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Ocular adnexal lymphoma: Subtype-specific clinical and genetic features

Acta Ophthalmol. 2022 Oct;100 Suppl 270:3-37. doi: 10.1111/aos.15248.

ABSTRACT

Ocular adnexal lymphoma is a relatively rare disease but is one of the most common malignancies in the ocular adnexa, and its incidence is steadily increasing. Ocular adnexal lymphoma consists mainly of four histopathological subtypes of non-Hodgkin B-cell lymphoma: extranodal marginal zone lymphoma (EMZL), follicular lymphoma (FL), mantle cell lymphoma (MCL) and large B-cell lymphoma (LBCL). The clinical characteristics associated with each of the subtypes are not well known due to the sparsity of cases. Furthermore, a number of molecular and phenotypic features have been identified as recurrent and prognosticating in LBCL but are not yet well documented for the ocular adnexal region: concurrent MYC and BCL2 and/or BCL6 rearrangements, MYC/BCL2 double-expressor phenotype (in diffuse large B-cell lymphomas), and MYD88 and CD79B mutations. Therefore, the present PhD study aimed to investigate the clinical features of (1) conjunctival lymphoma by subtype and (2) ocular adnexal MCL in an international multicentre cohort of 307 patients and (3) the clinical and genetic features of ocular adnexal LBCL in 34 Danish patients. This was performed by collecting clinical data on the patients and tissue samples of the LBCLs. The tissue samples were analysed immunohistochemically for phenotype, by allele-specific PCR and Sanger sequencing for the presence of the mutations, and by fluorescence in situ hybridisation for the rearrangements. Statistical analyses were performed to detect correlations with clinical features and survival. The analyses revealed that conjunctival EMZL and FL typically presented in individuals in their 60s as localised unilateral tumour masses and had favourable prognoses (5-year disease-specific survival: 82%-97%). LBCL and MCL were found in all the ocular adnexal structures, with the orbit being the most common location (82% and 58%, respectively). These lymphomas typically presented in patients in their 70s, with MCL having a male predominance. MCLs commonly presented with bilateral lesions and systemic involvement, while LBCLs were unilateral localised tumours. Both subtypes had poor prognoses, with 49%-62% of patients having succumbed to the disease within 5 years. Ocular adnexal LBCLs had presence of concurrent MYC and BCL2 and/or BCL6 rearrangements in 16% of cases, MYC/BCL2 double-expressor phenotype in 44% of diffuse large B-cell lymphomas, and MYD88 ± CD79B mutations in 29% of cases. MYC/BCL2 double-expressor phenotype and MYD88 mutations were associated with adverse prognoses. All in all, the results indicate that the histopathological subtype of ocular adnexal lymphoma is a major outcome predictor. Furthermore, the results underline the importance of analysing the expression of MYC and BCL2 by immunohistochemistry in diffuse large B-cell lymphoma patients and advocate for incorporating the analysis of MYD88 mutations in the routine diagnostic workup of ocular adnexal LBCL. SUMMARY IN DANISH: Lymfomer i øjenregionen (orbita, conjunctiva, øjenlåg, tårekirtel og tåresaek) er relativt sjaeldne tumorer, men er blandt de hyppigste cancerformer i denne region og forekomsten er hastigt stigende. Lymfomer i øjenregionen består hovedsageligt af 4 undertyper af non-Hodgkin B-celle lymfom: ekstranodalt marginal zone lymfom, follikulaert lymfom, storcellet B-celle lymfom og mantle celle lymfom. Grundet sygdommens sjaeldenhed er kliniske karakteristika ved de forskellige lymfomundertyper kun sparsomt undersøgt. Endvidere er der blevet identificeret en raekke prognostisk vigtige molekylaere og faenotypiske kendetegn ved storcellede B-celle lymfomer, som endnu ikke er velundersøgt i øjenregionen. Det drejer sig om samtidig rearrangement i MYC og BCL2 og/eller BCL6, samtidig overekspression af MYC og BCL2 samt MYD88 og CD79B mutationer. Dette ph.d.-studie havde derfor til formål at undersøge de kliniske kendetegn ved (1) mantle celle lymfomer i øjenregionen og (2) de forskellige undertyper af conjunktivale lymfomer i en international kohorte med 307 patienter samt (4) de kliniske, molekylaere og faenotypiske kendetegn ved storcellet B-celle lymfom i 34 danske patienter. Vaevsmaterialet med storcellede B-celle lymfomer blev undersøgt ved hjaelp af immunhistokemi for faenotypen, ved hjaelp af allel-specifik PCR og Sanger sekventering for mutationerne og ved hjaelp af fluorescens in situ-hybridisering for rearrangementerne. Der blev udført statistiske analyser med henblik på at finde eventuelle sammenhaenge med kliniske karakteristika og overlevelse. Analyserne viste, at conjunctivalt ekstranodalt marginal zone lymfom og follikulaert lymfom typisk forekom blandt patienter i 60erne som ensidige tumorer uden spredning og var forbundet med en god prognose (5-års sygdomsspecifik overlevelse på 82-97%). Storcellet B-celle lymfom og mantle celle lymfom blev fundet i samtlige strukturer i øjenregionen med orbita som den hyppigste lokalisation (hhv. 82% og 58%). Disse lymfomundertyper forekom primaert hos patienter i 70erne med overvaegt af maend blandt mantle celle lymfomerne. Mantle celle lymfomerne praesenterede sig typisk som dobbeltsidige laesioner i øjenregionen med systemisk involvering, mens storcellede B-celle lymfomer var ensidige tumorer uden spredning. Begge undertyper havde en dårlig prognose, hvor cirka halvdelen af patienterne døde af sygdommen indenfor 5 år. Genetisk var storcellede B-celle lymfomer i øjenregionen karakteriseret ved betydelig praevalens af MYD88 mutationer (29%), som var forbundet med en dårlig prognose. Rearrangementer i MYC og BCL2 og/eller BCL6 forekom i 16% af tilfaeldene. Derudover havde 44% af diffuse storcellede B-celle lymfomer samtidig overekspression af MYC og BCL2, som var associeret med en dårlig prognose for patienterne. Alt i alt viser resultaterne, at den histologiske undertype er en vigtig prognostisk faktor for lymfomer i øjenregionen. Derudover fremhaever resultaterne vigtigheden af undersøgelsen af MYC/BCL2 faenotypen og implementeringen af MYD88 mutationsundersøgelsen i rutinediagnostikken af storcellede B-celle lymfomer i øjenregionen.

