[Potential application of improved hard tissue section technique in the clinical pathological diagnosis of bone and bone marrow].

Objective: To discuss the application value of hard tissue section in the clinicopathology diagnosis. Methods: From March 2021 to December 2021, bone slices of 19 patients (1 patient with osteochondroma, 2 patients with chondrosarcoma, 4 patients with osteosarcoma, 2 patients with fibrous dysplasia, 2 patients with bone metastasis from thyroid papillary carcinoma, 2 patients with osteomyelitis, 4 patients with giant cell tumor of bone, 2 patients with Ewing sarcoma) and 16 hemopathy patients were collected from the Department of Pathology, Shanghai Sixth People's Hospital. Of the osteopathy patients, there were 14 male and 5 female with a median age of 31 (10-66) years. Meanwhile, there were 7 male and 9 female with a median age of 28 (16-65) years among these hemopathy patients. Thirty-five cases were treated with modified hard tissue slicing technique and paraffin embedding technique, respectively. The advantages and disadvantages of the two methods for clinical diagnosis of bone disease were compared by Hematoxylin-Eosin staining (H&E staining), immunohistochemical staining (IHC), fluorescence in situ hybridization (FISH) and Sanger sequencing. Results: The improved resin-embedded method showed better histological morphology and cell structure. Besides, the expression of Ki67, SATB2, CD34, SMA, CD68,MPO,CD4 and CD33 in immunohistochemical staining in bone tissues which were embedded in resin were more clear in the accurate positive localization than those using paraffin-embedded. MDM2 of FISH exhibited a higher fluorescence intensity and more accurate location. Meanwhile, both methods treated with Sanger sequencing met the requirements of DNA purity and mutation detection. Conclusion: The improved hard tissue section method is simple and short time-consuming, which is suitable for optimizing the clinical bone and bone marrow pathological diagnosis process.

A Multicenter Virtual Multidisciplinary Sarcoma Case Conference Improves Outcome for a Rare Soft Tissue Sarcoma (Dermatofibrosarcoma Protuberans).

INTRODUCTION: The purpose of this study is to analyze the impact of a virtual multidisciplinary sarcoma case conference (VMSCC) on the outcomes of dermatofibrosarcoma protuberans (DFSP). METHODS: We compared margin status after surgery and disease-free survival (DFS) on two cohorts of patients with DFSP, one diagnosed from 2010 to 2015 and one from 2016 to 2020 (before and after virtual multidisciplinary sarcoma case conference (VMSCC) within Kaiser Permanente Northern California (KPNC), using Kaplan-Meier curves and Cox proportional hazard regression models. RESULTS: There was no significant difference between the two cohorts on demographics, tumor location, type of surgery, receipt of radiation, receipt of imatinib, or size of tumor. However, the percent of patients with positive margin after final surgery and the percent of local recurrence were significantly different: 6.5% and 6.3% for the 2010-2015 cohort, and .8% and 0% for the 2016-2020 cohort, respectively. CONCLUSION: Our data suggest that the outcomes of DFSP improved significantly after the implementation of VMSCC.

[Influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome: A retrospective study].

Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.

Performance and reading time of lung nodule identification on multidetector CT with or without an artificial intelligence-powered computer-aided detection system.

AIM: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes. MATERIALS AND METHODS: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance. RESULTS: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001). CONCLUSION: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers.

Bouveret Syndrome: A Rare Case of Instance and Treatment in a Younger Patient.

Bouveret syndrome, a specific form of gallstone ileus, is the obstruction of the gastric outlet by a gallstone, which can enter the duodenum through a fistula. While the average age of individuals with Bouveret syndrome is 74 years, our patient was 42 years of age at the time of operation, significantly younger than the average patient afflicted with this condition. In the treatment of our patient's condition, the operation conducted entailed a partial duodenectomy, gastrojejunostomy, cholecystectomy, common bile duct exploration, extraction of bile duct stones, and insertion of a t-tube in the bile duct. The patient was found to be in healthy condition upon check-up six months after the operation. The outcome of our case suggests that younger Bouveret patients can safely undergo multiple surgical procedures in the treatment of Bouveret syndrome. Our case also suggests that a cholecystectomy and the removal of the obstructing gallstone can both be carried out within one operation, although coupling these two procedures in one operation might be riskier for patients within the normal age range of Bouveret syndrome. We also suggest that fistula repair be carried out for younger Bouveret patients in particular and that the patient be subjected to a CT scan in the diagnosis of Bouveret syndrome when this condition is suspected.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

[Study of iron overload assessment by T2* magnetic resonance imaging in patients with myelodysplastic syndromes].

