HTL V-I from Iranian Mashhadi Jews in Israel is phylogenetically related to that of Japan,India, and South America rather than to that of Africa and Melanesia

A new endemic focus of human T-lymphotropic virus type I (HTL V-I) was recently reported among Mashhadi Jews, a group of immigrants from northeastern Iran to Israel. We extracted DNAs from fresh peripheral blood mononuclear cells (PBMCs) and/or gargle mouthwash from 10 HTL V-I carriers, who consisted of members of one family, and HTL V-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL) patients. Long terminal repeat (LTR) regions of proviral DNAs were sequenced and analyzed phylogenetically. In a phylogenetic tree, all the Mashhadi HTL V-I isolates belonged to subtype A, one of the three subtypes of the cosmopolitan type of HTL V-I, and made a tight cluster distinct from the other isolates of subtype A from Japan, India, the Caribbean Basin, and South America. Although a few nucleotide substitutions were observed among the clones sequenced, no characteristic sequence variation was found in different disease manifestations, even in one family or different sources of DNA preparation.     

The relationships between endometrial thickness, and blood flow and pregnancy rates in in-vitro fertilization

To establish whether endometrial blood flow and thickness can predict the success rate of in-vitro fertilization, 156 cycles were evaluated. The parameters were: endometrial colour and power Doppler pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D) and endometrial thickness. Each patient was studied: on the day of ovum retrievalpickup, and on the day of embryo transfer. Non-endometrial parameters studied were: age, oestrestrogen and progesterone concentrations, number of oocytes, and number of embryos. Pregnancy was achieved in 31 cycles. On the day of ovum retrieval, patients who conceived had PI, RI, and S/D values of 0.997, 0.563, and 2.403, respectively. Patients who did not conceive had values of 0.994, 0.584, and 2.477 respectively. The power Doppler technique provided similar results. On the day of embryo transfer, pregnant patients had PI, RI and S/D values of 1.096, 0.590 and, 2.597 respectively, while in the non-pregnant patients the values were 1.104, 0.603 and, 2.723 respectively. Power Doppler showed similar numbers. The differences between pregnant and non-pregnant patients were not statistically significant in any of the parameters. Endometrial thickness and blood flow does not seem to correlate with pregnancy rate in IVF.     

Circulatory neurosteroid levels in underweight female adolescent anorexia nervosa inpatients and following weight restoration

Nineteen female adolescent inpatients diagnosed with anorexia nervosa, restricting type (AN-R) and 16 non-eating disordered (ED) controls were assessed for plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulphate (DHEA-S), and cortisol levels, and for eating-related and non-eating-related psychopathology. AN-R patients were assessed at admission, 1 month and 4 months following hospitalization. The non-ED controls were assessed once. No baseline between-group differences were found in plasma cortisol, DHEA, and DHEA-S levels, whereas the patient group had a significantly lower Cortisol/DHEA-S ratio and elevated scores on most psychopathological parameters. A significant increase was found in the body mass index of the AN-R patients at 4 months post-hospitalization, accompanied by a decrease in plasma cortisol levels and a trend towards decreased Cortisol/DHEA and Cortisol/DHEA-S ratios, whereas no change occurred in psychopathology. The difference in Cortisol/DHEA-S ratio between AN-R patients and non-ED controls, and the different patterns of change in cortisol vs. DHEA(-S) levels following weight restoration, may in part account for the feeding difficulties in AN, particularly during refeeding.     

Thiotepa‐based versus total body irradiation‐based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long‐established ones. This retrospective matched‐pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa‐based (n = 121) or a cyclophosphamide/total body irradiation‐based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA‐matched sibling or an unrelated donor. With a median follow‐up of 44 months, the outcome was similar in both groups. Acute graft‐versus‐host disease grade II‐IV was observed in 25% after thiotepa‐containing regimen versus 35% after TBI (P = 0.06). The 2‐yr cumulative incidence of chronic graft‐versus‐host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non‐relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia‐free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.     

