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Peripherin-2 (PRPH2) is a transmembrane glycoprotein crucial for the morphogenesis and stabilization of the photoreceptor outer segments. Variations in PRPH2 gene are associated with vision-threatening diseases. Clinical manifestations and multimodal imaging were presented, as well as treatment history and six-year follow-up. In addition, genetic testing was performed to confirm the diagnosis. In this report, we present an extremely rare case of choroidal neovascularization (CNV) secondary to pattern dystrophy simulating fundus flavimaculatus (PDSFF). Multimodal imaging showed typical symmetric yellow flecks in posterior pole and choroidal neovascularization requiring timely treatment. A novel nonsense variant of c.552 C > G; p.Y184X in PRPH2 gene was detected. The patient received intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment and maintained a good vision after six years. We described a novel PRPH2 variant (Y184X) associated with PDSFF, its multimodal imaging, and long-term prognosis. Intravitreal anti-VEGF treatment can offer excellent visual prognosis in patients with PDSFF-associated CNV. [ABSTRACT FROM AUTHOR]

CerSs (ceramide synthases), a group of enzymes that catalyze the formation of ceramides from sphingoid base and acyl-CoA substrates. As far, six types of CerSs (CerS1-CerS6) have been found in mammals. Each of these enzymes have unique characteristics, but maybe more noteworthy is the ability of individual CerS isoform to produce a ceramide with a characteristic acyl chain distribution. As key regulators of sphingolipid metabolism, CerSs highlight their unique characteristics and have emerging roles in regulating programmed cell death, cancer and many other aspects of biology. However, the role of CerSs in lung cancer has not been fully elucidated. In this study, there was no significant change in the sequence or copy number of CerSs gene, which could explain the stability of malignant tumor development through COSMIC database. In addition, gene expression in lung cancer was examined using the OncomineTM database, and the prognostic value of each gene in non-small cell lung cancer (NSCLC) was analyzed by Kaplan-Meier analysis. The results showed that high mRNA expression levels of CerS2, CerS3, CerS4 and CerS5 in all NSCLC patients were associated with improved prognosis. Among them, CerS2 and CerS5 are also highly expressed in adenocarcinoma (Ade), but not in squamous cell carcinoma (SCC). In contrast, high or low expression of CerS1 and CerS6 no difference was observed in patients with NSCLC, Ade and SCC. Integrated the data of this study suggested that these CerSs may be a potential tumor markers or drug target of new research direction. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK- ALCL) is a definite entity in the WHO 2016 Classification that represents 2–3% of non-Hodgkin lymphoma (NHL) and 12% of T-cell NHL cases. ALK- ALCL lacks ALK protein expression, but expresses CD30 and has morphologic features similar to ALK positive anaplastic large cell lymphoma (ALK+ ALCL). Some studies indicate that ALK- ALCL and ALK+ ALCL possess different molecular and genetic characteristics. Besides, ALK- ALCL is worse than ALK+ ALCL in terms of treatment outcome, prognosis, and long-term survival. This review is aimed at summarizing information about ALK- ALCL, especially with respect to the treatment and prognosis. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK- ALCL) is a definite entity in the WHO 2016 Classification that represents 2–3% of non-Hodgkin lymphoma (NHL) and 12% of T-cell NHL cases. ALK- ALCL lacks ALK protein expression, but expresses CD30 and has morphologic features similar to ALK positive anaplastic large cell lymphoma (ALK+ ALCL). Some studies indicate that ALK- ALCL and ALK+ ALCL possess different molecular and genetic characteristics. Besides, ALK- ALCL is worse than ALK+ ALCL in terms of treatment outcome, prognosis, and long-term survival. This review is aimed at summarizing information about ALK- ALCL, especially with respect to the treatment and prognosis. [ABSTRACT FROM AUTHOR]

