47 patients diagnosed with OSAS and 47 healthy volunteers included in the study. Non-invasive tear break-up time (NITBUT), corneal topography, meibography, and specular microscopy were performed. RESULTS: The mean ages of the study and control groups were 45.77±9.65 years and 44.26±8.54 years, respectively (P=0.229). The presence of floppy eye lid (17% vs. 0%; P=0.006) and lid margin abnormality score (1.09±0.8 vs. 0.21±0.51; P<0.001) were significantly different between the study and the control groups. There were insignificant differences between the groups in NITBUT and corneal topographic measurements, except for the ACT (556.96±42.4µm vs. 569±103µm, P=0.037). The mean endothelial cell density (CD) in the OSAS and control groups were 2609±259.96 and 2756±179 cells/mm2, respectively (P=0.002). Meibomian gland loss in the lower and upper eyelids was significantly higher in the OSAS group (P<0.001 for both). CONCLUSION: OSAS patients develop eyelid margin abnormalities, loss of meibomian glands, and morphological changes in the meibomian glands. A significant reduction in corneal endothelial CD indicates that systemic hypoxia in OSAS has an effect on the cornea.
Subject(s)
Dry Eye Syndromes , Eyelid Diseases , Sleep Apnea, Obstructive , Adult , Cornea/diagnostic imaging , Eyelid Diseases/diagnosis , Humans , Meibomian Glands/diagnostic imaging , Middle Aged , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , TearsABSTRACT
BACKGROUND: No single effective topical treatment is available for treating all pathogenic factors causing acne vulgaris (AV). Salicylic acid (SA), tretinoin (all-TRA) and clindamycin phosphate (CDP) are known to to be effective agents depending on their comedolytic and anti-inflammatory properties. OBJECTIVE: To compare the efficacy and tolerability of SA and CDP combination (SA+CDP) with all-TRA and CDP (all-TRA+CDP) in patients with mild to moderate facial AV. METHODS: Forty-six patients aged between 18 and 35 years were enrolled in a 12-week prospective, single-blind, randomized and comparative clinical study. Efficacy was assessed by lesion counts, global improvement, quality of life index and measurement of skin barrier functions. Local side effects were also evaluated. RESULTS: Both combinations were effective in reducing total lesion (TL), inflammatory lesion (IL) and non-inflammatory lesion (NIL) counts and showed significant global improvement as evaluated by the investigator. At the end of the study, there was no significant difference between the two groups in terms of all lesion counts. In addition, TL counts decreased faster in the all-TRA+CDP group compared with those in the SA+CDP group, with a significant difference between the two groups occurring as early as 2 weeks. Safety evaluations demonstrated that the incidence of mild to moderate side effects generally peaked at week 2 and declined gradually thereafter. Both combinations did not have an effect on stratum corneum hydration, although skin sebum values decreased with SA+CDP treatment. CONCLUSIONS: Combination of SA+CDP and all-TRA+CDP was effective in decreasing lesion counts and well tolerated with minimal local cutaneous reactions in patients with mild to moderate AV.
