Rhoa Mutation Is a Potential Biomarker Associated with Adverse Prognosis and High- Tumor Burden in Patients with Nodal Peripheral Lymphomas with T-Helper Follicular Phenotype (nPTCL-Thf): Data from a Brazilian Retrospective Cohort of Nodal PTCL

Introduction: Nodal PTCL constitute a rare group of aggressive malignancies with heterogeneous clinical-biological presentation and outcomes. In the last decade, its pathophysiological knowledge has been improved, with descriptions of gene mutations associated with epigenetic phenomena (IDH2, TET2 and DNMT3A) and of the RHOA G17V mutation playing a fundamental role in the lymphomagenesis. However, the prognostic impact of these alterations is still controversial, and particularly, in the case of the RHOA mutation, it has never been previously accessed in the literature. Our group has described and validated biomarkers with potential prognostic impact in nPTCL patients, including overexpression of the genes CCNA2, GATA3 and monocytosis in peripheral blood [1,2,3]. The identification of new potential molecular biomarkers can refine the prognostic stratification of these tumors and allow identification of targets for future specific therapies. The aim of this study was to evaluate the frequency and prognostic impact of mutations in the IDH2, TET2, DNMT3 and RHOA genes in Brazilian patients with nPTCL. Methods: In this observational, retrospective and unicentric study, we analyzed the clinical-epidemiological characteristics, outcomes and mutational profile of 59 Brazilian patients with nPTCL treated at the HC-FMUSP, from January 2000 to December 2017. All cases were submitted to centralized histopathological review and were classified according to the criteria proposed by WHO-2008. Cases initially categorized as PTCL/NOS were later reclassified according to WHO-2016 criteria. FFPE-tumor samples from patients with PTCL/NOS, AITL, ALK+/ALCL and ALK-/ALCL were submitted to DNA extraction using QIAmp DNA FFPE kit. For amplification of specific products of target-genes primers flanking the hot spots regions were designed. After this step, the PCR products were submitted to first generation sequencing in 3500 Genetic Analyzer. Absolute and relative frequencies of mutations were accessed for the total cohort and its pathological subtypes. OS and PFS curves were constructed using the Kaplan-Meier method. Log-rank test was used to estimate the prognostic impact of mutations. Results: The clinical-epidemiological characteristics of the 59 Brazilian-patients with nPTCL are summarized in Table 1. With a median follow-up of 3.70 years (0.90-12.4 years), the estimated 2-years OS and PFS were 59.1% and 47.2%, respectively. ORR was 55.9% (33/59), with early relapse rate (< 12 months) of 14.3% (5/59) and global death rate of 52.5% (31/59). In the total cohort, we found a mutation frequency of 3.4% (2/59) for the IDH2 gene, 62.7% (37/59) for DNMT3A, 23.7% (14/59) for RHOA and 50.8% (30/59) for TET2. There was no statistically significant difference in the frequency distribution of IDH2, DNMT3A and TET2 mutations between the different histological subtypes of nPTCL. However, there was a statistical trend towards a higher occurrence of the RHOA mutation in the AITL and PTCL/NOS subtypes (3/9-33.3% and 7/16-43.7%, respectively; p=0.07). Among 7 cases with RHOA mutation classified as PTCL/NOS according WHO-2008 criteria, 6/7 (85.7%) expressed the PD-1 marker in immunohistochemistry, being reclassified as nPTCL with THf phenotype according to WHO-2016 criteria. So, the mutation RHOA was predominantly found in THf cell-derived neoplasms in our cohort. The mutational status of DNMT3A, RHOA and TET2 genes had no prognostic impact on OS, with p=0.85, p=0.13 and p=0.95, respectively. The same was observed in relation to PFS for the DNMT3A (p=0.70) and TET2 (p=0.52) mutations. However, the presence of the RHOA mutation was associated with the unfavorable PFS in our cohort (HR:1.98, p=0.05). We observed 2-year PFS of 28.6% (95% CI: 8.8-52.4%) for mutated-RHOA cases versus 52.9% (95% CI: 37.3-66.3%) for wild-type-RHOA patients (p=0.05) [Figure 1]. We also demonstrated that RHOA mutation was a predictor of lower ORR to first-line therapy (p=0.01) and was associated with high tumor burden (p=0.03) [Figure 2]. Conclusion: In this study, for the first time was demonstrated the unfavorable prognostic impact of the RHOA mutation in patients with nPTCL-Thf (AITL and nPTCL-THf), making it a potential molecular biomarker predictor of poor-PFS, associated with resistance to primary therapy and with high tumor burden. Such results are preliminary and will need to be validated in series with a larger number of cases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Kesehatan Ibu Hamil

