The Effect of Phacoemulsification on the Intraocular Pressure of Patients with Open-angle Glaucoma: A Systematic Review and Meta-Analysis.

PRECIS: There is evidence that cataract surgery can reduce intraocular pressure in patients with primary open angle-, normal tension-, or exfoliative glaucoma. The complete effect of phacoemulsification is masked by topical intraocular pressure-lowering medications. PURPOSE: To assess the impact of phacoemulsification and intraocular lens implantation on intraocular pressure (IOP) level in individuals with primary open-angle glaucoma (POAG), exfoliative glaucoma (XFG), exfoliation syndrome (XFS), normal tension glaucoma (NTG), ocular hypertension (OH) or healthy controls 12 months after the surgery. METHODS: In July 2023, a comprehensive literature review was conducted across six databases. The analysis focused on the phacoemulsification arms of randomized controlled trials (RCTs). The primary outcome of interest was the mean IOP change observed 12 months after phacoemulsification. RESULTS: This meta-analysis included nine arms from nine RCTs, comprising a total of 502 participants. Overall, the average IOP was reduced by 3.77 mmHg (95%CI: -5.55 to -1.99, I2=67.9%) 12 months after surgery. The subgroup analysis, focused on whether a washout period was employed before measuring IOP, revealed that studies with a washout period exhibited a more pronounced IOP reduction of 5.25 mmHg (95%CI: -7.35 to -3.15, I2=0%), while studies without a washout period exhibited a reduction of 3.13 mmHg (95%CI: -5.46 to -0.81, I2=75.8%). The sensitivity analysis for the latter group, excluding an outlier study, showed a reduction of 1.81 mmHg (95%CI: -2.95 to -0.67, I2=0%). CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that cataract surgery meaningfully lowers IOP in POAG, XFG/XFS, or OH 12 months after surgery. However, the use of topical medications masks the precise impact of phacoemulsification upon postoperative IOP. Further research using appropriate washout periods is warranted.

The Fagerström Test for Nicotine Dependence, as a prognostic factor, in current smokers with and without COPD: A cross-sectional study in northern Greece.

BACKGROUND: Smoking poses the most common risk factor for chronic obstructive pulmonary disease (COPD) and aggravates disease progression. Tobacco dependence inhibits smoking cessation and may affect smoking patterns that increase tobacco exposure and predispose to lung function decline. AIMS AND OBJECTIVES: We aimed to assess tobacco dependence in current smokers with and without COPD and evaluate its role in disease development. METHOD: This cross-sectional study was conducted in Greek rural areas. Current smokers completed the Fagerström Test for Nicotine Dependence and were classified into COPD and non-COPD groups based on spirometry parameters. RESULTS: Among current smokers, 288 participants comprised the non-COPD and 71 the COPD group. Both presented moderate tobacco dependence, but smokers with COPD started to smoke earlier in the morning. Multiple logistic regression analysis revealed higher COPD prevalence in smokers with higher scores in the Fagerström test (odds ratio OR = 1.12, 95% confidence interval [1.01 - 1.24]) and older age (OR = 1.06 [1.03 - 1.09]), independently of pack-years smoking index. Multiple linear regression analysis in smokers with COPD showed that the forced expiratory volume in the 1st second decreased by 2.3% of the predicted value for each point increase in the Fagerström Test and 0.59% for each year of age, independently of participants' sex and pack-years smoking index. CONCLUSION: The Fagerström score appears to indicate a higher probability for COPD and lung function deterioration when assessed along with age in current smokers. Smoking cessation support programs are fundamental to COPD prevention and management.

Reporting of adverse events of treatment interventions in multiple myeloma: an overview of systematic reviews.

