Online Adaptive Magnetic Resonance-guided Radiation Therapy for Gynaecological Cancers: Preliminary Results of Feasibility and Outcome.

AIMS: To present the preliminary results on the clinical utilisation of an online daily adaptive magnetic resonance-guided radiation therapy (MRgRT) for various gynaecological cancers. MATERIALS AND METHODS: Twelve patients treated between September 2018 and June 2022 were included. Six patients (50%) were treated with pelvic radiation therapy followed by MRgRT boost as brachytherapy boost was ineligible or unavailable, three patients (25%) were treated with pelvic MRgRT followed by high dose rate brachytherapy, two patients (16.7%) were treated with only MRgRT, one patient (8.3%) was treated with linear accelerator-based radiation therapy followed by MRgRT boost for bulky iliac lymph nodes. RESULTS: The median age was 56.5 years (range 31-86 years). Eight patients (66.7%) had a complete response, three patients (25%) had a partial response and one patient (8.3%) died due to acute renal failure. The mean follow-up time was 11.2 months (range 3.1-42.6 months). The estimated 1-year overall survival was 88.9%. The median treatment time was 47 days (range 10-87 days). During external beam radiation therapy, 10 (83.3%) patients had concomitant chemoradiotherapy. Pelvic external beam radiation therapy doses for all cohorts were 45-50.4 Gy with a fraction dose of 1.8 Gy. The median magnetic resonance-guided boost dose was 32 Gy (range 20-50 Gy) and fraction doses ranged between 4 and 10 Gy. Three patients were treated with intracavitary high dose rate brachytherapy (26-28 Gy in four to five fractions). None of the patients had grade >3 late genitourinary toxicities. CONCLUSION: MRgRT is reliable and clinically feasible for treating patients with gynaecological cancers alone or in combination with brachytherapy with an acceptable toxicity and outcome. MRgRT boost could be an option when brachytherapy is not available or ineligible.

Can N-terminal pro B-type natriuretic peptide, neutrophil-to-lymphocyte ratio, C-reactive protein help to predict short and long term mortality?

BACKGROUND: There is limited data about ICU, short and long-term mortality prediction of severe CAP with neutrophil-to-lymphocyte ratio (NLR): N-terminal proB- type natriuretic peptide (NT-proBNP): C-reactive protein (CRP). AIM: Besides the known severity indexes of ICU, can NLR, NT-proBNP, CRP predict ICU, short and long term mortality? METHODS: A retrospective cohort study was carried out in a level III ICU of a tertiary training hospital for chest diseases and thoracic surgery. RESULTS: Over the study period, a total of 143 patients were enrolled in the study. The APACHE II scoring showed a significantly higher predicting performance for ICU mortality (p = 0.002). The performance for predicting short term mortality NLR (p = 0.039) and long term mortality NTproBNP (p = 0.002) had a significantly higher performance. The survival analysis revealed that mortality was significantly higher in patients with CURB65 score ≥ 4 (p = 0.047). CONCLUSION: NLR, NTproBNP > 2000pg/mL can be used to predict pneumonia severity in ICU alike CURB65 and PSI. Higher NLR, APACHE II and atrial fibrillation can cause an important mortality factor in long term. Consequently, clinicians should take an attention for good cardiac evaluation and cardiac follow-up of patients with CAP (Tab. 4, Fig. 3, Ref. 36).

