Treatment with plasma exchange of a pregnant woman with anti-PP1Pk alloimmunization: A case report.

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).

Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.

Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.

Increase in landslide activity after a low-magnitude earthquake as inferred from DInSAR interferometry.

On August 16th, 2018, a Mw 5.1 earthquake struck the Molise region (central Italy), inducing 84 earthquake-triggered landslides that predominantly involved soil covers of clayey materials and flysch on gently dipping slopes. To quantify the spatiotemporal landslide activity in the months immediately after the earthquake, a differential SAR interferometry (DInSAR) analysis was performed for a time span from 2 years before to one year after the earthquake, recognising both first-time and reactivated landslides. The results showed a clear increase in landslide activity following the low-magnitude earthquake with respect to the activities recorded in the same months of the previous years. Several coherent landslides (earth slides and earth flows) were observed following seasonally recurrent rainfall events. Such increases were observed for both reactivated and first-time landslides, showing decreases in inactive periods and activity over longer periods. Furthermore, the spatial density distribution of the landslides was investigated in the postseismic time interval along transects perpendicular and parallel to the direction of the tectonic element responsible for the seismic event. An asymmetrical distribution was deduced parallel to the fault strike with a higher number of landslides located inside the compressional sector according to a strike-slip faulting mechanism.

Intrathecal antibody kinetics in neuroborreliosis: A report on three cases and a literature review.

Borreliosis is a common affliction in northern countries and its neurological manifestations often mislead trained clinicians. We present three cases of Lyme neuroborreliosis, with intrathecal synthesis of specific antibodies, lymphocytic meningitis and magnetic-resonance imaging (MRI) findings. Our description aims at illustrating the natural history of the infection, highlighting persistent intrathecal synthesis of anti-Borrelia antibodies months after treatment completion, and its clinical significance. We then review the literature on MRI findings in neuroborreliosis and the kinetics of intrathecal synthesis of specific anti-Borrelia antibodies.

Widening the Neuroimaging Features of Adenosine Deaminase 2 Deficiency.

Adenosine deaminase 2 deficiency (OMIM #615688) is an autosomal recessive disorder characterized by a wide clinical spectrum, including small- and medium-sized vessel vasculopathies, but data focusing on the associated neuroimaging features are still scarce in the literature. Here, we describe the clinical neuroimaging features of 12 patients with genetically proven adenosine deaminase 2 deficiency (6 males; median age at disease onset, 1.3 years; median age at genetic diagnosis, 15.5 years). Our findings expand the neuroimaging phenotype of this condition demonstrating, in addition to multiple, recurrent brain lacunar ischemic and/or hemorrhagic strokes, spinal infarcts, and intracranial aneurysms, also cerebral microbleeds and a peculiar, likely inflammatory, perivascular tissue in the basal and peripontine cisterns. Together with early clinical onset, positive family history, inflammatory flares and systemic abnormalities, these findings should raise the suspicion of adenosine deaminase 2 deficiency, thus prompting genetic evaluation and institution of tumor necrosis factor inhibitors, with a potential great impact on neurologic outcome.

Intracranial Arterial Tortuosity in Marfan Syndrome and Loeys-Dietz Syndrome: Tortuosity Index Evaluation Is Useful in the Differential Diagnosis.

BACKGROUND AND PURPOSE: The association of arterial tortuosity and connective tissue diseases is widely reported in the literature, but only a few studies were based on a quantitative evaluation of this arterial phenotype, and none of the latter examined the intracranial vasculature. The aim of this study was to evaluate the degree of intracranial arterial tortuosity in patients with Marfan syndrome and those with Loeys-Dietz syndrome, and to assess its usefulness in the differential diagnosis. MATERIALS AND METHODS: We performed a retrospective analysis of 68 patients with genetically confirmed Marfan syndrome (n = 36) or Loeys-Dietz syndrome (n = 32), who underwent at least 1 MRA of the brain at our institution. Fifty-two controls were randomly selected among patients who presented with headache and without any known comorbidity. Tortuosity indexes of 4 intracranial arterial segments were measured on a 3D volume-rendered angiogram by using the following formula: [Formula: see text]. RESULTS: Both Marfan syndrome and Loeys-Dietz syndrome showed a significantly higher tortuosity index compared with controls in all examined vessels. The tortuosity index of the vertebrobasilar system showed an excellent interrater reliability (intraclass correlation coefficient, 0.99) and was the strongest independent predictor of Loeys-Dietz syndrome in patients with connective tissue disease (P = .002), with a 97% specificity for this pathology when its value was > 60. CONCLUSIONS: The tortuosity index of intracranial arteries is an easily calculated and highly reproducible measure, which shows a high specificity for Marfan syndrome and Loeys-Dietz syndrome and may be useful in differentiating these 2 entities.

An intensive task-oriented circuit training positively impacts gait biomechanics in MS patients.