Clinical and microbiological properties of Staphylococcus lugdunensis skin infections

Staphylococcus lugdunensis is an emerging pathogen in skin and soft tissue infections that was previously considered a commensal. The aim of this study was to elucidate the characteristics of skin infections by S. lugdunensis and its appropriate management, in a tertiary referral medical center. The clinical files, bacterial cultures and histopathology reports of all S. lugdunensis isolates from skin infections over a period of 8 years (September 2009–September 2017) were reviewed. S. lugdunensis was isolated from 29 patients with skin infections, aged 7–89 years (mean 33.3 years). A state of immune suppression (drug‐induced, malignancy or diabetes) was present in five patients (17%). Folliculitis and cutaneous pustulosis were the most common presentations (16 cases, 55%), followed by secondary infection of hidradenitis suppurativa (five cases, 17%). Other sources of isolation were infected molluscum contagiosum (two cases), folliculitis decalvans (one case), dissecting cellulitis (one case), abscess (one case), cyst (one case), impetigo (one case) and granuloma after trauma (one case). The in vitro antibiotic sensitivity tests showed susceptibility to most tested antibiotics, although a few isolates were resistant to gentamycin, penicillin and oxacillin. In 19 of 20 patients for whom follow ups were available, cutaneous manifestations improved or resolved with proper local and/or oral antibiotic therapy. S. lugdunensis may play a role as a primary or secondary pathogen in various skin infections, most commonly folliculitis and pustulosis. Proper antibiotic therapy may lead to improvement or resolution.     

Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.     

Effect of Matrix Metalloproteinase Inhibition by Doxycycline on Myocardial Healing and Remodeling after Myocardial Infarction

Summary The aim of conducting this study was to assess the clinical relevance of matrix metalloproteinase (MMP) inhibition by doxycycline, an effective MMP inhibitor, in a rat model of extensive myocardial infarction (MI) and left ventricular (LV) dysfunction. Rats (n = 22) were subjected to extensive anterior MI. Doxycycline (25 mg SC, daily) or saline (control) injections were started for nine days thereafter. The effect of doxycycline on MMP activity in the infarcted and remote myocardium was measured by zymography, in another subgroup (n = 8), nine days after MI. Echocardiography and magnetic resonance imaging (MRI) studies were performed at one and thirty days after MI to assess LV remodeling and function. After 4 weeks, hearts were fixed, and subjected to morphometric and histological analysis. Compared with control, doxycycline treatment attenuated MMP-9 and -2 activity in both infarcted and remote myocardium. Serial echocardiography studies showed that doxycycline failed to attenuate scar thinning, LV dilatation and dysfunction. MRI study showed that doxycycline impaired LV compensatory hypertrophy. Furthermore, compared with control, doxycycline reduced vessel density (/mm² ± SEM) in the infarcted myocardium (84 ± 16 vs. 46 ± 9/mm², respectively; p < 0.05). Our work suggest that effective MMPs’ inhibition in the infarcted and remote myocardium by doxycycline does not prevent LV remodeling and dysfunction but impairs angiogenesis and compensatory LV hypertrophy. Our findings caution against aggressive, non-selective inhibition of MMPs in the early healing phase after MI.     

Maternal medical compromise during pregnancy and pregnancy outcomes

Objective: To examine the outcomes of pregnancy and newborn following an event of maternal medical compromise during pregnancy.

Methods: A retrospective study was performed on all patients hospitalized following an event of medical compromise during pregnancy. Medical compromise was divided to acute or chronic bleeding, major or complicated operations, and admission to intensive care unit (ICU). Data collected included maternal, fetal, neonatal and child’s follow-up.

Results: The study included 51 pregnant patients and 58 fetuses. The study group had increased risk of preterm deliveries (35.0 versus 6.5%, p?p?p?=?0.002). Patients with acute bleeding had higher rates of cesarean sections, preterm deliveries, admissions to neonatal ICU and neonatal mortality. Two cases of fetal abnormalities included brain abnormalities and pericardial effusion. Three terminations of pregnancies were performed: two in patients in ICU due to severe maternal medical condition and one in the fetus with brain abnormalities.

Conclusions: Maternal medical compromise during pregnancy increases the risk for preterm deliveries, cesarean delivery and low Apgar scores. Acute bleeding was the main cause of medical compromised and with the higher rates of adverse outcomes.