Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

The relationship of bronchiectasis to airway obstruction and inflammation in patients with chronic obstructive pulmonary disease

Background: Chronic obstructive pulmonary disease (COPD) and bronchiectasis are diseases of respiratory tract with significant mortality and morbidity. These two diseases can be seen together occasionally and are thought to change each other's course by adversely affecting the prognosis. The aim of our study was to identify the signs of bronchiectasis in COPD patients, to investigate its possible effects on disease prognosis, and to evaluate these signs for diagnostic convenience. Materials and Methods: This prospective study included a total of s[table 60] moderate/severe COPD patients who were admitted to Yedikule Chest Diseases and Chest Surgery Training and Research Hospital between January 2015 and February 2016. The patients were divided into two groups according to the presence of bronchiectasis as confirmed radiologically: 35 patients in the bronchiectasis group and 25 patients in the control group. Demographic data of the patients were questioned and systemic inflammation parameters, spirometric measurements, blood gas analysis, and clinical evaluation findings were recorded. Results: Bronchiectasis was detected in 58.3% of COPD patients. Patients in two groups are similar in sociodemographical, spirometrical and clinical parameters (P > 0.05). Laboratory tests showed similar result in between two groups but carbon dioxide(CO2) values in the blood gas analysis were found to be higher in the bronchiectasis group (P < 0.05). The increase in the number of bronchiectasis segments was shown to reduce the FEV1/FVC (P < 0.05). In the overall evaluation, FEV1%, mMRC, FVC% and CRP levels were found to be associated with exacerbations in COPD (P < 0.05). The use of antibiotics increased as FEV1% and FEV1/FVC levels of patients decreased (P < 0.05). In addition, sputum polymorphonuclear leukocyte (PMNL) values were correlated with spirometric values and as sputum PMNL values increased, spirometric values were found to decrease (P < 0.05 for FEV1% and FVC%). Conclusion: Bronchiectasis is common in COPD patients. In two divided groups, blood gas carbon dioxide values, which affect mortality, were shown to be higher in the bronchiectasis group. This is a new addition to literature that bronchiectatic COPD patients are experiencing different respiratory failure patterns affecting mortality. Diffuse type bronchiectasis has more effect in spirometric results of COPD patients. Also, airway obstruction in COPD is well correlated with elevated sputum PMNL values which represent airway inflammation and if this is combined with high clinical suspicion it guides to a cost effective way for guiding radiological investigations for bronchiectasis

Treatment of planovalgus foot in cerebral palsy with lateral column lengthening using titanium cubic cage

High complication rates were reported with the graft usage when performing lateral column lengthening in cerebral palsy patients. In order to overcome such technical difficulties, we designed a titanium cubic cage and the purpose of this study was to describe this new fixation method and report results after calcaneal lengthening osteotomy using this new implant. Used in 86 feet of 55 patients. Average patient age was 11.6 years, and mean follow-up was 42.6 months. Clinical examination was performed preoperatively and in follow-up. In the anteroposterior radiographs, the talonavicular coverage and the talus-first metatarsal angles and in the lateral radiographs, the talocalcaneal and the talus-first metatarsal angles were measured. Forefoot abduction improvement and medial longitudinal arch was successfully reestablishment were detected in almost all of the patients. All patients showed significant improvement in mean talonavicular coverage, anterior talus-first metatarsal, lateral talocalcaneal, and lateral talus-first metatarsal angles. Our results show that TCC provides significant correction and stable fixation and reduced complication rates compared in CP. [Med-Science 2022; 11(1.000): 274-9

The comparative value of pleural fluid adenosine deaminase and neopterin levels in diagnostic utility of pleural tuberculosis

Introduction: The aim of the present study was to evaluate and compare the diagnostic accuracy of pleura levels of adenosinedeaminase (ADA) and neopterin for the differential diagnosis of pleural tuberculosis (TP)

Comparing Finger-stick β-Hydroxybutyrate with Dipstick Urine Tests in the Detection of Ketone Bodies

SUMMARY: Objectives: Blood ketone (beta-hydroxybutyrate) measurements are suggested instead of urine ketone (acetoacetate) measurements in the diagnosis of diabetic ketoacidosis. Urine ketone examination is difficult and time consuming, and may result in an incorrect interpretation. Studies performed in emergency departments on blood ketones are limited. Our objective is to compare urine ketones and capillary blood ketones in patients whose serum glucose levels were ≥150 mg/dl. Methods: In our cross-sectional prospective study, finger-stick blood beta-hydroxybutyrate, arterial blood gas and urine ketone measurements of patients whose serum glucose levels were 150 mg/dL and higher were performed in the emergency department. Results: A total of 265 patients were included in the study. The mean age of the patients was 62.4±14.9 years, and 65.7% of them were female. The mean of the capillary blood ketone levels of the patients was determined to be 0.524±0.9 mmol/L (min: 0 mmol/L, max: 6.7 mmol/L). In 29 (13.1%) of the 221 patients whose urine ketone levels were negative, the finger-stick blood ketone levels were positive. Three of these patients were severely ketonemic, six were moderately ketonemic, and 20 were mildly ketonemic. Conclusions: In patients admitted to the emergency department with a blood glucose level of 150 mg/dL or higher, performing a capillary blood ketone measurement instead of a urine ketone measurement was a better predictor of ketonemia. ÖZET: Amaç: Diyabetik keto asidoz tanısında idrar ketonu (asetoasetat) yerine kan ketonu (beta-hidroksibütirat) ölçümü önerilmektedir. İdrar ketonu bakılması zahmetli, zaman alıcı ve yanlış yorumlara yol açabilen bir testtir. Acil servislerde kan ketonu ile ilgili yapılan çalışmalar sınırlıdır. Bu çalışmadaki amacımız serum glikoz düzeyi ≥150 mg/dl tespit edilen hastalarda idrar ketonu ile kapiller kanda keton varlığını karşılaştırmaktır. Gereç ve Yöntem: İleriye yönelik kesitsel çalışmada, acil serviste serum glikoz düzeyi 150 mg/dL ve üzerinde olan hastaların parmak ucu kan beta-hidroksibütirat, venöz kan gazı ve idrar ketonu ölçümü yapıldı. Bulgular: Bu çalışmaya toplam 265 hasta dâhil edildi. Hastaların yaş ortalaması 62.4±14.9 yıl, %65.7'si kadındı. İdrar ketonu negatif olan 221 hastanın 29'unda (%13.1) parmak ucundan kan ketonu pozitif olarak saptandı. Bu hastaların üçü ağır, altısı orta düzeyli, 20'si hafif düzeyli ketonemikti. Olguların kapiller kan keton düzeyleri ortalaması 0.524±0.9 mmol/L (min.: 0 mmol/L, maks.: 6.7 mmol/L) tespit edildi. Sonuç: Acil servise başvuran ve kan glikoz değeri 150 mg/dL üzerindeki hastalar içinde, idrar keton ölçümü yerine kapiller kan keton ölçümünün kullanılması hastaların yönetiminde önemli değişikliğe yol açabilir. Key words: Diabetic ketoacidosis, hydroxybutyrates, ketosis, Anahtar sözcükler: Diyabetik ketoasidoz, hidroksibütirat, ketozi

Targeting soluble guanylate cyclase with Riociguat has potency to alleviate testicular ischaemia reperfusion injury via regulating various cellular pathways

Testicular ischaemia reperfusion (I/R) injury results with serious dysfunctions in testis. This study aims to explore effects of soluble guanylate cyclase (sGC) stimulator Riociguat on experimental testicular I/R injury in rats. Twenty-one male rats were divided into three groups (Control, IR and IRR). The control group was not exposed to any application. Bilateral testis from IR and IRR animals were rotated 720 degrees in opposite directions for 3 h to induce experimental testicular ischaemia. Animals in IR and IRR groups were subjected to 3 h of reperfusion. Isotonic and Riociguat were administered to the animals 30 min prior reperfusion by oral gavage. At the end of experiment, animals were sacrificed and tissue samples were used for analyses. Riociguat treatment significantly decreased tissue malondialdehyde and Luminol levels compared to the IR group (p < 0.05). The pathological changes, pro-apoptotic proteins (Bax, Caspase 3, and Caspase 9) and apoptotic index in the IR group were down regulated in Riociguat treated animals (p < 0.05). Riociguat treatment was also significantly increased anti-apoptotic Bcl-2 expression, but alleviated tissue injury via modulating pro-inflammatory cytokine IL-1 beta levels and significantly (p < 0.05) down-regulating NF-kappa B activity. Moreover, mTOR and ERK phosphorylation increased in IR group (p < 0.05), but Riociguat treatment reduced protein phosphorylation. Our experiment indicated that targeting sGC might support surgical interventions in testicular I/R injury by modulating oxidative stress, inflammation, and apoptotic protein expression levels, but more detailed studies are required to explore the protective activity of Riociguat and underlying mechanisms in testicular I/R injury