Subject(s)
Acne Vulgaris/drug therapy , Keratolytic Agents/therapeutic use , Salicylic Acid/therapeutic use , Tretinoin/therapeutic use , Acne Vulgaris/psychology , Administration, Topical , Adolescent , Adult , Clindamycin/administration & dosage , Clindamycin/adverse effects , Clindamycin/analogs & derivatives , Clindamycin/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Humans , Keratolytic Agents/administration & dosage , Keratolytic Agents/adverse effects , Male , Ointments , Prospective Studies , Quality of Life/psychology , Salicylic Acid/administration & dosage , Salicylic Acid/adverse effects , Severity of Illness Index , Single-Blind Method , Treatment Outcome , Tretinoin/administration & dosage , Tretinoin/adverse effects , Young AdultABSTRACT
OBJECTIVE: Febrile convulsion (FC) is one of the most common neurological findings in children. This study was aimed to investigate the difference in laboratory parameters between Febrile Seizure and control groups. PATIENTS AND METHODS: In this study, 169 children admitted to the pediatric emergency department with their first episode of FS and 189 control groups were retrospectively analyzed. The demographic characteristics and laboratory parameters of children were obtained from their files. RESULTS: Upper respiratory tract infection (URTI) was determined the most common disease (81.6%) in the FC group followed by acute gastroenteritis (AGE) (15.4%) and urinary tract infection (UTI) (3%), respectively. Similarly, URTI was detected as the most common disease (81.8%) in control groups. It was determined that there was no statistically significant difference between the two groups in terms of diseases. The leukocyte and neutrophil counts of the children with FC were significantly higher but the mean corpuscular volume of lenfosit and lenfosit/neutrophil ratio was significantly lower than the control groups (p= 0.009, <0.001, 0.001, <0.001, <0.001, respectively). Children with FC had significantly higher blood glucose, urea, creatinine, creatine kinase, alkaline phosphatase and albumin levels compared with the control groups (p<0.001, in all parameters). On the other hand, the potassium, sodium and chlorine levels of the Children with FCs were significantly lower than control groups (p=0.017, <0.001, p <0.001, respectively). CONCLUSIONS: To conclude, febrile patients with high leukocyte counts, high neutrophil counts, and several biochemical parameters should be carefully monitored for FCs due to the increasing seizure risk.
Subject(s)
Fever/blood , Seizures, Febrile/blood , Alkaline Phosphatase/blood , Blood Glucose/analysis , Child , Child, Preschool , Chlorine/blood , Creatine/blood , Creatine Kinase/blood , Female , Humans , Infant , Leukocyte Count , Male , Risk Factors , Serum Albumin/analysis , Sodium/blood , Urea/bloodABSTRACT
Peppermint is widely used medicinal plant with distinguished bioactive potential, therefore, the aim of present work was to develop novel peppermint extracts with high activity by application of traditional and emerging separation techniques. Conventional hydrodistillation and microwave-assisted hydrodistillation (MWHD) were applied for recovery of essential oil (EO), while organic solvent extraction using Soxhlet apparatus, microwave-assisted and ultrasound-assisted process and supercritical fluid extraction (SFE) were applied for non-selective recovery of peppermint lipophilic extracts. Extracts were characterized in terms of terpenoids profile with special emphasis on content of major compounds (mentol, menthone, isomenthol and eucalyptol). Antioxidant activity (DPPH, ABTS, CUPRAC, FRAP, chelating and phosphomolybdenum assay) and enzyme-inhibitory assays (acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase inhibition) were used for screening of peppermint bioactivity. MWHD was recognized as alternative for traditional process in EO recovery, while SFE extracts were useful for green production of solvent-free peppermint extracts rich in terpenoids and other lipophilic bioactives.
Subject(s)
Antioxidants/chemistry , Enzyme Inhibitors/chemistry , Mentha piperita/chemistry , Oils, Volatile/chemistry , Plant Extracts/chemistry , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Chromatography, Supercritical Fluid , Enzyme Inhibitors/metabolism , Mentha piperita/metabolism , Microwaves , Polyphenols/chemistry , Polyphenols/isolation & purification , Principal Component Analysis , Sonication , Terpenes/chemistry , Terpenes/isolation & purificationABSTRACT
OBJECTIVE: Relapsed/refractory AML cases are much more resistant to chemotherapy. Venetoclax is a highly sensitive BCL-2 inhibitor. It was aimed to evaluate the effects of venetoclax therapy on real-world R/R AML survival outcomes, the effects of the cytogenetic characteristics of the patients and previous clinical applications on treatment response, and venetoclax treatment toxicity. PATIENTS AND METHODS: The study included patients who only received a venetoclax-based salvage on R/R AML patients from Turkey. The study included a total of 62 patients from 6 different centers in Turkey. Response to 2 cycles of venetoclax treatment was assessed by bone marrow blast rate. The demographic data, cytogenetic characteristics, AML type, MDS type, response rates and overall survival of the patients after venetoclax combination treatment were assessed. Median age of the patients was 65 (19-85). Mean number of prior treatments was 2.67 ±1.75. RESULTS: 13 patients (21%) had a history of allogenic stem cell transplantation. 