Feasibility of salvage resection following locoregional failure after chemoradiotherapy and consolidation durvalumab for unresectable stage III non-small cell lung cancer.

INTRODUCTION: In patients with unresectable stage III non-small cell lung cancer, high-dose chemoradiotherapy (CRT) followed by consolidation durvalumab improves the 5-year overall survival compared to CRT alone. The feasibility and safety of salvage surgery for such patients who subsequently develop locoregional failure (LRF) is unclear. We evaluated our institutional experience with radical-intent salvage surgery in this patient population. MATERIALS AND METHODS: Details of patients undergoing salvage surgery for locoregional failure after CRT and durvalumab were identified from an institutional surgical database. Each patient's case underwent multidisciplinary discussion at initial disease presentation, and again at time of progression. RESULTS: Ten patients underwent salvage surgery for LRF after prior concurrent (n = 9) or sequential (n = 1) platinum-based high-dose chemo-radiotherapy followed by durvalumab. Consolidation durvalumab was completed in 4 patients, and discontinued in 6, due to either toxicity or disease progression. Median time between end of radiotherapy to detection of LRF was 19 months (range 6-75). Seven patients underwent a lobectomy, 1 a bilobectomy and 2 patients a pneumonectomy. Postoperative morbidity (Clavien-Dindo grade III-V) and 90-day mortality were 10% and 0%, respectively. Median follow-up after surgery was 7 months (range 1-25) during which 2 patients died (both 9 months post-operatively), one due to distant progression, and one of sepsis/bleeding. Eight patients are alive at 1-23 months post-surgery, with 6 showing no evidence of disease. CONCLUSIONS: Our results suggest that salvage pulmonary resection can be performed safely in selected patients with LRF following chemoradiotherapy and durvalumab. This radical-intent treatment option merits consideration by multidisciplinary lung tumor boards.

Long-Term Outcomes After Chemoradiotherapy and Surgery for Superior Sulcus Tumors.

Introduction: Superior sulcus tumors (SSTs) are uncommon, and their anatomical location can make treatment challenging. We analyzed late outcomes of patients with SST treated with concurrent chemoradiotherapy followed by surgical resection (trimodality) in a single tertiary institution. Methods: Patients with non-small cell SSTs, who underwent trimodality therapy between 2002 and 2017, were selected from a prospective institutional surgical database. Patients were uniformly staged with 18F-fluorodeoxyglucose-positron emission tomography, computed tomography scan of the chest and upper abdomen, and brain imaging. Patients undergoing resection of the lung plus chest wall were grouped as limited SST and those needing extensive resections (e.g., including the vertebral body) as extended SST. Kaplan-Meier survival analysis was performed to determine difference in survival. Multivariate Cox regression was used to identify prognostic factors. Results: A total of 123 patients were identified with a median follow-up of 4.9 years (interquartile range: 1.6-8.9 y). The 90-day postoperative mortality and morbidity (Clavien-Dindo grades III-V) were 6.5% and 21.1%, respectively. Patients with a radical resection (R0: 92.7%) had better survival (p = 0.002), as did those who had major pathologic response (73%) (p = 0.001). Ten-year overall survival (OS) and disease-free survival were 48.1% and 42.6%, respectively. There were no differences in 90-day mortality (p = 0.31) and OS (p = 0.79) between extended SST and limited SST patients. Conclusions: In patients with SST, trimodality resulted in a 10-year estimated OS and disease-free survival of 48.1% and 42.6%, respectively, which were improved after radical resection (R0) and major pathologic response. Survival for limited and extended resections was comparable, and distant relapse was the main pattern of failure. Better systemic treatments are therefore needed.

Anxiety level and clinical course of patients with sickle cell disease during the COVID-19 outbreak.

