Plane-wave dynamics of optical parametric oscillation with simultaneous sum-frequency generation

The plane wave dynamics of a single-crystal upconversion optical parametric oscillators (OPO) with simultaneous sum-frequency generation (SFG) was studied. It was presumed that simultaneous phase-matching of the SFG and OPO processes were achieved by utilizing birefringent phase matching (BPM). Potential polarization geometries for collinear BPM led to four different sets of coupled mode equations depending on which field components were common to the two processes. The sets were designated as classes A through D. Classes A and D were efficient frequency upconverters. The performance of class A OPO's was limited by crystal properties whereas classes C and D was optimized by adjusting the polarization rotation angle

Therapeutic plasma exchange in a patient with acute motor axonal neuropathy subtype of Guillain-Barre syndrome and systemic lupus erythematosus

A young female in her early 20s with a history of systemic lupus erythematosus presented to the emergency department due to 4 days of progressive bilateral extremity weakness and numbness. The patient reported flu-like symptoms that had spontaneously recovered 2 weeks prior to her presentation. She was 10 weeks pregnant at presentation. Lumbar puncture study and electrical muscle stimulation (EMS) were consistent with acute motor axonal neuropathy subtype of Guillain-Barre syndrome (GBS). Patient also had increased proteinuria and renal biopsy performed that was consistent with lupus nephritis. Despite treatment with pulse dose corticosteroids and IVIG, the patient had minimal neurological improvement and with continued decline required intubation. Her pregnancy was terminated at this point and a course of therapeutic plasma exchange (TPE) was started. Patient was also treated with cyclophosphamide. The patient responded to the combination of therapy and had slow but gradual neurologic recovery as well as improvement of proteinuria. Here we describe a case of an acute motor axonal neuropathy (AMAN) subtype of GBS in a young woman with active SLE and current pregnancy at the time of the presentation. Concurrent GBS and active SLE in the setting of pregnancy may be more treatment resistant, and combination therapy including TPE, immunosuppression, and termination of pregnancy may be indicated

Antifungal Activity of Caspofungin in Combination with Amphotericin B against Candida glabrata: Comparison of Disk Diffusion, Etest, and Time-Kill Methods▿

The in vitro activities of caspofungin plus amphotericin B against 50 Candida glabrata isolates were evaluated by the time-kill, disk diffusion, and Etest methods. In vitro experiments showed a positive interaction. Even though each of these methods uses different conditions and endpoints, the results of the different methods frequently agreed

Matrix-induced autologous mesenchymal stem cell implantation versus matrix-induced autologous chondrocyte implantation in the treatment of chondral defects of the knee: a 2-year randomized study

Cell-based strategies that combine in vitro- expanded autologous chondrocytes with matrix scaffolds are currently preferred for full-thickness cartilage lesions of the knee a parts per thousand yen2 cm(2). Although this approach is reasonable, continuing advances in the field of cartilage repair will further expand the options available to improve outcomes

Predicting Disease Severity and Outcome in COVID-19 Patients: A Review of Multiple Biomarkers

An abundance of clinical reports focused on specific laboratory parameters have been reported on coronavirus disease 19 (COVID-19), but a systematic analysis synthesizing these findings has not been performed. To review and summarize the current available literature on the predictive role of various biomarkers in COVID-19 patients. A literature search was performed using databases including PubMed, medRxiv, and bioRxiv. A total of 72 papers were reviewed, including 54 peer-reviewed papers and 18 non-peer-reviewed preprints. Although the markers are considered nonspecific, acute-phase reactants, including C-reactive protein (CRP), ferritin, serum amyloid A (SAA), and procalcitonin, were reported as sensitive markers of acute COVID-19 disease. Significantly elevated white blood cell count; marked lymphopenia; decreased CD3, CD4, or CD8 T-lymphocyte counts; high neutrophil count; thrombocytopenia; and markedly elevated inflammatory biomarkers were associated with severe disease and the risk of developing sepsis with rapid progression. Trends observed by serial laboratory measurements during hospitalization, including progressive decrease of lymphocyte count, thrombocytopenia, elevated CRP, procalcitonin, increased liver enzymes, decreased renal function, and coagulation derangements, were more common in critically ill patient groups and associated with a high incidence of clinical complications. Elevated interleukin 6 level and markedly increased SAA were most often reported in severely and critically ill patients. Indicators of systemic inflammation, such as neutrophil to lymphocyte ratio, systemic immune-inflammation index, or COVID-19 Severity Score, may be used to predict disease severity, outcome, and mortality. Interpretation of the data reported in the studies reviewed here is limited because of the study design (mostly retrospective), limited sample size, and a lack of defined clinical criteria

Review of Current Advances in Serologic Testing for COVID-19

To examine and summarize the current literature on serologic methods for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A literature review was performed using searches in databases including PubMed, medRxiv, and bioRxiv. Thirty-two peer-reviewed papers and 23 preprints were examined. The studies included lateral flow immunoassay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and neutralizing antibody assays. The use of all major SARS-CoV-2 antigens was demonstrated to have diagnostic value. Assays measuring total antibody reactivity had the highest sensitivity. In addition, all the methods provided opportunities to characterize the humoral immune response by isotype. The combined use of IgM and IgG detection resulted in a higher sensitivity than that observed when detecting either isotype alone. Although IgA was rarely studied, it was also demonstrated to be a sensitive marker of infection, and levels correlated with disease severity and neutralizing activity. The use of serologic testing, in conjunction with reverse transcription polymerase chain reaction testing, was demonstrated to significantly increase the sensitivity of detection of patients infected with SARS-CoV-2. There was conflicting evidence regarding whether antibody titers correlated with clinical severity. However, preliminary investigations indicated some immunoassays may be a surrogate for the prediction of neutralizing antibody titers and the selection of recovered patients for convalescent serum donation