The present study is an overview of systematic reviews focusing on adverse events of antimyeloma treatments. It provides a systematic description of adverse events as they are reported in the systematic reviews as well as a critical appraisal of included reviews. We conducted a comprehensive literature search in the most widely used electronic databases looking for systematic reviews that had an adverse event of an antimyeloma treatment intervention as primary outcome. Two independent reviewers conducted selection of included studies and data extraction on predesigned online forms and assessed study quality using AMSTAR 2. Overall corrected covered area (CCA) was calculated to examine the overlap of primary studies across systematic reviews. After screening eligible studies, 23 systematic reviews were included in this overview. Seven reviews with overall CCA of 14.7% examined cardiovascular adverse events of different drugs, including immunomodulatory drugs and proteasome inhibitors (mainly carfilzomib). Nine focused on infections, presenting with overall CCA of 5.8%, each one focused on a different drug or drug class. Three studied thromboembolism in patients treated either with lenalidomide, any immunomodulatory drug, or with daratumumab and had an overall CCA equal to 1.5%. Four more reviews focused on bortezomib-associated neurotoxicity, carfilzomib-associated renal toxicity, or second primary malignancies as an adverse event of lenalidomide or anti-CD38 monoclonal antibody treatment. The quality of included studies as judged by AMSTAR 2 was mostly critically low. Absence of a priori registered protocol and formal assessment of risk of bias of included primary studies were the most common shortcomings. Reporting of antimyeloma drug-associated toxicity is supported by multiple systematic reviews; nevertheless, methodological quality of existing reviews is mostly low.

The severity of menopausal symptoms is associated with diabetes, and cardiometabolic risk factors in middle-aged women.

BACKGROUND: Ovarian senescence is associated with increased cardiovascular risk. We aimed to evaluate the association between menopausal symptoms and cardiometabolic risk factors in a cohort of apparently healthy middle-aged women. METHODS: The cohort included 2793 peri- and postmenopausal women not on menopausal hormone therapy. Demographic/anthropometric and biochemical/hormonal data were assessed. The severity of menopausal symptoms was evaluated by the Greene Climacteric Scale (GCS). RESULTS: GCS-Total Score was associated with BMI (b=0.12, 95% CI: 0.04 to 0.20), T2DM (b=2.10, 95% CI: 0.06 to 4.15), and late-postmenopause (b=-1.24, 95% CI: -2.17 to -0.33). GCS-psychological score was associated with BMI (b=0.06, 95% CI: 0.00 to 0.11). GCS-Physical Score was associated with BMI (b=0.06, 95% CI: 0.03 to 0.09), central obesity (b=0.18, 95% CI: 0.02 to 0.34), and postmenopause (early-/late-postmenopause vs. perimenopause, b=-0.36, 95% CI: -0.59 to -0.13 and b=-0.65, 95% CI: -0.97 to -0.34, respectively). All GCS-scores were negatively associated with age. GCS-Sexual Score was associated with early-postmenopause (incidence rate ratio (IRR)=1.53, 95% CI: 1.21 to 1.94), central obesity (IRR=1.18, 95% CI: 1.00 to 1.39), smoking, diastolic blood pressure, age. Cox-regression analysis showed that incident T2DM was positively associated with increasing age, BMI, daily alcohol consumption, moderate-to-severe vasomotor symptoms (VMS, OR=1.045, 95% CI: 1.011 to 1.079), and negatively with moderate-to-strenuous physical activity. These associations persisted in lean but not in obese women. CONCLUSIONS: The severity of menopausal symptoms is associated with T2DM, obesity, and smoking in a cohort of peri-/postmenopausal women. VMS were associated with incident T2DM, especially in lean women. These associations must be considered in implementing primary and secondary prevention strategies.

Assessment of histologic risk factors for hepatocellular carcinoma in patients with chronic hepatitis B of advanced stage.