PMID:36196757 | DOI:10.1111/aos.15248

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CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019

Neuro Oncol. 2022 Oct 5;24(Supplement_5):v1-v95. doi: 10.1093/neuonc/noac202.

ABSTRACT

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.71 per 100,000 population (malignant AAAIR=7.02 and non-malignant AAAIR=17.69). This overall rate was higher in females compared to males (27.62 versus 21.60 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.09 versus 22.95 per 100,000). The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.1% of all malignant tumors), and the most common non-malignant histopathology was meningioma (39.7% of all tumors and 55.4% of all non-malignant tumors). Glioblastoma was more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.20 per 100,000 population. An estimated 93,470 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US population in 2022 (26,670 malignant and 66,806 non-malignant). There were 84,264 deaths attributed to malignant brain and other CNS tumors between 2015 and 2019. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 16,853 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, while for non-malignant brain and other CNS tumors the five-year relative survival rate was 91.8%.

PMID:36196752 | DOI:10.1093/neuonc/noac202

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Can transcription factors in the intervertebral disc of lopinavir/ritonavir prevent degeneration in the nucleus pulposus by mediating the regulation of inflammation through signaling pathways?

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6845-6855. doi: 10.26355/eurrev_202209_29788.

ABSTRACT

OBJECTIVE: This study was conducted to examine whether lopinavir/ritonavir (Lop/r), an HIV protease inhibitor, can improve disc physiology and slow down intervertebral disc (IVD) degeneration through in vitro experimental methods, as well as whether it can suppress inflammation with interleukin-1 beta (IL-1β) and sex-determining region Y (SRY) protein-related high-mobility group box genes-9 (SOX9) through hypoxia-inducible factor 1-alpha (HIF-1α) and the nuclear factor kappa B (NF-κB) signaling pathway. The aim was to investigate whether Lop/r application is toxic to IVD cells and the microenvironment simultaneously.

PATIENTS AND METHODS: Human primary cell cultures were prepared using herniated IVD tissues obtained from patients with lumbar disc hernia who were unresponsive to conservative and medical treatment, and thereby, were operated on. The untreated culture samples served as control group, and the samples treated with Lop/r served as study group. Microscopic evaluations were performed simultaneously using fluorescent and supravital dyes in all groups. In addition to cell viability, toxicity, and proliferation analysis through a commercial kit, IL-1β, SOX9, HIF-1α, and NF-κB protein expressions were evaluated using Western blotting. In the statistical comparison of the obtained data, an alpha value less than 0.05 was considered significant.

