[Efficacy and safety analysis of the zanubrutinib-based bridging regimen in chimeric antigen receptor T-cell therapy for relapsed/refractory diffuse large B-cell lymphoma].

Objective: To further elucidate the clinical efficacy and safety of a combination regimen based on the BTK inhibitor zebutanil bridging CD19 Chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) . Methods: Twenty-one patients with high-risk r/r DLBCL were treated with a zanubrutinib-based regimen bridging CAR-T between June 2020 and June 2023 at the Department of Hematology, Tongji Hospital, Tongji University and the Second Affiliated Hospital of Zhejiang University, and the efficacy and safety were retrospectively analyzed. Results: All 21 patients were enrolled, and the median age was 57 years (range: 38-76). Fourteen patients (66.7%) had an eastern cooperative oncology group performance status score (ECOG score) of ≥2. Eighteen patients (85.7%) had an international prognostic index (IPI) score of ≥3. Three patients (14.3%) had an IPI score of 2 but had extranodal infiltration. Fourteen patients (66.7%) had double-expression of DLBCL and seven (33.3%) had TP53 mutations. With a median follow-up of 24.8 (95% CI 17.0-31.6) months, the objective response rate was 81.0%, and 11 patients (52.4%) achieved complete remission. The median progression-free survival (PFS) was 12.8 months, and the median overall survival (OS) was not reached. The 1-year PFS rate was 52.4% (95% CI 29.8% -74.3%), and the 1-year OS rate was 80.1% (95% CI 58.1% -94.6%). Moreover, 18 patients (85.7%) had grade 1-2 cytokine-release syndrome, and two patients (9.5%) had grade 1 immune effector cell-associated neurotoxicity syndrome. Conclusion: Zanubrutinib-based combination bridging regimen of CAR-T therapy for r/r DLBCL has high efficacy and demonstrated a good safety profile.

[Efficacy and safety of fourth-generation CD19 CAR-T expressing IL7 and CCL19 along with PD-1 monoclonal antibody for relapsed or refractory large B-cell lymphoma].

Objective: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.

[Characteristics and impact factors of SARS-CoV-2 infection in adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma receiving chimeric antigen receptor T-cell therapy].

Objective: To explore the clinical characteristics and treatment of COVID-19 infection in patients with relapsed/refractory B-cell non-Hodgkin lymphoma before and after receiving chimeric antigen receptor T-cell therapy, and study the influencing factors of severe COVID-19 infection in these patients. Methods: The data of 59 patients with relapsed/refractory B-cell non-Hodgkin lymphoma who received chimeric antigen receptor T-cell therapy at the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology and Department of Hematology, the Second Affiliated Hospital, College of Medicine, Zhejiang University between December 2017 and February 2023, and who were infected with novel coronavirus between December 2022 and February 2023 were retrospectively studied. Patients were divided into light, medium, severe, and critical groups, and the differences between the groups were analyzed using the chi-square test. A univariate logistic regression model was used to evaluate the contribution of each variable and its relationship with severe infection. The chi-square and Fisher's exact tests were used to analyze the differences between the B-cell aplasia and B-cell recovery (BCR) groups. Results: Of the 59 pre- and post-infusion infections, 39 (66.1%) led to mild COVID-19, 9 (15.3%) resulted in moderate COVID-19, 10 (16.9%) resulted in severe COVID-19, and 1 (1.7%) led to critical COVID-19. Moroever, age greater than 55 years, having received autologous hematopoietic stem cell transplantation, progressive disease status, and B-cell aplasia at the time of diagnosis of COVID-19 infection are factors affecting severe infection. Patients with B-cell aplasia had a more severe infection with COVID-19 (P<0.001), a longer duration (P=0.015), a longer antiviral therapy course (P<0.001), and a higher hospitalization rate (P<0.001) than the BCR group. Conclusion: Active prevention and treatment of COVID-19 infection remains a crucial issue requiring urgent attention in managing patients with relapsed/refractory B-cell non-Hodgkin lymphoma treated with chimeric antigen receptor T-cell therapy.

[Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis].

To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.

[Paying more attention to burn induced coagulopathy].

Burn induced coagulopathy (BIC) is one of the common complications after burn injury. The types and clinical manifestations of BIC vary dramatically, which frequently leads serious consequences. However, at present BIC does not attract enough attention in clinic. In order to prevent and treat BIC more effectively, the authors suggest that it is necessary to strengthen coagulation surveillance, operation management, infection control, rational application of drugs, prevention and treatment of deep vein thrombosis, relative clinical and basic research, and others.