Anemia adalah suatu keadaan dimana tubuh memiliki jumlah sel darah merah (eritrosit) yang terlalu sedikit, yang mana sel darah merah itu mengandung hemoglobin yang berfungsi untuk membawa oksigen ke seluruh jaringan tubuh (Proverawati, 2013). Menurut WHO (2008), secara global prevalensi anemia pada ibu hamil di seluruh dunia adalah sebesar 41, 8 %. Prevalensi anemia pada ibu hamil diperkirakan di Asia sebesar 48,2 %, Afrika 57,1 %, Amerika 24,1 %, dan Eropa 25,1 %. (Salmariantity, 2012).

New Insights into the Biology and Diagnosis of Splenic Marginal Zone Lymphomas

Splenic marginal zone lymphoma (SMZL) is a small B-cell lymphoma, which has been recognized as a distinct pathological entity since the WHO 2008 classification. It classically presents an indolent evolution, but a third of patients progress rapidly and require aggressive treatments, such as immuno-chemotherapy or splenectomy, with all associated side effects. In recent years, advances in the comprehension of SMZL physiopathology have multiplied, thanks to the arrival of new devices in the panel of available molecular biology techniques, allowing the discovery of new molecular findings. In the era of targeted therapies, an update of current knowledge is needed to guide future researches, such as those on epigenetic modifications or the microenvironment of these lymphomas.

Incidence of Cancer in Adolescents and Young Adults in Jordan, 2000-2017

PURPOSE The epidemiology of cancer in adolescents and young adults (AYAs) is distinct and underinvestigated. Therefore, we investigated the incidence of cancer in AYAs in Jordan. PATIENTS AND METHODS We accessed all records submitted to the Jordan Cancer Registry between 2000 and 2017. We included all patients, age 15-39 years, who were ordinarily resident in Jordan. We then calculated frequencies, age-adjusted incidence rates (AAIRs), and annual percentage changes (APCs) and performed subgroup analyses by biologic sex, age subgroups, and site (SEER AYA site recode/WHO 2008). We also performed site-specific trend analyses using joinpoint models. RESULTS We identified 14,115 eligible patients, of whom 1,531 (10.8%), 4,278 (30.3%), and 8,306 (58.8%) were 15-19, 20-29, and 30-39 years old at diagnosis, respectively. The numbers of male and female AYAs were 5,792 (41.0%) and 8,323 (59.0%), respectively. The crude number of cases increased from 654 in 2000 to 954 in 2017 (APC, 2.6%). The overall AAIR ranged from 32.3 in 2000 to 24.3 in 2017 (APC, –1.7%). The AAIR was 27.6 over the full study period and was higher in females (34.1) than in males (21.6). Carcinomas, lymphomas, and leukemias were the most common cancers. The incidence rates of the majority of cancers trended downward over the study period. CONCLUSION The incidence of cancer in AYAs in Jordan is relatively low and declining. However, the absolute number of cases is increasing because this downtrend does not offset the effect of a high population growth rate; almost a 1,000 cases of cancer are now diagnosed every year, which represents a significant increase in the burden of cancer in a developing country with limited healthcare resources.