RESULTS: Cell proliferation decreased in the Lop/r group, but no cell death was observed (p < 0.05). Moreover, at the end of 72 hours after Lop/r application, IL-1β and NF-kB protein expressions decreased by 40% and 52%, respectively, while HIF-1α and SOX9 protein expressions increased by 4% and 59%, respectively (p< 0.05).

CONCLUSIONS: Although these data were obtained from an in vitro experimental study, it is believed that these findings could make significant contributions to the pharmaco-regenerative treatment modalities of IVD degeneration. Lop/r suppresses the IL-1β and NF-κB and induces SOX9 and HIF-1α, since these signaling pathways may be related to human IVD degeneration.

PMID:36196733 | DOI:10.26355/eurrev_202209_29788

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Happiness and social appearance anxiety in overweight young girls

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6821-6826. doi: 10.26355/eurrev_202209_29784.

ABSTRACT

OBJECTIVE: This research was conducted to determine the relationship between social appearance anxiety and happiness in overweight young girls.

SUBJECTS AND METHODS: This is a correlational descriptive study and the study sample included 343 overweight young female students from a university in eastern Turkey. A Personal Information Form, the Oxford Happiness Questionnaire-Short Form (OHQ-SF), and the Social Appearance Anxiety Scale (SAAS) were used for data collection. Descriptive statistics (percentage, mean, standard deviation), independent-samples t-test, analysis of variance, and correlation and regression analyses were used in data analysis.

RESULTS: The mean age of the participants was 21.55 ± 3.03 years. About a third of the participants (30.6%) was composed by year 3 university students, 60.6% had an income level equal to their expenditure level, and 50.7% was residing in the city center. The OHQ-SF mean total score of the participants was 17.03 ± 5.86, and the SAAS mean total score was 43.36 ± 17.07. There was a moderate negative correlation between the mean scores of the OHQ-SF and the SAAS (r: -.547, p<0.001). Social appearance anxiety explained 30% of happiness in young girls participating in the study (β: -.547, p<0.001).

CONCLUSIONS: Happiness in young girls was effective on social appearance anxiety. Health professionals may also evaluate the level of happiness in the care and counseling services they provide to young girls during extraordinary circumstances such as the COVID-19 pandemic.

PMID:36196730 | DOI:10.26355/eurrev_202209_29784

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Comparison of the effect of liraglutide and metformin therapy on the disease regulation and weight loss in obese patients with Type 2 diabetes mellitus

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6813-6820. doi: 10.26355/eurrev_202209_29783.

ABSTRACT

OBJECTIVE: Obesity and Type 2 diabetes mellitus are growing health problems all over the world. The aim of this study is the comparison of 3 mg liraglutide and metformin combination, metformin monotherapy on the blood glucose regulation, weight loss and lipid panel in the patients with Type 2 diabetes mellitus whose BMI is ≥ 30 kg/m2.

PATIENTS AND METHODS: 276 patients included in the study were divided into two groups (1:1); liraglutide (3 mg) + metformin combination (L+M) and metformin monotherapy (M) (2×1,000 mg) (exercise and diet were regulated in both groups). Patients’ body composition measurements were performed and fasting blood glucose, postprandial blood glucose, HbA1c, triglyceride, total cholesterol, LDL, HDL levels were measured by TANITA device prior to the therapy and in the week 12 of the therapy.

RESULTS: The average age of 276 patients included in the study was 49.70±7.93 years. A statistically significant decrease was noted in weight, BMI, fasting blood glucose, postprandial blood glucose, HbA1c values of both groups at the end of the third month. 11.3 kg of weight was lost on average in L+M group (-12.3%); 4.5 kg of weight was lost in the monotherapy group (-4.9%). A decrease of 14.3% was seen in the body fat mass, 2.1% in the muscle mass in L+M group and a decrease of 4.4% in the body fat mass and 6.1% in the muscle mass in the monotherapy group. The decrease in the body fat was higher at a statistically significant level in L+M group and the decrease in the muscle mass was higher in the monotherapy group. HbA1c decreased by 17.9% in L+M group (-1.49±0.46, Cohen’s d=2.68), 5.3% in the monotherapy group (-0.37±0.26, Cohen’s d=0.90). The decrease in TG, total cholesterol, LDL was higher at a statistically significant level in L+M group. The increase in HDL level was higher in the monotherapy group (L+M=22.7%, M=35.4%). A weight loss that was over 10% occurred in 4.3% of the patients in the monotherapy group and 68.1% of the combined therapy group at the end of 12 weeks (95% C.I. OR=19.49-121.65).

CONCLUSIONS: The effect of the combination of liraglutide 3 mg and metformin on blood glucose regulation, weight loss (fat loss, muscle conservation) was found to be superior to the metformin monotherapy in the obese patients with Type 2 diabetes mellitus according to the early period results.