Objectives: To analyze the cardiac T2* value, liver iron concentration (LIC) , and related laboratory parameters in myelodysplastic syndrome (MDS) with iron overload and evaluate the changes of organ functions after iron chelation therapy. To explore the value of magnetic resonance imaging (MRI) T2* in making early diagnosis and assessing organs iron overload. Methods: Retrospective investigation was used to observe the cardiac T2* value, LIC, iron metabolism parameters and related laboratory parameters of 85 MDS patients from Nov 2014 to Jan 2018. Among them, 7 MDS patients with Low/Int-1 have received iron chelation therapy for 6 months during two MRI examinations. The above parameters were collected before and after iron chelation therapy for comparison. Results: Correlations were found between heart T2* value and age (rs=-0.290, P=0.007) and left ventricular ejection fraction (LVEF) (rs=0.265, P=0.009) . There was a significant negative correlation between heart T2* value and blood transfusion units (rs=-0.701, P<0.001) . There was a significant positive correlation between LIC and serum ferritin (SF) (rs=0.577, P<0.001) . There was also a correlation between LIC and ALT (rs=0.268, P=0.014) and blood transfusion units (rs=0.244, P=0.034) . There was no correlation between heart T2* and pro-BNP, SF (all P>0.05) , and no correlation between LIC and age (P>0.05) . The increase of heart T2* between the normal and abnormal groups was statistically significant (P=0.005) , but the iron overload ratio of the heart T2*<20 ms was not significant between the two groups. There was statistical significance in the proportion of severe liver iron overload (LIC>15 mg/g DW) (P=0.045) . After iron chelation therapy, the values of SF, transferrin saturation, ALT, AST, pro-BNP and LIC of 7 patients were decreased compared with values before iron chelation therapy, and the peripheral blood cell level was increased. However, the changes of LVEF and T2* values after iron chelation were not obvious. Conclusion: MRI T2* may be a predictor of iron overload in patients with MDS in early stage, and may be more valuable compare with LVEF, SF and other laboratory indicators. The safety and repeatability of MRI cardiac T2* examination are recognized, and it can be used as an ideal detection for patients with iron overload.

General hospital admission rates in people diagnosed with personality disorder.

OBJECTIVE: To determine the frequency of all-cause general hospital admissions for individuals with personality disorder (PD) in a large clinical population using linked secondary mental healthcare and hospitalisation data. METHOD: A retrospective cohort study, using anonymised electronic mental health records from South London and Maudsley NHS Foundation Trust (SLaM), linked to Hospital Episodes Statistics in England. People with PD aged 15 years or older, receiving care within SLaM between April 2007 and March 2013, were identified and compared to residents from the local catchment area. Standardised admission ratios (SARs) were calculated for all major categories of causes of general hospital admission for this defined group, with local residents in 2011 UK Census as the standard population. RESULTS: For the 7677 people identified with PD, SAR for all causes of admission was 2.75 (95% CI: 2.70, 2.81). Both men and women with PD had increased SARs across multiple ICD-10 categories, including circulatory, respiratory, digestive, nervous, and musculoskeletal system disorders and endocrine, blood and infectious disorders. Sensitivity analysis (removing the impact of repeated admissions by same individual for same diagnosis in the same year) yielded similar findings. CONCLUSIONS: By comparison with members of the general population, individuals with a diagnosis of personality disorder are at significantly higher risk of hospital admission resulting from a wide range of physical health problems.

Long-term antipsychotic polypharmacy prescribing in secondary mental health care and the risk of mortality.

OBJECTIVES: To investigate the association between long-term antipsychotic polypharmacy use and mortality; and determine whether this risk varies by cause of death and antipsychotic dose. METHODS: Using data from a large anonymised mental healthcare database, we identified all adult patients with serious mental illness (SMI) who had been prescribed a single antipsychotic or polypharmacy, for six or more months between 2007 and 2014. Multivariable Cox regression models were constructed, adjusting for sociodemographic, socioeconomic, clinical factors and smoking, to examine the association between APP use and the risk of death. RESULTS: We identified 10 945 adults with SMI who had been prescribed long-term antipsychotic monotherapy (76.9%) or APP (23.1%). Patients on long-term APP had a small elevated risk of mortality, which was significant in some but not all models. The adjusted hazard ratios for death from natural and unnatural causes associated with APP were 1.2 (0.9-1.4, P = 0.111) and 1.1 (0.7-1.9, P = 0.619) respectively. The strengths of the associations between APP and mortality outcomes were similar after further adjusting for % BNF antipsychotic dose (P = 0.031) or olanzapine equivalence (P = 0.088). CONCLUSION: The findings suggest that the effect of long-term APP on mortality is not clear-cut, with limited evidence to indicate an association, even after controlling for the effect of dose.

Transformation of excess mortality in people with schizophrenia and bipolar disorder in Taiwan.