Histologic markers of increased risk for hepatocellular carcinoma can provide useful information for the management of patients with chronic hepatitis B. The expression of epithelial cell adhesion molecule (EpCAM, a marker of hepatic progenitor cells), p21 (a marker of hepatocyte senescence), glutamine synthetase (a marker of perivenular hepatocytes) and CD34 (a marker of sinusoidal capillarization) were assessed by immunohistochemistry in 52 liver biopsy specimens from patients with advanced stage chronic hepatitis B. Nineteen patients developed hepatocellular carcinoma during a follow-up period of 133 months. The findings were compared with those of 18 liver biopsy specimens from patients with early-stage chronic hepatitis B and 6 liver biopsy specimens without significant pathologic findings. EpCAM expression in hepatocytes was significantly increased in specimens with advanced stage, as compared with all other specimens. EpCAM positivity in over 30 % of hepatocytes was only seen in 3 specimens from patients who subsequently developed hepatocellular carcinoma. The expression of p21, glutamine synthetase and CD34 was not associated with hepatocellular carcinoma development. Nevertheless, glutamine synthetase immunostains highlighted zonality abnormalities that were useful in chronic hepatitis B staging. In conclusion, extensive immunopositivity of hepatocytes for EpCAM in chronic hepatitis B may represent a marker of increased hepatocellular carcinoma risk. Glutamine synthetase immunostaining represents a useful adjunct in determining the stage of chronic hepatitis B in diagnostic practice.

The Impact of the COVID-19 Pandemic on Breast and Cervical Cancer Screening: A Systematic Review.

BACKGROUND/AIM: COVID-19 has dramatically impacted non-pandemic-related care, including preventive medicine. Our objective was to quantify the alterations in the volume of screening tests for breast and cervical cancer during the COVID-19 era compared to pre-pandemic levels. Secondarily, we discussed the causes responsible for this change, presented suggestions for screening optimization and conducted a targeted search of the relevant literature for worsening of future mortality due to screening setback. MATERIALS AND METHODS: We systematically searched Pubmed, Google Scholar and Epistemonikos for articles in English or Greek, published from March 11th, 2020, until September 14th, 2022, that illustrated quantitative variations of mammograms or Pap/HPV tests. Preprint articles, editorials and speeches were excluded. Quality of included studies was assessed via the JBI critical appraisal checklist for studies reporting prevalence data. The evidence was narratively synthesized. RESULTS: A total of 56 articles were included, being either observational studies or reports from cancer registries. Large reductions were universally identified, peaked during the first wave but partially persisted after easing of the restrictions. CONCLUSION: Our systematic review provides an updated record of the variations in screening volume and approaches screening neglect from a multidimensional perspective answering why it happened and how we could achieve recovery. A strong awareness campaign is proposed, in conjunction with triaging citizens more likely to benefit from screening. Cervical self-sampling is emphasized in the literature. Various studies displayed a potential increase in cancer mortality in the future based on predictive statistical models.

Is thrombocytopenia and postnatal weight gain associated with treatment-requiring retinopathy of prematurity? A matched case-control study.

PURPOSE: The purpose of the study was to investigate the association of platelet parameters and postnatal weight gain with treatment-requiring ROP (TR-ROP). METHODS: In this retrospective matched case-control study, infants with TR-ROP were individually matched, according to gestational age and birth weight, with one or two untreated infants who developed no or spontaneously regressed ROP. Longitudinal data on platelet count (PLT), mean platelet volume (MPV), daily weight and platelet transfusions were collected. Platelet mass index (PMI) and weight standard deviation score (WSDS) were also calculated. Conditional logistic regression analysis was performed to adjust for matching. RESULTS: Fourteen cases, presenting type I ROP, and 25 matched controls were included. The odds of developing TR-ROP decreased as PLT increased during 31st week of postmenstrual age (PMA) or during 1st and 2nd week of postnatal age (PNA). The odds of developing TR-ROP were 16.7 times higher in infants receiving at least one platelet transfusion compared with those who were not transfused. The odds of developing TR-ROP increased by 31.2% as the mean volume of platelet transfusion per infant increased by 1 ml. The odds of developing TR-ROP decreased as PMI increased during 1st week PNA, and as weight and WSDS increased during 4th -6th week PNA. Analysis of MPV, number of thrombopenic episodes per infant, number of platelet transfusions per infant and days with WSDS < -2 showed no association with TR-ROP. CONCLUSION: To our knowledge, this is the first study ascertaining an association of platelet transfusions with type I ROP. Prospective cohort studies are required to confirm our findings.