PMID:36196729 | DOI:10.26355/eurrev_202209_29783

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Endothelial dysfunction in psoriatic arthritis patients: correlations between insulin resistance and disease activity

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6796-6804. doi: 10.26355/eurrev_202209_29781.

ABSTRACT

OBJECTIVE: Cardiovascular atherosclerotic comorbidities represent an important cause of morbidity and mortality in patients diagnosed with psoriatic arthritis. In both atherosclerosis and Psoriatic arthritis, inflammation plays a pivotal role. Psoriatic arthritis is considered as an independent risk factor for the development of atherosclerosis with accelerated evolution. Development of atherosclerosis is initiated by the endothelial cell dysfunction along with inflammation and insulin resistance. The main aim of the study was to evaluate the endothelial function in Psoriatic arthritis patients, and to identify if it is related to the insulin resistance and Psoriatic arthritis disease activity.

PATIENTS AND METHODS: In this case-control study, a group of 32 age and gender matched healthy controls was formed and compared to the group of 32 Psoriatic arthritis patients. We assessed the following parameters: Disease Activity in Psoriatic Arthritis Score, Homeostatic Model Assessment for Insulin Resistance, serum levels of the tumor necrosis factor alpha (TNFα), and the endothelial dysfunction by means of the flow-mediated dilation at brachial artery. The Student’s t-test, the Pearson correlation and the ANOVA test were used to perform the statistical analysis of the data obtained; p-value <0.05 was considered as statistically significant.

RESULTS: Compared to the patients in the control group, TNFα and Homeostatic Model Assessment for Insulin Resistance were increased (p-value <0.001), and flow-mediated dilation at brachial artery was decreased (p-value <0.001) in the disease group. In Psoriatic arthritis patients, significant correlations were found between Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance (r=0.8143, p-value <0.001), and between Disease Activity in Psoriatic Arthritis Score and flow-mediated dilation at brachial artery % (r= -0.8376, p-value <0.001). Psoriatic arthritis patients treated with Methotrexate exhibited reduced values of Disease Activity in Psoriatic Arthritis Score and Homeostatic Model Assessment for Insulin Resistance and increased values of flow-mediated dilation at brachial artery, when compared with the untreated patients.

CONCLUSIONS: Endothelial dysfunction is present in Psoriatic arthritis patients and has a significant correlation with both, the course of the disease and the insulin resistance.

PMID:36196728 | DOI:10.26355/eurrev_202209_29781

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DNA repair gene (XRCC1 and XPD) polymorphism and risk of primary ovarian failure

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6593-6599. doi: 10.26355/eurrev_202209_29759.

ABSTRACT

OBJECTIVE: DNA repair genes may be related with the onset of primary ovarian failure (POF). The study was planned to investigate whether the polymorphisms in the DNA repair genes modulate the risk of POF.

PATIENTS AND METHODS: This prospective study included 25 women diagnosed with POF and 25 healthy controls. The genotyping and allele of XRCC1 and XPD genes were determined by using Polymerase Chain Reaction and fluorescence melting curve analysis.

RESULTS: The genotype and allele distribution of the Arg194Trp and Arg399Lys polymorphism of the XRCC1 gene did not differ statistically between those of the POF and control groups. The frequency of the C (Gln) allele was significantly lower in patients diagnosed with POF when compared to that in healthy controls [48% vs. 76%, p=0.040, OR: 3.43 (CI: 1.03-11.48)]. The Lys/Lys genotype for XPD-Lys751Gln polymorphism in patients diagnosed with POF was more common than in healthy controls (p=0.028, 52% vs. 24%).

CONCLUSIONS: The genotype distribution and allele frequency of XPD-Lys751Gln, XRCC1-Arg194Trp and XRCC1-Arg399 Gln did not regulate the risk of developing POF. Gln/Gln+Lys/Gln and XPD-Lys751Gln polymorphism may have a possible protective role against the development of POF.

PMID:36196709 | DOI:10.26355/eurrev_202209_29759

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The pathophysiological role of inflammatory parameters in patients with varicocele

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6572-6577. doi: 10.26355/eurrev_202209_29756.

ABSTRACT

OBJECTIVE: Varicocele is the abnormal enlargement of the pampiniform plexus in the scrotum and is one of the diseases that have negative consequences on reproduction in men today. The aim of this study is to investigate the pathophysiological role of inflammatory parameters in patients diagnosed with varicocele.

