Pattern of Cytogenetic Abnormality by Fluorescence in Situ Hybridization (FISH) in Multiple Myeloma Patients in a Tertiary Hospital

Background: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance, with survival duration ranging from a few months to more than 10 years. Cytogenetic abnormalities (CA) detected by fluorescence in situ hybridization (FISH) are of major prognostic significance since e.g. patients with del(17p), t(4;14) or gain 1q21 show dismal outcome. Objective: To evaluate the cytogenetic patterns by fluorescence in situ hybridization (FISH) of clinically diagnosed cases of multiple myeloma.Methods:This cross-sectional study was conducted in Department of Haematology, Dhaka Medical College Hospital, Dhaka, from January 2018 to December 2018. A total number of 30 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 10.0.Results:Out of 30 diagnosed Multiple Myeloma cases the mean age was 56.37±10.38 years and male to female ratio was almost 3:1. Sixteen (56.7%) of 30 patients. Among 30 cases of 8 cases were thyrogenicity positive of 7(23.3%) patients was detected del 13q positive. Isolated del 13q was found in 4 cases. 2 cases were found coexistence of del 13q and del 17p positive ;1 case was found coexistence of del 13q and t(4;14) positive and rest of 1 case had del 17 p positive. There was no detectable t (11; 14) and t(14;16) in any of 30 cases.Conclusion:FISH panel for Multiple Myeloma including del (13q); t(11;14); t(4;14), del(17p), t(14;16) is very important molecular test for the prognosis , risk stratification, treatment modality of the patient. On the basis of cytogenetic abnormality Multiple Myeloma risk stratification is modified now a day. This Revised International Staging system R-ISS is a simple and powerful prognostic staging system.

Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients

Objectives Quantification of 24 h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24 h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300 mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. Methods From October 2013 paired 24 h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24 h-proteinuria and UACR at baseline was assessed by Pearson’s r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. Results A strong linear correlation was found between 24 h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31 months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36 months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. Conclusions UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24 h-proteinuria in clinical trials and individual patients’ management.

Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer

The importance of integrating biomarkers into the TNM staging has been emphasized in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8th edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.

Choroidal changes and associations with visual acuity in diabetic patients

Background The variable visual function observed in diabetic retinopathy (DR) patients is not fully explained by the classic staging system. Our purpose was to evaluate choroidal changes, in standardized sectors, in DR patients and to find associations between choroidal measurements and visual function. Methods Cross-sectional study that included the right eye of diabetic patients (n = 265) without active edema, ischemia or neovascularization and age-matched controls (n = 73). Optical coherence tomography (OCT) imaging was performed with enhanced depth imaging protocol. Choroidal vascularity index (CVI) was calculated in a 5 mm scan centered in the fovea. Results CVI decreased with age (p < 0.001) but was not influenced by axial length. A multivariate analysis adjusting for age confirmed a significant difference in CVI between DR eyes that had previous treatments (intravitreal injections and/or photocoagulation) compared to control eyes (p = 0.013) and to DR eyes that never required treatment (p = 0.002). There was no significant difference between non-DR diabetic patients and normal controls. Considering the group of DR patients that had previous treatments, in eyes without optic media opacification, BCVA correlated with CVI (r = − 0.362, p < 0.001), whereas full retina thickness and individual retinal layer thickness did not (p > 0.066). Conclusions A reduction in CVI was observed in patients with a more advanced stage of DR. In treated DR patients with stable disease, choroidal biomarkers correlated with best-corrected visual acuity whereas retinal biomarkers did not. Trial registration: N/A

Identification of a Glycosyltransferase Signature for Predicting Prognosis and Immune Microenvironment in Neuroblastoma