OBJECTIVES: Besides infectious pneumonia and death risks, the COVID-19 pandemic has prompted negative psychological impacts on communities, especially on people with chronic diseases. We aimed to evaluate COVID-19 and sickle cell disease (SCD)-related experiences, and the clinical course during the outbreak, to measure anxiety levels of adolescent and young adult patients with homozygous SCD, to analyze the correlations between their COVID-19 experiences and anxiety levels and painful episodes. METHODS: In this cross-sectional study, 47 patients aged between 14 and 24 years responded to a descriptive instrument and the State-Trait Anxiety Inventory. Clinical features requiring hospitalization for the same period (between March 10 and May 10) of two sequential years were compared. RESULTS: Sixty-six percent of the patients had at least one negative COVID-19 experience of dizziness, sleep disturbance, tonic immobility, appetite loss or nausea/abdominal distress. The number of negative COVID-19 experiences was correlated with the state anxiety score, the trait anxiety score, and the number of painful episodes (ρ=0.552, P<0.001; ρ=0.529, P<0.001; ρ=0.448, P=0.002, respectively). Both median state anxiety and trait anxiety scores were below the cut-off scores indicating significant clinical symptoms. The number of hospitalizations requiring vaso-occlusive crisis management and blood/exchange transfusion were similar for the same period of two sequential years, 2019 and 2020. CONCLUSION: These descriptive and correlation findings are the first reported on COVID-19-related anxiety in SCD patients. To develop screening and support strategies for mental health needs in pandemic times, further SCD studies should be conducted.

Temporal Trends in the Epidemiology of HIV in Turkey.

OBJECTIVE: The aim of this study was to analyze the temporal trends of HIV epidemiology in Turkey from 2011 to 2016. METHODS: Thirty-four teams from 28 centers at 17 different cities participated in this retrospective study. Participating centers were asked to complete a structured form containing questions about epidemiologic, demographic and clinical characteristics of patients presented with new HIV diagnosis between 2011 and 2016. Demographic data from all centers (complete or partial) were included in the analyses. For the cascade of care analysis, 15 centers that provided full data from 2011 to 2016 were included. Overall and annual distributions of the data were calculated as percentages and the Chi square test was used to determine temporal changes. RESULTS: A total of 2,953 patients between 2011 and 2016 were included. Overall male to female ratio was 5:1 with a significant increase in the number of male cases from 2011 to 2016 (p<0.001). The highest prevalence was among those aged 25-34 years followed by the 35-44 age bracket. The most common reason for HIV testing was illness (35%). While the frequency of sex among men who have sex with men increased from 16% to 30.6% (p<0.001) over the study period, heterosexual intercourse (53%) was found to be the most common transmission route. Overall, 29% of the cases presented with a CD4 count of >500 cells/mm3 while 46.7% presented with a CD4 T cell count of <350 cells/mm3. Among newly diagnosed cases, 79% were retained in care, and all such cases initiated ART with 73% achieving viral suppression after six months of antiretroviral therapy. CONCLUSION: The epidemiologic profile of HIV infected individuals is changing rapidly in Turkey with an increasing trend in the number of newly diagnosed people disclosing themselves as MSM. New diagnoses were mostly at a young age. The late diagnosis was found to be a challenging issue. Despite the unavailability of data for the first 90, Turkey is close to the last two steps of 90-90-90 targets.

Ultrastructural evaluation of urine alkalinization versus hydration on colistin-induced nephrotoxicity.

OBJECTIVES: Colistin is a vital antibiotic used in multidrug-resistant infections. Its most important side effect is nephrotoxicity. Colistin is a weak acid. This study aims to evaluate whether urine alkalinization is protective in the nephrotoxicity of colistin. METHODS: Twenty-eight male Sprague-Dawley rats were divided into groups. Group I (n = 4) was injected with intramuscular distilled water twice a day for 7 days. Group II (n = 8) was injected with 750,000 IU/kg/day colistin for 7 days. Group III (n = 8) was injected with the same dose of colistin after their urinary pH was ≥7 through the addition of bicarbonate in their drinking water. Group IV (n = 8) was injected with the same dose of colistin after their urine density fell below 1010 through the addition of NaCl molds in their food and 12.6 mg/L NaCl in their drinking water. RESULTS: According to tubular degenerations (scored 0-5), group I scored 0, group II scored 4.25, group III scored 2, and group IV scored 1.5. In groups III and IV, protection was achieved (p = 0.001). The bicarbonate group was not superior to the NaCl group (p = 0.789). In transmission electron microscopy, group III had more microvilli integrity and autophagic vacuoles compared to group IV. Group IV had mitochondrial swelling and cristae lysis. A lower urine density was related to lower tubular scores (p = 0.001). CONCLUSIONS: Colistin was highly nephrotoxic without protection. Light microscopy findings revealed that urinary alkalinization and NaCl hydration were similarly protective. Urine alkalinization further prevents ultrastructural changes as revealed by electron microscopy.

