Severe COVID-19 in a patient with chronic graft-versus-host disease after hematopoietic stem cell transplant successfully treated with ruxolitinib.

Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplant, which is known to be mediated by cytotoxic T-cell effectors and dysregulated inflammatory cytokines. Similarly, the lung injury observed in severe COVID-19 cases appears to be related to a massive production of pro-inflammatory cytokines. The selective JAK1/2 inhibitor ruxolitinib has shown promising results in the context of GVHD, and different trials are currently underway in patients with severe COVID-19; nevertheless, no clinical observation of safety or efficacy of treatment with ruxolitinib in this context has been published yet. We describe a first case of severe COVID-19 developed after hematopoietic stem cell transplantation in a patient with a concomitant chronic GVHD (cGVHD), in which a treatment with ruxolitinib was administered with good tolerance and positive outcome.

Prognostic role of immunohistochemical analysis of 5 mc in myelodysplastic syndromes.

BACKGROUND: Aberrant DNA methylation at CpG islands within promoters is increasingly recognised as a common event in human cancers and has been associated with the silencing of important tumour suppressor genes. Epigenetic therapy using hypomethylating agents has demonstrated clinical effectiveness; the drugs azacitidine and decitabine have been approved for the treatment of MDS. METHOD: We investigated the association between global DNA methylation and clinical outcome in MDS. We evaluated 134 MDS bone marrow trephine biopsies (BMTB) by immunohistochemistry and compared the results with those from an age-matched group of normal BMTB. Immunohistochemistry was performed on paraffin-embedded sections using the anti-5-methylcytosine (5mc) antibody. RESULTS: Our results showed that the 5mc immunostaining score (M-score) of patients with MDS was higher than those of normal controls and that overall survival significantly correlated with global DNA methylation, age and IPSS score. Therefore, we found that patients with high levels of methylation had a shorter median overall survival (OS) compared with patients with lower levels. These immunohistochemistry results were confirmed by analysing global DNA methylation on LINE-1 sequences using the COBRA method and pyrosequencing. CONCLUSION: This study reports that global DNA methylation detected by immunohistochemistry predicts OS in MDS.

Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility.

Microbiota are microorganismal communities colonizing human tissues exposed to the external environment, including the urogenital tract. The bacterial composition of the vaginal microbiota has been established and is partially related to obstetric outcome, while the uterine microbiota, considered to be a sterile environment for years, is now the focus of more extensive studies and debates. The characterization of the microbiota contained in the reproductive tract (RT) of asymptomatic and infertile women, could define a specific RT microbiota associated with implantation failure. In this pilot study, 34 women undergoing personalized hormonal stimulation were recruited and the biological samples of each patient, vaginal fluid, and endometrial biopsy, were collected immediately prior to oocyte-pick up, and sequenced. Women were subsequently divided into groups according to fertilization outcome. Analysis of the 16s rRNA V4-V5 region revealed a significant difference between vaginal and endometrial microbiota. The vaginal microbiota of pregnant women corroborated previous data, exhibiting a lactobacilli-dominant habitat compared to non-pregnant cases, while the endometrial bacterial colonization was characterized by a polymicrobial ecosystem in which lactobacilli were exclusively detected in the group that displayed unsuccessful in vitro fertilization. Overall, these preliminary results revisit our knowledge of the genitourinary microbiota, and highlight a putative relationship between vaginal/endometrial microbiota and reproductive success.

Could art cycles have a detrimental effect on ovarian reserve? A retrospective case control study.

BACKGROUND: Even if it is supposed damage of repeated ART (assisted reproductive technology) cycles on oocyte pool, there is still no evidence in literature. Aim of the study is to investigate whether infertile women who undergo to several ART cycles can show a lower ovarian reserve measured by AMH (Anti-Mullerian hormone) levels. METHODS: The study includes 282 infertile women, between 18 and 42 years, and allocated into two groups: 159 women previously submitted to two or more ART cycles (group A) and 123 women never submitted naïve to-ART cycles (group B). We tested whether AMH, FSH, LH and E2 levels were significantly different between the two groups, stratifying according to age. RESULTS: Regardless to the age ranges bands, the AMH in group A was statistically significant lower than in group B with a statistical significance (P=0.047). In particular women aged over 35 previously submitted to one or more ART cycles showed lower AMH levels, than those paired with age, which had never been treated with ART. CONCLUSIONS: Despite the limitations of the study, our data demonstrate a reduced AMH levels in women aged over 35 previously submitted to two or more repeated ART-cycles compared to patients never treated before. The strength of this study is the actuality of the topic that has not been discussed before in detail.

