Comparison of the effectiveness of liposomal doxorubicin and gemcitabine in patients with platinum-sensitive recurrent ovarian cancer receiving third-line chemotherapy.

OBJECTIVE: In this retrospective study, we compared the effectiveness and reliability of the third-line chemotherapies gemcitabine and liposomal doxorubicin, in patients with platinum-sensitive ovarian cancer (OC). PATIENTS AND METHODS: The retrospective study included platinum-sensitive epithelial ovarian cancer patients who had previously received paclitaxel and carboplatin therapy. Between 2013-2021, cross-matched 45 patients who received gemcitabine and 48 who received liposomal doxorubicin as third-line therapy were compared based on clinicopathological characteristics, biomarkers, and blood cancer antigen (CA) 125 levels. Time to treatment failure, survival, and quality of life were additional objectives. RESULTS: The study included a total of 93 patients. The reported mean survival durations for treatments, 19.45 months for gemcitabine and 17 months for liposomal doxorubicin, did not statistically significantly differ (p=0.398). The mean CA 125 levels for the liposomal doxorubicin and gemcitabine groups after treatment were 54.4±11.4 U/ml and 54.7±11.1 U/ml, respectively. There was no noticeable difference between the treatments when comparing the postop CA 125 value (p=0.37). CONCLUSIONS: For both pegylated liposomal doxorubicin (PLD) and gemcitabine as single agents in the third line, our data revealed comparable effectiveness results, and there was no substantial difference in progression-free survival (PFS) for recurrent ovarian cancer. These therapies were tolerated with an expected incidence of hematological toxicities.

Comparison of different cyclin-dependent kinase inhibitors and KI-67 levels on survival and toxicity in breast cancer treatment.

OBJECTIVE: As cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors, which play a crucial role in the cell cycle, palbociclib and ribociclib are two novel drugs that are recently being used in the treatment of breast cancer. Despite targeting the same pathway, these agents have different molecular activities and processes. KI-67 is known to play a significant role in cell proliferation that has been related to prognosis. This study investigated the impact of palbociclib, ribociclib, and KI-67 on toxicity and survival in breast cancer treatment. PATIENTS AND METHODS: The study included 140 breast cancer patients in total. Patients were divided into groups based on the use of different CDK inhibitors and KI-67 values. Mortality, progression, treatment response rates, frequency, and severity of adverse events were assessed retrospectively. RESULTS: The patients in our study had an average age of 53.62±12.71 years, and 62.9% of them were diagnosed at an early stage. 34.3% (n=48) of the patients progressed after receiving treatment, while 19.3% (n=27) of the patients died. The median follow-up time was 576 days, the maximum follow-up time was 1,471 days, and the median time to progression was 301 days (min=28-max=713). Mortality, progression, and treatment response rate between two different CDK inhibitors or KI-67 groups revealed no statistically significant differences. CONCLUSIONS: Our data show a comparison between the effectiveness of palbociclib and ribociclib, and no noticeable difference is found in breast cancer patients' survival, progression, or severity of adverse effects. Likewise, there is no meaningful difference in KI-67 expression subgroups between progression and survival following treatment.

Awareness and obscurity: demystifying genomic profiling in real-world practice for the members of the Turkish Society of Medical Oncology (TSMO).

OBJECTIVE: Molecular testing in oncology practice is increasingly being used to offer more relevant therapies to cancer patients. Our study aims to determine the real-world impact of routine incorporation of molecular testing among the Turkish Oncology community across all types of cancer and identify gaps for the first time. SUBJECTS AND METHODS: This research was conducted in Turkey among medical oncologists from different backgrounds. The survey attendance was entirely voluntary. A questionnaire with twelve items (multiple choice +/- closed-ended) was utilized in this study to assess the effect of molecular tests in real clinical situations. RESULTS: 102 oncologists with various levels of experience participated in this study. Most of the respondents (97%) reported successful implementation of molecular testing. About 10% of the participating oncologists said they preferred genetic tests at the early stages of cancer, compared to the majority who preferred genetic tests at the terminal stage. Molecular tests are often performed in separate locations and 47% of the oncologists were using a targeted panel specific to the type of malignancy. CONCLUSIONS: Several informational difficulties must be resolved in order to have early personalized therapy as the standard treatment. We need accessible, comprehensive, and regularly updated databases to compare genetic profiling and its therapeutic implications. We also need to continue educating patients and physicians.