Comparison of adverse events between intravitreal anti-VEGF and laser photocoagulation for treatment-requiring retinopathy of prematurity: a systematic review.

PURPOSE: To synthesize existing evidence on adverse events, complications, and unfavorable outcomes of current treatment modalities for treatment-requiring retinopathy of prematurity (TR-ROP). METHODS: PubMed, Cochrane Central Register of Controlled Trials, Scopus, EMBASE, Trip Database, and the gray literature available were searched. Randomized Clinical Trials and observational studies comparing the adverse events of intravitreal anti-VEGF injections (bevacizumab, ranibizumab, aflibercept, pegaptanib, conbercept) and laser photocoagulation (LPC) as treatment modalities for infants with TR-ROP were included. The main outcomes compared between the two treatment modalities were: 1. Refractive Errors and Biometry Parameters, 2. Adverse events, complications, and unfavorable outcomes, 3. Disease Recurrence/Disease Regression/Need for retreatment, 4. Neurodevelopmental Outcomes. RESULTS: Higher quality studies concluded that LPC leads to greater rates of myopia than intravitreal anti-VEGF treatment while the rate of adverse events and of unfavorable neurodevelopmental outcomes is similar. However, there was controversy among the included studies concerning the rate of ROP recurrence between intravitreal anti-VEGF injections and LPC. CONCLUSION: There is need for future primary studies assessing the adverse events of intravitreal anti-VEGF injections compared with LPC as treatment modalities for infants with TR-ROP.

Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews.

In this overview we present a summary of evidence from systematic reviews (SRs) on the safety and efficacy of carfilzomib in multiple myeloma (MM). Our search in electronic databases and conference proceedings yielded 14 eligible SRs, graded as of low overall quality with the AMSTAR-2 tool. The Corrected Covered Area index was 52.3% which shows very high overlap among studies. Carfilzomib was shown to increase progression free survival (HR=0.61, 95%CI=0.47-0.78, p = 0.01, I2 =73%), overall survival (HR=0.79,95%CI=0.66-0.95, p = 0.01, I2 =0) and overall response rate (OR=2.4,95% CI=1.6-3.4, p < 0.001, I2 =99%) in relapsed/refractory MM (RRMM); all with moderate quality of evidence assessed with the GRADE approach. Carfilzomib was associated with cardiovascular adverse events (AEs) (RR=2.2, 95%CI=1.6-2.9, p < 0.001, I2 =0), nephrotoxicity (RR=1.79, 95% CI=1.43-2.23, p < 0.001, I2 =39%) and serious infections (RR=1.40, 95%CI=1.17-1.69, p < 0.001, I2 =57%). Concluding, carfilzomib is effective in RRMM, but associated with certain AEs. More randomized clinical trials and high-quality SRs, especially on newly diagnosed patients are needed.

Diet and Risk of Gastric Cancer: An Umbrella Review.

