Microvessel Density (MVD) in Patients with Osteosarcoma: A Systematic Review and Meta-Analysis.

A meta-analysis was designed and conducted to estimate the effect of tumoral microvessel density (MVD) on the survival of patients with osteosarcoma. There was no difference between high and low MVD regarding the overall (OS) and disease-free (DFS) survival. Low MVD tumors displayed a lower DFS at the third year of follow-up. Although primary metastases did not affect the mean MVD measurements, tumors with a good chemotherapy response had a higher MVD value. Although no significant differences between tumoral MVD, OS and DFS were found, good adjuvant therapy responders had a significant higher vascularization pattern.

Updates on Systemic Therapy for Hepatocellular Carcinoma.

This review explores the dynamic landscape of hepatocellular carcinoma (HCC) treatment, emphasizing on recent developments across various stages and therapeutic approaches. Although curative strategies such as hepatectomy and thermal ablation are standard for early-stage cases, high relapse rates drive investigations into adjuvant and perioperative treatment. Adjuvant therapies face hurdles, but noteworthy advances include IMbrave050 setting a new standard with atezolizumab/bevacizumab. Locoregional treatments gain significance, especially for multifocal HCC, with the integration of innovative combinations with systemic therapies, showing improved outcomes. In the advanced setting, the evolution from sorafenib as the primary first-line option to new standards, such as atezolizumab/bevacizumab and tremelimumab/durvalumab, to other emerging therapies such as tislelizumab and pembrolizumab with lenvatinib, is explored. Additionally, second-line treatments and insights into the interplay between immunotherapies and antiangiogenic agents, as well as novel combination strategies that add complexity to treatment decisions, are discussed.

Microvessel density in patients with gastrointestinal stromal tumors: A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are considered the most common mesenchymal tumors of the gastrointestinal tract. Microvessel density (MVD) constitutes a direct method of vascularity quantification and has been associated with survival rates in multiple malignancies. AIM: To appraise the effect of MVD on the survival of patients with GIST. METHODS: This study adhered to Systematic reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Electronic scholar databases and grey literature repositories were systematically screened. The Fixed Effects or Random Effects models were used according to the Cochran Q test. RESULTS: In total, 6 eligible studies were identified. The pooled hazard ratio (HR) for disease free survival (DFS) was 8.52 (95%CI: 1.69-42.84, P = 0.009). The odds ratios of disease-free survival between high and low MVD groups at 12 and 60 mo did not reach statistical significance. Significant superiority of the low MVD group in terms of DFS was documented at 36 and 120 mo (OR: 8.46, P < 0.0001 and OR: 22.71, P = 0.0003, respectively) as well as at metastases rate (OR: 0.11, P = 0.0003). CONCLUSION: MVD significantly correlates with the HR of DFS and overall survival rates at 36 and 120 mo. Further prospective studies of higher methodological quality are required.

The Role of Preoperative Chemotherapy in the Management of Synchronous Resectable Colorectal Liver Metastases: A Meta-Analysis.

BACKGROUND: The indications of preoperative chemotherapy, for initially resectable synchronous colorectal liver metastases, remain controversial. This meta-analysis aimed to assess the efficacy and safety of preoperative chemotherapy in such patients. METHODS: Six retrospective studies were included in the meta-analysis with 1036 patients. Some 554 patients were allocated to the preoperative group, and 482 others were allocated to the surgery group. RESULTS: Major hepatectomy was more common in the preoperative group than in the surgery group (43.1% vs. 28.8%, p < 0.001). Furthermore, the percentage of patients with more than three liver metastases was higher in the preoperative group compared to the surgery group (12.6% vs. 5.4%, p < 0.002). Preoperative chemotherapy showed no statistically significant impact on overall survival. Combined disease free/relapse survival analysis of patients with high disease burden (liver metastases > 3, maximum diameter > 5 cm, clinical risk score ≥ 3) demonstrated that there is a 12% lower risk of recurrence in favor of preoperative chemotherapy. Combined analysis showed a statistically significant (77% higher probability) of postoperative morbidity in patients who received preoperative chemotherapy (p = 0.002). CONCLUSIONS: Preoperative chemotherapy should be suggested in patients with high disease burden. The number of cycles of preoperative chemotherapy should be low (3-4) to avoid increased postoperative morbidity. However more prospective studies are needed to clarify the exact role of preoperative chemotherapy in patients with synchronous resectable colorectal liver metastases.