BACKGROUND: An intensive task-oriented circuit training (TOCT) provides a valid approach in improving motor function in Multiple Sclerosis (MS). OBJECTIVE: We aimed at testing the efficacy of TOCT on gait kinematics in MS patients with mild-moderate disability. METHODS: Nineteen MS patients able of independent walking performed 3-D Gait Analysis before (T0) and after (T1) a two-week TOCT program. Patients were clustered in two different subgroups, according to clinical neurological impairments assessed with specific functional system of Expanded Disability Status Scale (EDSS): pyramidal (Group 1) and cerebellar (Group 2) subjects. Spatio-temporal and kinematic data were compared before and after the TOCT intervention in the total sample of patients and in the two selected subgroups at two time intervals. RESULTS: Data obtained revealed increased dynamic ROM at knee joint after training in the whole study sample. Of note, knee dynamic excursion improved significantly in Group 1 but not in Group 2 patients after TOCT. Moreover, sagittal plane kinematics revealed significant modifications on knee and ankle biomechanics in Group 1 after rehabilitation. CONCLUSIONS: These data point out the benefits of the task specific training on gait dynamics in mild impaired MS subjects, linking to treatment opportunity in patients with a prevalent pyramidal impairment.

Epidemiology of Lyme borreliosis through two surveillance systems: the national Sentinelles GP network and the national hospital discharge database, France, 2005 to 2016.

BACKGROUND: Lyme borreliosis (LB) is the most frequent vector-borne disease in France. Since 2009, surveillance of LB is conducted by a sentinel network of general practitioners (GPs). This system, in conjunction with the national hospitalisation database was used to estimate the incidence and describe the characteristics of LB in France. AIM: To describe the estimated incidence and trends in GP consultations and hospital admissions for LB in France and identify risk groups and high-incidence regions. RESULTS: From 2011 to 2016, the mean yearly incidence rate of LB cases was 53 per 100,000 inhabitants (95% CI: 41-65) ranging from 41 in 2011 to 84 per 100 000 in 2016. A mean of 799 cases per year were hospitalised with LB associated diagnoses 2005-16. The hospitalisation incidence rate (HIR) ranged from 1.1 cases per 100,000 inhabitants in 2005 to 1.5 in 2011 with no statistically significant trend. We observed seasonality with a peak during the summer, important inter-regional variations and a bimodal age distribution in LB incidence and HIR with higher incidence between 5 and 9 year olds and those aged 60 years. Erythema migrans affected 633/667 (95%) of the patients at primary care level. Among hospitalised cases, the most common manifestation was neuroborreliosis 4,906/9,594 (51%). CONCLUSION: Public health strategies should focus on high-incidence age groups and regions during the months with the highest incidences and should emphasise prevention measures such as regular tick checks after exposure and prompt removal to avoid infection.

Yeasts and moulds contaminants of food ice cubes and their survival in different drinks.

AIMS: To evaluate the levels of unicellular and filamentous fungi in ice cubes produced at different levels and to determine their survival in alcoholic beverages and soft drinks. METHODS AND RESULTS: Sixty samples of ice cubes collected from home level (HL) productions, bars and pubs (BP) and industrial manufacturing plants (MP) were investigated for the presence and cell density of yeasts and moulds. Moulds were detected in almost all samples, while yeasts developed from the majority of HL and MP samples. Representative colonies of microfungi were subjected to phenotypic and genotypic characterization. The identification was carried out by restriction fragment length polymorphism (RFLP) analysis of the region spanning the internal transcribed spacers (ITS1 and ITS2) and the 5·8S rRNA gene. The process of yeast identification was concluded by sequencing the D1/D2 region of the 26S rRNA gene. The fungal biodiversity associated with food ice was represented by nine yeast and nine mould species. Strains belonging to Candida parapsilosis and Cryptococcus curvatus, both opportunistic human pathogens, and Penicillium glabrum, an ubiquitous mould in the ice samples analysed, were selected to evaluate the effectiveness of the ice cubes to transfer pathogenic microfungi to consumers, after addition to alcoholic beverages and soft drinks. All strains retained their viability. CONCLUSIONS: The survival test indicated that the most common mode of consumption of ice cubes, through its direct addition to drinks and beverages, did not reduce the viability of microfungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study evidenced the presence of microfungi in food ice and ascertained their survival in soft drinks and alcoholic beverages.

Correlation between individual inflammation genetic profile and platelet rich plasma efficacy in hair follicle regeneration: a pilot study reveals prognostic value of IL-1a polymorphism.

OBJECTIVE: Hair loss generates severe psychosocial implications. To date, exploring the prognostic factors of possible clinical benefit of autologous blood concentrate platelet rich plasma (PRP) was failed. The aim of our pilot study was to explore the correlation between the individual inflammation genetic profile and PRP efficacy in the treatment of hair follicle regeneration. PATIENTS AND METHODS: 41 volunteers (25 men, 16 women) took part in this retrospective study. All the patients were scheduled for 4 sessions of PRP application with intervals of 40-60 days. All the patients were checked up at 6 weekly intervals for 6 months and, then, at the end of the first year. A panel of 5 polymorphisms on 4 genes (IL-1a, IL-1b, IL-6, and IL-10) implicated in the individual genetic inflammation profile were performed. RESULTS: A significant increase rate in hair density was noticed after the third month of treatment in 32/41 (78%) of the subjects. We found an interesting association between the pro-inflammatory cytokine IL-1α polymorphism C>A (rs17561) and responders to PRP treatment. The cases carrying C/C genotype (coding for Ser114) were 21 (66%) in responders and only 2 (22%) in non-responders (p<0.05). In addition, about IL-1a, the frequency of G/G genotype in responder patients was over two times lower in responder (31%) than in non-responder patients (78%). CONCLUSIONS: Our pilot study demonstrated a correlation between the individual genetic inflammatory profile and the efficacy of the PRP treatment in males. On the contrary, in females, it showed a negative correlation. IL-1a could be used as a prognostic value for PRP efficacy. Also, these results provide preliminary evidence that may encourage the design of controlled clinical trials to properly test this modus operandi on a large number of subjects.