Clinical behavior and treatment outcomes in angiosarcoma: A 10-year retrospective review

e23555 Background: Angiosarcoma (AS) is a highly aggressive sarcoma. Five-year overall survival (OS) with local disease is only about 60% despite multimodality treatment. In advanced disease, responses to cytotoxic chemotherapy are common; however, median OS is only 3-12 mos. Targeted therapies (TT) have not been consistently effective. Early results for immune checkpoint inhibitors (ICI) are promising but their efficacy has not been compared to chemotherapy. Here we present the outcome of AS patients by systemic regimen and multimodality approach. Methods: We identified 39 patients with pathologically confirmed AS treated at Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital from 2009 to 2019. Clinical characteristics, treatment, responses and survival were analized. We calculated OS using Kaplan-Meier method and statistical significance with Log-Rank Test and Cox regression to estimate hazard ratio (HR) and 95% confidence interval. Progression-free survival (PFS) was analyzed for different regimens in the palliative setting using same approach as for OS. Results: In our cohort, median follow-up is 2.3 years (95% CI = 2 to 3.3), 48% were women and median age at diagnosis was 63 (range 13-89). At presentation, 16 pts (41%) had local disease and 23 advanced or metastatic (59%). By location, 13 pts (33%) had primary cutaneous AS, 12 pts (31%) visceral AS, 5 pts (13%) primary breast AS, 2 (5%) extremity AS and 7 (18%) radiation associated AS. Multimodality treatment was used in 29 pts (74%). OS in the entire cohort at 3 years was 49% (95% CI = 28 to 67%). OS between local disease was (N = 16) and in advanced disease (N = 23) was not statistically significant (p = 0.485; HR = 1.1 [95% CI = 0.4 to 3.3]). In the neoadjuvant setting, objective response rates trended to favor doxorubicin-based regimen (DBR) over taxane-based regimens (TBR) (80% vs. 40%) but were not statistically different (p = 0.519). In the advanced setting, PFS for DBR was 3.9 mo (95% CI 1.1 to 4.9 mo), 5.9 mo for TBR (95% CI 2.3 to 10.9 mo), 6.1 mo for ICI (95% CI not estimable), and 2.4 mo for targeted therapy (TT) (95% CI 0.8 to 8.8 mo), most common TT agent was pazopanib (71% of TT agents). Conclusions: AS is highly aggressive and most patients with local presentation will relapse translating in similar OS to the advanced cohort. No significant activity was seen for TT. In the advanced setting, chemotherapy with TBR appears slightly superior to DBR. ICIs resulted in similar if not superior PFS despite its use in a later line setting. Studies incorporating ICIs into earlier lines of therapy are warranted

Genomic landscape of angiosarcoma: A targeted and immunotherapy biomarker analysis of 143 patients

11545 Background: Targeted therapies for angiosarcoma (AS) patients have limited efficacy. Although significant responses to immunotherapy (IO-therapy) have been observed in cutaneous AS, its efficacy across all types of AS is not known. Herein, we describe genetic and molecular biomarkers of AS in order to propose potential therapeutic options. Methods: We retrospectively reviewed 143 AS tumors profiled by Next-Generation Sequencing (NGS) 592-gene panel (Caris Life Sciences,Irving, TX, USA). Whole transcriptome sequencing (WTS) was performed on 53 tumors. Mutations and copy number amplifications (CNAs) were analyzed and grouped by pathway. Biomarkers potentially associated with response to IO-therapy (TMB-High [≥10/Mb], MSI-High, and PD-L1 [IHC ≥ 2+ and 5%]) were also analyzed. AS subtypes based on primary tumor site were compared. P-values were corrected using a Benjamini & Hochberg method. Results: Sample median age was 67 (range 22-89), 61% were female, and 29% were classified as metastatic/recurrent. The most commonly mutated genes were TP53 (29%), ARID1A (17%), POT1 (16%), and ATRX (13%); MYC CNA was found in 23% of cases. IO-therapy markers were present in 36.4% of cases (TMB-High in 26%, PD-L1+ 21.8%, MSI-High 0.7%). Pathway alterations were detected in 86% of AS cases. By pathway, TP53 was altered in 31%, cell cycle 30%, DNA damage repair (DDR) 21%, RAS 18%, PI3K 15% and chromatin remodeling 14%. By site, head/neck (HN) AS had the highest rate of IO-therapy markers (65%, p < 0.05) [TMB-High (63%, p < 0.0001)], TP53 mutation (51%, p = 0.07), and POT1A mutation (41%, p < 0.01). MYC CNA was highest in breast (63%) and extremity (40%) AS (p < 0.0001). DDR alterations were present in 56% (p = 0.09) of cutaneous AS and ranged from 12-27% in other subtypes (not significant, NS). RAS and PI3K alterations ranged from 6-27% across all subtypes (NS). Conclusions: Our findings suggest differential angiosarcoma biology across primary sites. HN AS had more frequent markers of potential IO-therapy response, as well as DDR alterations. Next in frequency, we found ARID1A which is possibly associated with overactive EZH2, a target of tazemetostat. MYC amplification suggests a role targeting cell cycle via cyclin-dependent kinase or bromodomain inhibitors in breast and extremity ASs. Finally, RAS and PI3K are mutated in a low percentage of cases, explaining the limited benefit of tyrosine kinase inhibitors in AS. Future AS clinical trials should be designed with consideration of primary site, IO-therapy response biomarkers, and activated pathway