Incisional hernias post renal transplant: a systematic review and meta-analysis.

PURPOSE: Incisional hernia (IH) post renal transplant (RT) is relatively uncommon and can be challenging to manage clinically due to the presence of the kidney graft and patient immunosuppression. This systematic review and meta-analysis synthesises the current literature in relation to IH rates, risk factors and outcomes post RT. METHODS: PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials (CENTRAL) were searched up to July 2023. The most up to date Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines were followed. Pertinent clinical information was synthesised. A meta-analysis of the pooled proportions of IH rates, the rates of patients requiring surgical repair and the rates of recurrence post RT are reported. RESULTS: Twenty studies comprising 16,018 patients were included in this analysis. The pooled rate of IH occurrence post RT was 4% (CI 3-5%). The pooled rate of IH repair post RT was 61% (CI 14-100%). The pooled rate of IH recurrence after repair was 16% (CI 9-23%). Risk factors identified for IH development post RT are BMI, immunosuppression, age, smoking, incision type, reoperation, concurrent abdominal wall hernia, lymphocele formation and pulmonary disease. CONCLUSIONS: IH post RT is uncommon and the majority of IH post RT are repaired surgically on an elective basis.

Incisional hernias post cytoreductive surgery/peritonectomy and hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis.

PURPOSE: Cytoreductive surgery (CRS) is often combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal tumour deposits. Considering CRS, the evidence relating the large incisions, local chemotherapy and abdominal wall trauma to incisional hernias (IH) has not been synthesized. This systematic review and meta-analysis was conducted to examine the proportion of IH present in patients post CRS and the effect HIPEC had on these rates. METHODS: PubMed, EMBASE, and Cochrane Central Registry of Trials were searched up to June 2023 to examine studies relating IH and CRS plus or minus HIPEC. The most up to date PRISMA guidelines were followed. Pertinent clinical information was synthesized in tabular form. A meta-analysis reporting the pooled proportions of IH post CRS plus or minus HIPEC, the odds of IH in HIPEC versus non-HIPEC CRS and the difference in follow-up time between groups was conducted. RESULTS: Nine studies comprising 1416 patients were included. The pooled proportion of IH post CRS was 12% (95% confidence interval (CI) 8-16%) in HIPEC and 7% (95% CI 4-10%) in non-HIPEC patients and 11% (95% CI 7-14%) overall. Previously reported rates of IH in midline laparotomy range from 10 to 30%. The odds of IH in the HIPEC was 1.9 times higher compared to non-HIPEC cohorts however this was not statistically significant (odds ratio (OR) 1.9, 95% 0.7-5.2; p = 0.21). There was no significant difference in average follow-up times between HIPEC and non-HIPEC cohorts. CONCLUSIONS: IH post CRS plus or minus HIPEC were in the expected range for midline laparotomies. IH in patients receiving HIPEC may occur at a greater proportion than in non-HIPEC patients, however, there were too few studies in our meta-analysis to determine this with statistical significance.

[Research progress on clinical and mechanisms of chronic pruritus with anxiety and depression].

Chronic pruritus seriously affects the quality of life of patients, which is closely related to stress, anxiety and depression. Prolonged and repeated pruritus can induce negative emotions such as anxiety and depression, while continued increased negative emotions can also promote exacerbation of pruritus, which drives the itch scratch cycle, thereby further aggravating skin damage. More and more studies have explored the mechanism of pruritus, anxiety and depression. This article mainly reviews the clinical relationship between pruritus and anxiety, depression and the new progress of its possible mechanism, providing reference for the prevention, control and effective treatment of chronic pruritus, anxiety and depression.

RESOLVE-based radiomics in cervical cancer: improved image quality means better feature reproducibility?

