Pseudomonas aeruginosa Bloodstream Infections Presenting with Septic Shock in Neutropenic Cancer Patients: Impact of Empirical Antibiotic Therapy.

This large, multicenter, retrospective cohort study including onco-hematological neutropenic patients with Pseudomonas aeruginosa bloodstream infection (PABSI) found that among 1213 episodes, 411 (33%) presented with septic shock. The presence of solid tumors (33.3% vs. 20.2%, p < 0.001), a high-risk Multinational Association for Supportive Care in Cancer (MASCC) index score (92.6% vs. 57.4%; p < 0.001), pneumonia (38% vs. 19.2% p < 0.001), and infection due to multidrug-resistant P. aeruginosa (MDRPA) (33.8% vs. 21.1%, p < 0.001) were statistically significantly higher in patients with septic shock compared to those without. Patients with septic shock were more likely to receive inadequate empirical antibiotic therapy (IEAT) (21.7% vs. 16.2%, p = 0.020) and to present poorer outcomes, including a need for ICU admission (74% vs. 10.5%; p < 0.001), mechanical ventilation (49.1% vs. 5.6%; p < 0.001), and higher 7-day and 30-day case fatality rates (58.2% vs. 12%, p < 0.001, and 74% vs. 23.1%, p < 0.001, respectively). Risk factors for 30-day case fatality rate in patients with septic shock were orotracheal intubation, IEAT, infection due to MDRPA, and persistent PABSI. Therapy with granulocyte colony-stimulating factor and BSI from the urinary tract were associated with improved survival. Carbapenems were the most frequent IEAT in patients with septic shock, and the use of empirical combination therapy showed a tendency towards improved survival. Our findings emphasize the need for tailored management strategies in this high-risk population.

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.

Effect of Combination Antibiotic Empirical Therapy on Mortality in Neutropenic Cancer Patients with Pseudomonas aeruginosa Pneumonia.

To assess the effect of combination antibiotic empirical therapy on 30-day case-fatality rate in neutropenic cancer patients with Pseudomonas aeruginosa (PA) bacteremic pneumonia. This was a multinational, retrospective cohort study of neutropenic onco-hematological patients with PA bloodstream infection (BSI) (2006−2018). The effect of appropriate empirical combination therapy, appropriate monotherapy and inappropriate empirical antibiotic therapy [IEAT] on 30-day case-fatality was assessed only in patients with PA bacteremic pneumonia. Among 1017 PA BSI episodes, pneumonia was the source of BSI in 294 (28.9%). Among those, 52 (17.7%) were caused by a multidrug-resistant (MDR) strain and 68 (23.1%) received IEAT, mainly when the infection was caused by an MDR strain [38/52 (73.1%) vs. 30/242 (12.4%); p < 0.001]. The 30-day case-fatality rate was higher in patients with PA bacteremic pneumonia than in those with PA BSI from other sources (55.1% vs. 31.4%; p < 0.001). IEAT was associated with increased 30-day case-fatality (aHR 1.44 [95%CI 1.01−2.03]; p = 0.042), whereas the use of appropriate combination empirical treatment was independently associated with improved survival (aHR 0.46 [95%CI 0.27−0.78]; p = 0.004). Appropriate empirical monotherapy was not associated with improved overall survival (aHR 1.25 [95%CI 0.76−2.05]; p = 0.39). Combination antibiotic empirical therapy should be administered promptly in febrile neutropenic patients with suspected pneumonia as the source of infection.

Real-life experience of ledipasvir and sofosbuvir single-tablet regimen among chronic hepatitis C patients in Turkey.