Strain wave elastography for evaluation of renal parenchyma in chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is an important and costly health problem in developed countries and has a tendency to progress to end-stage renal disease regardless of the aetiology. This progress ends in interstitial fibrosis, which decreases the elasticity of tissue. Elastography is a developing technique to assess tissue elasticity. The aim of this study was to determine the difference of strain index (SI) value of renal parenchyma between patients with CKD and healthy individuals. In addition, SI differences of inter-stages were studied. METHODS: Toshiba (Toshiba Medical Systems Corporation, Otawara, Japan) Aplio™ 500 ultrasound device and 3.5- to 5.0-MHz convex probe were used for the elastography examinations. RESULTS: A total of 58 patients with CKD from nephrology and endocrinology clinics (30 males and 28 females; mean age, 56.14 ± 11.60 years) and 40 normal healthy individuals (19 males and 21 females; mean age, 51.70 ± 11.71 years) were included in this prospective study. The mean SI of normal healthy individuals and patients with CKD (regardless of stages) was 0.42 ± 0.30 and 1.81 ± 0.88, respectively (p < 0.001). SI values were not statistically significant among the CKD stages (except CKD Stages 1 and 3). The area under the receiver operating characteristic curve was 0.956 for SI. The optimal cut-off value for the prediction of CKD was 0.935 (sensitivity, 88% and specificity, 95%). CONCLUSION: SI value of sonoelastography can be used to differentiate patients with CKD and healthy individuals. Sonoelastography is an acceptable technique to approach patients with CKD, but we have not shown that it can reliably differentiate different stages. ADVANCES IN KNOWLEDGE: Determining a cut-off SI value between normal and diseased renal parenchyma can help in the diagnosis of CKD.

The value of real-time ultrasound elastography in chronic autoimmune thyroiditis.

OBJECTIVE: Chronic autoimmune thyroiditis (CAT) (chronic lymphocytic thyroiditis-Hashimoto's thyroiditis), which is the most common inflammatory disorder of the thyroid gland, causes hypothyroidism. Ultrasound elastography is a newly developed sonographic technique that provides an estimation of tissue elasticity by measuring the degree of tissue displacement under the application of an external force. In this study, our aim was to evaluate the accuracy of strain index ratio with real-time ultrasound elastography and to calculate the cut-off point for the diagnosis of CAT. Our aim was also to lead further studies on other pathological changes such as lymphoma, malign nodules etc. based on CAT by using this cut-off point. The gains from this study and further studies will assist clinical diagnoses and follow-up. METHODS: Aplio™ 500 ultrasound machine (Toshiba Medical Systems Co. Ltd, Otawara, Japan) with linear 4.8-11.0 MHz transducers and elastography software was used. Routine B-mode (dimensions and parenchymal echogenicity) ultrasound evaluation was performed prior to the ultrasound elastography. RESULTS: A total of 31 randomized patients (3 males, 28 females) with a mean age of 39.13 ± 10.16 years (range, 16-58 years) with CAT and 21 healthy controls (6 males, 15 females) with mean age of 34.67 ± 16.31 years (range, 14-81 years) were prospectively examined. The mean values of thyroid-stimulating hormone (TSH; normal TSH value is 0.27-4.20 IU ml(-1)) and anti-thyroid peroxidase (anti-TPO; normal anti-TPO value is 0-34 IU ml(-1)) were 3.40 ± 2.70 and 373.66 ± 148.94 IU ml(-1), respectively. No correlation was detected between serum TSH and thyroid tissue strain index (Spearman r coefficient of TSH was -0.290). Positive-sided correlation was detected between anti-TPO values and thyroid tissue strain index ratio (Spearman r coefficient of anti-TPO was 0.682). The median strain index ratio of patients with CAT (1.39 ± 0.72) was significantly higher than the mean ratio of the controls (0.76 ± 0.55). The area under the receiver operating characteristic curve was 0.775 (95% confidence interval). The optimal cut-off value (in which the sum of sensitivity and specificity was highest) for the prediction of diffuse thyroid pathology was 0.677. For this cut-off ratio, thyroid stiffness had 96% sensitivity and 67% specificity. A total of 30 of 31 patients (96%) and a total of 7 of 21 healthy controls (33%) exceeded the cut-off points. CONCLUSION: The strain index ratio was higher in CAT than in normal thyroid parenchyma in real-time ultrasound elastography. Thus, it seems to be a useful method for the assessment of CAT with real-time ultrasound elastography, and further studies assessing the correlation of sonoelastography findings and histopathological subtypes of CAT would enrich the findings of the present study. ADVANCES IN KNOWLEDGE: In our study, we detected the stiffness ratio of the thyroid tissue in patients with CAT. The cut-off value should be helpful for diagnosis or follow-up of the recently developed lesions such as lymphoma, malign nodule, etc. based on CAT. This study should also encourage new studies about CAT and ultrasound elastography.