AIM: To compare the reproducibility of apparent diffusion coefficient (ADC)-based radiomic features between readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) and single-shot echo-planar diffusion-weighted imaging (SS-EPI DWI) in cervical cancer. MATERIALS AND METHODS: The RESOLVE and SS-EPI DWI images of 36 patients with histopathologically confirmed cervical cancer were collected retrospectively. Two observers independently delineated the whole tumour on RESOLVE and SS-EPI DWI, and then copied them to the corresponding ADC maps. Shape, first-order, and texture features were extracted from ADC maps in the original and filtered (Laplacian of Gaussian [LoG] and wavelet) images. Thereafter, 1,316 features were generated in each RESOLVE and SS-EPI DWI, respectively. The reproducibility of radiomic features was assessed using intraclass correlation coefficient (ICC). RESULTS: In the original images, RESOLVE showed 92.86%, 66.67%, and 86.67% of features with excellent reproducibility in shape, first-order, and texture features, while SS-EPI DWI showed 85.71%, 72.22%, and 60% of features with excellent reproducibility, respectively. In the LoG and wavelet filtered images, RESOLVE had 56.77% and 65.32% of features with excellent reproducibility and SS-EPI DWI had 44.95% and 61.96% of features with excellent reproducibility, respectively. CONCLUSION: Compared with SS-EPI DWI, the feature reproducibility of RESOLVE was better in cervical cancer, especially for texture features. The filtered images cannot improve the feature reproducibility compared with the original images for both SS-EPI DWI and RESOLVE.

Increase in skeletal muscle extracellular volume as an under-recognised change detected at cardiac MRI in hypertrophic cardiomyopathy.

AIM: To explore skeletal muscle change and its correlation with the myocardium in hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance imaging (cMRI) with T1 mapping and late gadolinium enhancement (LGE). MATERIALS AND METHODS: This retrospective study enrolled 50 HCM patients and 35 healthy controls. The extracellular volume (ECV) of the skeletal muscle and myocardium, the presence and absence of LGE of the myocardium, and cardiac troponin T (cTnT), were assessed. In the HCM group, the elevated ECVskeletal group was defined as ECVskeletal >2 standard deviations (SD) above the mean value of the controls. Statistical analyses included Student's t-test, the Mann-Whitney U-test, and linear regression. RESULTS: ECVskeletal in the HCM group was higher than in the control group (mean 13.0 versus 10.9%; p<0.001), with 20 (40%) HCM patients having elevated ECVskeletal (ECVskeletal ≥13.7%). In the HCM group, ECVskeletal had a positive linear correlation with global myocardial ECV (r=0.37, p=0.009). In addition, the elevated ECVskeletal group had a higher cTnT than the non-elevated group (log cTnT, mean 1.55 versus 1.16, p=0.045). Furthermore, segmental myocardial ECV in the elevated ECVskeletal group was higher than in the non-elevated group, despite the presence or absence of myocardial LGE (median 30.1 versus 27.2%; 26.5 versus 24.6%, both p<0.001) or hypertrophy (median 29.0 versus 26.0%; 26.8 versus 24.8%, both p<0.001). CONCLUSION: In the HCM patients, ECVskeletal was higher than in the healthy controls. Furthermore, some ECVskeletal changes had corresponding changes in the cTnT and myocardium.

[Effects of P311 on the angiogenesis ability of human microvascular endothelial cell 1 in vitro and its molecular mechanism].