Several dietary exposures have been associated with gastric cancer (GC), but the associations are often heterogenous and may be afflicted by inherent biases. In the context of an Umbrella Review (UR), we provide an overview and a critical evaluation of the strength and quality, and evidence classification of the associations of diet-related exposures in relation to the risk of GC. We searched PubMed and Scopus for eligible meta-analyses of observational studies published in English from inception to 12 December 2021, and for any identified association, we applied robust epidemiological validity evaluation criteria and individual study quality assessment using AMSTAR. We screened 3846 titles/abstracts and assessed 501 full articles for eligibility, of which 49 were included in the analysis, investigating 147 unique exposures in relation to GC, cardia (GCC) or non-cardia (GNCC) cancer. Supported by suggestive evidence, positive associations were found comparing the highest vs. lowest categories for: heavy (>42 g/day) alcohol consumption (Relative Risk (RR) = 1.42, 95% Confidence Interval (CI): 1.20−1.67), salted fish consumption (RR = 1.56, 95% CI:1.30−1.87) and waist circumference (RR = 1.48, 95% CI:1.24−1.78) and an inverse association for the healthy lifestyle index (RR = 0.60, 95% CI:0.48−0.74) in relation to GC. Additionally, a positive association was found comparing obese individuals (Body Mass Index (BMI) ≥ 30) to normal-weight individuals (BMI: 18.5−25) (RR = 1.82, 95% CI:1.32−2.49) in relation to GCC. Most of the meta-analyses were of medium-to-high quality (median items: 7.0, interquartile range: 6−9). Maintaining a normal body weight and adopting healthy dietary choices, in particular, limiting the consumption of salt-preserved foods and alcohol, can reduce the risk of gastric cancer.

Delayed intracranial hemorrhage of patients with mild traumatic brain injury under antithrombotics on routine repeat CT scan: a systematic review and meta-analysis.

BACKGROUND: Patients on antithrombotics experiencing mild traumatic brain injury (mTBI) may benefit from a routine repeat CT scan to detect delayed intracranial hemorrhage (dICH). OBJECTIVES: The primary outcome was the incidence of dICH on routine repeat CT scans of mTBI patients on antithrombotics within an intra-hospital observation period of up to 48 hours. The secondary outcomes were potential risk factors, readmissions, neurosurgical interventions, and mortality. METHODS: A systematic review and a meta-analysis of single proportions were performed according to the PRISMA and PRESS guidelines. The risk of bias was assessed using Newcastle-Ottawa Scale. RESULTS: Eighteen studies with 4613 patients were included. The pooled incidence of dICH was 2% [95% CI 1-2%] with similar rates between different antithrombotic regimens, even in combination. Of the 67 patients with dICH reported (1.45%), eleven required surgery (0.24%), while six died (0.13%). Loss of consciousness was a risk factor of dICH (risk ratio 3.04 [95%CI 0.96; 9.58]). A total of 48 patients were reported for readmission without associated death or surgical intervention. CONCLUSION: The contribution of this routine repeat CT scan should be questioned due to the low incidence, the limited clinical significance, and the unsubstantiated clinical benefit of early or systematic detection of dICH.

Comparative efficacy and safety of oral P2Y12 inhibitors for patients with chronic kidney disease and acute coronary syndrome: a network meta-analysis.

BACKGROUND: Currently, there is a paucity of data concerning the safety and effectiveness of P2Y12 inhibitors in the acute coronary syndrome (ACS) with chronic kidney disease (CKD) population. The aim of this study is to compare the different oral P2Y12 inhibitors in terms of efficacy and safety, focusing exclusively on patients with CKD who were treated for ACS. METHODS: We systematically searched PubMed, CENTRAL, and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with ACS with CKD. Efficacy outcomes included the major adverse cardiovascular events composite outcome and safety outcomes included major bleedings and major or minor bleedings combined. We performed a frequentist network meta-analysis. RESULTS: Twelve studies were included in the systematic review, 7 CKD subgroup analyses of RCTs (8878 patients) and 5 observational studies (20175 patients). After the exclusion of studies with conservative management, prasugrel resulted in significant primary endpoint reduction versus clopidogrel (HR 0.80 and 95% CI 0.64 - 0.99), while ticagrelor did not (HR 0.88 and 95% CI 0.73 - 1.06). Major bleedings did not differ between the interventions. Ticagrelor resulted in more major or minor bleedings than clopidogrel (HR 1.21 and 95% CI 1.06 - 1.38), whereas prasugrel did not (HR 1.12 and 95% CI 0.84 - 1.49). CONCLUSION: In patients with ACS with underlying CKD, who are intended to receive invasive management, there may be a significant reduction of the primary efficacy outcome with prasugrel as compared to clopidogrel but not with ticagrelor as compared to clopidogrel. There probably exists no difference among interventions in the major bleedings. Dedicated RCTs are needed to confirm these results.