An effective salvage regimen for the reinduction of remission is lacking for refractory or relapsed primary central nervous system lymphoma (r/r PCNSL). This study aimed to evaluate the efficacy and safety of cytarabine plus temozolomide in treating r/r PCNSL and to explore the associated prognostic factors. A single-center retrospective cohort study was conducted to assess the efficacy and safety of cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping was performed on peripheral blood samples. Thirty PCNSL patients receiving an AT regimen (cytarabine 3 g/m2 for 2 days combined with temozolomide 150 mg/m2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25–79 years). A total of 43.4% of patients (13/30) achieved an overall response within a median follow-up of 16 months (95% confidence interval [CI]: 11–23 months). The median PFS and OS of the cohort were 1.5 months (95% CI: 1–4 months) and 19.5 months (95% CI: 11 months to not calculable), respectively. Patients harboring KIR3DL1/HLA-B genotypes predicting low affinity had a higher response rate (p = 0.042) and longer median PFS (3 months) than those with KIR3DL1/HLA-B genotypes predicting high affinity (1 month) (p = 0.0047). Cox regression analysis indicated that KIR/HLA-B genotypes were independently associated with PFS (p = 0.043). However, KIR/HLA-B genotypes had no impact on the OS of the cohort. The toxicity of AT treatment was mild and manageable. The AT regimen was well tolerated, and patients with specific KIR-HLA genotypes may benefit from this regimen. [ABSTRACT FROM AUTHOR]

Prognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients. Totally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIlow and PNIhigh groups, the characteristics were compared between two groups. The PNIhigh was associated with better OS (Overall Survival) than PNIlow in MDS patients (Median OS, 28.03 months versus 19.63 months, P = 0.0205). But there were no statistical differences in PFS (Progression-Free-Survival) between the two groups (P = 0.9373). The univariable and multivariable COX proportional hazard analysis adjusted for age, gender, platelet count, HB level and IPSS-R scores, and the results showed that PNI is a useful index in the evaluation of the OS of MDS (HR 0.588, 95%CI 0.374–0.926, P = 0.024). PNI would be a simple and immediately available tool for predicting the prognosis of MDS. [ABSTRACT FROM AUTHOR]