Objective: To explore the effects of P311 on the angiogenesis ability of human microvascular endothelial cell 1 (HMEC-1) in vitro and the potential molecular mechanism. Methods: The experimental research method was used. HMEC-1 was collected and divided into P311 adenovirus group and empty adenovirus group according to the random number table (the same grouping method below), which were transfected correspondingly for 48 h. The cell proliferation activity was detected using the cell counting kit 8 on 1, 3, and 5 days of culture. The residual scratch area of cells at post scratch hour 6 and 11 was detected by scratch test, and the percentage of the residual scratch area was calculated. The blood vessel formation of cells at 8 h of culture was observed by angiogenesis experiment in vitro, and the number of nodes and total length of the tubular structure were measured. The protein expressions of vascular endothelial growth factor receptor 2 (VEGFR2), phosphorylated VEGFR2 (p-VEGFR2), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphorylated ERK1/2 (p-ERK1/2) in cells were detected by Western blotting. HMEC-1 was collected and divided into P311 adenovirus+small interfering RNA (siRNA) negative control group, empty adenovirus+siRNA negative control group, P311 adenovirus+siRNA-VEGFR2 group, and empty adenovirus+siRNA-VEGFG2 group, which were treated correspondingly. The protein expressions of VEGFR2, p-VEGFR2, ERK1/2, and p-ERK1/2 in cells were detected by Western blotting at 24 h of transfection. The blood vessel formation of cells at 24 h of transfection was observed by angiogenesis experiment in vitro, and the number of nodes and total length of the tubular structure were measured. HMEC-1 was collected and divided into P311 adenovirus+dimethylsulfoxide (DMSO) group, empty adenovirus+DMSO group, P311 adenovirus+ERK1/2 inhibitor group, and empty adenovirus+ERK1/2 inhibitor group, which were treated correspondingly. The protein expressions of ERK1/2 and p-ERK1/2 in cells were detected by Western blotting at 2 h of treatment. The blood vessel formation of cells at 2 h of treatment was observed by angiogenesis experiment in vitro, and the number of nodes and total length of the tubular structure were measured. The sample number at each time point in each group was 6. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, one-way analysis of variance, and least significant difference test. Results: Compared with that of empty adenovirus group, the proliferation activity of cells in P311 adenovirus group did not show significant difference on 1, 3, and 5 days of culture (with t values of -0.23, -1.30, and -1.52, respectively, P>0.05). The residual scratch area percentages of cells in P311 adenovirus group were significantly reduced at post scratch hour 6 and 11 compared with those of empty adenovirus group (with t values of -2.47 and -2.62, respectively, P<0.05). At 8 h of culture, compared with those of empty adenovirus group, the number of nodes and total length of the tubular structure of cells in P311 adenovirus group were significantly increased (with t values of 4.49 and 4.78, respectively, P<0.01). At 48 h of transfection, compared with those of empty adenovirus group, the protein expressions of VEGFR2 and ERK1/2 of cells in P311 adenovirus group showed no obvious changes (P>0.05), and the protein expressions of p-VEGFR2 and p-ERK1/2 of cells in P311 adenovirus group were significantly increased (with t values of 17.27 and 16.08, P<0.01). At 24 h of transfection, the protein expressions of p-VEGFR2 and p-ERK1/2 of cells in P311 adenovirus+siRNA negative control group were significantly higher than those in empty adenovirus+siRNA negative control group (P<0.01). The protein expressions of VEGFR2, p-VEGFR2, and p-ERK1/2 of cells in P311 adenovirus+siRNA negative control group were significantly higher than those in P311 adenovirus+siRNA-VEGFR2 group (P<0.01). The protein expressions of VEGFR2 and p-ERK1/2 of cells in empty adenovirus+siRNA negative control group were significantly higher than those in empty adenovirus+siRNA-VEGFR2 group (P<0.05 or P<0.01). At 24 h of transfection, the number of nodes of the tubular structure in cells of P311 adenovirus+siRNA negative control group was 720±62, which was significantly more than 428±38 in empty adenovirus+siRNA negative control group and 364±57 in P311 adenovirus+siRNA-VEGFR2 group (with P values both <0.01). The total length of the tubular structure of cells in P311 adenovirus+siRNA negative control group was (21 241±1 139) µm, which was significantly longer than (17 005±1 156) µm in empty adenovirus+siRNA negative control group and (13 494±2 465) µm in P311 adenovirus+siRNA-VEGFR2 group (with P values both <0.01). The number of nodes of the tubular structure in cells of empty adenovirus+siRNA negative control group was significantly more than 310±75 in empty adenovirus+siRNA-VEGFR2 group (P<0.01), and the total length of the tubular structure of cells in empty adenovirus+siRNA negative control group was significantly longer than (11 600±2 776) µm in empty adenovirus+siRNA-VEGFR2 group (P<0.01). At 2 h of treatment, the protein expression of p-ERK1/2 of cells in P311 adenovirus+DMSO group was significantly higher than that in empty adenovirus+DMSO group and P311 adenovirus+ERK1/2 inhibitor group (with P values both <0.01), and the protein expression of p-ERK1/2 of cells in empty adenovirus+DMSO group was significantly higher than that in empty adenovirus+ERK1/2 inhibitor group (P<0.05). At 2 h of treatment, the number of nodes of the tubular structure in cells of P311 adenovirus+DMSO group was 726±72, which was significantly more than 421±39 in empty adenovirus+DMSO group and 365±41 in P311 adenovirus+ERK1/2 inhibitor group (with P values both <0.01). The total length of the tubular structure of cells in P311 adenovirus+DMSO group was (20 318±1 433) µm, which was significantly longer than (16 846±1 464) µm in empty adenovirus+DMSO group and (15 114±1 950) µm in P311 adenovirus+ERK1/2 inhibitor group (with P values both <0.01). The number of nodes of the tubular structure in cells of empty adenovirus+DMSO group was significantly more than 317±67 in empty adenovirus+ERK1/2 inhibitor group (P<0.01), and the total length of the tubular structure of cells in empty adenovirus+DMSO group was significantly longer than (13 188±2 306) µm in empty adenovirus+ERK1/2 inhibitor group (P<0.01). Conclusions: P311 can enhance the angiogenesis ability of HMEC-1 by activating the VEGFR2/ERK1/2 signaling pathway.

