Germline genetic variants in Turkish familial multiple myeloma/monoclonal gammopathy of undetermined significance cases.

Multiple myeloma (MM) is a haematological malignancy primarily affecting the elderly, with a striking male predilection and ethnic disparities in incidence. Familial predisposition to MM has long been recognized, but the genetic underpinnings remain elusive. This study aimed to investigate germline variants in Turkish families with recurrent MM cases. A total of 37 MM-affected families, comprising 77 individuals, were included. Targeted next-generation sequencing analysis yielded no previously reported rare variants. Whole exome sequencing analysis in 11 families identified rare disease-causing variants in various genes, some previously linked to familial MM and others not previously associated. Notably, genes involved in ubiquitination, V(D)J recombination and the PI3K/AKT/mTOR pathway were among those identified. Furthermore, a specific variant in BNIP1 (rs28199) was found in 13 patients across nine families, indicating its potential significance in MM pathogenesis. While this study sheds light on genetic variations in familial MM in Turkey, its limitations include sample size and the absence of in vivo investigations. In conclusion, familial MM likely involves a polygenic inheritance pattern with rare, disease-causing variants in various genes, emphasizing the need for international collaborative efforts to unravel the intricate genetic basis of MM and develop targeted therapies.

Analysis of Treatment Strategies and Outcomes in Malignant Peritoneal Mesothelioma: Insights From a Multi-Center Study.

BACKGROUND: This study aimed to evaluate the demographic," clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population. METHODS: A retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients' diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study. RESULTS: The study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason. CONCLUSIONS: According to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable.

Determination of Risk Factors for Infectious Diarrhea in Patients with Hematological Malignancy.

BACKGROUND: This study aimed to determine the risk factors of infectious diarrhea in patients undergoing chemotherapy or hematopoietic stem cell transplantation for hematological malignancies. MATERIALS AND METHODS: This was a prospective, observational study. Patients in whom the infectious agent was determined by laboratory examination were considered to have infectious diarrhea. Patients with diarrhea were categorized as infectious or unidentified and compared in terms of demographic data, treatments, risk factors, laboratory findings, and prognosis. RESULTS: A total of 838 patients were hospitalized, among which 105 patients who met the inclusion criteria were included (12.5%). The patients were divided into two groups: 67 (63.8%) with unidentified diarrhea and 38 (36.2%) with infectious diarrhea. There were no differences between these groups in terms of age, sex, types of hematological malignancies, and presence of comorbidities. The most commonly isolated microorganism was Clostridioides difficile (12.4%). The rate of corticosteroid use was higher in the group with infectious diarrhea (39.5%) than in the group with unidentified diarrhea (7.5%) (P <0.001). The rate of granulocyte colony-stimulating factor (GCSF) use was higher in patients with unidentified diarrhea than in patients with infectious diarrhea (67.2% vs. 42.1%, P=0.022). The median duration of diarrhea was 9 (4-10) days in the group with infectious diarrhea and 5 (3-8) days in the group with unidentified diarrhea (P=0.012). According to the multivariate logistic regression model, corticosteroid treatment increased the risk of infectious diarrhea by a 4.75-fold (95% confidence interval [CI], 1.32-17.02) times. Moreover, the duration of diarrhea may result in a 1.15 (95% CI, 1.02-1.31) fold increase in the risk of infectious diarrhea, while GCSF treatment had a 2.84 (1/0.35) (95% CI, 0.12-0.96) fold risk-reducing effect against infectious diarrhea. CONCLUSION: Infectious diarrhea lasts longer than unidentified diarrhea in patients with hematological malignancies. Although corticosteroid use is a risk factor for developing infectious diarrhea, GCSF use has a protective effect.

Types and Rates of COVID-19 Vaccination in Patients With Newly Diagnosed Microsatellite Stable and Instable Non-Metastatic Colon Cancer.