PATIENTS AND METHODS: Patients who applied to Viransehir state hospital urology outpatient clinic between January 2016 and January 2022 were evaluated retrospectively. Among the patients whose varicocele diagnosis was evaluated by physical examination, 112 patients diagnosed with Grade III varicocele were included in the study. Obtained hemogram results [red blood cell, red cell distribution width (RDW), mean red cell volume, white blood cell, hematocrit, hemoglobin, mean hemoglobin amount, platelet, platelet distribution width (PDW), neutrophil, lymphocyte, monocytes, and mean platelet volume (MPV)] were compared with the control group values.

RESULTS: There was no statistical difference between the two groups in terms of mean age (p=0.270). Statistically significant parameters between both groups were erythrocyte (p=0.011), MCV (p=0.028), RDW (p=0.018), and PDW (p=0.004), respectively. However, Neutrophil/Lymphocyte ratio (NLR), PLT/Lymphocyte ratio (PLR) and MPV/PLT ratio (MPVPR) values were found to be statistically significantly higher in the varicocele group (p=0.034, p=0.043 and p=0.045, respectively).

CONCLUSIONS: According to our results, it is possible to recommend using the inflammatory parameters as markers to screen for the pathophysiological basis of varicocele.

PMID:36196706 | DOI:10.26355/eurrev_202209_29756

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Awareness of current mobile apps for smoking cessation among the dental and medical practitioners in Saudi Arabia

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6561-6568. doi: 10.26355/eurrev_202209_29754.

ABSTRACT

OBJECTIVE: This study aimed at assessing whether the dental and medical practitioners in Saudi Arabia are aware of the smoking cessation smartphone applications and their opinions about this method used in smoking cessation.

MATERIALS AND METHODS: A self-reporting questionnaire was designed to assess the level of knowledge and awareness among the dental and medical practitioners regarding the smartphone mobile applications for smoking cessation. The content of the questionnaire was validated and sent to individual physicians through email, WhatsApp, Twitter and other social media platforms, which also contained a consent form and explanation of the study. Responses were summarized using descriptive statistics by frequencies and percentages. A Chi-square test was used to observe the differences in opinions of smoking cessation apps between smokers and non-smokers among all the participants.

RESULTS: A total of 420 responses were obtained from the dental and medical professionals (291 males and 129 females) in different ranks. Among all the participants, 46.7% were in the age range of 30-40 years. The profession of the participants was divided into four groups and general dental practitioners are the most respondents compared to other practitioners. Among all the participants, 31% were smokers and the rest were non-smokers. Overall, 12.6% of participants and 20.8% of participants who were smokers were aware of the mobile applications which are used for smoking cessation.

CONCLUSIONS: The dental and medical practitioners in Saudi Arabia are not relatively acquainted with mobile apps for smoking cessation.

PMID:36196704 | DOI:10.26355/eurrev_202209_29754

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CBCT based study to analyze and classify root canal morphology of maxillary molars – A retrospective study

Eur Rev Med Pharmacol Sci. 2022 Sep;26(18):6550-6560. doi: 10.26355/eurrev_202209_29753.

ABSTRACT

OBJECTIVE: The study aims to evaluate maxillary molars’ root and root canal morphology among the Saudi population using Cone-Beam Computed Tomography scanning (CBCT).

SUBJECTS AND METHODS: Retrospectively, the CBCT scans of 483 Saudi nationals were evaluated to identify the number of roots and root canals in maxillary first and second molars. The records were tabulated and classified according to Vertucci and a new system for root and canal classification given by Ahmed and Dummer. Fisher’s exact test was used to analyze the data statistically. To check for symmetry, comparisons were made between all the maxillary first molars (MFM’s) and maxillary second molars (MSM’s) on opposing quadrants. Inter Observer variability was seen using Cohen’s Kappa test.

RESULTS: MFM’s presented with three roots with Type II Vertucci canal configuration (VC) commonly seen among them. MSM’s had more variations in the number of roots and canals, although three roots and Type I VC were predominantly seen. When comparing the two genders statistically significant difference was observed in both maxillary molars at a 5% level using Fisher’s exact test. Three roots with four canals (3R4C) were predominantly observed in the MFM’s (85.6%) and three roots with three canals (3R3C) identified in 51.95% were more common than 3R4C (43.55%) in MSM’s. Both the maxillary molars bilaterally, exhibited a high percentage of symmetry in root and canal configurations.

CONCLUSIONS: Identification of root canal morphology of molars would reduce the chances of root canal failures by making sure all canals are obturated. This study provides supplemental information about the root canals of maxillary molars in a Saudi Arabian subpopulation.

PMID:36196703 | DOI:10.26355/eurrev_202209_29753