Cross-talk between fetal membranes and visceral adipose tissue involves HMGB1-RAGE and VIP-VPAC2 pathways in human gestational diabetes mellitus.

AIMS: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy. Maternal adipose tissue and fetal membranes secrete various molecules that are relevant players in the pathogenesis of GDM. This pilot study aimed to examine whether the expression of the high mobility group box 1 protein (HMGB1) and its receptor for advanced glycation end products (RAGE), and the vasoactive intestinal peptide (VIP) and its receptors (VPAC-1,-2) were modified in pregnant women with GDM. METHODS: Fetal membranes (FMs), omental adipose tissue (VAT) explants, and serum samples were obtained from 12 women with GDM and 12 with normal glucose tolerance (NGT) at delivery. The expression of HMGB1, RAGE and VIP, VPAC-1,-2 was detected by Western Blotting in explants; circulating levels and "in vitro" release of HMGB1 and VIP were measured by ELISA tests. RESULTS: HMGB1 tissue expression was higher in FMs obtained from GDM women (p = 0.02) than in FMs from NGT women. VPAC2 (p = 0.03) and RAGE (p = 0.03) tissue expressions were significantly increased in VAT from GDM subjects. Only FMs of NGT released detectable levels of HMGB1, which was not observed in samples obtained from GDM. VAT of GDM released lower levels of VIP (p = 0.05) than NGT samples. CONCLUSIONS: This study indicates that a fine tuned regulation exists between FMs and VAT throughout pregnancy to maintain immune metabolic homeostasis. In GDM a balance between inflammatory and anti-inflammatory mediators has been observed. Further studies are needed to establish their exact role on fetal and maternal outcomes in GDM.

Ultrasonography reappraisal of tubal patency in assisted reproduction technology patients: comparison between 2D and 3D-sonohysterosalpingography. A pilot study.

BACKGROUND: The aim of this study was to compare 2D and 3D-sonohysterosalpingography (2D-3D-HyFoSy) with previous diagnostic laparoscopy in the diagnosis of tubal patency, and compare each procedure in terms of procedure's time, perceived pain and complication rate. METHODS: We prospectively recruited infertile women, previously submitted to laparoscopy and randomly allocated into 2D-HyFoSy (group I) and 3D-HyFoSy (group II). We analyzed the results in term of sensitivity, specificity, positive predictive value and negative predictive value in tubal patency evaluation of both procedures in comparison with laparoscopy. RESULTS: We enrolled 50 women, 25 in group I and 25 in group II. 2D-HyFoSy findings obtained in group I, were concordant with laparoscopy in 81% of cases, with a sensitivity of 80% and a specificity of 92%. In group II, a correspondence was present in 88% of examinations, with a sensitivity and specificity of 98% and 91.4% respectively. 3D-HyFoSy was found to be faster and less painful than 2D (P<0.001). CONCLUSIONS: In the diagnosis of tubal occlusion, in the high-risk population, it seems advisable to us using the 3D-HyFoSy as the first-level examination, while, in low-risk patients, if the tubes appear obstructed in 2D-HyFoSy, the 3D-HyFoSy should be indicated before submitting patients to operative laparoscopy.

Valproic acid for the treatment of low-risk myelodysplastic syndromes: A case report and a review of the literature.

Myelodysplastic syndromes are heterogeneous myeloid neoplasms ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukemia. Here we report a 51-year-old woman with depression and severe obesity who was diagnosed with an International Prognostic Scoring System low-risk myelodysplastic syndrome, presenting mainly with thrombocytopenia, treated with escalating dose of valproic acid as a single agent. After two years of treatment her platelet count is almost normal and the tolerance to therapy is good. It is already known that valproic acid could be used in high-risk myelodysplastic syndromes and acute myeloid leukemia, mainly in association with other drugs, but its role in low-risk myelodysplastic syndrome is not well established yet.

Telomere length, c-myc and mad-1 expression could represent prognosis markers of myelodysplastic syndrome.

Telomere dysfunction might generate genomic instability leading to the progression of myelodysplastic syndromes (MDS) into acute myeloid leukemia (AML). We investigated telomere length (TL), telomerase activity (TA) and hTERT, c-myc, mad1, and p53 expression in the bone marrow of patients with MDS (n=109), AML (n=47) and in controls (n=24). TL was lower in MDS patients than in controls (p<0.001) and higher in L-MDS (low, intermediate-1 IPSS, p<0.01) respect H-MDS (high, intermediate-2 IPSS, p<0.01) patients. Mad-1 expression was higher in MDS patients than in controls (p<0.01), c-myc expression was highest in AML and in H-MDS patients. Our results show that the telomere dynamics might be useful for stratifying patients according to a risk scoring system.