Introduction Microsatellite instable (deficient mismatch repair, dMMR) colon cancer is associated with hypermutability and immune infiltration-activation. COVID-19 vaccines stimulate immune-inflammation response. This study aimed to investigate the types and rates of COVID-19 vaccines in patients with newly diagnosed colon cancer and compare it according to the microsatellite status. Methods The study was a single-center case-control study. Patients diagnosed with colon cancer at least three months after the last COVID-19 vaccine (BNT162b2, CoronaVac) dose were included. Patients with dMMR and microsatellite stable (MSS) tumors were defined as cases and controls, respectively, between June 2021 and June 2023. Baseline characteristics and vaccine status between case-control groups were compared as univariable and multivariable. Inflammation markers were compared between MSS+CoronaVac and dMMR+BNT162b2 groups. Results A total of 76 patients were included. The BMI was higher in the MSS group (BMI>25 84.3% vs. 57.9%, p=0.00), and right-sided tumors were more common in the dMMR group (71% vs.46.4%, p=0.00). The dMMR group had a higher BNT162b2 vaccine history than the MSS group (86.8% vs. 63.2%, p=0.01), while there was no difference in CoronaVac history (p=0.32). Significant variables in univariable analysis (BMI, localization, and BNT162b2) were included in multivariable logistic regression. The BNT162b2 vaccine was significantly associated with dMMR status (OR: 6.39, 95% CI: 1.55-26.26, p=0.01). The dMMR+BNT162b2 group had higher median C-reactive protein (CRP) level (p=0.01), erythrocyte sedimentation rate (p=0.05), and lower lymphocyte/CRP ratio (p=0.04) than the MSS+CoronaVac group. Conclusion Immune infiltration in dMMR colon cancer may interact with COVID-19 vaccine-induced immune activation. Long-term clinical and preclinical studies are needed to confirm these findings.

Outcomes of allogeneic haematopoietic cell transplantation for myelofibrosis in children and adolescents: the retrospective study of the EBMT Paediatric Diseases WP.

This retrospective study evaluated 35 children (median age 5.2 years; range 0.4-18) with myelofibrosis (MF), including 33 with primary myelofibrosis and 2 with secondary myelofibrosis transplanted from matched sibling donor (MSD) (n = 17) or non-MSD (n = 18) between 2000 and 2022. Conditioning was usually chemotherapy-based (n = 33) and myeloablative (n = 32). Fifteen patients received bone marrow (BM), 14 haematopoietic cells (HC) from peripheral blood (PB), and 6 from cord blood (CB). Day +100 acute GvHD II-IV incidence was significantly lower after MSD-haematopoietic cell transplantation (MSD-HCT) than after non-MSD-HCT [18.8% (4.3-41.1) vs 58.8% (31-78.6); p = 0.01]. Six-year non-relapse mortality (NRM) was 18% (7.1-32.8), relapse incidence was 15.9% (5.6-30.9), progression-free survival (PFS) was 66.1% (47-79.7), GvHD-free relapse-free survival was 50% (30.6-66.7), and overall survival (OS) was 71.1% (51.4-84). Six-year PFS and OS were significantly higher after BM transplantation compared to HCT from other sources [85.1% (52.3-96.1) vs 50.8% (26.3-71), p = 0.03, and 90.9% (50.8-98.7) vs 54% (28.1-74.2), p = 0.01, respectively], whereas NRM was significantly lower [0% vs 32% (12.3-53.9); p = 0.02]. This first multicentre study on outcomes of allogeneic HCT in children with myelofibrosis proves feasibility and curative effect of transplantation in these children, suggests that bone marrow transplantation is associated with better outcomes, and indicates the need for further studies.

Vitamin D levels in patients with small and medium vessel vasculitis / Niveles de vitamina D en pacientes con vasculitis de pequeños y vasos medianos

Objectives: To determine the prevalence of vitamin D deficiency in patients with small and medium vessel systemic vasculitis. Methods: In this cross-sectional study, 25-hydroxy (OH) vitamin D3 levels were measured in adult patients with systemic small and medium vessel vasculitis including antineutrophil cytoplasmic antibody-associated vasculitis (AAV), cryoglobulinaemic vasculitis (CryV), IgA vasculitis (IgAV) and polyarteritis nodosa (PAN), and age- and sex-matched healthy subjects (HS) and patients with rheumatoid arthritis (RA) as control groups. 25OH vitamin D3 levels<30ng/ml and <20ng/ml were regarded as insufficiency and deficiency, respectively. Results: Fifty-seven patients (42 AAV, 2 CryV, 8 IgA vasculitis, 5 PAN) with systemic vasculitis, 101 HS, and 111 RA patients were included. The mean 25OH vitamin D3 level was 21.8±14.2ng/mL in patients with vasculitis, 42.7±27.6ng/mL in HS (p<.001) and 20.1±18.47ng/mL in patients with RA (p=.54). Vitamin D insufficiency and deficiency were significantly higher in patients with systemic vasculitis compared to HS (75.4% vs 33.7%, p<.001; %50 vs 21.8%, p<.001, respectively). Vitamin D status was not different in patients with systemic vasculitis compared to RA. There was a negative correlation between vitamin D status and CRP levels (=−.364, p=.007). The multivariate logistic regression analysis showed that renal involvement was significantly associated with vitamin D deficiency/insufficiency in patients with vasculitis (OR 22.5 [95% CI 1.6–128.9]. Conclusion: Vitamin D deficiency and insufficiency are more frequent in patients with systemic small and medium vessel vasculitis and RA than HS. Renal involvement is one of the factors associated with vitamin D deficiency/insufficiency in patients with vasculitis.(AU)