58 (93.5%) had received HMA therapy before venetoclax. 36 patients (58.1%) had de-novo AML, and 25 (40.3%) previously had MDS. Treatment response was evaluated as complete remission (n = 21, 33.9%), partial response (n = 17, 27.4%), and treatment failure (n = 24, 38.7%). Patients in the TF group were significantly more likely to have poor cytogenetic and to have received allogeneic transplants. The mean estimated overall survival after the venetoclax treatment was 9.13 ± 0.75 months. CONCLUSIONS: The study population consisted of a group of patients who had relapsed or primary refractory disease with poor prognosis, despite numerous rounds of chemotherapy. It is our belief that the high response rates obtained with the combination of venetoclax/HMA, and having obtained positive results with poor risk patients, indicated a promising perspective for R/R AML patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Leukemia, Myeloid, Acute/therapy , Neoplasm Recurrence, Local/drug therapy , Sulfonamides/therapeutic use , Adult , Aged , Aged, 80 and over , DNA Methylation , Female , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Salvage Therapy , Stem Cell Transplantation , Young AdultABSTRACT
Haploinsufficiency of transcriptional regulators causes human congenital heart disease (CHD); however, the underlying CHD gene regulatory network (GRN) imbalances are unknown. Here, we define transcriptional consequences of reduced dosage of the CHD transcription factor, TBX5, in individual cells during cardiomyocyte differentiation from human induced pluripotent stem cells (iPSCs). We discovered highly sensitive dysregulation of TBX5-dependent pathways-including lineage decisions and genes associated with heart development, cardiomyocyte function, and CHD genetics-in discrete subpopulations of cardiomyocytes. Spatial transcriptomic mapping revealed chamber-restricted expression for many TBX5-sensitive transcripts. GRN analysis indicated that cardiac network stability, including vulnerable CHD-linked nodes, is sensitive to TBX5 dosage. A GRN-predicted genetic interaction between Tbx5 and Mef2c, manifesting as ventricular septation defects, was validated in mice. These results demonstrate exquisite and diverse sensitivity to TBX5 dosage in heterogeneous subsets of iPSC-derived cardiomyocytes and predicts candidate GRNs for human CHDs, with implications for quantitative transcriptional regulation in disease.
Subject(s)
Gene Regulatory Networks , Haploinsufficiency/genetics , Heart Defects, Congenital/genetics , Models, Biological , T-Box Domain Proteins/genetics , Animals , Body Patterning/genetics , Cell Differentiation , Gene Dosage , Heart Ventricles/pathology , Humans , MEF2 Transcription Factors/metabolism , Mice , Mutation/genetics , Myocytes, Cardiac/metabolism , Transcription, GeneticABSTRACT
OBJECTIVES: The goal of this study was to demonstrate the posttraumatic neurochemical damage in normal-appearing brain and to assess mitochondrial dysfunction by measuring N-acetylaspartate (NAA) levels in patients with severe head injuries, using proton (1H) magnetic resonance (MR) spectroscopy. METHODS: Semiquantitative analysis of NAA relative to creatine-containing compounds (Cr) and choline (Cho) was carried out from proton spectra obtained by means of chemical shift (CS) imaging and single-voxel (SV) methods in 25 patients with severe traumatic brain injuries (TBIs) (Glasgow Coma Scale scores < or = 8) using a 1.5-tesla MR unit. Proton MR spectroscopy was also performed in 5 healthy volunteers (controls). RESULTS: The SV studies in patients with diffuse TBI showed partial reduction of NAA/Cho and NAA/Cr ratios within the first 10 days after injury (means +/- standard deviations 1.59 +/- 0.46 and 1.44 +/- 0.21, respectively, in the patients compared with 2.08 +/- 0.26 and 2.04 +/- 0.31, respectively, in the controls; nonsignificant difference). The ratios gradually declined in all patients as time from injury increased (mean minimum values NAA/Cho 1.05 +/- 0.44 and NAA/Cr 1.05 +/- 0.30, p < 0.03 and p < 0.02, respectively). This reduction was greater in patients with less favorable outcomes. In patients with focal injuries, the periphery of the lesions revealed identical trends of NAA/Cho and NAA/Cr decrease. These reductions correlated with outcome at 6 months (p < 0.01). Assessment with multivoxel methods (CS imaging) demonstrated that, in diffuse injury, NAA levels declined uniformly throughout the brain. At 40 days postinjury, initially low NAA/Cho levels had recovered to near baseline in patients who had good outcomes, whereas no recovery was evident in patients with poor outcomes (p < 0.01). CONCLUSIONS: Using (1)H-MR spectroscopy, it is possible to detect the posttraumatic neurochemical damage of the injured brain when conventional neuroimaging techniques reveal no abnormality. Reduction of NAA levels is a dynamic process, evolving over time, decreasing and remaining low throughout the involved tissue in patients with poor outcomes. Recovery of NAA levels in patients with favorable outcomes suggests marginal mitochondrial impairment and possible resynthesis from vital neurons.
