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1.
Turk J Med Sci ; 54(1): 229-238, 2024.
Article in English | MEDLINE | ID: mdl-38812646

ABSTRACT

Background/aim: The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer. Materials and methods: A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child. Results: The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed. Conclusion: Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.


Subject(s)
Breast Feeding , Breast Neoplasms , Parity , Humans , Female , Breast Neoplasms/pathology , Breast Feeding/statistics & numerical data , Adult , Middle Aged , Pregnancy , Aged , Surveys and Questionnaires , Receptors, Progesterone/metabolism
2.
J Trop Pediatr ; 69(2)2023 02 06.
Article in English | MEDLINE | ID: mdl-36897067

ABSTRACT

OBJECTIVE: Feeding intolerance (FI) is a common condition in preterm infants because they have an immature gastrointestinal tract. There are studies on the effects of the position on gastric residual volume (GRV) in preterm infants. Kangaroo mother care (KMC) may be an instrument for reducing FI by providing an upright position to infants. Moreover, numerous studies conducted with this therapeutic position applied by putting an infant on the mother's chest have indicated its positive effects on the infant's weight gain, growth and development, and vital signs. Therefore, this study aimed to reveal the impact of KMC on FI in preterm infants. METHODS: The population of the study, designed as a randomized trial, consisted of 168 preterm infants [KMC: 84, Standart Care (SC): 84] hospitalized in the neonatal intensive care unit of a university hospital between June and November 2020. Infants were randomly selected and divided into two groups. After the vital signs of the infants in both groups became stable, the infants were fed in the same position. KMC was applied to the infants in the intervention group for 1 h by preparing a suitable environment after feeding. Infants in the SC group were placed in the prone position after feeding. The GRVs of the infants in both groups were recorded on the Infant Follow-up Form before the next feeding. RESULTS: No statistically significant difference was detected between the groups upon comparing them in terms of demographic and clinical characteristics. The body temperatures and O2 saturations of the participants in the KMC group were statistically significantly higher, and their respiratory and heart rates were lower than the SC group. The transition time to full enteral feeding was statistically significantly shorter, and FI was experienced significantly less in the KMC group infants than in the SC group (p < 0.05). There was no statistically significant difference between the groups in terms of the infants' weight gain and length of hospital stay (p > 0.05). CONCLUSION: The present study demonstrated that KMC had a positive impact on FI in preterm infants. KMC is not only a safe care model providing the earliest contact between parents and infants but also a practice whose positive effect on the functioning of the digestive system in preterm infants we can use.


Subject(s)
Kangaroo-Mother Care Method , Child , Humans , Infant, Newborn , Infant, Low Birth Weight , Infant, Premature , Intensive Care Units, Neonatal , Weight Gain
3.
Int J Phytoremediation ; 25(1): 89-97, 2023.
Article in English | MEDLINE | ID: mdl-35400247

ABSTRACT

This research is to predict heavy metal levels in plants, particularly in Robinia pseudoacacia L., and soils using an effective artificial intelligence approach with some ecological parameters, thereby significantly eliminating common defects such as high cost and seriously tedious and time-consuming laboratory procedures. In this respect, the artificial neural network (ANN) is employed to estimate the concentrations of essential heavy metals such as Fe, Mn and Ni, depending on the Cu and Zn concentrations of plant and soil samples collected from five different locations. The derived relative errors for the constructed ANN model have been computed within the ranges 0.041-0.051, 0.017-0.025, and 0.026-0.029 for the training, testing and holdout data regarding Fe, Mn, and Ni, respectively. In addition, it has been realized that the relative errors could be diminished up to 0.007 for Fe, 0.014 for Mn and 0.022 for Ni by considering the Cu, Zn, location and plant parts as independent variables during the analysis. The results produced seem instructive and pioneering for environmentalists and scientists to design optimal study programs to leave a livable ecosystem.


The levels of essential heavy metals, Fe, Mn, Ni, based on Zn and Cu in plant and soil samples have been predicted through an AI-based prediction model, a class of feedforward artificial neural networks (ANNs) with a multilayer perceptron (MLP). Thereby common drawbacks such as high cost and severely time-consuming laboratory procedures have been significantly eradicated. In the evaluation of different pollution levels at locations, it has been shown that the ANN method can overcome several disadvantages of analytical element analyzers to monitor the amounts of heavy metals such as Fe, Mn, and Ni in soil and plants.