BACKGROUND: Given the concerns regarding the adverse health outcomes associated with weight gain and metabolic syndrome in relation to use of second-generation antipsychotics (SGAs), we aimed in this study to explore whether the increase in the use of SGAs would have any impacts on the trend of excess mortality in people with schizophrenia and bipolar disorder (BPD). METHOD: Two nationwide samples of individuals with schizophrenia and BPD were identified in Taiwan's National Health Insurance Research Database in 2003 and in 2008, respectively. Age- and gender-standardized mortality ratios (SMRs) were calculated for each of the 3-year observation periods. The SMRs were compared between the calendar year cohorts, by disease group, and by causes of death. RESULTS: The mortality gap for people with schizophrenia decreased slightly, revealing an SMR of 3.40 (95% CI 3.30-3.50) for the 2003 cohort and 3.14 (3.06-3.23) for the 2008 cohort. The mortality gap for BPD individuals remained relatively stable with only those aged 15-44 years having an SMR rising significantly from 7.04 (6.38-7.76) to 9.10 (8.44-9.79). Additionally, in this group of BPD patients aged 15-44 years, the natural-cause-SMR increased from 5.65 (4.93-6.44) to 7.16 (6.46-7.91). CONCLUSIONS: Compared with the general population, the gap in the excess mortality for people with schizophrenia reduced slightly. However, the over 200% difference between the cohorts in the excess mortality for BPD individuals aged 15-44 years could be a warning sign. Future research to further examine the related factors underlying those changes is warranted.

Contributions of specific causes of death to lost life expectancy in severe mental illness.

The life expectancy gap between people with severe mental illness (SMI) and the general population persists and may even be widening. This study aimed to estimate contributions of specific causes of death to the gap. Age of death and primary cause of death were used to estimate life expectancy at birth for people with SMI from a large mental healthcare case register during 2007-2012. Using data for England and Wales in 2010, death rates in the SMI cohort for each primary cause of death category were replaced with gender- and age-specific norms for that cause. Life expectancy in SMI was then re-calculated and, thus, the contribution of that specific cause of death estimated. Natural causes accounted for 79.2% of lost life-years in women with SMI and 78.6% in men. Deaths from circulatory disorders accounted for more life-years lost in women than men (22.0% versus 17.4%, respectively), as did deaths from cancer (8.1% versus 0%), but the contribution from respiratory disorders was lower in women than men (13.7% versus 16.5%). For women, cancer contributed more in those with non-affective than affective disorders, while suicide, respiratory and digestive disorders contributed more in those with affective disorders. In men, respiratory disorders contributed more in non-affective disorders. Other contributions were similar between gender and affective/non-affective groups. Loss of life expectancy in people with SMI is accounted for by a broad range of causes of death, varying by gender and diagnosis. Interventions focused on multiple rather than individual causes of death should be prioritised accordingly.

[Predict response to decitabine in patients with myelodysplastic syndrome and related neoplasms].

Objective: To identify clinical and molecular signatures for predicting response to decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and related neoplasms. Methods: The clinical characteristics of 109 patients with MDS and related neoplasms who were treated with DAC were analyzed retrospectively and the next target sequencing was performed to define recurrently mutated genes in these disease samples, to examine the association of the clinical and molecular signatures with response to DAC treatment. Results: Of 109 MDS and related neoplasms patients, there were 70 males and 39 females, the median age was 61 years old (ranges: 17-85 years old) . According to the international prognostic scoring system (IPSS) , 46 cases were included in the relatively low risk group (low risk and intermediate-1 risk) , 63 in the relative high risk group (intermediate-2 and high risk) . There were 21 cases with complex karyotype, 17 chromosome 7 abnormality and 17 monosomal karyotype. The median courses of DAC treatment was 4 (2-11) . A total of 74 patients achieved response (67.9%) and 30 (27.5%) achieved complete response (CR) . Univariate analysis found that CR was higher in patients with high risk of IPSS, complex karyotypes, monosomal karyotypes, chromosome 7 abnormality, and platelet doubling after one cycle of DAC treatment. Patients with TP53 gene mutation were more likely to receive CR, 10 of 15 patients with TP53 mutations achieved CR. (66.7%) , which was significantly higher than that of the patients without TP53 gene mutation (21.3%) (P=0.001) . Multivariate analysis showed that TP53 gene mutation, platelet doubling after one cycle of DAC treatment and the complex karyotype were independent prognostic factors for CR. Of them, TP53 gene mutation is the strongest predictor (OR=4.39, 95%CI, 1.20-16.06, P=0.026) . Conclusion: TP53 mutation, platelet doubling after one cycle of DAC treatment and complex karyotypes could predict CR to DAC.

The incidence and risk factors for the development of vitreomacular interface abnormality in diabetic macular edema treated with intravitreal injection of anti-VEGF.