The Mental Health Burden of Patients with Colorectal Cancer Receiving Care during the COVID-19 Pandemic: Results of the PICO-SM Study.

The COVID-19 pandemic has resulted in unprecedented changes to the lives of patients with cancer. To evaluate the impact of the COVID-19 pandemic on the mental health and well-being of patients with colorectal cancer, we conducted a prospective longitudinal questionnaire study at a UK tertiary cancer centre. In total, 216 participants were included: mean age 65 years, 57% (n = 122) male, 92% (n = 198) of white ethnicity. Amongst participants who completed the screening psychometric questionnaire, 24% (n = 48/203) reported anxiety (GAD-7 ≥ 5), 15% (n = 31/204) depressive symptoms (PHQ-9 ≥ 10), 3% (n = 5/190) probable post-traumatic stress disorder (PC-PTSD-5 ≥ 4), and 31% (n = 66/213) poor well-being (WHO-5 < 50). In the subgroup (n = 95/216, 44%) who consented to and completed a follow-up survey 6 months later, there was a significant increase in the number of participants at risk of depression (4% vs. 13%, p = 0.021). Self-reported concern about the COVID-19 pandemic impacting one's mental health is associated with increased likelihood of anxiety, depression, and poor well-being, in respective multivariate analyses. In conclusion, screening for the mental health impact of the COVID-19 pandemic is essential to ensure timely action from all key stakeholders and to avoid potentially longer-term detrimental consequences.

TAMs and PD-1 Networking in Gastric Cancer: A Review of the Literature.

BACKGROUND: Gastric cancer (GC) is one of the most common and aggressive types of cancer. Immune checkpoint inhibitors (ICIs) have proven effective in treating various types of cancer. The use of ICIs in GC patients is currently an area of ongoing research. The tumor microenvironment (TME) also seems to play a crucial role in cancer progression. Tumor-associated macrophages (TAMs) are the most abundant population in the TME. TAMs are capable of displaying programmed cell death protein 1 (PD-1) on their surface and can form a ligand with programmed death ligand 1 (PD-L1), which is found on the surface of cancer cells. Therefore, it is expected that TAMs may significantly influence the immune response related to immune checkpoint inhibitors (ICIs). AIM OF THE STUDY: Understanding the role of TAMs and PD-1/PD-L1 networking in GC. METHODS: A systematic review of published data was performed using MEDLINE (PubMed), Embase, and Cochrane databases. We retrieved articles investigating the co-existence of TAMs and PD-1 in GC and the prognosis of patients expressing high levels of PD-1+ TAMs. RESULTS: Ten articles with a total of 2277 patients were included in the systematic review. The examined data suggest that the expression of PD-L1 has a positive correlation with the infiltration of TAMs and that patients who express high levels of PD-1+ TAMs may have a worse prognosis than those who express low levels of PD-1+ TAMs. CONCLUSIONS: TAMs play a pivotal role in the regulation of PD-1/PD-L1 networking and the progression of GC cells. Nevertheless, additional studies are needed to better define the role of TAMs and PD-1/PD-L1 networking in GC.

Microvessel density in differentiated thyroid carcinoma: A systematic review and meta-analysis.

BACKGROUND: Microvessel density (MVD) has been proposed as a direct quantification method of tumor neovascularization. However, the current literature regarding the role of MVD in differentiated thyroid carcinoma (DTC) remains inconclusive. AIM: To appraise the effect of tumoral MVD on the survival of patients with DTC. METHODS: This meta-analysis was based on the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The electronic databases Medline, Web of Science, and Scopus were systematically screened. A fixed-effects or random-effects model was used, according to the Cochran Q test. The data were then extracted and assessed on the basis of the Reference Citation Analysis (https://www.referencecitationanalysis.com/). RESULTS: A total of nine studies were included in the present study. Superiority of low MVD tumors in terms of 10-year disease free survival (OR: 0.21, 95%CI: 0.08-0.53) was recorded. Lowly vascularized thyroid cancers had a lower recurrence rate (OR: 13.66, 95%CI: 3.03-61.48). Moreover, relapsing tumors [weighed mean difference (WMD): 11.92, 95%CI: 6.32-17.52] or malignancies with regional lymph node involvement (WMD: 8.53, 95%CI: 0.04-17.02) presented with higher tumoral MVD values. CONCLUSION: MVD significantly correlates with the survival outcomes of thyroid cancer patients. However, considering several study limitations, further prospective studies of higher methodological and quality level are required.

Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte, Platelet-to-Lymphocyte Ratio and Systemic Immune-Inflammatory Index in Different States of Bipolar Disorder.

The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammatory (SII) index, which provide a simple, rapid, inexpensive method to measure the level of inflammation, have been examined as potential inflammatory biomarkers of bipolar disorder (BD) in several studies. We conducted a case-control study recruiting 180 BD patients and 407 healthy controls. BD patients who met the inclusion criteria and were hospitalized due to BD at the psychiatry clinic of the University General Hospital of Larisa, Greece, until September 2021 were included in the study. Among them, 111 patients experienced a manic episode and 69 patients experienced a depressive episode. Data including a complete blood count were retrieved from their first admission to the hospital. Bipolar patients had a higher NLR, MLR and SII index compared to healthy controls when they were experiencing a manic episode (p < 0.001) and a depressive episode (p < 0.001). MLR was increased with large effect size only in patients expressing manic episodes. Neutrophils and NLR had the highest area under the curve with a cutoff of 4.38 and 2.15 in the ROC curve, respectively. Gender-related differences were mainly observed in the SII index, with males who were expressing manic episodes and females expressing depressive episodes having an increased index compared to healthy controls. The NLR, MLR and SII index were significantly higher in patients with BD than in healthy controls, which implies a higher grade of inflammation in BD patients.

Association between white matter lesions and Parkinson's disease: an impact on Postural/Gait difficulty phenotype and cognitive performance.

BACKGROUND: White matter hyperintensities (WMHs) may be observed on Magnetic Resonance Imaging (MRI) in patients with Parkinson disease with or without vascular risk factors. Whether WMHs may influence motor and non-motor aspects of Parkinson disease is a subject of debate. The aim of this study is to evaluate the impact of WMH severity on various aspects of Parkinson disease in combination to the estimation of the impact of cerebrovascular risk factors. MATERIALS AND METHODS: We included a cohort of patients with Parkinson's disease who underwent MRI examination. The Fazekas visual rating scale was used to assess the severity and location of WMHs, and patient clinical characteristics were correlated with MRI data. RESULTS: All vascular risk factors were associated with higher Fazekas score in both periventricular and deep white matter. Periventricular white matter hyperintensities (PWMHs) and deep white matter hyperintensities (DWMHs) were associated with lower scores in the ACE-R cognitive assessment scale (p < 0.001). Furthermore, PWMHs and DWMHs severity was associated with higher UPDRS motor score (p < 0.001), while the Postural Instability Gait Difficulty (PIGD) phenotype was correlated with higher burden of WMHs. CONCLUSIONS: Comorbid WMHs may contribute to multi-dimension dysfunction in patients with Parkinson disease and consequently the management of vascular risk factors may be crucial to maintain motor and non-motor functions in PD.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

BACKGROUND: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations. METHODS: Most of the available COVID-19 vaccination guidance for cancer patients was screened and scrutinized by the European Cancer Patients Coalition (ECPC) and an international oncology panel of 52 physicians from 33 countries. RESULTS: A summary guidance was developed and provided in 28 languages in order to reach more than 70 percent of the global population. CONCLUSION: Language barrier and e-guidance availability in the native language are the most important barriers when communicating with patients. E-guidance availability in various native languages should be considered a major priority by international medical and health organizations that are communicating with patients at the global level.

Immunotherapy Efficacy in the Initial Lines of Treatment in Advanced Upper Gastrointestinal Malignancies: A Systematic Review of the Literature.

Background: The therapeutic role of immune checkpoint inhibitors (ICIs) has represented the cutting edge of clinical research in upper gastrointestinal (GI) malignancies, with these agents now included in the armamentarium of treatment options for advanced gastric and esophageal cancers. Methods: We performed a systematic literature review and pooled analysis to map out the currently available robust clinical evidence for the use of ICIs in upper GI cancers. Immunotherapy (IO), either as monotherapy or in combination with chemotherapy, and its role in first-line, maintenance, and second-line settings, as well as in specific clinical and biological subgroups, were critically appraised. All statistical tests were 2-sided. Results: ICIs, in combination with chemotherapy, have provided statistically significant overall survival benefit in the first-line setting in gastric and gastro-esophageal adenocarcinomas (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.76 to 0.90, P < .001; based on 4 studies) and esophageal squamous cell carcinoma (HR = 0.72, 95% CI = 0.64 to 0.81, P < .001; based on 3 studies), albeit with heterogeneous efficacy according to biomarker expression. Patients with esophageal squamous cell carcinoma, and in particular high programmed cell death ligand-1 expression, derive survival benefit when treated with IO in the second-line setting (HR = 0.74, 95% CI = 0.68 to 0.82, P < .001; for any level of programmed cell death ligand-1 expression). Clinical trials interrogating the combination of IO with chemotherapy in second-line treatment should be seriously considered in upper GI adenocarcinomas. The role of maintenance IO after initial disease control is still unclear and cannot be recommended. Impressive response rates and survival benefit from IO have been reported in patients with microsatellite instability-high tumors (HR = 0.33, 95% CI = 0.19 to 0.57, P < .001), and this warrants further prospective biomarker-driven studies. Conclusions: IO is changing the treatment landscape in upper GI malignancies. The rapidly developing evidence in the field needs to be critically appraised while further validation of the existing information from ongoing trials is awaited.