BACKGROUND/AIMS: Ledipasvir (LDV) and sofosbuvir (SOF) as single-tablet regimen (STR) has been approved for treatment of chronic HCV infection (CHC) for treatment-naïve or experienced cirrhotic or non-cirrhotic patients. Our aim was to analyse the effectiveness and safety of 12-24 weeks treatment of LDV/SOF (90mg/400 mg)±ribavirin in a real-life setting in Turkey. MATERIALS AND METHODS: Between May-Dec 2016, 104 treatment-naïve or experienced adult patients with CHC and with or without cirrhosis (including decompensated cirrhosis) were included in this observational study. Patients were administered LDV/SOF STR± ribavirin once daily for 12 -24 weeks. SVR12 rates and effects of the baseline characteristics on SVR12 rates were assessed. RESULTS: Out of 104 enrolled patients (61.5% female, mean age 62.0 years); 60.6% were cirrhotic, 76.0% previously used peg-IFN, 94.2% had GT1. At the end of the treatment, 77.8% (77/99, no data for 21 patients) had undetectable HCV-RNA and 98.9% (94/95) had SVR12. In the baseline characteristics subgroups, the SVR12 rates varied between 94.4% and 100%, and none of the baseline characteristics had a significant effect on the SVR12 rates. During the study, 6 (5.8%) patients died and none of the deaths was suspected to be related to the LDV/SOF. No treatment-emergent adverse event was reported. CONCLUSION: In conclusion, LDV/SOF±ribavirin yielded very high SVR12 rates, without any safety or tolerability concern in Turkey. The effectiveness of the LDV/SOF treatment was not affected by the patient demographics or medical characteristics such as fibrosis level, cirrhosis status, previous treatment status, HCV-RNA level or HCV genotype.

Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meninigitis: Results of Haydarpasa-III study.

AIMS: There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS: This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS: In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS: In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.

Assessment of the requisites of microbiology based infectious disease training under the pressure of consultation needs.

BACKGROUND: Training of infectious disease (ID) specialists is structured on classical clinical microbiology training in Turkey and ID specialists work as clinical microbiologists at the same time. Hence, this study aimed to determine the clinical skills and knowledge required by clinical microbiologists. METHODS: A cross-sectional study was carried out between June 1, 2010 and September 15, 2010 in 32 ID departments in Turkey. Only patients hospitalized and followed up in the ID departments between January-June 2010 who required consultation with other disciplines were included. RESULTS: A total of 605 patients undergoing 1343 consultations were included, with pulmonology, neurology, cardiology, gastroenterology, nephrology, dermatology, haematology, and endocrinology being the most frequent consultation specialties. The consultation patterns were quite similar and were not affected by either the nature of infections or the critical clinical status of ID patients. CONCLUSIONS: The results of our study show that certain internal medicine subdisciplines such as pulmonology, neurology and dermatology appear to be the principal clinical requisites in the training of ID specialists, rather than internal medicine as a whole.

Comparison of the i-gel and the LMA-Unique laryngeal mask airway in patients with mild to moderate obesity during elective short-term surgery.

The aim of our study was to compare leakage pressure, ease and time of insertion of the i-gel and the LMA-Unique laryngeal mask airway in patients with mild to moderate obesity during elective short-term surgery. In this prospective, randomised crossover trial, we included patients with a body mass index (BMI) >25 and <35 kg.m(-2) , and , age >18 years, undergoing elective surgery in the supine position with an expected duration of surgery <2 h. Leakage pressures, insertion difficulty, time and number of insertion attempts were evaluated. We included 50 patients consisting of 29 mildly (BMI>25 and < 30 kg.mg(-2) ) and 21 moderately (BMI>30 and < 35 kg.mg(-2) ) obese patients. Mean (SD) leakage pressures were 23.7 (9.2) cmH2O (i-gel) and 17.4 (7.0) cmH2O (LMA-Unique) (p<0.01). Subgroup analyses showed leakage pressures of 22.2 (9.4) cmH2O (i-gel) and 17.5 (7.5) cmH2O (LMA-Unique) (p=0.013) in the mild subgroup, and 25.7 (8.6) cmH2O (i-gel) and 17.0 (6.2) cmH2O (LMA-Unique) (p<0.01), in the moderate subgroup. Insertion of the i-gel was associated with significantly higher leakage pressures compared with the LMA-Unique in mildly and moderately obese patients.

FISH detection of chimerism in pediatric hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established curative therapy for various malignant and non-malignant diseases. Successful outcome after allogeneic HSCT has been associated with donor chimerism (DC). However, the detection of residual host cells or mixed hemopoietic chimerism (MC) has indicated that donor chimerism is not obligatory following HSCT. More recently, fluorescence in situ hybridization (FISH) analysis has been applied to engraftment studies for the identification of polymorphic or sex chromosomes. In this study, chimerism status was evaluated in 48 sex-mismatched HSCT pediatric patients (17 women/31 men, mean age: 9.02 +/- 3.95 years, range: 2-19) by FISH and the effect of DC or MC on outcome and long-term disease-free survival was documented. The stem cell source was bone marrow in all cases. All of the donors were human leucocyte antigen-identical siblings. FISH was performed on 156 specimens between days +13 and +1878. Donor chimerism was found in 47.9% (23/48) and MC was found in 52.1% (25/48) of the patients. Fifteen of 48 (31.25%) patients died, of whom 12 (80%) were MC and three patients (20%) were DC. The difference in chimerism status (MC or DC) was statistically significant between those patients who died and those still alive (chi(2) = 6.813; P = 0.009).

