Sperm cryopreservation during the SARS-CoV-2 pandemic.

PURPOSE: Sperm cryopreservation is fundamental in the management of patients undergoing gonadotoxic treatments. Concerns have risen in relation to SARS-CoV-2 and its potential for testicular involvement, since SARS-CoV-2-positive cryopreserved samples may have unknown effects on fertilization and embryo safety. This study therefore aimed to analyze the safety of sperm cryopreservation for cancer patients after the onset of the pandemic in Italy, through assessment of the risk of SARS-CoV-2 exposure and viral RNA testing of semen samples. METHODS: We recruited 10 cancer patients (mean age 30.5 ± 9.6 years) referred to our Sperm Bank during the Italian lockdown (from March 11th to May 4th 2020) who had not undergone a nasopharyngeal swab for SARS-CoV-2 testing. Patients were administered a questionnaire on their exposure to COVID-19, and semen samples were taken. Before cryopreservation, SARS-CoV-2 RNA was extracted from a 150 µl aliquot of seminal fluid in toto using QIAamp viral RNA kit (Qiagen) and amplified by a real time RT PCR system (RealStar SARS-CoV2 RT PCR, Altona Diagnostics) targeting the E and S genes. RESULTS: The questionnaire and medical interview revealed that all patients were asymptomatic and had had no previous contact with COVID-19 infected patients. All semen samples were negative for SARS-CoV-2 RNA. CONCLUSION: This preliminary assessment suggests that a thorough evaluation (especially in the setting of a multidisciplinary team) and molecular confirmation of the absence of SARS-CoV-2 in seminal fluid from asymptomatic cancer patients may assist in ensuring the safety of sperm cryopreservation.

HIV MDR is still a relevant issue despite its dramatic drop over the years.

OBJECTIVES: To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy. METHODS: Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999-2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm). RESULTS: Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010-18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance. CONCLUSIONS: A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.

Fatal respiratory infection due to ST308 VIM-1-producing Pseudomonas aeruginosa in a lung transplant recipient: case report and review of the literature.

BACKGROUND: Data regarding the prevalence of metallo-ß-lactamases (MBLs) among Pseudomonas aeruginosa isolates in cystic fibrosis patients are scarce. Furthermore, there is limited knowledge on the effect of MBL production on patient outcomes. Here we describe a fatal respiratory infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient and the results of the subsequent epidemiological investigation. CASE PRESENTATION: P. aeruginosa isolates collected in the index patient and among patients temporally or spatially linked with the index patient were analyzed in terms of antibiotic susceptibility profile and MBL production. Whole-genome sequencing and phylogenetic reconstruction were also performed for all P. aeruginosa isolates producing VIM-type MBLs. A VIM-producing P. aeruginosa strain was identified in a lung biopsy of a lung transplant recipient with cystic fibrosis. The strain was VIM-1-producer and belonged to the ST308. Despite aggressive treatment, the transplant patient succumbed to the pulmonary infection due to the ST308 strain. A VIM-producing P. aeruginosa strain was also collected from the respiratory samples of a different cystic fibrosis patient attending the same cystic fibrosis center. This isolate harbored the blaVIM-2 gene and belonged to the clone ST175. This patient did not experience an adverse outcome. CONCLUSIONS: This is the first description of a fatal infection due to P. aeruginosa producing VIM-type MBLs in a lung transplant recipient. The circulation of P. aeruginosa isolates harboring MBLs pose a substantial risk to the cystic fibrosis population due to the limited therapeutic options available and their spreading potential.

Comparison of coronal leakage of different root canal filling techniques: an ex vivo study.