Global mapping of overviews of systematic reviews in healthcare published between 2000 and 2020: a bibliometric analysis.

OBJECTIVE: To conduct a bibliometric analysis using a large sample of overviews of systematic reviews (OoSRs) and reveal research trends and areas of interest about these studies. STUDY DESIGN AND SETTING: We searched MEDLINE, Scopus and Cochrane Database of Systematic Reviews from 1/1/2000 to 15/10/2020. We used Scopus meta-data and two authors recorded supplementary information independently. We summarized the data using frequencies with percentages. RESULTS: A total of 1558 studies were considered eligible for analysis. We found that the publications have been increasing yearly and their nomenclature was not uniform (the most frequent label in the title was "overview of systematic reviews"). The largest number of papers and the most cited ones were published by corresponding authors from the UK. The publications were distributed across 737 scholarly journals and many of them were published in the field of complementary/alternative medicine, psychiatry/psychology, nutrition/dietetics, and pediatrics. The co-authorship analysis revealed collaborations among countries. The most common clinical conditions were depression, diabetes, cancer, dementia, pain, cardiovascular disease, stroke, obesity, and schizophrenia. CONCLUSION: OoSRs have recently become a popular approach of evidence synthesis. International collaborations between overview authors from countries with increased research productivity and countries with less research activity should be encouraged.

The effect of N-acetylcysteine on bipolar depression: a systematic review and meta-analysis of randomized controlled trials.

RATIONALE: The current pharmacotherapy of bipolar depression often presents limited efficacy and increased risk for adverse events. N-acetylcysteine (NAC) has been suggested as potentially effective and well-tolerated adjunctive treatment for bipolar disorder (BD). OBJECTIVES: This systematic review and meta-analysis aimed to examine the efficacy of N-acetylcysteine, as an adjunctive therapy, for treating bipolar depression. METHODS: PubMed, Cochrane Library, Scopus databases, and grey literature were searched for studies retrieval. Randomized controlled trials including patients with a diagnosed bipolar disorder and a current depressive episode were included in the analysis. The measured variables included symptoms, functioning, and quality of life scales. The mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) was set as the primary outcome. RESULTS: A total of five studies were included in the analysis. A significant improvement was not observed from the addition of NAC to standard therapy in symptomatology [MADRS (MD = -3.32; 95% CI = -12.79 to 6.16), Young Mania Rating Scale (MD = -0.7; 95% CI = -2.15 to 0.75), Bipolar Depression Rating Scale (MD = -3.19; 95% CI = -15.48 to 9.1), and Clinical Global Impression for severity (MD = -0.13; 95% CI = -0.33 to 0.08)], functioning, [Global Assessment of Functioning Scale (MD = 3.21; 95% CI = -12.55 to 18.97), Social and Occupational Functioning Assessment Scale (MD = 0.47; 95% CI = -4.60 to 5.53), or quality of life [Quality of Life Enjoyment and Satisfaction Questionnaire (MD = 2.27; 95% CI = -9.13 to 13.67)]. CONCLUSIONS: There is no evidence indicating that NAC has beneficial effects as an adjunctive treatment for bipolar depression. Future trials with improved methodological design and efficient sample sizes are required to draw safer conclusions.

Limb-salvage surgery offers better five-year survival rate than amputation in patients with limb osteosarcoma treated with neoadjuvant chemotherapy. A systematic review and meta-analysis.