Investigating the role of GLUL as a survival factor in cellular adaptation to glutamine depletion via targeted stable isotope resolved metabolomics.

Cellular glutamine synthesis is thought to be an important resistance factor in protecting cells from nutrient deprivation and may also contribute to drug resistance. The application of ?targeted stable isotope resolved metabolomics" allowed to directly measure the activity of glutamine synthetase in the cell. With the help of this method, the fate of glutamine derived nitrogen within the biochemical network of the cells was traced. The application of stable isotope labelled substrates and analyses of isotope enrichment in metabolic intermediates allows the determination of metabolic activity and flux in biological systems. In our study we used stable isotope labelled substrates of glutamine synthetase to demonstrate its role in the starvation response of cancer cells. We applied 13C labelled glutamate and 15N labelled ammonium and determined the enrichment of both isotopes in glutamine and nucleotide species. Our results show that the metabolic compensatory pathways to overcome glutamine depletion depend on the ability to synthesise glutamine via glutamine synthetase. We demonstrate that the application of dual-isotope tracing can be used to address specific reactions within the biochemical network directly. Our study highlights the potential of concurrent isotope tracing methods in medical research.

Clinical, electrophysiological and genetic characteristics of childhood hereditary polyneuropathies.

BACKGROUND: Hereditary polyneuropathies are heterogeneous group of diseases of the peripheral nervous system. In this study, we investigated the demographic, clinical, electrophysiological, and genetic characteristics of hereditary polyneuropathy patients diagnosed and followed up in our tertiary center clinic in Izmir, Turkey. METHODS: Patients who were diagnosed with hereditary polyneuropathies during nerve conduction studies in our center were evaluated retrospectively. RESULTS: In a total of 1484 nerve conduction studies, 207 patients were diagnosed with polyneuropathy. Ninety-nine of those patients were determined to have hereditary polyneuropathy, 52 of which were male and 47 were female. Sixty-nine patients with hereditary polyneuropathy were compatible with axonal and 30 were compatible with demyelinating polyneuropathy. Genetic analysis was performed in 69 patients, and 49 of those patients were genetically diagnosed, leading to a diagnosis rate of 71%. CONCLUSIONS: Advances in genetics have led to an increase in the heterogeneity of hereditary polyneuropathies, causing difficulties in the use of existing classifications. Although typical mutations expected in childhood-onset polyneuropathies are seen less frequently, polyneuropathies are frequently encountered as findings of complex, multisystemic diseases.

Thoracic sympathetic nuclei ischemia: Effects on lower heart rates following experimentally induced spinal subarachnoid hemorrhage.