To explore the prognostic value of red blood cell distribution width (RDW) in newly diagnosed aplastic anemia (AA) patients treated with cyclosporine A (CsA) plus androgen or CsA alone. We retrospectively analyzed the clinical outcome of 220 patients with AA. According to the baseline level of RDW before treatment, the patients were divided into the high-RDW group (RDW ≥ 15%) and the normal-RDW group (RDW < 15%). The median RDW of non-severe AA (NSAA) and severe AA (SAA) patients was 15.65% and 15.35%, respectively; this were significantly higher than that of very severe AA (VSAA) patients (13.35%). With median follow-up being 46 months, AA patients in the high-RDW group showed better 5-year OS and PFS than the normal-RDW group (93%: 75.3%; 74.3%: 61%). There was a higher ORR in the high-RDW group than the normal-RDW group (68.7%: 52.3%). The ORR of NSAA patients in the high-RDW group was better than that in the normal RDW group (75.8%: 60%). The 5-year OS of SAA/VSAA patients in the high-RDW group was significantly higher than the normal-RDW group (81.8%: 50.8%). This is the first documentation on the prognostic value of RDW in AA patients receiving CsA treatment with long-term follow-up, which had shown that high RDW at diagnosis was a better prognostic factor. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis. Therefore, there is an urgent need to identify prognostic markers to improve current treatment and therapeutic strategies. The transcriptional factor ZNF503 has been reported to promote aggressive breast cancer development through the down-regulation of GATA3 expression and has been identified as a candidate predictive marker. In this study, we explored whether ZNF503 and GATA3 could serve as prognostic markers independently or in combination. We performed a survival analysis of 989 breast cancer patients from The Cancer Genome Atlas (TCGA), and validated the findings in 202 breast cancer patients from tissue microarray (TMA). In TCGA database, the mRNA expression of GATA3 and ZNF503 could not predict TNBC prognosis alone, though the ratio index, ZNF503/GATA3 could be a novel prognostic biomarker in TNBC patients. In TMA database, we detected the protein expression of ZNF503 and GATA3 and found that the combination of the two genes, ZNF503-GATA3, significantly improved the predictive ability of clinical outcomes. The results indicated that the binding index of ZNF503 and GATA3 could be used as a prognostic biomarker in TNBC. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) with t(8;21) is generally associated with a favorable clinical course. Loss of sex chromosome (LOS) are frequently observed in t (8;21) AML, but the prognostic value of LOS remains uncertain. A total of 73 patients with AML with t(8;21) were studied and divided into t(8;21) with LOS group (n = 36) and t(8;21) alone group (n = 37). The patients with t(8;21) AML with ACAs other than LOS were excluded. The clinical characteristics of these two groups were compared, and the prognostic value of LOS was evaluated based on disease-free survival (DFS) and overall survival (OS). The clinical characteristics (except for gender) were found to have no significant difference between these two groups, and the male patients tended to account for a larger proportion in the former group (P =.001). The OS of the t(8;21) AML with LOS group was significantly longer than that of the t(8;21) AML alone group (P =.005). While not obvious, the patients with LOS seemed to have longer DFS (P =.061). The multivariable analysis also showed LOS to be an independent favorable prognostic factor of t(8;21) AML (P =.022). Our results suggested that LOS could be associated with a favorable prognosis in t(8;21) AML patients without other ACAs, and for this subtype of AML, longer DFS and a satisfactory and stable survival can be achieved with high-dose cytarabine (HDAC) consolidation treatment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the clinicopathological characteristics and prognosis of normotensive and hypertensive IgAN patients with ischemic renal injury. A total of 344 cases of IgAN with ischemic renal injury were included in the study, including 99 normotensive IgAN patients (28.8%) and 245 hypertensive IgAN patients (71.2%). In addition, 467 IgAN patients without ischemic renal injury were included as controls, including 205 normotensive patients and 262 hypertensive patients. Clinicopathological and prognostic data were collected and analyzed. Compared with patients without ischemic renal injury, IgAN patients with ischemic renal injury displayed a higher proportion of hypertention, a higher proportion of ischemic glomerulosclerosis, tubular atrophy/interstitial fibrosis and vascular lesions (all p <.05). There was no significant difference in cumulative survival between the normotensive IgAN patients groups (Log-rank χ2 = 0.479; p =.489). Furthermore, ischemic renal injury was not a risk factor for end-point events in normotensive IgAN patients (HR = 1.103; 95% CI: 0.279–4.365; p =.889). There was lower cumulative survival in hypertensive IgAN patients with ischemic renal injury (Log-rank χ2 = 11.352, p =.001). Moreover, ischemic renal injury was a risk factor for end-point events in hypertensive IgAN patients (HR = 1.889; 95% CI: 1.124–3.178; p =.016). Ischemic renal injury can occur in normotensive IgAN patients. Although the pathological changes may not affect the long-term prognosis of normotensive IgAN patients, the prognosis for hypertensive IgAN patients remains poor. Therefore, increased attention should be paid to the clinical management of ischemic lesions in hypertensive IgAN patients. [ABSTRACT FROM AUTHOR]

Antibiotics (ATBs) induce dysbiosis of the gut microbiota by altering the diversity and composition of the microbiota, which mediates the efficacy and toxicity of cancer therapy. The influence of dysbiosis induced by ATB administration on primary resistance to chemotherapy in patients with advanced gastric cancer (GC) has been rarely studied. We evaluated the effect of ATB administration on chemotherapy efficacy in patients with advanced GC. Patients with GC were divided into two groups according to the status of ATB administration: ATB-treated and control groups. Tumor responses, progression-free survival (PFS) and overall survival (OS) were assessed. We found that the incidence of progressive disease in the ATB-treated group was significantly higher when compared with that in the control group that received no ATB treatment (72.73% vs. 29.55%, p = 0.007). In addition, ATB administration was associated with shorter PFS [median PFS: 1.47 vs. 4.97 months, hazard ratio (HR): 2.296, 95% confidence interval (CI): 1.214 − 4.342, p = 0.011] and reduced OS (median OS: 9.97 vs. 13.3 months, HR: 2.101, 95% CI: 1.030 − 4.286, p = 0.041) based on univariate analysis. Subsequent multivariate analysis also indicated that ATB administration was an independent prognostic factor for PFS (HR: 3.361, 95% CI: 1.592 − 7.097, p = 0.001) and OS (HR: 2.280, 95% CI: 1.042 − 4.991, p = 0.039). ATB administration is associated with reduced chemotherapy efficacy and poor prognosis in patients with advanced GC. Modulations in ATB-related dysbiosis and gut microbiota composition improve the clinical outcomes of chemotherapy. Supplemental data for this article is available online at https://dx.doi.org/10.1080/13102818.2021.1953400. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphoma (PTCL) is a rare and highly heterogeneous non-Hodgkin lymphoma (NHL). Although a few prognostic models have been put forward to predict the prognosis of PTCL, some patients with poor prognosis remain unidentified. Therefore, we conducted a retrospective study of 213 adult PTCL patients and assessed the prognostic role of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) in the complete response (CR) and survival of PTCL patients. Patients with PLR ≥ 232.5 achieved a lower CR rate than patients with PLR < 232.5 (18.5% vs. 56.6%, p <.001). Moreover, there was a statistical significance in CR rate between patients with NLR ≥ 3.7 and < 3.7 (31.7% vs. 60.7%, p <.001). The univariable analysis indicated that both PLR and NLR were related with worse OS. However, only PLR remained an independent prognostic indicator of OS (p =.002) by multivariable analysis. [ABSTRACT FROM AUTHOR]