Subject(s)
Metals, Heavy , Soil Pollutants , Environmental Monitoring/methods , Artificial Intelligence , Ecosystem , Soil Pollutants/analysis , Biodegradation, Environmental , Neural Networks, Computer , Soil , Metals, Heavy/analysis
4.
Nonlinear Dyn ; 111(12): 11685-11702, 2023.
Article in English | MEDLINE | ID: mdl-37168840

ABSTRACT

Compartmental models are commonly used in practice to investigate the dynamical response of infectious diseases such as the COVID-19 outbreak. Such models generally assume exponentially distributed latency and infectiousness periods. However, the exponential distribution assumption fails when the sojourn times are expected to distribute around their means. This study aims to derive a novel S (Susceptible)-E (Exposed)-P (Presymptomatic)-A (Asymptomatic)-D (Symptomatic)-C (Reported) model with arbitrarily distributed latency, presymptomatic infectiousness, asymptomatic infectiousness, and symptomatic infectiousness periods. The SEPADC model is represented by nonlinear Volterra integral equations that generalize ordinary differential equation-based models. Our primary aim is the derivation of a general relation between intrinsic growth rate r and basic reproduction number R0 with the help of the well-known Lotka-Euler equation. The resulting r-R0 equation includes separate roles of various stages of the infection and their sojourn time distributions. We show that R0 estimates are considerably affected by the choice of the sojourn time distributions for relatively higher values of r. The well-known exponential distribution assumption has led to the underestimation of R0 values for most of the countries. Exponential and delta-distributed sojourn times have been shown to yield lower and upper bounds of the R0 values depending on the r values. In quantitative experiments, R0 values of 152 countries around the world were estimated through our novel formulae utilizing the parameter values and sojourn time distributions of the COVID-19 pandemic. The global convergence, R0=4.58, has been estimated through our novel formulation. Additionally, we have shown that increasing the shape parameter of the Erlang distributed sojourn times increases the skewness of the epidemic curves in entire dynamics.

5.
Environ Monit Assess ; 195(5): 536, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37010616

ABSTRACT

This paper aims to predict heavy metal pollution based on ecological factors with a new approach, using artificial neural networks (ANNs), by significantly removing typical obstacles like time-consuming laboratory procedures and high implementation costs. Pollution prediction is crucial for the safety of all living things, for sustainable development, and for policymakers to make the right decisions. This study focuses on predicting heavy metal contamination in an ecosystem at a significantly lower cost because pollution assessment still primarily relies on conventional methods, which are recognized to have disadvantages. To accomplish this, the data collected for 800 plant and soil materials have been utilized in the production of an ANN. This research is the first to use an ANN to predict pollution very accurately and has found the network models to be very suitable systemic tools for modelling in pollution data analysis. The findings appear are promising to be very illuminating and pioneering for scientists, conservationists, and governments to swiftly and optimally develop their appropriate work programs to leave a functioning ecosystem for all living things. It has been observed that the relative errors calculated for each of the polluting heavy metals for training, testing, and holdout data are significantly low.


Subject(s)
Metals, Heavy , Soil Pollutants , Ecosystem , Soil Pollutants/analysis , Environmental Monitoring/methods , Metals, Heavy/analysis , Soil , Risk Assessment , China , Cadmium/analysis
6.
Anticancer Drugs ; 33(7): 663-670, 2022 08 01.
Article in English | MEDLINE | ID: mdl-35703239

ABSTRACT

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.