Objetivos: Determinar la prevalencia de la deficiencia de vitamina D en los pacientes con vasculitis sistémica de pequeños y medianos vasos. Métodos: En este estudio transversal se midieron los niveles de 25-hidroxivitamina D3 en pacientes adultos con vasculitis sistémica de pequeños y medianos vasos, incluyendo vasculitis asociada a anticuerpos anticitoplasma de neutrófilos (AAV), vasculitis crioglobulinémica (CryV), vasculitis IgA (IgAV) y poliarteritis nodosa (PAN), y sujetos sanos pareados por edad y sexo (SS) y pacientes con artritis reumatoide (AR) como grupos control. Se consideraron insuficientes y deficientes los niveles de 25-hidroxivitamina D3<30ng/ml y <20ng/ml, respectivamente. Resultados: Se incluyeron 57 pacientes (42 de AAV, 2 de CryV, 8 de vasculitis IgA y 5 de PAN) con vasculitis sistémica, 101 SS y 111 pacientes de AR. El nivel medio de 25-hidroxivitamina D3 fue de 21,8±14,2ng/ml en pacientes con vasculitis, 42,7±27,6ng/ml en SS (p<0,001) y 20,1±18,47ng/ml en pacientes con AR (p=0,54). La insuficiencia y deficiencia de vitamina D fueron significativamente más altas en los pacientes con vasculitis sistémica en comparación con los SS (75,4 vs. 33,7%; p<0,001; 50 vs. 21,8%; p<0,001, respectivamente). El estatus de vitamina D no fue diferente en los pacientes con vasculitis sistémica en comparación con AR. Existió una correlación negativa entre el estatus de vitamina D y los niveles de PCR=−0,364; p=0,007. El análisis de regresión logística multivariante reflejó que el compromiso renal estuvo significativamente asociado a la deficiencia/insuficiencia de vitamina D en los pacientes con vasculitis (OR: 22,5; IC 95%: 1,6-128,9). Conclusión: La insuficiencia y deficiencia de vitamina D son más frecuentes en los pacientes con vasculitis sistémica de pequeños y medianos vasos y AR que en los SS. El compromiso renal es uno de los factores asociados a la deficiencia/insuficiencia de vitamina D en los pacientes con vasculitis.(AU)

The association of the circle of Willis anomaly and risk of stroke in patients with carotid artery disease / A associação de anomalia de Círculo de Willis e o risco de AVC em pacientes com doença carotídea

ABSTRACT The circle of Willis is an important collateral system that maintains perfusion to the stenotic area from the contralateral carotid and basilar artery to the region of reduced brain perfusion. The aim of the present study was to compare the circle of Willis anomaly in patients with unilateral symptomatic and asymptomatic carotid artery disease. Results In this retrospective study, we analyzed 175 patients who presented at our outpatient stroke clinic between January, 2013 and June, 2015 with either unilateral symptomatic or asymptomatic carotid artery disease, and who had had CT angiography imaging performed. Demographic properties, carotid artery stenosis and the anomaly of the circle of Willis was recorded. Conclusion There was no statistically significant difference in patients with symptomatic and asymptomatic carotid artery disease in terms of the anomaly of the circle of Willis.

RESUMO O Círculo de Willis é um importante sistema colateral que mantém a perfusão à área estenótica da carótida contralateral e da artéria basilar para a região de perfusão cerebral reduzida. O objetivo do presente estudo foi comparar a anomalia do Círculo de Willis em pacientes com doença carotídea assintomática e sintomática unilateral. Resultados Neste estudo retrospectivo, foram analisados 175 pacientes que foram à nossa clínica ambulatorial de AVC, entre janeiro de 2013 e junho de 2015, com doença carotídea assintomática ou sintomática unilateral, e que fizeram angiografia por tomografia computadorizada. Propriedades demográficas, estenose da artéria carótida e anomalia do Círculo de Willis foram registradas. Conclusão Não houve diferença estatisticamente significativa em pacientes com doença carotídea sintomática e assintomática em termos de anomalia do Círculo de Willis.