Confirmation of C4 gene copy number variation and the association with systemic lupus erythematosus in Chinese Han population

The distribution of complement component 4 (C4) gene copy number (GCN) has been validated in European populations. Meanwhile, C4 gene has been identified as a susceptibility gene for systemic lupus erythematosus (SLE). However, the association and the possible phenotype significance remain to be determined intensely in the Chinese population. This study was designed to validate the distribution of C4 GCNs in Chinese Han and the correlation between C4 GCNs and SLE using quantitative real-time polymerase chain reaction in 924 SLE patients and 1,007 controls. The results presented distribution of C4 GCNs in healthy populations and also showed that lower C4 GCN was a risk factor for SLE and higher C4 GCN was a protective factor against the disease susceptibility, which was similar to the report in the Caucasian population. Furthermore, we found the association between C4A GCN and disease subphenotypes of arthritis with SLE. We conclude that the association of C4 GCN with SLE was replicated in Chinese Han population, which highlighted the importance of C4 in SLE pathogenesis of diverse populations.     

Population pharmacokinetics of cyclophosphamide in patients with thalassemia major undergoing HSCT

CY in combination with BU is a widely used conditioning regimen for haematopoietic SCT (HSCT). The aim of this study was to evaluate the pharmacokinetics (PK) of CY and its major metabolite 4-hydroxyCY (HCY) in patients with thalassemia undergoing HSCT. A total of 55 patients received BU (16 mg/kg) followed by CY (160-200 mg/kg) both over 4 days before HSCT. A population PK model was developed to describe the disposition of CY and HCY and the inter-individual (IIV) and inter-occasion variability (IOV). The model was also used to determine the effects covariates including: demographics, Lucarelli classification and polymorphisms in enzymes involved in the metabolism or biotransformation of CY had on CY and HCY disposition. Overall, 17-114% IIV and 12-103% IOV in CY and HCY PK parameters were observed. Body weight and age were the main covariates, which explained the largest portion of the IIV. In addition, CYP2C9*2 explained a significant portion of the IIV in the clearance (P<0.002) and thus the area under the concentration curve (P<0.05) of CY. This covariate model may be used to design and plan targeted dose therapy in this group of pediatric patients, if clinical outcome association with CY PK are proved and target range established.     

Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.     

Ewing's sarcoma of the lesser sac masquerading as a pancreatic tumor

Extraosseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is an uncommon, aggressive, and malignant tumor with a poor patient outcome. Its occurrence in the lesser sac is a rare event and to the best of our knowledge, has not been previously described. The present case was clinically and radiologically misdiagnosed as a pancreatic tumor/gastrointestinal stromal tumor. Histopathology revealed a tumor with "small round cells" that were positive for CD99, confirming the diagnosis of ES/PNET. This report highlights the importance of considering Ewing's sarcoma in the differential diagnosis of intraabdominal, extraintestinal masses.     

The relationship between clinical outcomes and quality of life in first‐episode mania: a longitudinal analysis

Objectives: Despite growing attention to the relationship between bipolar disorder (BD) and quality of life (QoL), there remains a lack of information about QoL in the early stages of BD, and about the course of QoL in people with BD over time. Here, we report on QoL and symptomatic outcomes over a 1.5‐year period in a Canadian sample of first‐episode mania patients. Methods: Patients (n = 63) with DSM‐IV‐TR BD type I recovering from a recent episode of mania were recruited from a university‐based hospital setting in Vancouver, BC, Canada and assessed at six monthly intervals for 18 months. In addition to symptomatic and cognitive assessments, two self‐report QoL scales [the Quality of Life Enjoyment and Satisfaction Questionnaire (Q‐LES‐Q) and the Medical Outcomes Study Short Form 36 (SF‐36)] were administered. Results: Baseline QoL scores were high, with mean Q‐LES‐Q scores at 70% of the maximum possible score; QoL continued to show a trend towards improvement over time. Multiple hierarchical regressions were used to explore predictors of QoL over time, finding that: (i) length of illness and severity of depressive symptoms at baseline predicted Q‐LES‐Q scores at both baseline and six months; (ii) the number of previous depressive episodes and severity of depression at baseline and 12 months all predicted QoL at 12 months; and (iii) only severity of depressive symptoms at 12 months predicted QoL at 18 months. Conclusions: Our observation that QoL in patients who have recently experienced an episode of mania can be relatively preserved offers hope, both for healthcare providers and for those newly diagnosed. Further, that severity of depressive symptoms even in the early stages of the disease was the consistent predictor of QoL suggests that depressive symptoms need to be aggressively treated to improve QoL.     