Subject(s)
Breast Neoplasms , Carcinoma, Intraductal, Noninfiltrating , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Carcinoma, Intraductal, Noninfiltrating/etiology , Docetaxel/therapeutic use , Female , Humans , Middle Aged , Neoadjuvant Therapy/methods , Receptor, ErbB-2/metabolism , Trastuzumab/adverse effects
7.
Eur Arch Otorhinolaryngol ; 276(11): 3123-3130, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31468129

ABSTRACT

OBJECTIVE: Rhinitis medicamentosa is drug-induced rhinitis which occurs by prolonged and overdose usage of topical nasal decongestants. There is not much of treatment choice rather than nasal steroids. In this pathological study, we have been aimed to represent the healing effects of xylitol on damaged nasal mucosa due to rhinitis medicamentosa. METHOD: 30 Wistar rats were separated into 5 groups. During 2 months, oxymetazoline was given to the first group, and saline was given to second group intranasally. First and second group animals were examined at the end of 2 months and rhinitis medicamentosa was detected. Oxymetazoline was given to the third, fourth, and fifth groups during 2 months. Then xylitol solution, mometasone, and saline were applied, respectively, for 15 days. After the experiment, rats' nasal mucosas were evaluated histopathologically. RESULTS: Xylitol and mometasone were found to be more effective than the control group in terms of histopathological changes. Effectivity of xylitol and mometasone was compared and not a significant value was determined. CONCLUSIONS: According to the results, xylitol solution is effective as mometasone, usable and well-priced in the treatment of rhinitis medicamentosa. More comprehensive and ultrastructural studies on animals and human studies with rhinometric evaluation should be performed.


Subject(s)
Mometasone Furoate/administration & dosage , Nasal Decongestants/adverse effects , Nasal Mucosa , Oxymetazoline/adverse effects , Rhinitis , Xylitol/administration & dosage , Administration, Intranasal , Animals , Anti-Inflammatory Agents/administration & dosage , Disease Models, Animal , Male , Nasal Decongestants/administration & dosage , Nasal Mucosa/drug effects , Nasal Mucosa/pathology , Rats , Rats, Wistar , Rhinitis/chemically induced , Rhinitis/pathology , Rhinitis/therapy , Sweetening Agents/administration & dosage , Time , Treatment Outcome
8.
Eur Arch Otorhinolaryngol ; 274(6): 2499-2504, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28251322

ABSTRACT

Calprotectin is an S100 protein and marker of inflammation found in neutrophils and monocytes; S100 proteins are a family of calcium-modulated proteins. The aim of this study was to determine if the serum concentration of calprotectin is higher in patients with laryngeal carcinoma than in patients with benign laryngeal pathologies and controls. The study included 107 participants. The serum calprotectin concentration was analyzed using the calprotectin ELISA (enzyme-linked immunosorbent assay) kit (Calpo AS, Norway). EDTA-serum for analysis was collected prior to surgery from patients with laryngeal carcinoma (n = 41), those with a benign laryngeal pathology (Reinke's edema, vocal nodules, etc.) (n = 32), and healthy controls (n = 34). The median serum calprotectin concentration was significantly higher in the laryngeal carcinoma group (2179.6 µg L-1) than in the benign laryngeal pathology group (727.84 µg L-1) and control group (733.73 µg L-1) (P < 0.05). The median serum calprotectin concentration in patients with advanced-stage laryngeal cancer (5854.,4 µg L-1) was significantly higher than in those with early-stage laryngeal cancer (971.84 µg L-1) (P < 0.05); however, there was not a significant difference in the median calprotectin concentration between the control and benign laryngeal pathology groups (P > 0.05). Furthermore, the median serum calprotectin concentration in the patients with early-stage laryngeal cancer (n = 21) (971.84 µg L-1) was significantly higher than that in the benign laryngeal pathology and control groups (n = 64) (730.6 µg L-1) (P < 0.05). The serum calprotectin concentration was strongly correlated with poor survival and advanced-stage laryngeal carcinoma. Malignant laryngeal cancer patients (n = 4) that died during follow-up had a higher median serum calprotectin concentration (9468.4 µg L-1) than those that remained alive (n = 37) (857.78 µg L-1) (P < 0.05). The serum calprotectin concentration is higher in patients with laryngeal carcinoma than in those with benign laryngeal pathologies and healthy controls. The present findings show that the serum calprotectin concentration might be used as a marker to discriminate between laryngeal carcinoma and benign laryngeal pathologies. Additional research is needed to further assess the value of this parameter as a useful tumor marker for the diagnosis, treatment, and follow-up of laryngeal carcinoma.