Evaluation of Mediterranean diet adherence in patients with a history of coronary revascularization. / Evaluación de la adherencia a la dieta mediterránea en pacientes con antecedentes de revascularización coronaria.

INTRODUCTION: Lifestyle modification is an important component of the secondary prevention strategies; and a healthy diet is one of the cornerstones in management of the coronary heart disease. We aimed to investigate the dietary habits of the patients with history of coronary revascularization, characteristics of the ones with good adherence by using alternate MedDiet questionnaire. METHODS: We included outpatients who had a history of coronary revascularization at least 6 months prior to enrollment. Each participant filled out a questionnaire to collect the data of demographics and clinical characteristics. Alternate MedDiet score was calculated to evaluate the Mediterranean style dietary adherence. Alternate MedDiet was originally based on 14-item questionnaire; we adjusted it to our population (max 13 points). RESULTS: We enrolled 226 consecutive outpatients (age 61.7±10.9 years, 72% males). The median duration after revascularization was 60 months. A total of 112 (49.6%) patients had previous percutaneous coronary intervention (PCI), 77 (34.1%) had coronary by-pass graft surgery (CABG), and 36 (15.9%) had both revascularization procedures. The median MedDiet score was 6. Patients were stratified into two subgroups (MedDiet score ≥7 vs. <7). A total of 61 (26.9%) patients had MedDiet score ≥7. By univariate analysis, good MedDiet scores were associated with older age, waist circumference, body mass index, high education level, regular follow-up, duration after first revascularization and revascularization with CABG+PCI. In the multivariate analysis, high education level (P=.002, OR=8.212, 95%CI: 2.155-31.291) and duration after revascularization (P=.034, OR=1.007, 95%CI: 1.001-1.013) were independent predictors of good MedDiet scores. CONCLUSION: The adherence rate to a healthy diet was low in patients with previous coronary revascularization. MedDiet score seems to be practical and useful item to evaluate the dietary habits in outpatient setting. Mediterranean diet adherence rates were associated with high education level, and duration after revascularization.

Tp-e interval and Tp-e/QT ratio in patients with celiac disease.

OBJECTIVES: Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. MATERIAL AND METHODS: This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. RESULTS: Tp-e interval (64.2±11.0 vs. 44.5±6.0; p<0.001), Tp-e/QT ratio (0.18±0.02 vs. 0.13±0.02; p<0.001) and Tp-e/QTc ratio (0.16±0.02 vs. 0.11±0.01; p<0.001) were significantly higher in patients with celiac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, p<0.001). CONCLUSIONS: Our study showed that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in patients with celiac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies.

The effects of certain enzymes on the rheology of dough and the quality characteristics of bread prepared from wheat meal.