PurposeTo report the incidence and associated factors for the development of vitreomacular interface abnormality (VMIA) in patients with diabetic macular edema (DME) who received intravitreal injection (IVI) of anti-VEGF (Bevacizumab and Ranibizumab) treatment.MethodsA retrospective observational study. Patients with DME followed at least 6 months were reviewed. Baseline best-corrected visual acuity (BCVA), central retinal thickness (CRT) and final BCVA, CRT in eyes with and without VMIA were compared. Multiple logistic regression was also used to investigate the risk factors of VMIA formation in patients with DME treated by anti-VEGF.ResultsA total of 201 eyes in 142 patients met the inclusion criteria of the study. VMIA developed in 44 eyes (21.89%) of patients during a mean follow-up period of 40.84 months. The estimated mean incidence of VMIA formation was 6.43% per year. Poor baseline BCVA was found to be a risk factor for VMIA development (P=0.001, odds ratio=5.299, 95% confidence interval: 1.972 to 14.238). There was no difference between eyes with and without VMIA formation in improving BCVA (P=0.557) and lowering the macular edema (eyes without VMIA formation: -107.72±171.91 µm; eyes with VMIA formation: -155.02±212.27 µm, P=0.133).ConclusionsThis study revealed the incidence of VMIA formation in IVI anti-VEGF treated DME eyes was 6.43%. Poor baseline BCVA was found to be a risk factor for VMIA formation. Both eyes with and without VMIA development had favorable response to anti-VEGF treatment.

New metal chalcogenides found in MnN-1(Gd2-xInx)SN+2 (N = 3, 4, 5): syntheses, structures, and magnetic properties.

Three new metal chalcogenides have been identified in MnN-1(Gd2-xInx)SN+2 with N = 3, 4, and 5 via a flux-growth synthesis. All compounds crystallize in the same space group of orthorhombic Cmcm with cell constants: Mn2GdInS5 (1), a = 3.789(1) Å, b = 12.411(1) Å, and c = 15.489(1) Å; Mn3Gd2S6 (2), a = 3.778(1) Å, b = 12.505(2) Å, and c = 19.114(2) Å; Mn4Gd2S7 (3), a = 3.769(1) Å, b = 12.466(2) Å, and c = 22.289(3) Å. Compounds 1-3 form a homologous series through the modulation of the MnS unit, whose structures represent a complete system of the corresponding lillianites (N1,N2L) of 3,3L, 4,4L and 5,5L. The gradually wider slabs formed in the series result in a monotonic increase along the c dimensions from 1 to 3. Crystal 3 is the first to achieve a predicted structure of 5,5L. Mn2GdInS5 (1) displays a weak antiferromagnetic (AFM) ordering at 10 K and the Weiss constant (θ) of -0.76 K. Mn2Gd1.5In0.5S5 (1a), an isostructure of 1, shifts the AFM transition temperature to 12 K and possesses a slightly larger θ constant of -6.06 K. Mn4Gd2S7 (3), featuring the thickest slabs in this series, shows a significant antiferromagnetic behavior beginning at a high temperature of 70 K and has a largest θ constant of -40.25 K. A small amount of impurity α-Gd2S3 with an AFM transition temperature around 4 K was characterized in sample 3, which does not interfere with the magnetic ordering of 3 at much higher temperatures. These magnetic chalcogenides display band gaps of 1.66 eV for 1, 1.75 eV for 1a, and 1.44 eV for 3.

Prevention of perceptual-motor decline by branched-chain amino acids, arginine, citrulline after tennis match.

Perceptual-motor performance in prolonged tennis matches may be affected by central fatigue. The purpose of this study was to investigate the supplementation of branched-chain amino acids (BCAA), arginine, and citrulline on tennis-specific perceptual-motor performance after a simulated match. Nine male tennis players consumed 0.17 g/kg BCAA, 0.05 g/kg arginine, and 0.05 g/kg citrulline (AA trial), or placebo (PB trial) 1 h before the match. In the perceptual-motor performance test before and after the match, the subjects hit balls to the opposite direction of the examiner's movement. The AA trial showed significantly higher rate of correct direction than the PB trial after the match (AA trial: 93.63 ± 1.28%, PB trial: 69.09 ± 2.40%). The AA trial also demonstrated significantly higher post-match accuracy and consistency than the PB trial. The AA trial showed significantly lower heart rate and ratings of perceive exertion during the match, concurrently with a significantly lower plasma total tryptophan/BCAA ratio. Similar post-match plasma NH3 concentrations were found in both trials while the AA trial was significantly higher in NOx concentration. This study suggested that the supplementation could prevent the decline in perceptual-motor performance through alleviation of central fatigue by BCAA and prevention of excess hyperammonemia by arginine and citrulline.