Advanced germ cell tumors and chemotherapy in G6PD deficient patients: Yes to chemotherapy but no to rasburicase and some premedications.

PURPOSE: Glucose-6 phosphate dehydrogenase (G6PD) deficiency has an estimated prevalence of 5 -7.5% of the global population. Administration of some drugs in G6PD deficient patients may result in clinical conditions of varying severity, including potentially fatal sequels. For these reasons, in case of G6PD deficiency, the use of high dose toxic chemotherapy regimens in potentially curable malignancies with associated risk of tumor lysis syndrome, such as in advanced germ cell tumors, raises both physicians' preoccupations and issues for safeguard patients' health. Nonetheless no systematic information is actually available for safety in premedication to be administered, chemotherapy regimens adopted, and supportive care drugs needed to be provided in some particular situations. METHODS: We present a case of a patient with metastatic testicular cancer and known g6pd deficiency, admitted in our department. We also performed a literature review in tree medical libraries searching for articles addressing the overmentioned security issues. RESULTS: Available literature is particularly scant. nonetheless, there is no evidence contradicting the administration of cytotoxic chemotherapy to G6PD deficient individuals. Our patient was able to complete the preplaned chemotherapy cycles, without any complications. CONCLUSION: Given the absence of data supporting the limitation of chemotherapy to G6PD deficient patients, the latter should not be deprived of the indicated antineoplastic treatment. However, certain premedication agents must be avoided. Continuous patient monitoring during treatment may alleviate physicians' and patients' anxiety and preoccupations.

Clinically Silent Small Vessel Disease of the Brain in Patients with Obstructive Sleep Apnea Hypopnea Syndrome.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with increased risk of cerebrovascular disease. The aim of the present study was to investigate the association between the presence of the small vessel disease (SVD) of the brain in patients with OSAHS. The study included 24 patients with moderate to severe OSAHS and 34 healthy volunteers. All the subjects underwent magnetic resonance imaging (MRI) of the brain, in order to sought periventricular white matter (PVWM), deep white matter (DWM) and brainstem SVD. Among patients with OSAHS, 79.1% had SVD (grade 1-3, Fazekas score) in DWM and 91.7% in PVWM while 22.4% had brainstem-white matter hyperintensities (B-WMH). Patients with OSAHS had a much higher degree of SVD in the DWM and PVWM compared to the control group (p < 0.001). The multivariate analysis showed an independent significant association of OSAHS with SVD (DWM and PVWM) (p = 0.033, OR 95% CI: 8.66 (1.19-63.08) and: p = 0.002, OR 95% CI: 104.98 (5.15-2141)). The same analysis showed a moderate association of OSAHS with B-WMH (p = 0.050, OR 15.07 (0.97-234.65)). Our study demonstrated an independent significant association of OSAHS with SVD and a moderate association of OSAHS with B-WMH.

Is there a role for Gallium-67 SPECT in distinguishing progression and pseudoprogresion in oncologic patients receiving immunotherapy?