BACKGROUND: The neuropathological mechanism of heart rhythm disorders, following spinal cord pathologies, to our knowledge, has not yet been adequately investigated. In this study, the effect of the ischemic neurodegeneration of the thoracic sympathetic nuclei (TSN) on the heart rate (HR) was examined following a spinal subarachnoid hemorrhage (SSAH). METHODS: This study was conducted on 22 rabbits. Five rabbits were used as a control group, five as SHAM, and twelve as a study group. The animals' HRs were recorded via monitoring devices on the first day, and those results were accepted as baseline values. The HRs were remeasured after injecting 0.5 cc of isotonic saline for SHAM and 0.5 cc of autolog arterial blood into the thoracic spinal subarachnoid space at T4-T5 for the study group. After a three-week follow-up with continuous monitoring of their HRs, the rabbit's thoracic spinal cords and stellate ganglia were extracted. The specimens were evaluated by histopathological methods. The densities of degenerated neurons in the TSN and stellate ganglia were compared with the HRs. RESULTS: The mean HRs and mean degenerated neuron density of the TSN and stellate ganglia in control group were 251±18/min, 5±2/mm3, and 3±1/mm3, respectively. The mean HRs and the mean degenerated neuron density of the TSN and stellate ganglia were detected as 242±13/min, 6±2/mm3, and 4±2/mm3 in SHAM (P>0.05 vs. control); 176±19/min, 94±12/mm3, and 28±6/mm3 in the study group (P<0.0001 vs. control and P<0.005 vs. SHAM), respectively. CONCLUSIONS: SAH induced TSN neurodegeneration may have been responsible for low HRs following SSAH. To date this has not been mentioned in the literature.

Evaluation of calcium silicate cement bond strength after using gutta-percha solvents.

OBJECTIVES: To determine the effect of different gutta-percha solvents (chloroform, Endosolv E, orange oil, and eucalyptol) on the push-out bond strength of calcium silicate cements (CSCs; white mineral trioxide aggregate [WMTA]; capsule-form mineral trioxide aggregate [CMTA], and Biodentine). MATERIALS AND METHODS: One hundred and fifty extracted single-rooted human mandibular premolars were sectioned into 3-mm-thick slices. The canal lumens were enlarged for 1.35-mm-diameter standardized cavities. The samples were randomly divided into five groups (n = 30) according to the solvent type: G1, chloroform; G2, Endosolv E; G3, eucalyptol; G4, orange oil; G5, no solvent (control). After application of the solvents for 5 min, the specimens were divided into three subgroups (n = 10): (i) WMTA, (ii) CMTA, and (iii) Biodentine. The push-out bond strength was measured. Two-way ANOVA analysis of variance and post hoc Tukey tests were used for analyses (P = 0.05). RESULTS: The highest push-out bond strength was observed in the Biodentine (P < 0.05), and the values of WMTA and CMTA were not significantly different in all solvent groups (P > 0.05). There were no statistically significant differences among the gutta-percha solvents and control group in WMTA (P > 0.05). CONCLUSIONS: Gutta-percha solvents used during retreatment decreased the bond strength of Biodentine and CMTA to root dentin. The bond strength of WMTA was not affected by the use of gutta-percha solvents.

Association between "Malnutrition Inflammation Score" and airway obstruction in patients awaiting renal transplantation: a preliminary study.

BACKGROUND: A chronic inflammatory state is a prominent feature in patients with end-stage renal disease (ESRD) who are undergoing maintenance hemodialysis (MHD). "Malnutrition Inflammation Score" (MIS) is a comprehensive scoring system that measures nutrition and inflammation in MHD patients. Inflammation and malnutrition are important risk factors in ESRD patients with pulmonary diseases. The aim of the study was to determine if pulmonary dysfunction, as assessed by airway obstruction, was associated with malnutrition and inflammatory factors in ESRD patients awaiting renal transplantation (RT). METHODS: Patients with ESRD who were on MHD and had pulmonary function tests (PFTs) were retrospectively enrolled in the study. Patients' renal function tests, albumin, C-reactive protein (CRP) levels, white blood cell count, and PFTs (forced expiratory flow rate in one second [FEV1], forced vital capacity [FVC], forced expiratory flow at 25%-75% [FEF25%-75%], and peak expiratory flow [PEF]) were recorded. MIS was calculated for each patient. RESULTS: A total of 81 patients (male=54; mean age: 50.6±13 years) were recruited. Mean body mass index (BMI) was 22.5±4.4 kg/m2, mean MIS was 7.1±3.3, mean CRP level was 24.9±48.1 mg/L, mean FEV1% was 94±22, and mean FEF25%-75% was found to be 72.3±30.3. Mean duration of MHD was 10.5±5.2 years. There was a negative correlation between FEV1, FVC, FEF25%- 75%, PEF, and MIS (r=-0.3, P=.00; r=-0.32, P=.00; r=-0.22, P=.04; r=-0.30, P=.00, respectively). Nevertheless, FEV1 values significantly correlated with BMI (P=.03) and the MIS (P=.00). CONCLUSION: Impaired pulmonary function could be a marker of inflammation and malnutrition in ESRD patients awaiting RT. Prospective studies are needed to investigate the relationship between pulmonary function, inflammation, and malnutrition in larger populations of ESRD patients. Treatment geared towards malnutrition and inflammation markers may help maintain PFTs within normal range, which may prevent pulmonary complications following RT.

