Data_Sheet_1_The outcome and the risk factors of mucormycosis among patients with hematological diseases: a systematic and meta-analysis.docx

ObjectivesMucorale has come into a significant pathogen over recent decades. Nonetheless, mucormycosis-related mortality rates among patients with hematological disorders remain unascertained. Thus, we conducted a meta-analysis to determine mortality rates of mucormycosis in patients with hematology-related conditions.MethodsWe scoured PubMed, Embase, and Web of Science for original papers exploring the intersection of Mucormycosis and Hematological Diseases (from 2000 to 2022). We scrutinized the overall mortality across three distinct periods, as well as differentiating between high-income and middle-income nations. We further evaluated the pooled mortality and the risk differential (RD) across several subgroups.ResultsThe overall mortality rate for hematology patients with mucormycosis was 61%, within a 95% confidence interval (CI) of 0.54–0.68. A significant observation was that mortality rates were somewhat lower in high-income countries compared to middle-income countries (0.60 versus 0.64, p = 0.45). Importantly, we discovered that a combination of surgical and medical treatment significantly improved survival rates compared to medical treatment alone [mortality 0.49 versus 0.67, RD -0.19 (95%CI -0.38-0.00, I2 63.7%)]. As might be expected, disseminated mucormycosis posed a significantly higher risk of death compared to isolated mucormycosis [0.60 versus 0.57, RD death 0.16 (95%CI 0.03–0.28)]. Additionally, our analysis showed no discernible differences in survival rates between genders, between patients with and without breakthrough infection, between those who received mucor-active or mucor-inactive drugs prior to mucor infection, or between those on a multi-drug regimen and those on a single drug treatment.ConclusionDespite the high mortality rates associated with mucormycosis in patients with hematological disorders, those receiving both medical and surgical interventions, as well as those with isolated infection sites, exhibited improved survival outcomes. Conversely, factors such as gender, the presence of breakthrough infection, the use of mucor-active drugs before mucor infection, and multi-drug administration did not significantly influence patient outcomes.</p

Table_1_Mucor indicus caused disseminated infection diagnosed by metagenomic next-generation sequencing in an acute myeloid leukemia patient: A case report.docx

BackgroundMucormycosis commonly occurs in immunosuppressed patients with hematological diseases, which can be life-threatening. However, many cases are often misdiagnosed due to lack of specific clinical manifestations. Additionally, the traditional blood culture or serological testing, with a high false-negative rate, is time-consuming. Thus, precise and timely diagnosis of infections is essential for the clinical care of infected patients.Case presentationWe report a 29-year-old Chinese man with acute myeloid leukemia (AML) who developed febrile neutropenia after the first course of induction chemotherapy. He received empirical antibiotics, which did not relieve his symptoms. No pathogen was detected by traditional microbiologic assays, while Mucor indicus was identified by metagenomic next-generation sequencing (mNGS) in the blood specimen. Liposomal amphotericin B (LAmB) was used, resulting in the patient’s temperature returning to normal. A few days later, abdominal computed tomography (CT) scan showed multiple liver abscesses; fluorescence staining, histopathology, and mNGS identified the causative agent—M. indicus. Posaconazole was combined with LAmB as long-term antifungal treatment. Finally, the patient received allogeneic hematopoietic stem cell transplantation successfully after controlled infection. During follow-up 1 year after transplantation, the number of liver abscesses was reduced to one and remained stable.ConclusionThis report described the first case of an AML patient diagnosed with culture-negative disseminated infections caused by M. indicus leading to rare hepatic manifestations using mNGS of peripheral blood and liver biopsy. LAmB combined with posaconazole was given in time, resulting in a favorable outcome. mNGS is a new method that assists in detecting the probable pathogen and increases the accuracy of identifying an etiology.</p

Table_1_Causal relationships between type 2 diabetes, glycemic traits and keratoconus.XLSX

PurposeThe relationship between diabetes mellitus and keratoconus remains controversial. This study aimed to assess the potential causal relationships among type 2 diabetes, glycemic traits, and the risk of keratoconus.MethodsWe used a two-sample Mendelian randomization (MR) design based on genome-wide association summary statistics. Fasting glucose, proinsulin levels, adiponectin, hemoglobin A1c (HbA1c) and type 2 diabetes with and without body mass index (BMI) adjustment were used as exposures and keratoconus was used as the outcome. MR analysis was performed using the inverse-variance weighted method, MR-Egger regression method, weighted-mode method, weighted median method and the MR-pleiotropy residual sum and outlier test (PRESSO).ResultsResults showed that genetically predicted lower fasting glucose were significantly associated with a higher risk of keratoconus [IVW: odds ratio (OR) = 0.382; 95% confidence interval (CI) = 0.261–0.560; p = 8.162 × 10−7]. Genetically predicted lower proinsulin levels were potentially linked to a higher risk of keratoconus (IVW: OR = 0.739; 95% CI = 0.568–0.963; p = 0.025). In addition, genetically predicted type 2 diabetes negatively correlated with keratoconus (IVW: BMI-unadjusted: OR = 0.869; 95% CI = 0.775–0.974, p = 0.016; BMI-adjusted: OR = 0.880, 95% CI = 0.789–0.982, p = 0.022). These associations were further corroborated by the evidence from all sensitivity analyses.ConclusionThese findings provide genetic evidence that higher fasting glucose levels are associated with a lower risk of keratoconus. However, further studies are required to confirmed this hypothesis and to understand the mechanisms underlying this putative causative relationship.</p