Immuno-oncology (IO) with immune checkpoint inhibitors (ICIs) is the new landmark in cancer treatment. However, due to its economical-related burden and the possibility of tumor pseudoprogression with late response patterns, it is imperative to find new ways for early discrimination of patients with IO-sensitive versus IO-resistant disease. ICI-mediated antitumor responses depend on tumor immune infiltration by T-cells capable of recognizing and killing tumor cells. Nevertheless, patients may experience different responses to immunotherapy according to their tumor microenvironment and inflammatory infiltration. T-cell infiltrated tumors are referred to as 'hot' and are potential candidates for a good response to ICIs, whereas 'cold' are those tumors lacking T-cell infiltration and exhibit a narrow likelihood of response to IO therapy. Gallium-67 (67Ga) scintigraphy may hold potential for separating 'hot' from 'cold' tumors, thus providing an imaging tool to distinguish 'hot' ICI-induced pseudoprogression from real early 'cold' progression. Even so, various tumors (lymphomas, lung cancer, breast cancer, hepatoma, malignant melanoma) exhibit an inherent affinity for 67Ga that is independent of the ICI-induced immune infiltration, and this raises issues about false positivity. For that reason, future investigational studies to evaluate the prospective role of this radiotracer in the early prediction of ICI response should be confined to tumors with an inherently low 67Ga affinity (thyroid carcinoma, gastrointestinal and genitourinary tract tumors). We describe our experience with a patient with recurrent metastatic lung adenocarcinoma under ICI therapy that was submitted to 67Ga scanning for a fever of unknown origin and we discuss the aforementioned topics, alongside current imaging trends and future perspectives in the field.

Ureteral carcinoma metastasizing to the testicle: Can misdiagnosis of orchiepididymitis be avoided?

Testicular metastases from ureteral carcinoma are rare and they are generally mimic orchiepididymitis. For this reason, these are associated to misleading diagnoses and cancer treatment delay. We believe that both timing and knowledge of genital blood and lymph reverse flow routes may represent two important parameters for avoiding misleading diagnoses and speed proper anticancer treatment. We describe a case and discuss pathophysiological data and relevant literature.

Fahr's syndrome due to hypoparathyroidism revisited: A case of parkinsonism and a review of all published cases.

INTRODUCTION: Fahr's syndrome due to hypoparathyroidism refers to bilateral basal ganglia (BG) calcifications and manifests with movement disorders, seizures, cognitive and behavioral symptoms. CASE PRESENTATION: We report a case of a 74-year-old woman, who presented with parkinsonism due to post-surgical hypoparathyroidism and normal DaT scan, despite extensive calcifications of the BG, periventricular white matter, and cerebellum. METHODS: A comprehensive literature review of all reported cases of Fahr's syndrome due to hypoparathyroidism was conducted in the electronic databases PubMed and Web of science. Moreover, demographic and clinical characteristics of the patients overall were calculated and associated with radiological findings. RESULTS: We reviewed a total of 223 cases with Fahr's syndrome due to hypoparathyroidism (124 female, 99 male). Mean age on presentation was 44.6 ± 17.7 years. Thirty nine percent of patients had idiopathic hypoparathyroidism, 35.4 % acquired and 25.6 % pseudohypoparathyroidism. Almost half of the patients had tetany, seizures or a movement disorder and approximately 40 % neuropsychiatric symptoms. The patients with a movement disorder had a 2.23 likelihood of having neuropsychiatric symptoms as well (OR 2.23, 95 % CI 1.29-3.87). Moreover, there was a statistically significant association between the phenotype severity (i.e. the presence of more than one symptom) and the extent of brain calcifications (χ2 = 32.383, p = 0.009). CONCLUSION: Fahr's syndrome is a rare disorder, which nonetheless manifests with several neurological symptoms. A head CT should be considered for patients with hypoparathyroidism and neurological symptoms. More studies using DaT scan are needed to elucidate the effects of calcifications on the dopaminergic function of the BG.

Geography of hospital admissions for multiple sclerosis in Greece.