Second primary malignancy risk after Hodgkin lymphoma treatment among HIV-uninfected and HIV-infected survivors.

We compared secondary primary malignancy risk (SPM) in HIV-uninfected and HIV-infected Hodgkin lymphoma (HL) survivors. We used data from the California Cancer Registry on patients diagnosed with HL from 1990 to 2015 (all ages included), and standardized incidence ratios (SIRs) and multivariable competing risk models for analyses. Of 19,667 survivors, 735 were HIV-infected. Compared with the general population, the risk of SPM was increased by 2.66-fold in HIV-infected and 1.92-fold in HIV-uninfected survivors. Among HIV-infected survivors, median time to development of SPM was shorter (5.4 years) than in HIV-uninfected patients (8.1 years). Additionally, the highest risk of SPM was observed <2 years after diagnosis in HIV-infected survivors (SIR = 4.47), whereas risk was highest ≥20 years after diagnosis (SIR = 2.39) in HIV-uninfected survivors. The risk of SPMs persisted for decades and was higher among HIV-infected survivors, suggesting that these patients should benefit from long-term surveillance and cancer prevention practices.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Chronic medical conditions and late effects after acute myeloid leukaemia in adolescents and young adults: a population-based study.

BACKGROUND: Curative-intent treatment of acute myeloid leukaemia (AML) can lead to multiple chronic medical conditions ('late effects'). Little is known about the burden of late effects in adolescent and young adult (AYA, 15-39 years) survivors of AML. We aimed to estimate the cumulative incidence and investigate the main predictors of late effects among these patients. METHODS: During 1996-2012, 1168 eligible AYAs with AML who survived ≥2 years after diagnosis were identified in the California Cancer Registry. Late effects were reported from State hospital discharge data, and patients were followed through 2014. Hazard ratios and 95% confidence intervals of late effects occurrence were estimated using Cox proportional hazard models, adjusted for sociodemographic and clinical factors. RESULTS: The most common late effects at 10 years after diagnosis were: endocrine (26.1%), cardiovascular (18.6%) and respiratory (6.6%), followed by neurologic (4.9%), liver/pancreatic (4.3%), renal (3.1%), avascular necrosis (2.7%) and second primary malignancies (2.4%). Of 1168 survivors, 547 (46.8%) received a haematopoietic stem cell transplant (HSCT). After multivariable adjustments, AYAs who underwent HSCT or had a non-favourable risk AML experienced ∼2-fold or higher increased likelihood of all late effects. Additionally, AYAs of Hispanic, Black or Asian/Pacific Islander (vs non-Hispanic White) race/ethnicity and those who resided in lower socio-economic neighbourhoods were at higher risk of numerous late effects. CONCLUSIONS: Our findings underscore the need for long-term surveillance for the prevention, early detection and treatment of late effects, and can inform the development of AYA-focused consensus-based guidelines that will ultimately improve the quality of life and survival of these young vulnerable patients.

Proposal of a prediction score for hematoma expansion after intracerebral hemorrhage / Propuesta de una puntuación de predicción de la expansión del hematoma tras una hemorragia cerebral