Bronchoscopy as an indicator of tracheobronchial fungal infection in non-neutropenic intensive-care unit patients.

We aimed to establish that a bronchoscopic view can be as reliable as microbiology, and support an empirical tracheobronchial fungal infection (TBFI) treatment decision. We retrospectively studied 95 respiratory failure patients with suspected TBFI admitted to the intensive-care unit (ICU) in 2008 with sticky secretions, hyperaemic mucosa, and whitish plaques on bronchoscopic view. Patients not suspected of having TBFI were chosen as a control group (n = 151). Broncheoalveolar lavage (BAL) fluid was cultured, and biopsy samples were taken from the lesions. Biopsy samples positive for fungi were defined as 'proven', only BAL-positive (+ fungi) cases were 'probable TBFI', and BAL-negative (- fungi) cases were 'possible TBFI'. BAL (+ fungi) and BAL (- fungi) in the control group were defined as 'colonization' and 'no TBFI', respectively. The sensitivity, specificity and positive and negative predictive values of BAL (+ fungi) were 85.1% (63/74), 81.4% (140/172), 66.3% (63/95), and 92.7% (140/151), respectively. Biopsies were performed in 78 of 95 patients, and 28 were proven TBFI with fungal elements, and 100% were BAL (+ fungi). Probable TBFI was seen in 30 of 95 patients with BAL (+ fungi), and possible TBFI (BAL(- fungi)) in 25 of 95. Among the 95 patients, microbiology revealed fungi (90.5% Candida species; 9.5% Aspergillus) in 63 (66.3%). In the controls, the colonization and no TBFI rates were 11 of 151 and 140 of 151, respectively. Observing sticky secretions, hyperaemic mucosa and whitish plaques by bronchoscopy is faster than and may be as reliable as microbiology for diagnosing TBFI. These findings are relevant for empirical antifungal therapy in suspected TBFI patients in the ICU.

Dosimetric comparison of robotic and conventional linac-based stereotactic lung irradiation in early-stage lung cancer.

We aimed to compare dosimetric characteristics of conventional linear accerator-based treatment plans to those created using the robotic CyberKnife® (CK) treatment planning system for patients with early-stage lung cancer. Eight early-stage lung cancer patients treated with stereotactic body radiotherapy (SBRT) using a conventional linac-based (LIN) system were included in this study. New treatment plans were created for the patients with the CK treatment planning system in order to compare the two platforms' dosimetric characteristics. Planning computed tomographies (CT) were obtained in three phases: free-breathing, full exhalation and inhalation. The three GTVs were then added together for internal target volume (ITV) with LIN, whereas no ITV was used for CK. Planning target volumes (PTV) were constituted by adding 5-mm margin to GTV and ITV. Treatment plan was 54 Gy in three fractions. Five-field, seven-field, and dynamic-conformal arc planning techniques were used in LIN plans. Plans were compared according to dose heterogenity (D(max)-maximum dose), volume of 54 Gy (V54) and 27 Gy isodose (V27), conformity index (CI(54) and CI(27)) and lung volumes. PTVs were significantly smaller in CK plans (p=0.012). D(max) was significantly lower in ARC plans (p=0.01). Among all plans, CK had significantly tightest isodose shell received 54 Gy and 27 Gy (p=0.0001). Among LIN plans, V54 was significantly (p=0.03) smaller in ARC plans; but no difference was observed for V27 values. LIN plans have better plan quality (CI(27) and CI(54)) than CK. No statistically significant difference was observed for lung volumes. CK plans had superior V54 and V27 values compared to LIN plans due to smaller PTV. LIN plans had better CI(27) and CI(54) values. Advantages of LIN treatment were no neccessity for fiducial marker use, which may cause pneumothorax, and significantly shorter beam-on treatment times. Both CK and LIN methods are suitable for lung SBRT.