BACKGROUND: Osteosarcoma is the most common primary bone sarcoma. Currently, the main treatment option for high-grade osteosarcomas is neoadjuvant chemotherapy, followed by surgical resection of the lesion and adjuvant chemotherapy. Limb salvage surgery (LSS) and amputation are the main surgical techniques; however, controversy still exists concerning the best surgical method. Our meta-analysis compared the effectiveness of LSS and amputation combined with neoadjuvant chemotherapy in patients with limb osteosarcoma, in terms of 5-year overall survival (OS), 5-year disease-free survival (DFS) and local recurrence rate. METHODS: Following the established methodology of PRISMA guidelines, a literature search was conducted in PubMed, Cochrane, Google Scholar from 1975 until January 2020. Two independent reviewers evaluated the study quality based on the Newcastle-Ottawa scale. Odds ratio and 95% confidence interval of the OS, DFS and local recurrence rate were calculated. RESULTS: Thirteen studies were finally included with a total of 2884 patients; 1986 patients undergone LSS and 898 amputations. Five-year overall survival was almost 2-fold in patients treated with LSS than those treated with amputation (OR: 1.99; 95% CI: 1.35-2.93; I2 = 74%, p < 0.001). No difference was found in 5-year DFS between LSS patients and amputees (OR: 1.24; 95% CI: 0.55-2.79; I2 = 67%, p = 0.01). The odds of local recurrence was numerically higher in LSS compared to amputation but not statistically significant (OR: 2.29; 95% CI: 0.95-5.53; I2 = 47%, p = 0.05). However, the included studies did not clearly define differences in the stages of patients of the two groups. CONCLUSION: Our study demonstrated that in patients with limb osteosarcoma treated with neoadjuvant chemotherapy, LSS is associated with a higher 5-year overall survival and the odds of local recurrence may be increased but these results should be interpreted with caution due to high heterogeneity.

Evaluation of a 10color protocol as part of a 2tube screening panel for flow cytometric assessment of peripheral blood leukocytic subsets.

Peripheral blood (PB) immunophenotyping is commonly required for initial evaluation of various suspected disease entities. Several approaches have been proposed. The objective of this work is to explore the value of a 10color protocol developed in our laboratory for flow cytometric assessment of PB leukocytic subsets, as part of a 2tube screening panel. A combination of CD16/CD56/CD34/CD33/CD19/CD4/CD8/CD3/CD20/CD45 antibodies in 1 tube was applied routinely during flow cytometric analysis of PB samples for diagnostic purposes. The protocol was systematically complemented by a 2nd tube with anti-kappa, anti-lambda, CD5, CD19, and CD45 antibodies for adults and selected pediatric patients, and specifically oriented panels when necessary. 25 samples with no detectable neoplastic PB involvement and 31 samples with a hematolymphoid disorder were investigated retrospectively. The contribution of CD33 in the separation of leukocytic populations, as well as the benefits from the simultaneous assessment of CD20/CD19/CD45, CD16/CD56 and the detection of CD34+ cells were examined. The gating strategy with the use of CD33 provided additional information in certain cases. The protocol enabled recognition of differential expression of CD20 and CD45 in CD19+ cells with chronic lymphocytic leukemia phenotype, overall evaluation of NK and NK like T cells, estimation of CD16- granulocytes and CD56/CD16 expression in monocytes, as well as identification of minor cell subsets, such as CD34+ cells. The proposed 10color combination of antibodies analyzed in a standardized manner can offer significant information in the initial evaluation of PB samples, thus, guiding subsequent investigation if needed.

Neurologic complications after allogeneic transplantation: a meta-analysis.