Neuroblastoma (NB) is one of the most common solid tumors in children. Glycosyltransferases (GTs) play a crucial role in tumor development and immune escape and have been used as prognostic biomarkers in various tumors. However, the biological functions and prognostic significance of GTs in NB remain poorly understood. The expression data from Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were collected as training and testing data. Based on a progression status, differentially expressed GTs were identified. We constructed a GTscore through support vector machine, least absolute shrinkage and selection operator, and Cox regression in NB, which included four prognostic GTs and was an independent prognostic risk factor for NB. Patients in the high GTscore group had an older age, MYCN amplification, advanced International Neuroblastoma Staging System stage, and high risk. Samples with high GTscores revealed high disialoganglioside (GD2) and neuron-specific enolase expression levels. In addition, a lack of immune cell infiltration was observed in the high GTscore group. This GTscore was also associated with the expression of chemokines (CCL2, CXCL9, and CXCL10) and immune checkpoint genes (cytotoxic T-lymphocyte–associated protein 4, granzyme H, and granzyme K). A low GTscore was also linked to an enhanced response to anti–PD-1 immunotherapy in melanoma patients, and one type of tumor was also derived from neuroectodermal cells such as NB. In conclusion, the constructed GTscore revealed the relationship between GT expression and the NB outcome, GD2 phenotype, and immune infiltration and provided novel clues for the prediction of prognosis and immunotherapy response in NB.

Amino Acid and Proliferation PET/CT for the Diagnosis of Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy characterized by infiltration of monoclonal plasma cells in the bone marrow (BM). The standard examination performed for the assessment of bone lesions has progressed from radiographic skeletal survey to the more advanced imaging modalities of computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). The Durie–Salmon PLUS staging system (upgraded from the Durie–Salmon staging system) applies 2-[18F]-fluoro-2-deoxy-glucose (18F-FDG) PET/CT, and MRI findings to the staging of MM, and 18F-FDG PET/CT has been incorporated into the International Myeloma Working Group (IMWG) guidelines for the diagnosis and staging of MM. However, 18F-FDG PET/CT has significant limitations in the assessment of diffuse BM infiltration and in the differentiation of MM lesions from inflammatory or infectious lesions. The potential of several new PET tracers that exploit the underlying disease mechanism of MM has been evaluated in terms of improving the diagnosis. L-type amino acid transporter 1 (LAT1), a membrane protein that transports neutral amino acids, is associated with cell proliferation and has strong ability to represent the status of MM. This review evaluates the potential of amino acid and proliferation PET tracers for diagnosis and compares the characteristics and accuracy of non-FDG tracers in the management of patients with MM.

The utility of the Edmonton Obesity Staging System for the prediction of COVID-19 outcomes: a multi-centre study

Background Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. Methods 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. Results The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02–1.97 and 2.78, 95% CI 1.83–4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06–2.74, and 2.62, 95% CI 1.65–4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42–0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03–2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50–3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. Conclusions EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.

Favourable outcomes of repeat one-stage exchange for periprosthetic joint infection of the hip

Aims One-stage exchange for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) is gaining popularity. The outcome for a repeat one-stage revision THA after a failed one-stage exchange for infection remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat one-stage exchange, and to investigate the association between the Musculoskeletal Infection Society (MSIS) staging system and further infection-related failure. Methods We retrospectively reviewed all repeat one-stage revision THAs performed after failed one-stage exchange THA for infection between January 2008 and December 2016. The final cohort included 32 patients. The mean follow-up after repeat one-stage exchange was 5.3 years (1.2 to 13.0). The patients with a further infection-related failure and/or all-cause revision were reported, and Kaplan-Meier survival for these endpoints determined. Patients were categorized according to the MSIS system, and its association with further infection was analyzed. Results A total of eight repeat septic revisions (25%) developed a further infection-related failure, and the five-year infection-free survival was 81% (95% confidence interval (CI) 57 to 92). Nine (28%) underwent a further all-cause revision and the five-year all-cause revision-free survival was 74% (95% CI 52 to 88). Neither the MSIS classification of the host status (p = 0.423) nor the limb status (p = 0.366) was significantly associated with further infection-related failure. Conclusion Repeat one-stage exchange for PJI in THA is associated with a favourable five-year infection-free and all-cause revision-free survival. Notably, the rate of infection control is encouraging when compared with the reported rates after repeat two-stage exchange. The results can be used to counsel patients and help clinicians make informed decisions about treatment. With the available number of patients, further infection-related failure was not associated with the MSIS host or limb status. Cite this article: Bone Joint J 2022;104-B(1):27–33.