Confirmed prevalence of food allergy and non-allergic food hypersensitivity in a Mediterranean population.

BACKGROUND: Until the present, no comprehensive studies evaluating the prevalence of food allergy and non-allergic food hypersensitivity (FA/NAFH) in adults have been done in Turkey or its surrounding countries. OBJECTIVE: This large population-based study was planned to identify the confirmed prevalence of adverse reactions to food in adults in Istanbul. METHODS: A total of 17 064 telephone numbers were randomly selected from both the European and Asian sides of Istanbul, and the 11 816 subjects who agreed to participate in the study were addressed with a questionnaire of eight items. Those who disclosed food-related complaints in this survey were called again and a similar questionnaire was repeated. The respondents who were suspected of having food allergy or food hypersensitivity were invited for a personal clinical investigation that included double-blind, placebo-controlled food challenge tests. RESULTS: The lifetime prevalence of self-reported FA/NAFH was found to be 9.5% [1118/11 816; 95% confidence interval (CI): 8.94-10.00%]. After the clinical investigations, the point prevalence of FA/NAFH, which also included the 'possible FA/NAFH group', was found to be as low as 0.3% (30/11 816; 95% CI: 0.17-0.36%), and the FA/NAFH rates assessed by double-blind, placebo-controlled food challenge tests were 0.1% (12/11 816; 95% CI: 0.05-0.18%) and 0.1% (11/11 816; 95% CI: 0.05-0.17%), respectively. The most significant factor influencing FA/NAFH was familial atopy (adjusted OR 4.3; 95% CI: 3.67-4.99), and the most related atopic disease was itching dermatitis/urticaria (adjusted OR: 3.9; 95% CI: 3.31-4.54). CONCLUSION: We may conclude that FA/NAFH in the Turkish population seems to be low when compared with Northern and Western European countries. This may be due to genetic, cultural or dietary factors, and further studies evaluating the reasons for this low prevalence of FA/NAFH in our population are needed.

The role of surgery and fluoroquinolones in the treatment of multidrug-resistant tuberculosis.

SETTING: Although modern tuberculosis treatment relies on chemotherapy, surgery is accepted as adjuvant treatment for multidrug-resistant tuberculosis (MDR-TB). OBJECTIVE: To evaluate the effect of resectional surgery and fluoroquinolones on long-term treatment success and survival in a large group of MDR-TB cases. DESIGN: A total of 252 patients with MDR-TB were included in this retrospective cohort study. Multiple logistic regression was used to determine independent predictive factors for long-term treatment success, and survival analyses were done based on different treatment approaches with or without surgery. RESULTS: The mean age of the study cohort was 37.9 +/- 12.5 years; 204 (80%) were males. Long-term treatment success was associated with resistance to fewer drugs, female sex, younger age and limited disease. Sixty-six patients (26.2%) had undergone resectional surgery after 2-16 months of treatment. The highest long-term treatment success and survival rates were achieved in patients who both received fluoroquinolones and underwent surgery (P = 0.001 vs. other groups). CONCLUSION: Although the treatment success rate was higher in patients treated with surgery and fluoroquinolones compared to other groups, an additional significant benefit from surgery could not be demonstrated. Larger scale studies are needed to clarify this issue.

Effects of sevoflurane and desflurane on cytokine response during tympanoplasty surgery.