OBJECTIVE: Neurologic adverse events remain challenging complications with poor morbidity and mortality post adult allogeneic hematopoietic cell transplantation (allo-HCT) for hematologic diseases. We conducted a systematic review and meta-analysis to determine their spectrum, incidence, and impact on survival. METHODS: We searched MEDLINE, COCHRANE, EMBASE through March 2019 for all types of primary studies. Two independent reviewers screened, extracted data, and assessed risk of bias (RoB). RESULTS: We identified 552 eligible studies describing 57.972 patients; one randomized controlled trial, two case-control, 17 prospective, 86 retrospective cohort studies, 21 case series, and 425 case reports. RoB ranged from fair to high although case series were low-risk. The majority of studies traced infectious or drug-related neurologic manifestations. Infectious complications were present in 2.7% (95% CI 1.9-3.6) and 3.3% (95% CI 0.8-7.1) of patients in retrospective and prospective cohort studies, respectively. In retrospective studies, 3.4% (95% CI 2.1-4.9) of patients suffered from drug-related neurologic events. In prospective cohorts the equivalent incidence was 13% (95% CI 4.2-24.8). Neurologic complications had a detrimental impact on survival. INTERPRETATION: Our study highlights the wide spectrum and significant impact of neurologic complications on survival post allo-HCT. This systematic review summarizes existing data and provides the necessary background information for every physician involved in the management of these patients.

Infections Due to Multidrug-Resistant Bacteria in Oncological Patients: Insights from a Five-Year Epidemiological and Clinical Analysis.

Bacterial infections are frequent complications in cancer patients. Among them, those caused by multidrug-resistant (MDR) bacteria increase morbidity and mortality mainly because of limited therapeutic options. Current knowledge regarding MDR infections in patients with solid tumors is limited. We assessed the epidemiology and risk factors of increased mortality in these patients. In this retrospective five-year single cohort observational study, we included all oncological patients with MDR infections. Cancer-related parameters, comorbidities, prior use of antibiotics, previous surgical interventions and hospitalization, as well as the use of invasive procedures were investigated as potential risk factors causing adverse outcomes. Seventy-three patients with MDR infection were included: 37% with carbapenem-resistant Klebsiella pneumoniae, 24% with oxacillin-resistant Staphylococcus aureus (MRSA) and 21% with carbapenem-resistant Acinetobacter baumanni. Previous colonization with MDR bacteria was detected in 14% patients, while 20% of the patients presented MDR colonization or infection at ward admission. Mortality during the infection episode was 32%. Duration of hospitalization and CRP were statistically significant risk factors of mortality, whereas administration of guided antibiotics was a protective factor. Knowledge of local epidemiology of MDR bacteria can help physicians promptly identify cancer patients at risk of MDR infections and initiate timely effective empirical antibiotic treatment that can eventually improve the overall therapeutic management.

Performance of Baveno VI and Expanded Baveno VI Criteria for Excluding High-Risk Varices in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: We aimed to assess the accuracy of Baveno VI criteria for identification of high-risk varices (HRVs) and varices of any size in patients with compensated advanced chronic liver disease (cACLD). METHODS: We performed a systematic search of publications through December 2018 for studies that assessed the accuracy of Baveno VI criteria for screening for varices in patients with cACLD. We used hierarchical models to synthesize evidence. We also conducted a post hoc analysis to assess the accuracy of Εxpanded Baveno VI criteria. We appraised the confidence in estimates using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We identified 30 studies (8469 participants). Pooled values of Baveno VI criteria for HRVs (26 studies) were a sensitivity of 0.97 (95% CI, 0.95-0.98) and a specificity of 0.32 (95% CI, 0.26-0.39). Pooled sensitivity of Εxpanded Baveno VI criteria for HRVs (12 studies) was 0.90 (95% CI, 0.85-0.93) and specificity was 0.51 (95% CI, 0.45-0.57). In 1000 patients with cACLD, with a prevalence of HRVs of 20%, Baveno VI criteria would prevent endoscopy in 262 patients, but 6 patients with HRVs would be missed. Instead, use of the Εxpanded Baveno VI criteria would result in 428 patients avoiding endoscopy, but 20 patients with HRVs would be missed. The credibility of our findings is moderate or low, mainly owing to the retrospective design of most studies. CONCLUSIONS: Baveno VI criteria have high diagnostic accuracy as a triage test for screening for HRVs in patients with cACLD. Expanded Baveno VI criteria could reduce the proportion of unnecessary endoscopies further, nevertheless with a higher rate of missed HRVs.