A importância da atividade física e alimentação na hipertensão arterial

A hipertensão arterial sistêmica (HAS) é o maior fator de risco para mortalidade no mundo e transformou-se progressivamente em dos mais graves problemas de saúde pública. Em 2018, estimava-se que 12,8% das mortes foram decorrentes da HAS. Associada às várias diversidades sua prevalência sofre influência de múltiplos fatores, com destaque para os demográficos, hereditários, socioeconômicos, comportamentais e antropométricos. A maioria desses fatores podem ser controlado ou modificado, sendo então possível reduzir a incidência da hipertensão e de suas complicações. Além do que contribuiu nas últimas décadas para o aumento das cardiopatias, dos acidentes cerebrovasculares, a insuficiência renal e para as incapacidades prematuras (WHO, 2008; OLIVEIRA et al 2012; OMS 2013; MARQUES et al 2020; BARROSO et al 2021; OLIVEIRA et al 2021). As evidências científicas apontaram que nos últimos anos as condutas não medicamentosas, como adesão aos programas de atividades físicas e alimentação adequada, constituem-se em estratégias iniciais na hipertensão leve a moderada. São ações de baixo custo e risco mínimo, capazes de contribuir para a regulação da pressão arterial, tratamento de dislipidemias e da obesidade. Na revisão sistemática, Marques et al (2020) referem que dentre os fatores de risco, a baixa atividade física representou maior chance de um indivíduo apresentar HAS (TAYLOR, 2014; CASSIANO et al 2020). As Diretrizes Brasileiras para Hipertensão Arterial 2020 citam que há uma associação direta do sedentarismo com a elevação da PA e da HA. A falta de atividade física a maior prevalência estava entre as mulheres (31,7%) do que nos homens (23,4%). O que foi identificado em 2019 pelo inquérito telefônico Vigitel, onde 44,8% dos adultos não alcançaram um nível suficiente de prática de atividade física, sendo esse percentual maior entre mulheres (52,2%) em relação aos homens (36,1%) (PICCINI et al 2012). Existem muitas possibilidades de associar as atividades físicas a uma dieta equilibrada para prevenir e controlar a HA, sejam elas de baixa quantidade de gordura, mediterrânea, vegetariana, baixo teor de carboidratos e outras, além de incluir a baixa ingestão de sódio. No entanto, o maior desafio seja considerar e ser levados em conta os aspectos e as dificuldades socioeconômicos e culturais de cada população. Cassiano et al (2020) concluíram e recomendaram no seu estudo que um programa prolongado de exercícios físicos, associado ao acompanhamento nutricional possibilitará a redução do risco para o desenvolvimento de eventos cardiovasculares nos próximos dez anos, além de favorecer uma melhor qualidade de vida (OLIVEIRA et al 2012; ZAAR et al 2014; BRICARELLO et al 2020).

How Does 2016 WHO Criteria for Polycythemia Vera Contribute to Our Daily Practice? A Single-Center Study from Turkey

Background: We evaluated the frequency of subnormal erythropoietin levels, JAK2V617F positivity and polycythemia vera (PV) in patients who did not meet WHO 2008 criterion for hemoglobin levels but were suggested to be investigated for PV in 2016 revision. Materials and Methods: We assessed the data of 92 patients, who were further evaluated with JAK2V617F mutation and serum erythropoietin (EPO) levels and bone marrow biopsy, if necessary. We also compared this patient group with 20 patients whose Hgb>18.5 g/dL for men and >16.5 g/dL for women. Results: Nine patients (45%) in the higher hemoglobin group were JAK2V617F positive, while 4 patients (4.3%) in the lower hemoglobin group were JAK2V617F positive (p<0.001). The number of patients with serum EPO levels <4.3 mIU/mL was significantly higher in the higher hemoglobin group (n=13, 65%) than the lower hemoglobin group (n=7, 7.6%) (p<0.001). Finally, the number of patients who received a diagnosis of PV was significantly higher in the higher hemoglobin group (n=13, 65%) than the lower hemoglobin group (n=9, 9.8%) (p<0.001). Conclusion: We found a substantial increase in patients who were candidates for testing for PV with the introduction of WHO 2016 criteria; these patients were diagnosed with PV with a rate (9.8%) that cannot be underestimated.

PEMBENTUKAN DAN PELATIHAN DUTA ANTI ROKOK PADA KOMUNITAS SAKA BAKTI HUSADA DI SMK KESEHATAN X KOTA TASIKMALAYA TAHUN 2019