BACKGROUND: This study was devised to compare the effects of sevoflurane and desflurane anaesthesia on the cytokine response. METHODS: Sixty ASA I-II patients, scheduled for tympanoplasty, were randomly allocated to be anaesthetized with either sevoflurane or desflurane at maintenance inspiratory concentrations of 1-1.5 MAC of either agent. Blood samples were taken for plasma tumour necrosis factor alpha (TNFalpha), interleukin 1beta and interleukin-6 assay before induction of anaesthesia, before surgery, and at the end of surgery. Alveolar cells were obtained after induction of anaesthesia and at the end of surgery. RESULTS: Plasma TNFalpha was greater with desflurane than sevoflurane both before surgery (45.1 +/- 3.5 pg ml(-1) for desflurane vs. 23.2 +/- 2.5 pg ml(-1) for sevoflurane, P < 0.01) and (62.0 +/- 5.3 pg ml(-1) vs. 35.5 +/- 4.6 pg ml(-1), P < 0.001). Interleukin 1beta was similarly greater with desflurane than sevoflurane before (39.3 +/- 4.0 pg ml(-1) vs. 17.4 +/- 3.0 pg ml(-1); P < 0.01) and after surgery (46.0 +/- 3.4 pg ml(-1) vs. 23.3 +/- 3.2 pg ml(-1), P < 0.001). There were similar results for interleukin 6 before (42.3 +/- 3.5 pg mls(-1). 29.0 +/- 2.6 pg ml(-1), P < 0.001) and after surgery (86.0 +/- 4.5 pg ml(-1) vs. 45.9 +/- 6.3 pg ml(-1), P < 0.001). Alveolar cell TNFalpha concentrations after surgery were also greater with desflurane than sevoflurane (96.3 +/- 12.4 pg ml(-1) vs. 64.8 +/- 10.1 pg ml(-1), P < 0.001), as were interleukin 1beta (75.4 +/- 6.2 pg ml(-1) vs. 32.0 +/- 8.3 pg ml(-1), P < 0.001) and interleukin 6 concentrations (540.1 +/- 65.3 pg ml(-1) vs. 363.6 +/- 29.2 pg ml(-1), P < 0.001). CONCLUSION: Desflurane appears to cause a greater systemic and intrapulmonary pro-inflammatory response than sevoflurane during anaesthesia for ear surgery.

Side effects associated with the treatment of multidrug-resistant tuberculosis.

SETTING: Süreyyapasa Centre for Chest Diseases and Thoracic Surgery, Istanbul, Turkey. OBJECTIVE: To report the frequency of treatment side effects in cases of multidrug-resistant (MDR-TB) tuberculosis. DESIGN: A retrospective review of the medical records of 263 patients who received individualised treatment for MDR-TB between April 1992 and June 2004. RESULTS: One or more side effects developed in 182 cases (69.2%). These effects led the clinicians to withdraw one or more drugs from the treatment regimen in 146 cases (55.5%). Side effects observed most frequently included: ototoxicity (41.8%), psychiatric disorders (21.3%), gastrointestinal disturbance (14.0%), arthralgia (11.4%), epileptic seizures (9.9%), hepatitis (4.5%), and dermatological effects (4.5%). At the time of analysis, treatment was successful in 204 (77.6%) cases. Fifty-nine patients (22.4%) had poor outcomes. CONCLUSION: Timely and aggressive management of drug side effects means that high side effect rates in MDR-TB treatment need not compromise success rates.

Antibiotic resistance of bacterial ventilator-associated pneumonia in surgical intensive care units.

Ventilator-associated pneumonia (VAP) is the most common infection in intensive care units. It is caused by prolonged hospitalization and results in high mortality rates. This retrospective clinical study, of 140 patients in a surgical intensive care unit, aimed to identify the bacterial agents responsible for VAP infection, and determine antibiotic resistance rates in VAP. Antibiotic sensitivity was evaluated by culturing and testing tracheal aspirates from patients with clinical and radiological findings of VAP. The bacteria isolated most frequently were Pseudomonas aeruginosa (33.9%), Staphylococcus aureus (30.0%), Acinetobacter baumannii (26.1%), and Enterobacter species (4.3%). A. baumannii was more prevalent than in previous years. The results of antibiotic sensitivity testing suggested sulbactam/cefoperazone as the most appropriate drug for treating these patients. We suggest, however, that when staphylococcal pneumonia is suspected, a glycopeptide (vancomycin or teicoplanin) or combined trimethoprim-sulfamethoxazole is used as first-line therapy until sensitivity results are obtained. In conclusion, development of antibiotic policies for individual hospitals can reduce high antibiotic resistance rates due to VAP.

Treatment outcome of relapse and defaulter pulmonary tuberculosis patients.