This study was carried out to evaluate the effects of amyloglucosidase, glucose oxidase, hemicellulase (mainly consist of endo-1,4-ß-xylanase), cellulase, lipase, and the combination of phospholipase and hemicellulase (phospholipase + hemicellulase) on the extensographic properties of dough and the quality characteristics of bread prepared from wheat meal. The enzymes were added separately in two different amounts. The addition of glucose oxidase (at 0.0003-0.001%) caused a significant decrease in the resistance to extension, ratio of resistance to extensibility and energy values of the wheat meal dough compared with the control dough. The addition of hemicellulase (at 0.001-0.005%) and phospholipase + hemicellulase (at 0.0006-0.0009%) also improved the wheat meal dough rheology by reducing the resistance to extension and the ratio of resistance to extensibility. Glucose oxidase (at 0.0003-0.001%), hemicellulase (at 0.001-0.005%) and phospholipase + hemicellulase (at 0.0006-0.0009%) addition improved the specific volume of wheat meal bread compared with the control bread. Increasing the dosage of glucose oxidase from 0.0003 to 0.001% caused a further increase in the specific volume of wheat meal bread. The addition of hemicellulase (at 0.001-0.005%) caused a significant decrease in the baking loss and an increase in the moisture content of wheat meal bread compared with the control bread. The addition of amyloglucosidase (at 0.000875-0.001%), lipase (at 0.0002-0.001%) and cellulase (at 0.0003-0.0005%) did not considerably affected the dough rheological and the quality characteristics of wheat meal bread.

Infections related to Granulicatella adiacens: Report of two cases and review of literature.

Infections due to nutritionally variant streptococci are diagnosed rarely due to difficulties encountered during identification and isolation. Mortality rate in these infections is high therefore appropriate supplemented media and reliable detection systems should be implemented to isolate these fastidious organisms. Here, we describe two cases of Granulicatella adiacens infections. All microbiologic identifications were made with MALDI-TOF Vitek MS (BioMerieux, France), and the results confirmed by 16S ribotyping.

Molecular data reveal a cryptic species within the Culex pipiens mosquito complex.

The Culex pipiens mosquito complex is a group of evolutionarily closely related species including C. pipiens and Culex quinquefasciatus, both infected by the cytoplasmically inherited Wolbachia symbiont. A Wolbachia-uninfected population of C. pipiens was however described in South Africa and was recently proposed to represent a cryptic species. In this study, we reconsidered the existence of this species by undertaking an extensive screening for the presence of Wolbachia-uninfected C. pipiens specimens and by characterizing their genetic relatedness with known members of the complex. We first report on the presence of Wolbachia-uninfected specimens in several breeding sites. We next confirm that these uninfected specimens unambiguously belong to the C. pipiens complex. Remarkably, all uninfected specimens harbour mitochondrial haplotypes that are either novel or identical to those previously found in South Africa. In all cases, these mitochondrial haplotypes are closely related, but different, to those found in other C. pipiens complex members known to be infected by Wolbachia. Altogether, these results corroborate the presence of a widespread cryptic species within the C. pipiens species complex. The potential role of this cryptic C. pipiens species in the transmission of pathogens remains however to be determined. The designation 'Culex juppi nov. sp.' is proposed for this mosquito species.

Altered isotope charge distribution of acetylcholine neurotransmitter and Myasthenia Gravis.

Acetylcholine (ACh) is a central neurotransmitter that is used for signal transmission among neurons. For signal transmission in neurons, a neurotransmitter must bind to its receptor in order to produce an action potential. It is known that in Myasthenia Gravis (MG) cases, autoantibodies could block this binding. In the future, the treatment of MG could be achieved via modulation of molecular interaction between ACh and acetylcholine receptor (AChR). This study suggests that if an atom on a ligand (i.e. a neurotransmitter) is replaced with its isotope, it may cause charge redistribution such as that the binding between ligand and its receptor may be improved. Hence suggesting that with replacement of atoms with their isotopes in any biologically important ligand could alter its affinity towards its corresponding receptor, which would have a wide array of applications in medicine.

[Transition in diabetology]. / Transition en diabétologie.

For patients with type I diabetes, transition from pediatric to adult care is a challenge due to complex treatment requirements and the physical, psychological and social changes of adolescence. Members of the care team must recognize that while these emerging adults need to develop self-management skills, this may conflict at times with the developmentally appropriate desire for increasing autonomy. The role of nursing in coordinating a successful transition is critical for maintaining continuity of patient-centered care that responds to the specific needs of these young adults.

The effect of intravenous preemptive paracetamol on postoperative fentanyl consumption in patients undergoing open nephrectomy: a prospective randomized study.