Table_2_Causal relationships between type 2 diabetes, glycemic traits and keratoconus.XLSX

PurposeThe relationship between diabetes mellitus and keratoconus remains controversial. This study aimed to assess the potential causal relationships among type 2 diabetes, glycemic traits, and the risk of keratoconus.MethodsWe used a two-sample Mendelian randomization (MR) design based on genome-wide association summary statistics. Fasting glucose, proinsulin levels, adiponectin, hemoglobin A1c (HbA1c) and type 2 diabetes with and without body mass index (BMI) adjustment were used as exposures and keratoconus was used as the outcome. MR analysis was performed using the inverse-variance weighted method, MR-Egger regression method, weighted-mode method, weighted median method and the MR-pleiotropy residual sum and outlier test (PRESSO).ResultsResults showed that genetically predicted lower fasting glucose were significantly associated with a higher risk of keratoconus [IVW: odds ratio (OR) = 0.382; 95% confidence interval (CI) = 0.261–0.560; p = 8.162 × 10−7]. Genetically predicted lower proinsulin levels were potentially linked to a higher risk of keratoconus (IVW: OR = 0.739; 95% CI = 0.568–0.963; p = 0.025). In addition, genetically predicted type 2 diabetes negatively correlated with keratoconus (IVW: BMI-unadjusted: OR = 0.869; 95% CI = 0.775–0.974, p = 0.016; BMI-adjusted: OR = 0.880, 95% CI = 0.789–0.982, p = 0.022). These associations were further corroborated by the evidence from all sensitivity analyses.ConclusionThese findings provide genetic evidence that higher fasting glucose levels are associated with a lower risk of keratoconus. However, further studies are required to confirmed this hypothesis and to understand the mechanisms underlying this putative causative relationship.</p

All calculated pooled HRs in meta-analysis.

<p>Abbreviations: HCC: hepatocellular carcinoma; ICC: intrahepatic cholangiocarcinoma; HNC: head and neck carcinoma, NSCLC: non-small-cell lung cancer; RCC: renal cell carcinoma; Gastric: gastric carcinoma; ND: not done. OS: overall survival; CSS: cancer-specific survival; RFS: recurrence-free survival; DFS: disease-free survival; a: maximally adjusted association HR ( When both unadjusted and adjusted HRs were extracted from the original papers, the adjusted HRs were included into analysis ); b: crude association HR ( When both unadjusted and adjusted HRs were extracted from the original papers, the unadjusted HRs were included into our analysis).</p

Bland-Altman plots of thickness measurements determined with the automated segmentation algorithm on UHR-OCT and RTVue100 images.

<p>Only the images along the horizontal meridian were analyzed. The horizontal full lines represent the mean of thickness differences, and the horizontal dashed lines represent the mean differences ±1.96 standard deviation.</p

Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Review and Meta-Analysis

<div><p>Purpose</p><p>Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer.</p><p>Method</p><p>Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed.</p><p>Results</p><p>A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36–2.07, I² = 55.8%, <i>p</i><0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08–5.42, I² = 0%, <i>p</i><0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37–2.01, I² = 70.5%, <i>p</i><0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47–2.22, I² = 67.7%, <i>p</i><0.001) for CD66b, and 1.44 (95%CI: 0.90–2.30, I² = 45.9%, <i>p</i> = 0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15.</p><p>Conclusion</p><p>High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival.</p></div

Segmentation errors in scans of lower image quality and corresponding corrected segmentation after applying the semi-automated approach.

<p>(A) The algorithm mistakenly identified the OPL/ONL interface. (B) Corrected segmentation corresponding (A) after applying the semi-automated approach. (C) The algorithm mistakenly identified the RNFL/GCL boundary. (D) Corrected segmentation corresponding (C) after applying the semi-automated approach.</p

Boundaries of intra-retinal layers in OCT macular images.

<p>As seen in this image taken by UHR-OCT in the horizontal meridian, nine boundaries of intra-retinal layers were visualized. Images taken in the vertical meridian by UHR-OCT and in both meridians by the RTVue100 were similar to this.</p

The detailed sequence in the boundary segmentation process.

<p>(a) Original image. (b) Image smoothing. (c) Gradient image. (d) The ILM and the boundary between the RPE and choroid layers were first segmented. (e) Limiting detection area and search the minimum-weighted path. (f) Segmented image.</p