Background: Adult secondary hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome characterized by excessive activation of mononuclear-phagocytic system resulting in hyperinflammatory response. To date, the factors influencing early death of HLH are still not fully elucidated. Patients and Methods: We did a retrospective study of 171 adult patients with newly diagnosed HLH at our institution from January 2012 to April 2018. All patients' clinical features, laboratory findings, treatments and prognosis were reviewed. Results: The median age was 49 years (range, 18–88 years), and 110 (64.3%) were male. The major underlying trigger of HLH was malignancy (88/171, 51.5%), especially non-Hodgkin lymphoma. In a multivariate analysis, age ≥54 years (P = 0.002), platelet ≤39.5 × 109/L (P = 0.028), activated partial thromboplastin time (APTT) ≥54 sec (P = 0.048), triglyceride ≥3.23 mmol/L (P < 0.001), lactate dehydrogenase (LDH) ≥1300 U/L (P = 0.012) and malignancy (P = 0.001) were significantly associated with early death in HLH. Then, patients were classified into four groups according to the number of risk factors at the time of diagnosis: low risk (zero, one or two risk factors), low intermediate risk (three risk factors), high intermediate risk (four risk factors) and high risk (at least five risk factors), with the 30-day overall survival (OS) of 92.4%, 58.8%, 30.0% and 4.8%, respectively (P < 0.001). Conclusions: Patients with old age, thrombocytopenia, prolonged APTT, hypertriglyceridemia, elevated LDH and malignancy had inferior survival. It is important to identify those patients at risk of early death, which may guide treatment and reduce mortality. [ABSTRACT FROM AUTHOR]

Background: Adult secondary hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome characterized by excessive activation of mononuclear-phagocytic system resulting in hyperinflammatory response. To date, the factors influencing early death of HLH are still not fully elucidated. Patients and Methods: We did a retrospective study of 171 adult patients with newly diagnosed HLH at our institution from January 2012 to April 2018. All patients’ clinical features, laboratory findings, treatments and prognosis were reviewed. Results: The median age was 49 years (range, 18–88 years), and 110 (64.3%) were male. The major underlying trigger of HLH was malignancy (88/171, 51.5%), especially non-Hodgkin lymphoma. In a multivariate analysis, age ≥54 years (P = 0.002), platelet ≤39.5 × 109/L (P = 0.028), activated partial thromboplastin time (APTT) ≥54 sec (P = 0.048), triglyceride ≥3.23 mmol/L (P < 0.001), lactate dehydrogenase (LDH) ≥1300 U/L (P = 0.012) and malignancy (P = 0.001) were significantly associated with early death in HLH. Then, patients were classified into four groups according to the number of risk factors at the time of diagnosis: low risk (zero, one or two risk factors), low intermediate risk (three risk factors), high intermediate risk (four risk factors) and high risk (at least five risk factors), with the 30-day overall survival (OS) of 92.4%, 58.8%, 30.0% and 4.8%, respectively (P < 0.001). Conclusions: Patients with old age, thrombocytopenia, prolonged APTT, hypertriglyceridemia, elevated LDH and malignancy had inferior survival. It is important to identify those patients at risk of early death, which may guide treatment and reduce mortality. [ABSTRACT FROM AUTHOR]