Estimating cortical activity from VEPS with the shrinking ellipsoid inverse.

An iterative inverse method using Tikhonov regularization (the shrinking ellipsoid method) previously tested in a model system is used to invert the sequence of bioelectric scalp fields evoked by the onset of a checkerboard pattern in either the right or left lower hemifield. The shrinking ellipsoid method is modified from its original description to accommodate simultaneously inverting a sequence of thirteen VEP scalp fields measured from 65 to 125 ms after stimulus onset. This allows the evoked cortical activity to be tracked in 5-ms intervals without distortion due to occasional VEP scalp fields in the sequence that have too low a signal-to-noise ratio to be reliably inverted in isolation. A new method is described to identify the surface of the cortex from MRI data. This is required to implement the shrinking ellipsoid inverse. Results from two subjects studied in detail are presented. The earliest cortical activity occurs either in area MT (the middle temporal area) or simultaneously in MT and striate cortex (V1). However when it does occur in both areas, the activity in V1 is relatively weak and quickly subsides. Seventy-five ms after stimulus onset activity is seen mainly near MT corresponding to a region identified from PET studies as one that subserves motion processing. Activity moves to V1 by 90-100 ms after stimulus onset. Near 120 ms after stimulus onset, cortical activity returns to the region near MT. Virtually all activity identified in this time epoch occurs in the cortical hemisphere contralateral to the location of the stimulus in the visual field.

Human brain responses to different image contrasts.

Human brain activity was evoked by a dynamic random-dot display in which a square-wave grating appeared and disappeared at regular intervals. Grating visibility was determined by one of four different contrasts: texture, stereo disparity, luminance, or color. Scalp fields measured with 31 electrodes were used to estimate epicortical potential fields. The estimation procedure required detailed anatomical data for each subject. These were obtained from magnetic resonance images. A three-dimensional digitizer and a stereotactic headgear were used to accurately merge the frame of reference of the magnetic resonance image with that of the evoked potential. Epicortical potential fields provided a better indicator of where brain activity is evoked than did scalp fields. These procedures also corrected for anatomical variations between scalp and brain from subject to subject. In two right-handed female subjects, evoked activity was observed in the left posterior parietal and the right occipital, parieto-occipital and posterior temporal cortices. Evoked activity was observed in the left parietal cortex for luminance processing, in the right parietal cortex for texture processing and in the right temporal cortex for color processing, which was selective for the particular contrast.

Functional brain imaging: dipole localization and Laplacian methods.

The performance of two methods, used to localize brain activity from evoked potential fields measured on the scalp, was assessed in a tank model of the human head. This physical model contained a human skull encased in a polymer simulating the resistivity and geometry of brain and scalp. The dipole localization method mislocalized the positions of known dipole sources by several centimeters. The mislocalization was systematic. The dipoles were localized too deeply in the head. The Laplacian method yielded a field resembling the brain surface field (epicortical potential field) provided that the iso-potential contours of the scalp field closed within the measurement range. Clipping resulted in a serious mislocalization of the position of the peak of the epicortical potential field.

Estimating regional brain activity from evoked potential fields on the scalp.

Potential fields on the surface of the brain were estimated from discretely sampled scalp fields in human subjects. Relatively simple methods of linear algebra were combined with detailed anatomical information from magnetic resonance imaging. The method was verified using a tank model of the human head that encased a fully hydrated human skull in a polymer matrix of controlled resistivity matching that of human brain and scalp. Brain surface fields evoked by checkerboard contrast reversal, spread less than their scalp field counterparts, and provided information helpful in localizing brain activity.

Inferring regional brain activity from evoked potential fields on the scalp.

A new method is described to calculate epicortical potential fields from scalp fields based on linear algebra. It requires detailed anatomical information, for each subject, obtained from MR images. The calculation is validated in a physical model of the human head and applied to human subjects. The results suggest that the method yields reliable epicortical fields that help to localize evoked cortical activity in humans.