Subject(s)
Laryngeal Neoplasms , Leukocyte L1 Antigen Complex/blood , Aged , Biomarkers, Tumor/blood , Female , Humans , Laryngeal Neoplasms/blood , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Male , Middle Aged , Neoplasm Staging , Preoperative Period , Reproducibility of Results , Survival Analysis , Turkey
9.
Eur Arch Otorhinolaryngol ; 274(8): 3065-3069, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28470359

ABSTRACT

The aim of the study was to analyze whether the measurement of changes in the anatomical position and volume of middle concha, the volume changes in the area between the middle concha and lamina papyracea, the evaluation of opacification in major paranasal sinuses, and osteomeatal complex occlusion in cases with middle concha by out-fracture technique during endoscopic endonasal transsphenoidal approach is a minimally invasive surgery, and also to find out whether these changes lead to the development of tendency to rhinosinusitis. It was a retrospective clinical study. Forty-five cases, between 2013 and 2015, planned for endoscopic endonasal transsphenoidal surgery due to hypophyseal pathology at the Neurosurgery Departments of Marmara University Hospital were evaluated retrospectively. The patients were evaluated for the changes in the anatomy of the middle concha and the effects of these changes to paranasal sinuses by paranasal computed tomographies were studied at the preoperative second week and postoperative 12 month. The Lund-Mackay scoring system was used for the evaluation of opacification in the five major paranasal sinuses and occlusion of the osteomeatal complex in the pre- and postoperative period. The Lund-Mackay scoring system was used to analyze the paranasal computed tomography of the patients at the preoperative 2 weeks and postoperative first year. According to the Lund-Mackay scoring system, no significant difference was detected between the preoperative and postoperative opacification of paranasal sinuses (p > 0.05). Besides, there was also no significant difference between the preoperative and postoperative osteomeatal complex occlusion (p > 0.05). Considering the distance between middle concha and lamina papyracea following the out-fracture of the middle concha, a significant lateralization of 0.5 mm between the preoperative and postoperative period was observed (p < 0.05). In addition, a significant change was also detected in the volume of middle concha (p < 0.05). The volume of the area between the middle concha and lamina papyracea was decreased with a statistical significance (p < 0.05). The endoscopic endonasal transsphenoidal surgery causes some variations in the structures of the middle concha, paranasal sinuses, and OMC, but these changes do not lead to significant rhinologic pathologies.


Subject(s)
Natural Orifice Endoscopic Surgery , Rhinitis/etiology , Sinusitis/etiology , Adult , Aged , Disease Susceptibility , Female , Humans , Male , Middle Aged , Natural Orifice Endoscopic Surgery/adverse effects , Nose , Paranasal Sinuses/diagnostic imaging , Pituitary Diseases/surgery , Retrospective Studies , Sphenoid Bone , Turbinates/diagnostic imaging , Young Adult
10.
Eur Arch Otorhinolaryngol ; 273(9): 2819-23, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27020270

ABSTRACT

This retrospective review aims to evaluate the postoperative morbidity and mortality of 30 patients with Down syndrome who underwent adenotonsillectomy between June 2012 and December 2015 in a tertiary referral center. Mean age was 7.8 with a range of 3-12. There were 20 (66.6 %) male and ten (33.3 %) female patients. Mean follow-up was 23 months with a range of 7-43 months. 23 (76.6 %) of 30 patients had been operated due to obstructive tonsillar and adenoid hypertrophy, whereas seven (23.3 %) of them operated for chronic recurrent infections. All of the patients had undergone adenotonsillectomy operation; one patient had also bilateral tympanostomy tube insertion. Hospital stay was noted 1.3 days in average with a range of 1-3 days. Anesthetic complications of persistent bradycardia and postextubation respiratory difficulty occurred in two (6.6) patients. Patient who had intraoperative bradycardia necessitated intensive care unit stay and pacemaker implantation during follow-up. 3 (10 %) patients had late onset hemorrhage between days 7 and 10 and required intraoperative bleeding control. We did not experience any other morbidity and mortality except the abovementioned ones. In conclusion, adenotonsillectomy in patients with Down syndrome is a worthwhile operation with certain risks and these operations should better be performed by the tertiary referral centers which have the capacity to deal with the complications.