BACKGROUND: Multiple sclerosis (MS) is the 2nd most common, disability causing neurological disorder in young adults, known for its differences in prevalence according to geographical position. Data on MS epidemiology is lacking in Greece. In this study, we aimed to examine the pattern of MS related hospital admissions in Greece and analyze their spatial distribution. Data for hospital admissions due to MS was obtained from the Hellenic Statistical Authority (ELSTAT) database and they were available from 1999 to 2012. METHODS: We used the proportional hospitalization ratio (PHR) which was age and sex adjusted according to hospitalizations of Greek population, in order to calculate the ratio between hospitalizations in each regional unit (RU) and hospitalizations of national population. PHR was calculated for each RU, which is categorized as level 3 based on the Nomenclature of Territorial Units for Statistics (NUTS level 3). The classification of MS was based on International Classification of Diseases, Ninth Revision (ICD-9), code 340. Descriptive analysis was conducted to understand the epidemiological characteristics and time series analysis was used to investigate the trend of annual PHR's values during the study period. Global spatial autocorrelation analysis was conducted to assess spatial homogeneity of MS across the country. Moreover, local spatial autocorrelation analysis was performed using the LISA statistic to detect any potential clusters of similar values. Finally, multiple linear regression was conducted to examine correlations between PHR and latitude. RESULTS: Over the 14-year period the number of hospitalizations increased while the proportion of hospitalizations remained higher for females compared to males, as well as for the 25-44 year age group. RUs that appeared to be most affected included Evros with a sex- and age- adjusted PHR of 2.00 (95%CI: 1.89-2.10), Larisa with a PHR of 1.74 (95%CI: 1.67-1.81) and Chios with a PHR of 1.77 (95%CI: 1.60-1.95). The least affected RU was Arkadia with a PHR of 0.29 (95%CI: 0.24-0.36). CONCLUSION: In this study we present a rise in hospital admissions related to MS over a 14-year period, possibly indicating a parallel rise in incidence. A combinational analysis of the number of hospitalizations along with incidence studies could be further performed to be used to design public health interventions.

Interior Design: A New Perspective in Supportive Care of Patients with Acute Onset of Debilitating Diseases.

Background: Upon the onset of a debilitating rapidly evolving condition (such as cancer or a rapidly progressing myopathy, neuropathy, respiratory disease, or a severe traumatic injury), individuals have limited time to find a new home or make radical structural modifications in their residence. How the affected patients can continue sharing the same house with their families, while meeting their own special requirements, is thus rising as a critical issue. Household and daily routine rearrangements, either temporary or permanent, may be necessary, to ameliorate the life of patients with impairments, lasting for months or even years. Objectives: Interior design may provide a highly efficient "living" palliation for debilitating medical conditions directly at patients' home-site. Methods: Research of relevant literature, using keywords "debilitating conditions," "home care," "end of life care," "care of advanced cancer patients," "care of patients with mental disorders," "home care of covid-19 affected patients," and "care of patients with degenerative illnesses." Results: We found that patients and their relatives may not be aware of the probable interior design solutions to their daily life challenges, imposed by a disease-related impairment. In parallel, interior design experts may equally be unaware of these issues, as well as of who needs the available solutions.Similarly, medical and architectural sciences are not connected, eventually failing to meet patients' everyday needs. Conclusions: Interior architecture and health scientists are called to cooperate, aiming to provide a highly efficient and meaningful support to patients and families affected by unforeseen debilitating medical conditions.

Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases.

Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with isolated and complex early-onset generalized dystonia. We describe clinico-genetic features on a Greek patient with a novel de novo variant and demonstrate the phenotypic spectrum of KMT2B variants. We performed whole exome sequencing (WES), in a Greek patient with sporadic generalized dystonia. Additionally, we performed a systematic review of all published cases with KMT2B variants. The patient presented with isolated and mild generalized dystonia. We identified a novel splice site variant that was confirmed by Sanger sequencing and was not found in parents. This is the first reported KMT2B variant, in the Greek population. This case report further highlights the growing trend of identifying genetic diseases previously restricted to few cases in many different ethnic groups worldwide via exome sequencing. In the systematic review, we evaluated the mutation pathogenicity in all previously reported cases to investigate possible phenotype-genotype correlations. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various KMT2B variants.

Chemotherapy Associated Ovarian Failure.

As the incidence of malignancies in young adults is increasing, fertility preservation in cancer survivors arises as a major concern. Especially among female cancer patients, pregnancy rates are estimated to be 40% lower compared to women of the same age. Nowadays oncologists are to be preoccupied not only with their patients' successful treatment, but also with the maintenance of the potential of the latter to conceive and obtain children. Chemotherapy associated ovarian failure (COF), refers to disruption of ovarian function both as an endocrine gland and as a reproductive organ, due to previous exposure to chemotherapy agents. Although the underlying mechanism is not fully understood, it is supposed that chemotherapy agents may induce either DNA damage of premature ovarian follicle or early activation and apoptosis of them, resulting into early exhaustion of available follicle deposit. Various chemotherapy agents have been associated with COF with the highest incidence being reported for patients undergoing combination regimens. Although a variety of alternatives in order to maintain ovarian function and fertility in female cancer survivors are available, adequately established practices to do so are lacking. Thus, it is of major importance to investigate further and collect sufficient evidence, aiming to guide patients and physicians in everyday clinical practice.