Di Indonesia, merokok meningkatkan resiko kematian 1,3-8,2 kali diantara penderita penyakit kronik. Merokok juga dapat menimbulkan dampak negatif bagi orang yang berbeda di sekelilingnya. Resiko yang ditanggung perokok pasif lebih berbahaya dari pada perokok aktif karena daya tahan terhadap zat-zat yang berbahaya sangat rendah (WHO, 2008). Sekolah Menengah Kejuruan X yang berada di kota Tasikmalaya. Hasil dari survey pendahuluan yang dilakukan didapatkan data sebagai berikut : sebagian besar siswa diperoleh informasi pubertas dan permasalahan remaja dari teman sebayanya yaitu 87,3%,.Permasalahan remaja yang diperoleh adalah siswa laki-laki sebagian besar merokok (73,2%). Dan 90% siswa telah memilik pacar serta rata-rata telah melakukan aktifitas praseksual seperti pegangan tangan pelukan serta ciuman. Berdasarkan hasil wawancara dengan kepala sekolah menyatakan bahwa di sekolah tidak ada kegiatan PIKR (Pusat Informasi dan Konseling Remaja) yang dibina oleh pihak puskesmas. Dari hasil survey tersebut penulis memfokuskan meyelesaikan masalah merokok pada remaja laki-laki. Karena permasalahan remaja laki-laki yang merokok sangat besar. Untuk itu penulis membuat sebuah program untuk mengurangi dan memberantas yang merokok di SMK X. program ini bertujuan untuk menciptakan generasi muda bebas rokok dengan cara membuat Komunitas Remaja Anti Rokok.

Penerapan Peningkatan Budaya Keselamatan Pasien Di Rumah Sakit Jiwa

Keselamatan pasien adalah prinsip dasar kesehatan, dalam setiap proses pemberianpelayanan kesehatan berkaitan dengan tindakan yang tidak aman (WHO, 2008). Dari pada itu,keselamatan pasien merupakan tuntutan dari struktur atau pihak rumah sakit tersebut. Seperti kitatahu bahwa rumah sakit akan memberi pelayanan yang bertujuan membantu dalam proseskesembuhan pada pasien, peningkatan kualitas pelayanan yang diberikan rumah sakit kepadapasien akan meningkat apabila proses kesembuhan pasien yang semakin baik dengan masaperawatan yang semakin pendek. Namun tanggung jawab yang dimiliki pihak rumah sakit takhanya membantu dalam proses kesembuhan pasien akan tetapi juga meningkatkan serta menjagakualitas dan keamanan pelayanan meski terdapat perbedaan perbedaan dalam struktur,akuntabilitas, sumberdaya, dan prioritas. Keselamatan pasien merupakan komponen yang palingpenting dalam kesehatan. Keselamatan pasien di rumah sakit jiwa merupakan tantangan disetiapdomain kesehatan masyarakat. Selain itu rumah sakit juga perlu melakukan pengawasan danpenilaian secara berkala terhadap kompetensi tenaga medis dan memberikan pelatihanketerampilan tenaga medis agar kualitas pelayanan semakin lebih meningkat lagi.

Clinical And Prognostic Features Of Non Hodgkin Lymphoma And Preliminary Effective Evaluation Of R-Chop Regimen In Patients With Diffuse Large B-Cell Lymphoma

Background: WHO 2008 classification of Non Hodgkin Lymphoma (NHL) has been introduced and got consensus internationally. However, studies on NHL according to WHO 2008 classification are limited in Vietnam. In terms of treatment, the R-CHOP regimen is still the most commonly used regimen for the treatment of moderate or high grade malignant lymphoma tumors. However, its effectiveness on each type has not been specifically studied. Purpose of this research is to evaluate of clinical and subclinical characteristics of NHL patients according to the 2008 WHO classification on lymphoid neoplasms and to evaluate preliminary effective of diffuse large B cell lymphoma (DLBCL) patients with R-CHOP regimen. Materials and methods: A prospective descriptive study was conducted on 48 patients diagnosed with NHL undergoing treatment at the Hue University Hospital from July 2019 and Hue Central Hospital from April 2020 to present. Results: The mean age was 52.4 years, male/female ratio = 1.3/1, the most common primary tumor site was lymph nodes with 54.3%. Stage IV was found in 37.5% of all cases. DLBCL was the most common type, accounted for 58.3%, whereas marginal zone lymphoma had the lowest incidence (2.1%). According to the International Prognostic Index (IPI), low risk, low-intermediate risk, high-intermediate risk, high risk group were 43.6%; 25.0%; 18.8%; 12.6% respectively. 34.8% patients responsed completely after 3 cycles and after 6 – 8 cycles, 58.8% patients achieved complete response. Grade III, IV neutropenia, grade I, II peripheral neuropathy and grade I, II thrompocytopenia were the most common side effect observed. Conclusions: DLBCL is the most common Non Hodgkin Lymphoma. R-CHOP regimen has a good response after 6-8 cycles in DLBCL diseases and is well tolerated that the adverse events are mostly able to control effectively.