The aim of this study was to compare the quality of the coronal seal, using an in vitro bacterial invasion test, of three different root canal filling systems. Twenty-seven freshly extracted mandibular premolars were selected and divided into three experimental groups (G1, G2 and G3 n=7) and two control groups (Ct+ and Ct- n=3). All teeth in the experimental groups were prepared using NiTi Mtwo rotating instruments and then the endodontic treatments were completed using the three-tested warm guttapercha root filling techniques: Microseal (G1), Thermafil (G2) and System B (G3). All root filling techniques were performed using the same endodontic sealer (Pulp Canal Sealer). Three teeth were instrumented and not filled, serving as positive controls (Ct+) and the last three teeth, with intact crowns and no endodontic treatment, served as negative controls (Ct-). All samples were mounted in a two-chamber apparatus and exposed to Enterococcus faecalis performing a bacterial infiltration test. All samples were observed for a maximum period of 60 days checking for turbidity of the BHI broth on a daily basis recording when contamination occurred. A quantitative evaluation of the bacterial CFU/ml was performed using the URO-QUICK™ system. On day 32 an overall value was recorded of contamination of 42.85% for group G1, 71.42% for G2 and 42.85% for G3; after 60 days, the final contamination result was 85.71% for group G1, and 100% for both G2 and G3 groups. Considering the number of contaminated samples at the end of the observation period, the three techniques showed no statistically significant differences. The study highlighted the bacterial permeability of gutta-percha/seal barrier, underlining the importance of an effective coronal restoration to ensure a durable seal after root canal treatment.

Successful Treatment of Kaposi Sarcoma-Associated Herpesvirus Inflammatory Cytokine Syndrome After Kidney-Liver Transplant: Correlations With the Human Herpesvirus 8 miRNome and Specific T Cell Response.

After transplant, patient infection with human herpesvirus 8 (HHV-8) and Kaposi sarcoma-associated herpesvirus (KSHV) is known to cause aggressive tumors and severe nonneoplastic complications. These latter syndromes are driven by HHV-8/KSHV lytic reactivations and related hyperinflammatory host responses typically characterized by high viral loads, elevated levels of cytokines and other inflammation biomarkers, cytopenia, organ failure, high fever, and worsening conditions (with no evidence of B cell neoplasias). These disorders are associated with a high mortality rate, often due to lack of prompt diagnosis, effective therapeutic approaches, and adequate follow-up. These features resemble most of those defining the so-called KSHV-associated inflammatory cytokine syndrome (KICS), which was recently recognized in patients positive for human immunodeficiency virus (HIV). In this report, we describe-for the first time-a case of a KICS-like nonneoplastic recurrent complication occurring after transplant in an HIV-negative patient that was successfully treated by a combination of anti-CD20 monoclonal therapy, antivirals, and modification of the immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3-year follow-up, we report novel experimental data on HHV-8-specific T cell dynamics and circulating microRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, C-reactive protein, and cytokine levels), providing useful information about abnormal cellular and cytokine dynamics underlying HHV-8-associated inflammatory disorders in posttransplant patients.

Pre-existent NRTI and NNRTI resistance impacts on maintenance of virological suppression in HIV-1-infected patients who switch to a tenofovir/emtricitabine/rilpivirine single-tablet regimen.

Objectives: To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes). Methods: pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated. Results: Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P < 0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P < 0.001); and (iii) patients with pre-therapy viraemia >500 000 copies/mL compared with those with lower viraemia levels (>500 000: 16.0%; 100 000-500 000: 9.3%; <100 000 copies/mL: 4.8%, P = 0.009). pRes and pre-therapy viraemia >500 000 copies/mL were independent predictors of VR by multivariable Cox regression. Conclusions: TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia >500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification.

Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000-14.

Background: Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. Methods: In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Results: Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P < 0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P = 0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P = 0.047]. Conclusions: The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread.

Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens.

OBJECTIVES: We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor. METHODS: Data from 206 drug-naïve and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined. RESULTS: DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug-naïve and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naïve patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1-10.3) months; 100 000-500 000 copies/mL: median (IQR) 4.9 (3.8-6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5-4.8) months; P < 0.001] and in PI-experienced patients [≥100 000 copies/mL: median (IQR) 7.2 (5.7-11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4-3.3) months; P < 0.001]. In PI-experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for ≥100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug-naïve: 95%; PI-experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800. CONCLUSIONS: In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier.