Inferior pancreaticoduodenal artery false aneurysm: a rare cause of gastrointestinal bleeding diagnosed by three-dimensional computed tomography.

We report a 57-year-old man who presented with a two-month history of persistent epigastric pain associated with indigestion, weight loss and jaundice. Contrast-enhanced computed tomography revealed a large pseudoaneurysm 87 mm x 68 mm in diameter, with its origin from the inferior pancreaticoduodenal artery of the superior mesenteric artery and in continuity with an ectatic gastroduodenal artery. The aneurysmal mass exerted direct pressure over the head of the pancreas, common bile duct and duodenum, causing obstruction. Non-selective abdominal angiography confirmed the aneurysm stemming from the inferior pancreaticoduodenal artery. Because of the obstructive symptoms and the size of the aneurysm, surgery was planned, but the patient refused and died from massive gastrointestinal bleeding one month later.

The role of neuron numbers of the petrosal ganglion in the determination of blood pressure: an experimental study.

BACKGROUND: Baroreceptor reflexes are regulated by nerve terminals of the glossopharyngeal and vagal nerves. The body of pressure-sensitive neurons of these nerves is located in the petrosal ganglion of both nerves. We examined whether there is a relationship between the neuron numbers of the inferior ganglion of the glossopharyngeal nerve and blood pressure values. METHODS: Petrosal ganglions were examined in 18 male hybrid rabbits divided into three equal groups: Group A normotensive (TA=90-100 mmHg), Group B hypertensive (TA>100 mmHg); and Group C hypotensive (TA<90 mmHg). After examination of blood pressure for one week, all animals were sacrificed, and the petrosal ganglions extracted bilaterally and examined histopathologically using the physical dissector method. RESULTS: The mean (+/-SD) neuronal density was: Group A 8700+/-200, Group B 7800+/-250 and Group C 9800+/-300, respectively. The difference between the groups B and C as compared to A was significant (p<0.01) while the difference between Groups B and C was highly significant (p<0.001). CONCLUSIONS: An inverse relationship was noticed between the neuronal density in the petrosal ganglion and blood pressure values with potential implications in the study of the etiology of hypertension.

Effects of trimetazidine on lipid peroxidation, antioxidant enzyme activities and plasma brain natriuretic peptide levels in patients with chronic cor pulmonale.

An oxidant/antioxidant imbalance in favour of oxidants appears to occur in chronic cor pulmonale (CCP). Oxidative stress could also be a critical event in the pathogenesis of this condition. Trimetazidine (TMZ) has antioxidant properties and may affect the utilization of oxygen radicals. We investigated the effect of TMZ (20 mg three times daily, orally) on activities of erythrocyte malondialdehyde (MDA) and catalase (eCAT), erythrocyte and plasma glutathione peroxidase (GSH-Px) and plasma superoxide dismutase (pSOD) in CCP patients. We also assessed changes in plasma levels of brain natriuretic peptide (BNP) with TMZ therapy. Sixty CCP patients with significantly higher MDA and markedly lower pSOD, eCAT and GSH-Px (erythrocyte) activities than 24 healthy controls were randomly allocated to receive routine treatment or routine treatment plus TMZ. After 3 months' therapy, greater pSOD, eCAT and GSH-Px (erythrocyte and plasma) activities and lower MDA activity were found with TMZ treatment compared with routine treatment. Plasma BNP levels were significantly lower in TMZ-treated patients and higher in the routine treatment group than in the control group. TMZ improved antioxidant levels, decreased oxidative stress and decreased plasma BNP levels in CCP patients.