Subject(s)
Adenoidectomy/methods , Down Syndrome/complications , Postoperative Complications/epidemiology , Sleep Apnea, Obstructive/complications , Tonsillectomy/methods , Tonsillitis/surgery , Child , Child, Preschool , Down Syndrome/mortality , Female , Humans , Intensive Care Units , Length of Stay , Male , Morbidity/trends , Retrospective Studies , Sleep Apnea, Obstructive/surgery , Survival Rate/trends , Tonsillitis/complications , Turkey/epidemiology
12.
Curr Opin Crit Care ; 21(2): 91-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25689126

ABSTRACT

PURPOSE OF REVIEW: Large hemispheric infarction is a devastating disease that continues to be associated with significant mortality and morbidity. Most often these patients are admitted to the ICU requiring significant physician and nursing resources. This review will address some of the ICU management issues and review the evidence supporting medical and surgical management of malignant cerebral edema. RECENT FINDINGS: The most recent changes in management of large hemispheric infarct include the American Heart Association and Neurocritical Care Guidelines. These guidelines address airway management and mechanical ventilation, blood pressure control, fluid management, and glucose and temperature control. In addition, they addressed the indication for surgical management of cerebral edema. We review the recent guidelines updates and trials of surgical management of large hemispheric infarcts. SUMMARY: Large hemispheric infarcts continue to have significant morbidity and mortality. Recent guidelines have provided an excellent framework to help intensivists manage these complicated patients. Recent surgical data continue to support early hemicraniectomy even in elderly patients.


Subject(s)
Anticoagulants/therapeutic use , Cerebral Infarction/therapy , Brain Edema/etiology , Brain Edema/surgery , Cerebral Infarction/complications , Cerebral Infarction/diagnosis , Decompressive Craniectomy/methods , Guideline Adherence , Guidelines as Topic , Humans , Intensive Care Units
15.
Aging Clin Exp Res ; 26(1): 73-5, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23949974

ABSTRACT

The incidence of deep vein thrombosis (DVT) and pulmonary embolism has been increasing in the elderly because of hypercoagulability associated with aging. Age has also been identified as an independent risk factor for bleeding complications related to anticoagulation therapy. Inferior vena cava filters could be used as alternatives to anticoagulant therapy for the prevention of pulmonary embolism when anticoagulation is either contraindicated or ineffective. Here, we report two geriatric patients who had documented acute DVT and in whom inferior vena caval filter was used because of the patients have a contraindication to use an anticoagulation.


Subject(s)
Anticoagulants/therapeutic use , Vena Cava Filters , Venous Thrombosis/prevention & control , Aged , Female , Humans , Male , Pulmonary Embolism/prevention & control
16.
J Craniofac Surg ; 25(4): e328-30, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24978683

ABSTRACT

Parapharyngeal space tumors are very rarely seen, and surgical approach to these tumors has not been well established. Most of these tumors are benign and originated from salivary glands and neurogenic in nature. In this case, we report a patient who has a trigeminal schwannoma extending into the deep parapharyngeal space and explain our surgical approach.


Subject(s)
Cranial Nerve Neoplasms/surgery , Neurilemmoma/surgery , Neurosurgical Procedures/methods , Pharyngeal Neoplasms/surgery , Trigeminal Nerve Diseases/surgery , Adult , Cranial Nerve Neoplasms/pathology , Humans , Male , Neck/surgery , Neurilemmoma/pathology , Pharyngeal Neoplasms/pathology , Treatment Outcome
17.
J Craniofac Surg ; 25(1): e70-2, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24406606

ABSTRACT

Larynx and adjacent anatomical structures have complicated physiological functions and mechanical features. Traffic accidents, penetrating stab wounds and shot wounds, sports matches, and occupational accidents cause external laryngeal trauma. In the management of laryngeal trauma, maintenance of airway patency has priority. In this case report, we will mention of a 15-year-old male patient with a blunt laryngeal trauma and also the approach to laryngeal traumas.