Subject(s)
Brain Injuries/complications , Magnetic Resonance Spectroscopy , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/etiology , Adolescent , Adult , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Brain Injuries/metabolism , Choline/metabolism , Creatine/metabolism , Female , Follow-Up Studies , Humans , Male , Middle Aged , Outcome Assessment, Health Care , Predictive Value of Tests , Time FactorsABSTRACT
Parental perceptions in the importance of dental care and preferences with regard to its provision while profiling the level of dental health knowledge of parents of leukaemic children were elicited. The setting was the Paediatric Dental Care Unit located in Medical Faculty. Data were collected by means of a structured interview, employing a questionnaire. Level of knowledge on both dental facts and preventive dentistry of the participants was insufficient. Major source of dental care was the resident paediatric dentist both in prior to (78.2%) and following (100%) diagnosis. Tooth extraction (17.6%) was the only treatment provided prior to diagnosis. Following diagnosis, 60 (69%) of these children had received operative dental treatment. The source of preventive advice was inconsistent. Parents appeared to place a high level of importance on their children's dental care and the preference for this to be provided within the hospitals in which the child has been treated. There is clearly a need to establish dental care units in hospitals in which treatment of childhood malignancy is provided. The provision for the future should be the continuous education of dentists, physicians and nurses who work in hospitals and public health services.
Subject(s)
Attitude to Health , Dental Care for Chronically Ill/psychology , Leukemia/therapy , Parents/psychology , Adolescent , Child , Child, Preschool , Dental Care for Children/psychology , Dental Care for Chronically Ill/standards , Female , Humans , Leukemia/psychology , Male , Surveys and QuestionnairesABSTRACT
BACKGROUND: We believe that in traumatic brain injury (TBI), the reduction of N-acetyl aspartate (NAA) occurs in the presence of adequate cerebral blood flow (CBF) which would lend support to the concept of mitochondrial impairment. The objective of this study was to test this hypothesis in severely injured patients (GCS 8 or less) by obtaining simultaneous measures of CBF and NAA. METHODS: Fourteen patients were studied of which six patients presented as diffuse injury at admission CT, while focal lesions were present in eight patients. CBF using stable xenon method was measured at the same time that NAA was measured by magnetic resonance proton spectroscopy (1HMRS) in the MR suite. Additionally, diffusion weighted imaging (DWI) and maps of the apparent diffusion coefficient (ADC) were assessed. FINDINGS: In diffuse injury, NAA/Cr reduction occurred uniformly throughout the brain where the values of CBF in all patients were well above ischemic threshold. In focal injury, we observed ischemic CBF values in the core of the lesions. However, in areas other than the core, CBF was above ischemic levels and NAA/Cr levels were decreased. CONCLUSIONS: Considering the direct link between energy metabolism and NAA synthesis in the mitochondria, this study showed that in the absence of an ischemic insult, reductions in NAA concentration reflects mitochondrial dysfunction.