Objective To propose and validate a prediction score for intracerebral hemorrhage (ICH) patients at risk of hematoma expansion (HE). Design A retrospective observational study was designed to propose and validate the score. Setting Sanxiang Road branch and Xuguan branch belonging to the Second Affiliated Hospital of Soochow University (China). Patients A total of 317 ICH patients in Sanxiang Road branch were registered as the development cohort, and 109 ICH patients in Xuguan branch were enrolled as the validation cohort. Procedure Independent risk factors for HE were identified using multiple logistic regression analysis. A prediction score was then proposed based on β coefficients and preliminarily verified in the validation cohort. Main variables All clinical data of the patients were compiled from the electronic medical records. Hematoma expansion was defined as an increase in hematoma volume >33% or absolute hematoma growth >6ml from the initial scan. Specific non-contrast CT(NCCT) signs were identified by two observers independently. Results Our score demonstrated satisfactory discrimination ability for HE (area under the ROC curve 0.854 in the development cohort versus 0.893 in the validation cohort). Appropriate calibration was found in the development cohort, whereas calibration in the validation cohort was slightly lower but still within the accuracy range (maximum deviation, average deviation and P were 0.070, 0.028, 0.773, respectively, versus 0.114, 0.056, 0.156). Decision curve analysis of the score from two samples were both far from the curve of treat all and curve of treat none, which verified its security and reliability. Patients with a total score ≥4.5 were at greatest risk of HE. Conclusion The score may provide some reference and help in accurately identifying individuals at high risk of HE, allowing rapid guidance of clinical management and also serving as an aid in clinical trials. (AU)

Objetivo Proponer y validar una puntuación de predicción de hemorragia cerebral (HC) en paciente con riesgo de expansión del hematoma (EH). Diseño Se diseñó un estudio observacional retrospectivo para proponer y validar la puntuación. Ámbito ramas de Sanxiang Road y Xuguan pertenecientes al Segundo Hospital Afiliado de la Universidad de Soochow. Pacientes 317 pacientes con HE de la rama de Sanxiang Road fueron incluidos como la cohorte de desarrollo, y 109 pacientes con HC de la rama de Xuguan fueron incluidos como la cohorte de validación. Procedimiento Se obtuvieron los factores de riesgo independientes de EH de a partir de un análisis de regresión múltiple. A continuación, se propuso una puntuación de predicción basada en coeficientes β y se verificó de forma preliminar en la cohorte de validación. Variables principales Todos los datos clínicos de los pacientes se registraron consultando historias electrónicas. La EH se definió como un aumento del volumen del hematoma >33% o un crecimiento absoluto del hematoma >6ml respecto a la exploración inicial. Los signos específicos de la tomografía computerizada sin contraste (TCSC) fueron identificados de manera independiente por dos observadores. Resultados Nuestra puntuación demostró de manera satisfactoria su capacidad de discriminación para la EH (el área bajo la curva ROC fue 0.854 en la cohorte de desarrollo frente a 0.893 en la cohorte de validación). Se observó un calibrado adecuado en la cohorte de desarrollo, mientras que el calibrado de la cohorte de validación fue ligeramente inferior, si bien se mantuvo dentro del intervalo de precisión (la desviación máxima, la desviación promedio y el valor P fueron respectivamente 0.070, 0.028 y 0.773, frente a 0.114, 0.056 y 0.156)... (AU)

Feasibility of single-shot compressed sensing cine imaging for analysis of left ventricular function and strain in cardiac MRI.

AIM: To compare single-shot compressed sensing (CS) cine imaging with conventional segmented cine imaging for reliable quantification of left ventricular (LV) volume and strain assessment during cardiac magnetic resonance imaging (CMRI). MATERIALS AND METHODS: Thirty-seven participants underwent both single-shot CS and conventional segmented cines that covered the entire LV. LV volumetric and strain values were obtained. LV volumes, global strain, the standard deviation of time to peak strain (SD-TPS) in the radial, longitudinal, and circumferential directions were compared using the Student's t-test and intraclass correlation coefficient (ICC). Interobserver and intra-observer variabilities of the LV strain values for the two cines method were determined using ICC. RESULTS: Single-shot CS cine-derived LV volumes and myocardial mass measurements correlated strongly with segmented cines (ICC >0.798) and minor systematic end-systolic volume overestimations resulting in ejection fraction underestimations. Single-shot CS cine-derived global strain and SD-TPS were poorly to moderately correlated with segmented cines (ICC from 0.045-0.706). All global strain values derived from single-shot CS cines were underestimated compared with segmented cine-derived values; however, no significant differences in radial and longitudinal SD-TPS between the two cines were found. Among the patient-related factors, heart rate was a strong predictive factor of global longitudinal strain underestimations (p=0.039) in the CS cines. Inter- and intra-observer LV strain variabilities derived from CS and segmented cines were good to excellent. CONCLUSION: Single-shot CS cine CMRI is feasible for the quantitative assessment of LV function. Currently, strain values derived from the two techniques are not interchangeable.