AIM: We investigated the efficacy of intravenous (IV) preemptive paracetamol on postoperative total fentanyl consumption and fentanyl-related side effects in patients undergoing open nephrectomy. MATERIALS AND METHODS: A total of 60 patients scheduled for elective open nephrectomy under general anesthesia were included. All patients received Patient-controlled IV analgesia with fentanyl postoperatively. Patients were randomly allocated into three equal groups: The fentanyl group received 100 mL of IV normal saline as a placebo, with the first dose ending 30 min before intubation. In paracetamol group, IV 1 g paracetamol was given to the patients 30 min after extubation with repeated doses every 6 h totally 4 times a day. In preemptive paracetamol group, patients received IV 1 g paracetamol every 6 h, with the first dose ending 30 min before intubation. RESULTS: Postoperative cumulative fentanyl consumption for 24 h was significantly higher in the fentanyl group (1009 ± 139.361 µg) than those of paracetamol (752.25 ± 112.665 µg) and preemptive paracetamol groups (761.10 ± 226.625 µg) (P = 0.001 for both). In early postoperative period (0-4 h); whereas total fentanyl consumption showed no statistically significant difference among groups (P = 0.186), the nausea-vomiting scores were significantly higher in the fentanyl group compared with other groups (P = 0.012). CONCLUSION: In patients undergoing open nephrectomy, use of preemptive or postoperative paracetamol reduces fentanyl related nausea-vomiting without a decrease in total fentanyl consumption in the early postoperative period. Furthermore, use of preemptive or postoperative paracetamol reduces total fentanyl requirements in the first 24 h postoperatively providing a safe and effective postoperative analgesia.

Effectiveness of a multidimensional approach for prevention of ventilator-associated pneumonia in 11 adult intensive care units from 10 cities of Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).

PURPOSE: To evaluate the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional approach on the reduction of ventilator-associated pneumonia (VAP) in adult patients hospitalized in 11 intensive care units (ICUs), from 10 hospitals, members of the INICC, in 10 cities of Turkey. METHODS: A prospective active before-after surveillance study was conducted to determine the effect of the INICC multidimensional approach in the VAP rate. The study was divided into two phases. In phase 1, active prospective surveillance of VAP was conducted using the definitions of the Centers for Disease Control and Prevention National Health Safety Network, and the INICC methods. In phase 2, we implemented the multidimensional approach for VAP. The INICC multidimensional approach included the following measures: (1) bundle of infection control interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback of VAP rates, and (6) performance feedback of infection control practices. We compared the rates of VAP obtained in each phase. A time series analysis was performed to assess the impact of our approach. RESULTS: In phase 1, we recorded 2,376 mechanical ventilator (MV)-days, and in phase 2, after implementing the multidimensional approach, we recorded 28,181 MV-days. The rate of VAP was 31.14 per 1,000 MV-days during phase 1, and 16.82 per 1,000 MV-days during phase 2, amounting to a 46 % VAP rate reduction (RR, 0.54; 95 % CI, 0.42-0.7; P value, 0.0001.) CONCLUSIONS: The INICC multidimensional approach was associated with a significant reduction in the VAP rate in these adult ICUs of Turkey.

Central venous catheter-related biofilm infections: An up-to-date focus on meticillin-resistant Staphylococcus aureus.

Central venous catheters are indispensable for the long-term treatment of seriously and chronically ill patients, but their use is often associated with a variety of complications; indeed, 90% of primary bloodstream infections are related to patients having a catheter. In studies performed in France, Germany and Italy, meticillin-resistant Staphylococcus aureus (MRSA) accounted for >50% of all S. aureus isolates obtained in catheter-related bloodstream infections (CRBSIs). These infections have a serious impact on long-term disability of the patient, a substantial additional financial burden for health systems, and high costs for patients. Decreasing the rate of CRBSIs requires a multidisciplinary approach, including behavioural and educational interventions and the insertion of the correct type of catheter. Although vancomycin remains the cornerstone of empirical therapy for CRBSIs caused by MRSA, combination of different antimicrobials and new approaches are indispensable to enhance the eradication of S. aureus biofilms and to manage the patient appropriately.