Neuro-ophthalmic presentation of COVID-19 disease: A case report

COVID-19 is a respiratory virus, which has affected various organ systems as well. Here we report a neuro-ophthalmic presentation of pituitary apoplexy under the setting of COVID-19 infection in a middle-aged man who presented to ophthalmic emergency with sudden bilateral loss of vision along with a history of fever past 10 days. There was sluggishly reacting pupils and RT-PCR for COVID was positive. Imaging pointed the diagnosis as pituitary macroadenoma with apopexy. In view of pandemic situation, patient was given symptomatic treatment as per the protocols and stabilized. Vision also showed improvement to some extent and the patient is awaiting neurosurgery     

Highly efficient catalyst-free domino conjugate addition,decarboxylation and esterification/amidation of coumarin carboxylic acid/esters with pyrazolones: a green chemistry approach

Tandem conjugate addition, decarboxylation and esterification/amidation of coumarin 3-carboxylic acid derivatives with pyrazolones have been developed. The reactions were performed with coumarin 3-carboxylic acid/esters and pyrazolone in alcohol as a solvent to afford the corresponding pyrazolyl 2-hydroxy phenylpropionate derivatives. Amines and green solvents were employed for amidation in the addition reaction. The methodology has advantages such as excellent yields, a broad substrate scope, catalyst-free, easy purification by simple filtration without any workup, mild conditions and does not require any organic solvents, ligands, base or any additives. This is a green and general synthetic protocol, which could be applicable for the synthesis of substituted pyrazolyl phenyl propionate/amide derivatives. This approach demonstrates the importance of the coumarin 3-carboxylic acid/ester core structure for Michael addition.

Tandem conjugate addition, decarboxylation and esterification/amidation of coumarin 3-carboxylic acid derivatives with pyrazolones have been developed.     

Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: Impact of mandatory central pathology review at a large referral hospital

Background and objectiveUrothelial carcinoma (UC) demonstrating variant histologic differentiation is associated with poor outcomes, and certain variants exhibit differing therapeutic responses compared with pure conventional UC. Little is known about the awareness and reporting practices of UC with variant histology in community practice.Materials and MethodsPatients diagnosed with UC based on an outside pathologic review had their pathology centrally reviewed before instituting therapy. A discordant diagnosis was defined as the presence of variant histologic differentiation not reported by the referring institution. Variant histologic differentiation was quantitated as focal (10%–50%) or extensive (>50%).ResultsOf 589 transurethral biopsies (TURBTs), 115 (19.5%) UCs demonstrated variant histologic differentiation. Muscle invasion at TURBT and extravesical disease at cystectomy was present in 69% and 52%, respectively. Of 56 patients with at least 1 year follow-up, recurrence-free survival was 56%. The majority (90%) showed a single variant histology, which was extensive in 58% of cases. Squamous differentiation (32%) was the most common variant histology identified, followed by small cell (16%), glandular (13%), micropapillary (12%), nested (8%), sarcomatoid (6%), lymphoepithelial (3%), and plasmacytoid (1%) type. Variant histologic differentiation was not documented by the referring institution in 44% of cases, of which 47% were extensive. Commonly under-recognized patterns included lymphoepithelial (2) and plasmacytoid (1) types (100%), nested (7, 87%), micropapillary (10, 83%), and small cell (7, 44%).ConclusionsThis study emphasizes the importance of central pathology review in the management of bladder cancer patients and the need for increased awareness of this relatively common phenomenon in UC.