Identification of the culprit artery involved in inferior wall acute myocardial infarction using electrocardiographic criteria.

We tested whether particular electrocardiogram (ECG) changes can identify the right coronary (RCA) or left circumflex (LCX) artery as the responsible vessel in inferior wall acute myocardial infarction (AMI) in 73 patients. A standard 12-lead ECG was performed within 6 h of onset of chest pain. Coronary angiography was performed between 1 week and 6 weeks after the infarction. RCA and LCX lesions were detected in 53 and 20 patients, respectively. The most useful ECG parameters for implicating the RCA were a higher ST elevation in lead III than lead II (specificity 94%, sensitivity 86%) and an S/R wave ratio > 0.33 plus ST segment depression > 1 mm in lead aVL (specificity 94%, sensitivity 92%). Absence of these criteria was associated with LCX occlusion (specificity 100%, sensitivity 87%). These results indicate that composite ECG criteria are useful in predicting the artery involved in inferior wall AMI.

Emission tuned-aperture computed tomography: a novel approach to scintimammography.

UNLABELLED: Emission tuned-aperture computed tomography (ETACT) is a new approach to acquiring and processing scintimammography data. A gamma camera with a pinhole collimator is used to acquire projections of the radionuclide distribution within the breast. Fiducial markers are used to reconstruct these projections into tomographic slices. Simulation and phantom experiments were performed to evaluate the potential of the ETACT method. METHODS: In the simulation study, a hemispheric object of 15 cm in diameter was constructed to model a breast. A ray-tracing technique was used to generate ideal projections. These were blurred and noise was added to create images that resemble scintigraphic images. Tumor size, pinhole size, and target-to-nontarget radioactivity ratios (TNTs) were varied. The simulated projections were reconstructed into slices, and contrast and contrast-to-noise ratios were calculated to evaluate the effect of pinhole size. These results were compared with a simulated planar acquisition of the same object. A preliminary phantom evaluation was performed using an 8-mm "tumor" with a 10:1 TNT to validate the simulation results. RESULTS: A 3-mm pinhole was shown by the simulation study to be the optimal size. The ETACT images consistently yielded higher contrast than simulated planar images. The phantom study validated the simulation results and showed the feasibility of ETACT in a simulated clinical environment. CONCLUSION: ETACT is shown to be useful for imaging tumors <1 cm in diameter. Because ETACT requires only a gamma camera with a pinhole collimator, it has the potential to be applied in any hospital in a simple, flexible, and practical manner.

[Automatic, implantible cardioverter-defibrillator in a patient with chronic Chagas cardiopathy and sustained ventricular tachycardia]. / Cardioverter desfibrilador automático implantable en una paciente con cardiopatía chagásica crónica y taquicardia ventricular sostenida.

We studied a 48 years old woman, with chronic Chagasic cardiopathy, manifested with cardiomegaly, heart failure and syncope, due to a sustained ventricular tachycardia (SVT) of two different configurations (left bundle branch block and right bundle branch block). During electrophysiological testing, both types of ventricular tachycardia were reproduced. Successful ablation therapy of the right branch of His was performed due to suspicion of the bundle branch reentrant tachycardia, with a left bundle branch block. The patient continued to show SVT episodes, now with right bundle branch block pattern. Cardioverter Defibrillator was implanted. We report this case due to the rare frequency of Chagas' disease, where it could be a cause of heart disease, since the existence of the parasite (trypanosoma cruzi) and its vector (Triatoma) has been identified in some rural and suburban zones in the state of Aguascalientes, Mexico.