Subject(s)
Larynx/injuries , Neck Injuries/complications , Wounds, Nonpenetrating/complications , Adolescent , Humans , Male , Thyroid Cartilage/injuries , Vocal Cord Paralysis/etiology
18.
Acta Crystallogr Sect E Struct Rep Online ; 70(Pt 9): o989-90, 2014 Sep 01.
Article in English | MEDLINE | ID: mdl-25309296

ABSTRACT

The title hydrated mol-ecular organic salt, C10H10N2 (2+)·C10H6O6S2 (2-)·2H2O, crystallized with half a bipyridinium cation, half a naphthalene-2,6-di-sulfonate anion and a water mol-ecule in the asymmetric unit. The whole cation and anion are generated by inversion symmetry, the inversion centers being at the center of the bridging C-C bond of the cation, and at the center of the fused C-C bond of the naphthalene group of the anion. In the crystal, the anions and cations stack alternately along the a axis with π-π inter-actions [inter-centroid distance = 3.491 (1) Å]. The anions are linked via O-H⋯O(sulfonate) hydrogen bonds involving two inversion-related water mol-ecules, forming chains along [10-1]. These chains are bridged by bifurcated N-H⋯(O,O) hydrogen bonds, forming a three-dimensional framework structure. There are also C-H⋯O hydrogen bonds present, reinforcing the framework structure.

19.
PeerJ ; 12: e16917, 2024.
Article in English | MEDLINE | ID: mdl-38426146

ABSTRACT

Background: The emergence and spread of antibiotic-resistant pathogens have led to the exploration of antibiotic combinations to enhance clinical effectiveness and counter resistance development. Synergistic and antagonistic interactions between antibiotics can intensify or diminish the combined therapy's impact. Moreover, these interactions can evolve as bacteria transition from wildtype to mutant (resistant) strains. Experimental studies have shown that the antagonistically interacting antibiotics against wildtype bacteria slow down the evolution of resistance. Interestingly, other studies have shown that antibiotics that interact antagonistically against mutants accelerate resistance. However, it is unclear if the beneficial effect of antagonism in the wildtype bacteria is more critical than the detrimental effect of antagonism in the mutants. This study aims to illuminate the importance of antibiotic interactions against wildtype bacteria and mutants on the deacceleration of antimicrobial resistance. Methods: To address this, we developed and analyzed a mathematical model that explores the population dynamics of wildtype and mutant bacteria under the influence of interacting antibiotics. The model investigates the relationship between synergistic and antagonistic antibiotic interactions with respect to the growth rate of mutant bacteria acquiring resistance. Stability analysis was conducted for equilibrium points representing bacteria-free conditions, all-mutant scenarios, and coexistence of both types. Numerical simulations corroborated the analytical findings, illustrating the temporal dynamics of wildtype and mutant bacteria under different combination therapies. Results: Our analysis provides analytical clarification and numerical validation that antibiotic interactions against wildtype bacteria exert a more significant effect on reducing the rate of resistance development than interactions against mutants. Specifically, our findings highlight the crucial role of antagonistic antibiotic interactions against wildtype bacteria in slowing the growth rate of resistant mutants. In contrast, antagonistic interactions against mutants only marginally affect resistance evolution and may even accelerate it. Conclusion: Our results emphasize the importance of considering the nature of antibiotic interactions against wildtype bacteria rather than mutants when aiming to slow down the acquisition of antibiotic resistance.


Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Humans , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Models, Theoretical , Bacteria
20.
Biomol Biomed ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38920621

ABSTRACT

Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or ICI-tyrosine kinase inhibitor (TKI) combinations. As a result, predictive markers are necessary to identify patients who may benefit from single-agent TKIs for long-term response. This study aims to identify such parameters. This was a multi-centre, retrospective study of patients with mRCC who were undergoing first-line treatment with sunitinib or pazopanib. Patients who had been diagnosed with mRCC and had not experienced disease progression for 36 months or more were deemed to have achieved a long-term response. Predictive clinical and pathological characteristics of patients who did not experience long-term disease progression were investigated. A total of 320 patients from four hospitals were included in the study. The median age of the patients was 60 years (range 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were classified as having favourable risk and 211 were in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responder's group, the median PFS was 78.4 months. Among all patients, prior nephrectomy, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <1, and the absence of brain metastasis were predictive factors for long-term response. For patients in the favourable risk group, the lack of brain metastasis was a predictor of long-term response. In the intermediate-poor risk group, prior nephrectomy and ECOG PS <1 were predictive factors for long-term response. Some individuals with mRCC may experience a durable response to TKIs. The likelihood of a long-term response can be determined by factors such as nephrectomy, ECOG PS < 1, and the absence of brain metastases.

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