Serum thymosin α 1 levels in patients with chronic inflammatory autoimmune diseases.

Thymosin alpha 1 (Tα1) is a powerful modulator of immunity and inflammation. Despite years of studies, there are a few reports evaluating serum Tα1 in health and disease. We studied a cohort of healthy individuals in comparison with patients affected by chronic inflammatory autoimmune diseases. Sera from 120 blood donors (healthy controls, HC), 120 patients with psoriatic arthritis (PsA), 40 with rheumatoid arthritis (RA) and 40 with systemic lupus erythematosus (SLE), attending the Transfusion Medicine or the Rheumatology Clinic at the Policlinico Tor Vergata, Rome, Italy, were tested for Tα1 content by means of a commercial enzyme-linked immunosorbent assay (ELISA) kit. Data were analysed in relation to demographic and clinical characteristics of patients and controls. A gender difference was found in the HC group, where females had lower serum Tα1 levels than males (P < 0·0001). Patients had lower serum Tα1 levels than HC (P < 0·0001), the lowest were observed in PsA group (P < 0·0001 versus all the other groups). Among all patients, those who at the time of blood collection were taking disease-modifying anti-rheumatic drugs (DMARD) plus steroids had significantly higher Tα1 levels than those taking DMARD alone (P = 0·044) or no treatment (P < 0·0001), but not of those taking steroids alone (P = 0·280). However, whichever type of treatment was taken by the patients, serum Tα1 was still significantly lower than in HC and there was no treatment-related difference in PsA group. Further prospective studies are necessary to confirm and deepen these observations. They might improve our understanding on the regulatory role of Tα1 in health and disease and increase our knowledge of the pathogenesis of chronic inflammatory autoimmune diseases.

HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia.

OBJECTIVES: Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase genotyping success rate at low-level viraemia (LLV, 51-1000 copies/mL) and resistance in raltegravir-failing patients. METHODS: An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006-13. Genotyping success rate was determined according to the following viraemia levels: 51-500, 501-1000, 1001-10 000, 10 001-100 000 and >100 000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients. RESULTS: Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51-500 and 501-1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51-500 copies/mL = 18.2%; 501-1000 = 37.5%; 1001-10 000 = 53.7%; 10 001-100 000 = 30.0%; and >100 000 = 30.8%). At viraemia ≤500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL. CONCLUSIONS: Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.

Well-plate mechanical confinement platform for studies of mechanical mutagenesis.

Limited space for cell division, perhaps similar to the compressed microenvironment of a growing tumor, has been shown to induce phenotypic and karyotypic changes to a cell during mitosis. To expand understanding of this missegregation of chromosomes in aberrant multi-daughter or asymmetric cell divisions, we present a simple technique for subjecting mammalian cells to adjustable levels of confinement which allows subsequent interrogation of intracellular molecular components using high resolution confocal imaging. PDMS micropatterned confinement structures of subcellular height with neighboring taller media reservoir channels were secured on top of confluent cells with a custom compression well-plate system. The system improved ease of use over previous devices since confined cells could be initially grown on glass coverslips in a 12-well plate, and subsequently be imaged by high resolution confocal imaging, or during compression by live cell imaging. Live cell imaging showed a significant increase in abnormal divisions of confined cells across three different cell lines (HeLa, A375, and A549). Immunofluoresecence stains revealed a significant increase in cell diameter and chromosome area of confined cells, but no significant increase in centrosome-centromere distance upon division when compared to unconfined cells. The developed system could open up studies more broadly on confinement effects on mitotic processes, and increase the throughput of such studies.

Alcohol consumption and awareness of the risks related in alcohol-abuse in high school students: evidence from a Health Education program.

BACKGROUND: The unceasing and widespread increase of alcohol consumption represents an important problem for the European Union. For this reason, we wanted to investigate the patterns of alcohol consumption among high-school students of Rieti, a city in central Italy, and of surrounding rural areas. Furthermore, the study intends to investigate students' awareness on alcohol-related health risks and on the consequences of driving in a state of intoxication. METHODS: In the investigation 7 schools including senior high schools and technical schools were involved, for a total of 669 students aged between 15 and 19 years. As part of a program of health education, a self-administered anonymous questionnaire was proposed to each student. A descriptive and multivariate analysis was carried out. RESULTS: The prevalence of usual drinkers was equal to 12.7 per cent. The logistic regression analysis showed a statistically significant association between usual consumption of alcohol and the attendance of Technical Institutes (OR=3.43; 95% IC: 2.07 - 5.69), and the residence in rural areas (OR=2.19; 95% IC: 1.38 - 3.47). The area of residence in the multivariate analysis loses significance. Only 54.6 % of the students answered the questions regarding the state of driving under the effect of alcohol; of these, 11.0 % declared of having driven at least once under the effect of alcohol, whereas 18.0 % declared that they had been passengers of a driver who was drunk. The answer to the question whether the consumption of alcohol is harmful to health was "no" for 15.7 % of usual drinkers against 2.2 % of the non drinkers or occasional (episodic) drinkers. CONCLUSIONS: Our study shows that the drinking habits of high school students of Rieti are worse for those attending technical schools. Usual drinkers show lower consciousness of alcohol-related harm. Our study may provide clues useful for the identification of the target population at high risk for alcohol abuse in order to create targeted prevention programs.

Coexistence of flavum ligament ossification with diffuse idiopathic skeletal hyperostosis in the cervical spine: Review of literature and technical note starting from a rare case.

BACKGROUND: Cervical flavum ligament ossification (C-OLF) is very rare source of myeloradiculopathy. Less than 100 cases have been reported in modern English literature up to 2020. Association between C-OLF and Diffuse Idiopathic Skeletal Hyperostosis (DISH) at cervical level has never been described. METHODS: In this article we performed a systematic review about epidemiology, physiopathology, clinical and surgical management of C-OLF. Moreover, we research its possible association with other cervical spine ligament ossification and in particular with anterior longitudinal ligament ossification. We report a case of 73 years-old woman experiencing mild cervical myeloradiculopathy caused by C6-C7 C-OLF compression and coexistence of DISH at cervico-thoracic level. A brief technical note about intraoperative management of C-OLF has also been described. RESULT: Our research found 81 previous reported case of C-OLF. The coexistence of Posterior longitudinal ligament ossification has been reported in 21.3% of C-OLF case. Conversely, we reported the first case describing the association between DISH and C-OLF. Posterior surgical decompression is the only useful treatment providing good long-term functional outcome. Instrumentation should be tailored according to pre-operative findings. CONCLUSIONS: C-OLF is a rare source of myeloradiculopathy and it may coexists with DISH probably due to alteration in the cervical mechanical stress and tendency of bone formation in patients harboring coexistent ligament ossifications. According to our result, skip en-bloc microsurgical laminectomy is safe and less invasive method to avoid complication and to provide optimal cervical spinal cord and nerve decompression avoiding CSF-leak.

Natural history of SARS-CoV-2 infection in healthcare workers in Northern Italy.

At present, the time-frame used for the quarantine of individuals with coronavirus disease 2019 (COVID-19) is the entire duration of symptoms plus 14 days after symptom recovery; however, no data have been reported specifically for healthcare workers (HCWs). In the study population of 142 HCWs with COVID-19, the mean time for viral clearance was 31.8 days. Asymptomatic subjects cleared the virus more quickly than symptomatic subjects (22 vs 34.2 days; P<0.0001). The presence of fever at the time of diagnosis was associated with a longer time to viral clearance (relative risk 11.45, 95% confidence interval 8.66-14.25; P<0.0001). These findings may have a significant impact on healthcare strategies for the future management of the COVID-19 pandemic.

Flow-Diversion Treatment for Unruptured Nonsaccular Intracranial Aneurysms of the Posterior and Distal Anterior Circulation: A Meta-Analysis.

BACKGROUND: Treatment management and outcomes of unruptured nonsaccular aneurysms are different compared with their saccular counterparts. PURPOSE: Our aim was to analyze the outcomes after flow diversion among nonsaccular unruptured lesions. DATA SOURCES: A systematic search of 3 data bases (2005-2019) was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. STUDY SELECTION: We included studies reporting flow diversion for nonsaccular unruptured aneurysms of the posterior and distal anterior circulations. Anterior circulation lesions were included if located distal to the petrocavernous and supraclinoid ICA (MCA, A1, anterior communicating artery, A2). Giant dolichoectatic holobasilar lesions were excluded because of their poor treatment outcomes. DATA ANALYSIS: Aneurysm occlusion and complication rates were calculated (random effects meta-analysis). DATA SYNTHESIS: We included 15 studies (213 aneurysms). The long-term adequate occlusion rate was 85.3% (137/168; 95% CI, 78.2%-92.4%; I2 = 42.3%). Treatment-related complications were 17.4% (41/213; 95% CI, 12.45%-22.4%; I2 = 0%). Overall, 15% (37/213; 95% CI, 10%-20%; I2 = 0%) were ischemic events. Procedure-related morbidity was 8% (20/213; 95% CI, 5%-12%; I2 = 0%). Fusiform or dissecting types had comparable adequate occlusion (116/146 = 83%; 95% CI, 74%-92%; I2 = 48% versus 33/36 = 89%; 95% CI, 80%-98%; I2 = 0%; P = .31) and complication rates (35/162 = 17%; 95% CI, 10%-25%; I2 = 24% versus 11/51 = 19%; 95% CI, 10%-31%; I2 = 0%; P = .72). Aneurysm size (>10 versus ≤10 mm) was independently associated with a higher rate of complications (OR = 6.6; 95% CI, 1.3-15; P = .02). The rate of ischemic events after discontinuation of the antiplatelet therapy was 5% (5/93; 95% CI, 2%-9%; I2 = 0%). LIMITATIONS: Small and retrospective studies were available for this meta-analysis. CONCLUSIONS: Unruptured nonsaccular aneurysms located in the posterior and distal anterior circulations can be effectively treated with flow diversion. Nevertheless, treatment-related complications are not negligible, with about 15% ischemic events and 8% morbidity. Larger size (>10 mm) significantly increases the risk of procedure-related adverse events.

Sequentially addressable dielectrophoretic array for high-throughput sorting of large-volume biological compartments.

Droplet microfluidics has become a powerful tool in precision medicine, green biotechnology, and cell therapy for single-cell analysis and selection by virtue of its ability to effectively confine cells. However, there remains a fundamental trade-off between droplet volume and sorting throughput, limiting the advantages of droplet microfluidics to small droplets (<10 pl) that are incompatible with long-term maintenance and growth of most cells. We present a sequentially addressable dielectrophoretic array (SADA) sorter to overcome this problem. The SADA sorter uses an on-chip array of electrodes activated and deactivated in a sequence synchronized to the speed and position of a passing target droplet to deliver an accumulated dielectrophoretic force and gently pull it in the direction of sorting in a high-speed flow. We use it to demonstrate large-droplet sorting with ~20-fold higher throughputs than conventional techniques and apply it to long-term single-cell analysis of Saccharomyces cerevisiae based on their growth rate.

Flow-Diversion Treatment of Unruptured Saccular Anterior Communicating Artery Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Flow diversion for anterior communicating artery aneurysms required further investigation. PURPOSE: Our aim was to analyze outcomes after treatment of anterior communicating artery aneurysms with flow-diverter stents. DATA SOURCES: A systematic search of 3 data bases was performed for studies published from 2008 to 2018. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies reporting anterior communicating artery aneurysms treated with flow diversion. DATA ANALYSIS: Random-effects meta-analysis was used to pool the following: aneurysm occlusion rate, complications, and factors influencing the studied outcomes. DATA SYNTHESIS: We included 14 studies and 148 unruptured saccular anterior communicating artery aneurysms treated with flow diversion. The long-term complete/near-complete (O'Kelly-Marotta C-D) occlusion rate was 87.4% (91/105; 95% CI, 81.3%-93.6%; I2 = 0%) (mean radiologic follow-up of 11 months). The treatment-related complication rate was 8.6% (14/126; 95% CI, 4%-13.1%; I2 = 0%), with morbidity and mortality rates of 3.5% (5/126; 95% CI, 2%-7%; I2 = 0%) and 2.5% (2/148; 95% CI, 0.3%-5%; I2 = 0%), respectively. Most complications were periprocedural (12/126 = 7%; 95% CI, 3%-11%; I2 = 0%). Thromboembolic events were slightly higher compared with hemorrhagic complications (10/126 = 6%; 95% CI, 2%-10%; I2 = 0% and 4/126 = 3%; 95% CI, 1%-6%; I2 = 0%). Branching arteries (A2 or the recurrent artery of Heubner) covered by the stent were occluded in 16% (7/34; 95% CI, 3.5%-28%; I2 = 25%) of cases. Pre- and posttreatment low-dose and high-dose of antiplatelet therapy was not associated with significantly different complication and occlusion rates. LIMITATIONS: We reviewed small and retrospective series. CONCLUSIONS: Flow diversion for unruptured saccular anterior communicating artery aneurysms appears to be an effective alternative treatment for lesions difficult to treat with coiling or microsurgical clipping. The treatment-related complication rate was relatively low. However, larger studies are needed to confirm these results.

Y-Stent-Assisted Coiling of Wide-Neck Bifurcation Intracranial Aneurysms: A Meta-Analysis.

BACKGROUND: Y-stent-assisted coiling for wide-neck intracranial aneurysms required further investigation. PURPOSE: Our aim was to analyze outcomes after Y-stent placement in wide-neck aneurysms. DATA SOURCES: We performed a systematic search of 3 data bases for studies published from 2000 to 2018. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included studies reporting Y-stent-assisted coiling of wide-neck aneurysms. DATA ANALYSIS: Random-effects meta-analysis was used to pool the following: aneurysm occlusion rate, complications, and factors influencing the studied outcomes. DATA SYNTHESIS: We included 27 studies and 750 aneurysms treated with Y-stent placement. The immediate complete/near-complete occlusion rate was 82.2% (352/468; 95% CI, 71.4%-93%; I2 = 92%), whereas the long-term complete/near-complete occlusion rate was 95.4% (564/598; 95% CI, 93.7%-97%; I2 = 0%) (mean radiologic follow-up of 14 months). The aneurysm recanalization rate was 3% (20/496; 95% CI, 1.5%-4.5%; I2 = 0%), and half of the recanalized aneurysms required retreatment. The treatment-related complication rate was 8.9% (63/614; 95% CI, 5.8%-12.1%; I2 = 44%). Morbidity and mortality after treatment were 2.4% (18/540; 95% CI, 1.2%-3.7%; I2 = 0%) and 1.1% (5/668; 95% CI, 0.3%-1.9%; I2 = 0%), respectively. Crossing Y-stent placement was associated with a slightly lower complication rate compared with the kissing configuration (56/572 = 8.4%; 95% CI, 5%-11%; I2 = 46% versus 4/30 = 12.7%; 95% CI, 3%-24%; I2 = 0%). Occlusion rates were quite comparable among Enterprise, Neuroform, and LVIS stents, whereas the Enterprise stent was associated with lower rates of complications (8/89 = 6.5%; 95% CI, 1.6%-11%; I2 = 0%) compared with the others (20/131 = 14%; 95% CI, 5%-26%; I2 = 69% and 9/64 = 11%; 95% CI, 3%-20%; I2 = 18%). LIMITATIONS: This was a small, retrospective series. CONCLUSIONS: Y-stent-assisted coiling yields high rates of long-term angiographic occlusion, with a relatively low rate of treatment-related complications. Y-stent placement with a crossing configuration appears to be associated with better outcomes. Although Y-configuration can be obtained using many types of stents with comparable occlusion rates, the Enterprise stent is associated with lower complication rates.