SETTING: Tuberculosis clinic in a referral hospital. OBJECTIVE: To evaluate the effect of risk factors on the outcome of retreatment in relapse and defaulter pulmonary tuberculosis patients. DESIGN: A total of 57 retreatment tuberculosis patients treated and monitored in our centre between January 1997 and June 1999 were evaluated with respect to treatment outcome. Factors which have on effect on treatment outcome were investigated. RESULTS: Of 57 patients, 37 (64.9%) were classified as relapse cases and 20 (35.1%) as defaulters. The treatment success rate was 71.9% (68.4% cure rate and 3.5% completion rate). Failure was encountered in 22.8%. Twenty-six patients (45.6%) exhibited resistance to at least one drug, namely rifampicin. The multidrug-resistance (MDR) rate was 18.5%. Treatment success rates were 100% and 50%, respectively, in patients in whom susceptibility to all drugs and resistance to at least one drug were detected. Successful outcome was possible in 68.8% of patients with any rifampicin resistance and in 20% of patients with MDR tuberculosis. Retreatment resulted in failure in 80% and 100%, respectively, of patients whose sputum cultures remained positive at the end of the second and third months. CONCLUSION: Drug resistance proved the most important factor affecting treatment outcome. Success rates in retreatment of patients with any rifampicin resistance or MDR tuberculosis are low. Conversion to negative sputum results at the end of the second and third months of retreatment seems to be a significant parameter for a successful outcome.

Alarming drug-resistance rates for tuberculosis in Süreyyapasa Hospital, Turkey.

The susceptibility patterns to 'classic' tuberculous pleuritis can reflect the circulating strains in a society. The records of patients with 'classic' tuberculous pleuritis were reviewed retrospectively. Eighty-six patients were selected who were hospitalized between January 1990 and April 1994. Pleural fluid and tissue samples of patients were cultured in Lowenstein-Jensen medium. The isolated strains were subjected to drug susceptibility testing based on the absolute concentration method. We obtained 40 positive cultures in 86 patients with 'classic' tuberculous pleuritis. The resistance rate was 75% to one or more drugs, 27.5% to two drugs, 15% to three drugs, and 10% to four drugs. The resistance rates to isoniazid, rifampicin, streptomycin, and ethambutol were 32.5, 55,42.5 and 32.5%, respectively. The resistance to isoniazid + rifampicin was 7.5%. Our findings indicate that the resistance rates for 'classic' tuberculous pleuritis are considerably high, reflecting the currently circulating resistance patterns in our region. The best regimen for new tuberculous cases and the appropriate regimens for drug-resistant cases should be designed and conducted by a nationwide institution.

Detection of beta-glucosidase activity on sodium dodecyl sulphate-polyacrylamide gels.

Maize beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) was incubated in the presence of SDS concentrations varying from 0.025 to 3.2% at two different pHs (5 and 8), electrophoresed through 10% SDS-polyacrylamide gels, and stained for activity. The zymogram patterns of SDS-treated samples were similar to those of untreated (control) samples. The same samples were also analyzed by native PAGE and IEF, yielding similar patterns for controls and for SDS-treated samples. However, zymogram patterns were severely distorted on IEF gels when SDS concentration of the sample medium was at or above 1.6%. These results suggest that the beta-glucosidase monomer (a 60 kD polypeptide) is either catalytically active or it re-forms dimers upon the removal of SDS during equilibration washes, since the in vivo form of the functional enzyme is thought to be a dimer. The activity of maize beta-glucosidase on SDS-gels after SDS-PAGE does not seem to be limited to this enzyme alone, because beta-glucosidases from other sources (e.g., almond, Trichoderma, and Penicillium) were also active on SDS-gels. Enzyme activity in the presence of SDS or after SDS treatment may be more common than one would expect on the basis of the conventional biochemical dictum that ionic detergents denature and inactivate enzymes. Enzyme activity in the presence of SDS and development of zymograms on SDS-gels offer new approaches to studies of enzyme structure and activity.