[Neurosyphilis: A retrospective study of 13 cases at Strasbourg University Hospital]. / La neurosyphilis, étude rétrospective de 13 cas survenus aux hôpitaux universitaires de Strasbourg.

OBJECTIVE: After a decade of constant decline, the number of syphilis cases has been steadily increasing since the 2000s, particularly in HIV infected patients. Neurosyphilis is a rare manifestation of this sexually transmitted disease for which we performed a retrospective study and analyzed clinical manifestations. PATIENTS AND METHODS: We reviewed retrospectively all the neurosyphilis cases admitted to Strasbourg University Hospital between 2004 and 2014. We included and analyzed 13 patients admitted during this period who met the diagnostic criteria for neurosyphilis. RESULTS: Nine of 13 patients had isolated visual manifestations; three (23.1%) experienced posterior uveitis, two (15.4%), panuveitis, and 4 (30.8%) had papillitis. Out of five patients (38.5%) who were HIV positive, three (60%) had a CD4 cell count above 400/mm3 at the time of diagnosis of neurosyphilis. All patients received parenteral penicillin G or cephalosporin, and 5/13 (38.5%) received systemic corticotherapy. CONCLUSION: Ophthalmologists appear as key players in the identification, management and follow-up of neurosyphilis, since ocular findings are key diagnostic features in these patients.

Gait dynamics in Pisa syndrome and Camptocormia: The role of stride length and hip kinematics.

This is an observational cross-sectional study evaluating gait dynamics in patients with Parkinson's Disease (PD) and severe postural deformities, PD without axial deviations and healthy subjects. Ten PS individuals with Pisa syndrome (PS) and nine subjects with Camptocormia (CC) performed 3-D Gait Analysis and were evaluated with walking and balance scales. Correlations with clinical and functional scales were investigated. Spatio-temporal and kinematic data were compared to ten PD subjects without postural deformities (PP) and ten healthy matched individuals (CG). Data obtained showed decreased walking velocity, stride and step length in PP, PS and CC groups compared to controls. The correlation analysis showed that stride and step length were associated with reduced functional abilities and disease severity in PS and CC groups. Kinematic data revealed marked reduction in range of movements (ROMs) at all lower-extremity joints in PS group. While, in CC group the main differences were pronounced in hip and knee joints. PS and CC groups presented a more pronounced reduction in hip articular excursion compared to PP subjects, revealing an increased hip flexion pattern during gait cycle. Moreover, the increased hip and knee flexion pattern adversely affected functional performance during walking tests. Results obtained provide evidence that step length, along with stride length, can be proposed as simple and clear indicators of disease severity and reduced functional abilities. The reduction of ROMs at hip joint represented an important mechanism contributing to decreased walking velocity, balance impairment and reduced gait performance in PD patients with postural deformities.

A foot tumour as late cutaneous Lyme borreliosis: a new entity?

Acrodermatitis chronica atrophicans (ACA) is the late cutaneous form of Lyme borreliosis. The early inflammatory phase manifests with a bluish-red discoloration and doughy swelling of the skin. The atrophic phase represents a late-phase process with red discoloration, and a thin and wrinkled appearance of the skin. We present a patient who exhibited a previously undescribed form of late cutaneous Lyme borreliosis (LCLB) with a foot tumour. A 64-year-old woman had a large tumorous lesion on the right sole. The tumour size and deformation of the feet made wearing shoes difficult. On skin histology, a granulomatous lymphohistiocytic infiltrate with plasma cells was noticed. In fact, the patient recalled tick bites 2 or 3 years before. Borrelia burgdorferi (Bb) serology was highly positive and a polymerase chain reaction analysis on the skin biopsy detected Bb sensu lato, genospecies B. afzelii. We diagnosed LCLB and antibiotics were prescribed. On the more recent examination, the tumour had totally disappeared; the skin was atrophic and dry with only few scales. We report an atypical case of European LCLB, suggesting that ACA is not the only possible presentation of LCLB. The diagnosis of ACA is often clinically missed for months or years, and may be mistaken at the inflammation phase for vascular disorders, erysipelas or bursitis/arthritis, and at the atrophic phase for lichen sclerosus atrophicus, morphoea or anetoderma. To our knowledge, no such tumorous LCLB has previously been described.

Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.

OBJECTIVE: Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy. MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1). RESULTS: The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy. CONCLUSIONS: Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy.