Search

Introduction Gordonia species, aerobic, weakly acid-fast, Gram-positive bacilli, are a rare cause of peritonitis in patients undergoing peritoneal dialysis (PD). We report the first pediatric case of PD-related peritonitis caused by Gordonia bronchialis. Case presentation A 13-year-old girl with chronic kidney disease (CKD) stage 5D, on continuous cycling PD (CCPD) for 8 years, presented with cloudy PD effluent, with no abdominal discomfort or fever. Intra-peritoneal (IP) loading doses of vancomycin and ceftazidime were started at home after obtaining a PD effluent sample, which showed WBC 2,340 × 10 /L (59% neutrophils) and Gram-positive bacilli. On admission, she was clinically well and afebrile, with no history of methicillin-resistant Staphylococcus aureus (MRSA) infection, so vancomycin was discontinued, and IP ceftazidime and cefazolin were started, following a loading dose of intravenous cefazolin. Gordonia species grew after 5 days of incubation and later identified as Gordonia bronchialis. IP vancomycin was restarted as monotherapy, empirically for a total of 3 weeks therapy. A 2-week course of oral ciprofloxacin was added, based on susceptibility testing. PD catheter replacement was advised due to the risk of recurrence but was refused. A relapse occurred 16 days after discontinuing antibiotics, successfully treated with a 2-week course of IP ceftazidime and vancomycin. The PD catheter was removed and hemodialysis initiated. She received a further 2-week course of oral ciprofloxacin and amoxicillin-clavulanate post PD catheter removal. Conclusions Gordonia bronchialis is an emerging pathogen in PD peritonitis and appears to be associated with a high risk of relapse. PD catheter replacement is strongly suggested.

Epithelial ovarian cancer (EOC) is the scariest gynaecological cancer. Many advances have been done with evolving knowledge, leading to the introduction of new drugs, most in maintenance setting. The antiangiogenic Bevacizumab and the three approved PARP-inhibitors—olaparib, niraparib and rucaparib—are gradually improving PFS of patients with EOC, with initial effects on OS too. But recurrence is still a heavy sentence and lethality continues to be high. Ovarian cancer is a complex disease, with different clinical presentation, histological aspect, and molecular expression, leading to disappointing results, when using a single drug. Implementation of biobanking and analysis of patients’ tumour samples, before starting a treatment, could be a promising way to better understand molecular aspects of this disease, to identify markers predictive of response and to allow a better use of experimental drugs, as immunomodulators, targeted therapies, and combinations of these, to fight tumour growth and clinical progression. We reviewed the literature on the updated treatments for recurrent ovarian cancer, summarizing all the available drugs and combinations to treat patients with this diagnosis, and focusing the attention on the new approved molecules and the contemporary Clinical Trials, investigating new target therapies and new associations.

RPL is a very debated condition, in which many issues concerning definition, etiological factors to investigate or therapies to apply are still controversial. ML could help clinicians to reach an objectiveness in RPL classification and access to care. Our aim was to stratify RPL patients in different risk classes by applying an ML algorithm, through a diagnostic work-up to validate it for the appropriate prognosis and potential therapeutic approach. 734 patients were enrolled and divided into 4 risk classes, according to the numbers of miscarriages. ML method, called Support Vector Machine (SVM), was used to analyze data. Using the whole set of 43 features and the set of the most informative 18 features we obtained comparable results: respectively 81.86 ± 0.35% and 81.71 ± 0.37% Unbalanced Accuracy. Applying the same method, introducing the only features recommended by ESHRE, a correct classification was obtained only in 58.52 ± 0.58%. ML approach could provide a Support Decision System tool to stratify RPL patients and address them objectively to the proper clinical management.

Introduction/Background* Endometrial cancer (EC) patients have a good prognosis at early stages, but for recurrent or metastatic EC the prognosis remains poor. EC treatments are related to known prognostic factors included in ESMO-ESGO-ESTRO risk classes classification, but they are not sufficient to predict outcomes or recurrence rate of early stages. To improve patient clinical management and allow personalized therapy a better characterization of risk classes in EC is needed. To fill this gap, we investigated EC immune escape processes, customized on the knowledge of maternal-fetal interface immune mechanisms, since the two processes share common pathways. Methodology This has been addressed by the identification of potential shared immune-based signatures between maternal-fetal interface and EC, such as those linked to lectin-type oxidized LDL receptor 1 (LOX-1) and NALP3 inflammasome, in order to achieve a potential immune score implementation to better characterize EC risk classes. The immunohistochemical assessment of LOX-1 and NALP3 was performed on formalin-fixed paraffin-embedded (FFPE) endometrial tissues. Result(s)* 41 patients divided in 3 groups were enrolled: healthy endometrial tissue, endometrial hyperplasia and EC. We detected an increased expression of LOX-1, by immunohistochemistry (IHC), within the endometrial carcinoma tissues, a lower expression in cases of hyperplasia, to arrive to an absent staining in the healthy endometrial tissue (*p Conclusion* An increased LOX-1 and a decreased NALP3 expression seems be associated with EC progression. To identify patients at risk of developing EC from pre-cancerous lesions, by searching potential immune prognostic factors, such as LOX-1 and NALP3 on endometrial biopsy, could re-defy the actual EC risk classes through a potential ’immune score’ creation. Nevertheless, further studies are needed to define EC transcriptome immune-based signature. Furthermore, pathways detected by deciphering the immune changes linked to EC progression, could be potential target for immunotherapy.

Breast reconstruction plays a fundamental role in the therapeutic process of breast cancer treatment and breast implants represents the leading breast reconstruction strategy. Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL), locoregional recurrence in the skin flap, and skin flap necrosis are well-known complications following mastectomy and immediate breast reconstruction (IBR). We report a case of locoregional cancer recurrence in the mastectomy flap mimicking BIA-ALCL, in a patient who underwent 6 breast procedures in four facilities across 15 years including immediate breast reconstruction with macrotextured breast implants. Despite the rate and onset of the disease, clinicians should be aware of BIA-ALCL. Due to the risk of false negative results of fine needle aspiration, clinical suspicion of BIA-ALCL should drive clinicians' choices, aside from cytological results. In the present case, surgical capsulectomy of the abnormal periprosthesic tissue revealed locoregional recurrence.

Purpose The lateral elbow musculature conveys a dynamic valgus moment to the elbow, increasing joint stability. Muscular or tendinous lesions to the anterior half of the common extensor origin (CEO) may provoke a deficiency in the elbow dynamic stabilizers, regardless of their traumatic, degenerative, or iatrogenic aetiology. Furthermore, a role for the radial band of the lateral collateral ligament (R-LCL) has been postulated in the aetiology of lateral elbow pain. This study aimed to evaluate the effects of sequential lateral releases with dynamic ultrasound, evaluating its capability to detect lesions of the CEO and of the R-LCL. Methods Ultrasound investigation of the lateral compartment of the elbow was performed on nine cadaveric specimens with a 10 MHz linear probe in basal conditions, after the release of the anterior half of the CEO and after complete R-LCL release. The lateral joint line widening (λ) was the primary outcome parameter, measured as the linear distance between the humeral and radial articular surfaces. Results The release of the anterior half of the CEO significantly increased λ by 200% compared to the starting position (p = 0.0008) and the previously loaded position (p = 0.0015). Conversely, further release of the R-LCL caused only a marginal, non-significant increase in λ. Conclusions Ultrasound evaluation can detect changes related to tendon tears or muscular avulsions of the CEO and can depict lateral elbow compartmental patholaxity by assessing articular space widening while scanning under dynamic stress. However, it cannot reliably define if the R-LCL is injured. Iatrogenic damage to the CEO should be carefully avoided, since it causes a massive increase in compartmental laxity.

IntroductionElderly endometrial cancer (EEC) patients represent a challenging clinical situation because of the increasing number of clinical morbidities. In this setting of patients, minimally invasive surgery (MIS) has been shown to improve surgical and clinical outcomes. The aim of this study was to evaluate the peri-operative and oncological outcomes of EEC patients who had undergone laparoscopic (LS) or robotic surgery (RS).Materials and MethodsThis is a retrospective multi-institutional study in which endometrial cancer patients of 70 years or older who had undergone MIS for EC from April 2002 to October 2018 were considered. Owing to the non-randomized nature of the study design and the possible allocation biases arising from the retrospective comparison between LS and RS groups, we also performed a propensity score-matched analysis (PSMA).ResultsA total of 537 patients with EC were included in the study: 346 who underwent LS and 191 who underwent RS. No significant statistical differences were found between the two groups in terms of surgical and survival outcomes. 188 were analyzed after PSMA (94 patients in the LS group were matched with 94 patients in the RS group). The median estimated blood loss was higher in the LS group (p=0.001) and the median operative time was higher in the RS group (p=0.0003). No differences emerged between LS and RS in terms of disease free survival (DFS) (p=0.890) and overall survival (OS) (p=0.683).ConclusionsOur study showed that when compared LS and RS, RS showed lower blood losses and higher operative times. However, none of the two approaches demonstrated to be superior in terms of survival outcomes. For this reason, each patient should be evaluated individually to determine the best surgical approach.

The clinical effects of the Covid-19 pandemic are now the subject of numerous studies worldwide. But what are the effects of the quarantine imposed by the states that implemented the measures of lockdown? The present research aims to explore, in a preliminary way, the major stress-related symptoms during the lockdown, due to Covid-19, in the Italian population. Subjects were asked to fill out a survey, that traced a line identifying the most relevant psychophysiological symptoms that took into account factors such as perceived stress, body perception, perceived pain, quality of sleep, perceptive variations (i.e., olfactory, gustatory, visual, acoustic, and haptic perception). A network approach formulating a hypothesis-generating exploratory analysis was adopted. Main results of the network analysis showed that the beliefs of having had the Covid-19 was related to individual variables (i.e., gender, working in presence, sleep quality, anxiety symptoms), while the familiarity of Covid-19 disease was related to contextual factors (e.g., number of recorded cases in the Region, working in presence). The self-perception of olfactory and perceptive alterations highlighted a great sensorial cross-modality, additionally, the olfactory impairment was related to the belief of having had the Covid-19. Compared to general network data, BAI, perceived stress, anxiety and chronic pain were in relation to daily sleep disturbance. Main study's results show how the management of the Covid-19 stressful representation, in its cognitive aspects, can modulate the psychophysiological responses.

Highlights • Superficial myofibroblastoma of the Labia Majora. • Differential diagnosis between vulvar superficial myofibroblastoma and cyst/hydrocele of Nuck duct. • Differential diagnosis between vulvar superficial myofibroblastoma and inguinal/crural hernia.

Introduction The aim of this study is to revise the experience of two reference centers for vulvar cancer treatment during the last 2 years, evaluating the ECT procedure in terms of clinical outcome and side effects profile. Methods Data were retrospectively collected from November 2017 to November 2019 in two Italian oncologic Institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli. ECT was offered in a palliative setting to patients with a primary or recurrent vulvar cancer diagnosis unsuitable for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anaesthesia. Intravenous Bleomycin was administered. Follow-up examinations were performed at 1, 3 and 6 months. Results 15 patients were included in the study. No intra-procedure complications occurred. 1 patient had pneumonia during post-operative stay. 1-month overall response rate (2 CR and 10 PR) was 80%. At 3-month follow-up, 3 patients (20%) showed PD, 3 patients (20%) died from the ongoing disease, 1 patients (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. 8 out of 13 patients (61.5%) were alive at 6-month follow-up, whereas 6 out of 12 patients (50%) were alive at 1-year follow-up. Conclusion ECT has proven to be a feasible, easy to perform, reproducible and repeatable procedure. For these reasons, it may have a role in the management of VC, especially as palliative treatment when other therapies are no longer applicable.

Problem While there are several known causes for recurrent pregnancy loss (RPL), about 50% are unexplained (uRPL), and in these cases, an aberrant immune regulation seems to be involved. Although fetally derived trophoblast cells have a key role in immune regulation, it is difficult to study their immune function during pregnancy, and it is not known whether trophoblast function may be an inherent aberration in uRPL or whether it is associated with the outcome of the current pregnancy. Method of study Chorionic villus sampling (CVS) was performed for clinical indications at 12 weeks of gestation. Superfluous materials, divided in small explants, were cultured for 20-24 hours, and supernatants (conditioned medium) were collected from 36 women with singleton normal pregnancies, of whom 9 women had a history of RPL. The secreted immune protein profile was measured by proximity extension assay, and the conditioned medium was further used in functional ex vivo models to assess ability to polarize blood monocytes and CD4(+)T cells into immune regulatory phenotypes, as detected by flow cytometry. Results Conditioned medium from chorionic villi, human fetally derived placental tissue, was able to induce a decidual-type of M2-like macrophages, as well as an expansion of Treg cells ex vivo, both in women with uRPL and in control women. The preserved immunological properties were confirmed by a maintained immune protein profile in RPL compared with controls. Conclusion Trophoblasts in an ex vivo model maintain tolerogenic and proteomic profile features in successful pregnancies, despite a previous history of RPL. Funding Agencies|Swedish Research CouncilSwedish Research Council [2018-02776]; Linkoping University; Tor Vergata University; ALF Grants

Background/aim Coronavirus disease is spreading worldwide. Due to fast transmission and high fatality rate drastic emergency restrictions were issued. During the lockdown, only urgent medical services are guaranteed. All non-urgent services, as breast cancer (BC) screening, are temporarily suspended. The potential of breast cancer screening programs in increasing the survival rate and decreasing the mortality rate has been widely confirmed. Suspension could lead to worse outcomes for breast cancer patients. Our study aimed to analyse the data and provide estimates regarding the temporary BC screening suspension. Patients and methods Data regarding breast cancer and respective screening programs were achieved through literature research and analysis. Results Considering three different scenarios with respect to the lockdown's impact on breast cancer screening, we estimate that approximately 10,000 patients could have a missed diagnosis during these 3 months. Considering a 6-month period, as suggested by the Imperial college model, the number of patients who will not receive a diagnosis will rise to 16,000. Conclusion Breast cancer screening should be resumed as soon as possible in order to avoid further breast cancer missed diagnosis and reduce the impact of delayed diagnosis.

Surgery in suspected/confirmed COVID-19 patients is a high-risk venture. In infected patients, COVID-19 is present in the body cavity. During surgery it could be nebulized in the spray generated by surgical instruments and could theoretically infect members of the surgical team. Nevertheless, some surgical gynecologic pathologies cannot be postponed. We present a list of the most frequent gynecologic diseases and recommendations on their surgical management during the COVID-19 pandemic, based on expert opinion, current available information, and international scientific society recommendations to support the work of gynecologists worldwide. In brief, any kind of surgical treatment should be scrutinized and postponed if possible. Nonoperative conservative treatment including pharmacological therapies for hormone-sensitive pathologies should be implemented. Health risk assessment by patient history and COVID-19 test before elective surgery are pivotal to protect both patients and healthcare providers. In confirmed COVID-19 patients or highly suspected cases, elective surgery should be postponed until full recovery.

Objective: The objective of this study is to assess whether the subpubic arch angle (SPA) changes throughout pregnancy. Materials and Methods: We recruited a group of nulliparous women in the first trimester of pregnancy. Each woman was assessed 3 times throughout pregnancy, once per each trimester, by measuring SPA using a recently described highly reproducible three-dimensional transperineal ultrasound (linear reconstruction with contrast enhancement technique; OmniView-volume contrast imaging). Repeated measures analysis of variance was used to study SPA changes during pregnancy. Results: Overall, 97 women were included in the final analysis. SPA increased progressively and significantly (F = 27.824, p < 0.001) from the first to the second trimester (121.8 ± 8.7 vs. 123.5 ± 8.4°, p = 0.01) and from the second to the third trimester (123.5 ± 8.4 vs. 125.3 ± 8.1°, p = 0.01). Conclusion: SPA width increases progressively but slightly during pregnancy. Although this finding is interesting, the extremely small difference detected is unlikely to be clinically significant.

ObjectiveSince vulvar cancer is such a rare disease, the international experience with electrochemotherapy has been derived from only a few centers. The aim of this study was to evaluate clinical outcome and side effects profile with the use of electrochemotherapy in patients with primary or recurrent vulvar cancer.MethodsData were retrospectively collected from November 2017 to November 2019 in two major Italian oncologic institutes: Regina Elena Institute and Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Electrochemotherapy was offered in a palliative setting to patients with a primary or recurrent vulvar cancer who were not candidates for surgery or any other treatment, because of poor performance status or previous delivered treatments. All patients underwent general anesthesia. Electrical pulses were delivered using a pulse generator. Intravenous bleomycin was administered in conjunction with electrochemotherapy. Follow-up examinations were performed at 1, 3, and 6 months. Primary endpoint was to assess the response rate of electrochemotherapy as palliative treatment in patients with vulvar cancer.ResultsA total of 15 patients were included in the study. Fourteen patients (93.3%) had a squamous cell carcinoma and one patient had vulvar carcinosarcoma. Ten patients (66.7 %) had a single lesion and 5 patients (33.3%) had multiple lesions. Median number of electrical pulses was 22 (range 3–42) and median operative time was 13 (range 7–20) min. No intra-procedure complications occurred. One patient had pneumonia during their post-operative stay. Overall response rate after 1 month was 80%. At the 3-month follow-up, 3 patients (20%) had disease progression, 3 patients (20%) had died from ongoing disease, 1 patient (6.7%) died for other reasons, whereas the other patients maintained their 1-month clinical response. A total of 8/13 patients (61.5%) were alive at 6-month follow-up, whereas 6/12 patients (50%) were alive at 1-year follow-up.ConclusionsElectrochemotherapy is a feasible, easy to perform, and reproducible procedure in patients with primary or recurrent vulvar cancer who are unable to undergo surgery. Survival after 1 year in this population was 50%. Electrochemotherapy may have a role in the management of vulvar cancer, especially as palliative treatment when other therapies are no longer applicable.

The immune escape mechanisms at the base of tumor progression in endometrial cancer mimic immune tolerance mechanisms occurring at the maternal–fetal interface. The biological and immunological processes behind the maternal–fetal interface are finely tuned in time and space during embryo implantation and subsequent pregnancy stages; conversely, those behind cancer progression are often aberrant. The environment composition at the maternal–fetal interface parallels the pro-tumor microenvironment identified in many cancers, pointing to the possibility for the use of the maternal–fetal interface as a model to depict immune therapeutic targets in cancer. The framework of cancer environment signatures involved in immune adaptations, precisely timed in cancer progression, could reveal a specific “immune clock” in endometrial cancer, which might guide clinicians in patient risk class assessment, diagnostic workup, management, surgical and therapeutic approach, and surveillance strategies. Here, we review studies approaching this hypothesis, focusing on what is known so far about oncofetal similarities in immunity with the idea to individualize personalized immunotherapy targets, through the downregulation of the immune escape stage or the reactivation of the pro-inflammatory processes suppressed by the tumor.

Introduction/Background Endometrial cancer (EC) is mostly diagnosed at an early stage with a favorable overall survival. 5-year survival decreases from 95% for localized disease to less than 20% for metastatic disease. Survival is related to known prognostic factors. Nevertheless, they are not sufficient to predict either outcome or recurrence rate/site: to decipher the underlying aberrant biomolecular pathways seems to be promising, although it is not yet applicable in a clinical setting. In that purpose, to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for an early recurrences detection and treatment with a survival rate improvement. Methodology 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and high risk HR) and surgically treated as recommended, followed by adjuvant therapy, when appropriated. Results Recurrences were detected in 19,5%. Higher recurrence rate (RR) was significantly detected (p Conclusion These results strengthen the need to identify biological factors to stratify patients at higher risk of relapse, independently or in addition to their risk class prognosis and current surgical and clinical managements. Disclosure Nothing to disclose.

Aim The aim of this study was to investigate the possible association between recurrent miscarriage (RM) and ectopic pregnancy (EP). Methods In this case-control retrospective study, the clinical cards of women followed as outpatients in the RM and low-risk pregnancy offices of the Obstetrics and Gynecology Unit at the Policlinico Tor Vergata University Hospital were carefully reviewed for the occurrence of EP. Results Overall, 598 women with RM and 2043 normal women without RM (controls) were included in the study. Among these women, 4974 pregnancies were analyzed, in which 2028 miscarriages occurred. The EP rate (3.51%) was significantly higher in RM than in control women (1.51%) [odds ratio = 2.31 (95% confidence interval: 2.3-2.4)]; it was particularly high in women with primary RM (5.11%). However, when EP rates were calculated not by women but by overall pregnancies, no differences could be found between RM and control women. In control women, the absence of a miscarriage in the reproductive history was associated with a lower rate of EP. Conclusions Women with RM, particularly primary RM, are at increased risk of EP. This increased risk seems to be dependent on the high number of pregnancies occurring in women with RM rather than to specific characteristics of these women.

Background The direct role of antiphospholipid antibodies (aPL) at maternal-fetal interface has not been fully investigated, especially whether they are involved in physiological and pathological implantation conditions, in an antiphospholipid syndrome (APS)-independent manner. In fact, trophoblast cells and placental endothelial cells at the implantation site express potential aPL targeted-phospholipid antigens (PL Ags); thus, the local production and presence of their specific antibodies, not related to APS (characterized by aPL presence in the peripheral blood), could be a potential marker of aberrant invasion, implantation and fetal-maternal immune tolerance processes. Methods Anti-Beta2glycoprotein I (anti-β2GPI) and anticardiolipin (aCL Ab) antibodies (the most clinically relevant aPL) were detected by immunoenzymatic assay (ELISA), in the amniotic fluid (AF) of 167 women with physiological and complicated common pregnancy conditions, sharing an aberrant implantation process, such as recurrent pregnancy loss (RPL), autoimmune hypothyroidism (ahT) and smoking. All women included in the study were negative to peripheral blood aPL. Results aCL and anti-β2GPI antibodies were detectable in all the AF samples. RPL, ahT and smoking patients had higher level of anti-β2GPI Abs (IgM) compared to women with physiological pregnancies (p stimuli, could be hypothesized. Conclusions The presence of aPL in the AF (not related to APS) could reveal a potential clinical significance at maternal-fetal interface in selected pregnancy complications, in which an aberrant implantation process, and in turn an impaired fetal-maternal immune tolerance cross-talk, could occur.

Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule.758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate.Higher recurrence rate (RR) was significantly detected (p 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01).To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

Low-molecular-weight heparin (LMWH) is widely used to treat recurrent pregnancy loss (RPL) because of its anti-coagulant effects. Although in vitro studies have suggested additional immunological effects, these are debated. We therefore investigated whether LMWH could modulate immune responses in vivo during pregnancy of women with unexplained RPL. A Swedish open multi-centre randomised controlled trial included 45 women treated with tinzaparin and 42 untreated women. Longitudinally collected plasma samples were obtained at gestational weeks (gw) 6, 18, 28 and 34 and analysed by multiplex bead technology for levels of 11 cytokines and chemokines, chosen to represent inflammation and T-helper subset-associated immunity. Mixed linear models test on LMWH-treated and untreated women showed differences during pregnancy of the Th1-associated chemokines CXCL10 (p = 0.01), CXCL11 (p amp;lt; 0.001) and the Th17-associated chemokine CCL20 (p = 0.04), while CCL2, CCL17, CCL22, CXCL1, CXCL8, CXCL12, CXCL13 and IL-6 did not differ. Subsequent Students t-test showed significantly higher plasma levels of CXCL10 and CXCL11 in treated than untreated women at gw 28 and 34. The consistent increase in the two Th1-associated chemokines suggests a potential proinflammatory and unfavourable effect of LMWH treatment during later stages of pregnancy, when Th1 immunity is known to disrupt immunological tolerance. Funding Agencies|Stig and Ragna Gorthon foundation, Helsingborg; Thelma Zoegas foundation for medical research, Lund; Medical Research Council of Southeast Sweden [FORSS-159721]; ALF grants, Region Ostergotland, Linkoping University; Skane County Councils Research and Development

Background The potential role of antinuclear antibodies (ANA) in recurrent pregnancy loss (RPL) pathogenesis is still debated, although some evidences suggest that they could affect pregnancy outcome, leading to a higher miscarriage rate in these patients. A hypothesized mechanism is through changes in uterine flow in pre-conceptional stage, by modifying endometrial receptivity in RPL. However, scant data are available, in pregnancy, about their role in RPL placental perfusion, also in relation to its potential treatments, such as low molecular weight heparin (LMWH). The aim of this study is to retrospectively further investigate the correlation between two-dimensional (2D) and three-dimensional (3D) uterine and placental flow indexes and the presence or the absence of ANA in women with unexplained RPL (uRPL), treated or not treated with LMWH. Methods 2D Doppler measurement of pulsatility index (PI) of the uterine arteries and 3D ultrasonography determination of vascularization index (VI), flow index (FI) and vascularization flow index (VFI) was carried out with the aid of the virtual organ computer-aided analysis (VOCAL) technique in LMWH treated (n 24) and not treated-uRPL patients (n 20) and in the relative control group (n 27), each group divided in ANA+ and ANA- subgroups. Serum assay for the presence of ANA was performed in all women. Results No differences were found in PI, VFI and VI values, by comparing the different groups. A difference in VI values was found for ANA- patients between RPL women not treated with LMWH and the treated ones (p = 0,01), which have lower VI values and similar to controls. By considering only ANA- treated and not treated RPL patients, the ROC curve shows an area of 0,80 and at the VI cut-off of 11,08 a sensitivity of 85% and a specificity of 67%. Conclusions LMWH could exert a potential beneficial effect in restoring the physiological blood flow supply in terms of VI in uRPL ANA- status, suggesting to include ANA and VI investigations in the RPL diagnostic algorithm in a research context, since further studies are needed to clarify this challenging hypothesis in order to try to ameliorate ANA and abnormal placental vascularization negative influence on RPL pregnancy outcome .

Phantom limb is a common sensation in amputees, who often report vivid experiences of voluntarily moving their phantom. Previous studies showed that phantom movement can be functionally disentangled from imagined movement comparable to the actual movement of an intact limb. How and to what extent phantom movement and real movement share similar physiological mechanisms? Here, we focused on a specific aspect of motor control, the motor inhibition, and we asked whether inhibitory physiological responses are implemented when a phantom movement has to be suppressed. Sixteen two-handed controls and two left upper-limb amputees (with and without phantom movement) underwent a Go/Nogo paradigm, while event-related potentials (ERPs) were recorded. The task was performed with both the right (intact) and the left (phantom) hand, either in real or imagery conditions. Opposite results between the moving-phantom case and the static-phantom case were found. In the real condition, moving-phantom case showed the classical motor-inhibition related ERP pattern, with large P300 inhibitory wave when the movements of both (right) intact and (left) phantom limbs have to be suppressed. This inhibitory response was not different from that found in controls (who performed the task with an existing hand; real condition), but, crucially, it was significantly different from the imagery condition of controls. Contrariwise, in the static-phantom case, the ERP responses to Nogo trials during the real condition were different from the real condition in controls, but were not different from their imagery condition. Importantly, in the real condition, Nogo-ERP responses were significantly different between the two phantom cases. Taken together, these findings provide compelling evidence that phantom movements share the same neurophysiological correlates of real movements, not only when an action has to be executed, but also when it should be inhibited.

Congenital Muscular Dystrophies (CMDs) are a heterogeneous group of autosomal recessive disorders presenting at birth with psychomotor delay, cognitive impairment, muscle weakness and hypotonia. Here we described an alteration of mitochondrial inner membrane potential and mitochondrial network in cells derived from Italian patients carrying three novel mutations in CHKB gene, recently associated with "megaconial CMD". On the bases of our findings, we hypothesize that the mitochondrial membrane potential alteration, presumably as a consequence of the altered biosynthesis of phosphatidylcholine, could be responsible for the peculiar morphological aspect of mitochondria in this disease and might be involved in the disease pathogenesis.

Introduction Evidence about altered bimanual coordination has been reported in Parkinson's Disease. However, no previous study has explored such an alteration quantifying the interference effect that the trajectory of each hand might impose on the other one. Thus, in the present research, we applied the traditional Circles-Lines Coupling Task, which allowed assessing the motor coordination of the two hands, in the context of Parkinson's Disease. Methods Thirty-six individuals affected by Parkinson's Disease were consecutively recruited and assigned to two groups according to their symptoms' lateralization. Moreover, eighteen age-matched healthy controls participated in the study. We capitalized on the Circles-Lines Coupling Task, in which the performance during incongruent movements (drawing lines with one hand and circles with the other hand) was compared with the performance during congruent movements (drawing lines with both hands). A bimanual coupling index was computed to compare the interference effect of each hand on the other one. Results In healthy controls, the bimanual coupling index did not differ between the two hands. Crucially, in both groups of individuals affected by Parkinson's Disease, the less affected hand showed a significantly higher bimanual coupling index, due to the abnormal interference exerted by the most affected one, than vice versa. Conclusions Our results highlighted an altered spatial bimanual coupling in Parkinson's disease, depending on the symptoms' lateralization. We offered different explanations of our results according to the theoretical frameworks about the mechanisms subserving bimanual coordination.

Problem To investigate whether antinuclear autoantibodies (ANA) could be related to the outcome of the successive pregnancy in women with unexplained recurrent miscarriage (uRM). Methods Circulating ANA were measured by indirect immunofluorescence in 86 women with uRM before pregnancy, repeated in the first trimester of the successive gestation and correlated with pregnancy outcome. Results Forty-one women were ANA− and 45 were ANA+ before pregnancy. No relation was found between pre-pregnancy ANA status and the outcome of the successive pregnancy. However, when these women were monitored at 7th week during their pregnancy for ANA, of the 22 ANA+ women who remained ANA+ seven miscarriages (31.8%) were observed, whereas all of the 23 ANA+ women who became ANA− had pregnancies ongoing beyond the 20th week without miscarriage. Conclusions ANA status could have a role in uRM. Disappearance of ANA in early pregnancy could have a favorable prognostic value in the successive pregnancy.

Objective: To evaluate the effects of chorionic villus sampling (CVS) on placental volume (PV), perfusion, and vasculature in the first trimester of pregnancy. Method: Uterine artery pulsatility index (PI), PV, vascularization index (VI), flow index (FI), and Vascularization Flow Index (VFI) were serially measured in 38 pregnant women who underwent CVS. Thirty-eight women who did not undergo invasive prenatal diagnosis were recruited as controls. Results: CVS was associated with a mild reduction of PI, a reduction of placental VI, FI, and VFI and with an increase in PV detected one week after the procedure. The outcome of pregnancy was similar between women of the two groups. Conclusion: Our findings showed that CVS is associated with mild placental vascular and morphological changes. However, these changes do not seem to be associated with adverse outcome.

Clozapine is a major atypical antipsychotic drug used in treatment-resistant schizophrenia (Patel and Allin. Ther Adv Psychopharmacol 2011;1:25-29). It interferes with dopamine binding to D1, D2, D3, and D5 receptors but has high affinity to D4. It also has an anticholinergic effect and antagonizes α-adrenergic, histaminergic, and serotoninergic receptors (Oerther and Ahlenius. J Pharmacol Exp Ther 2000;292:731-736). Clozapine has proved effective in treating positive and negative symptoms in patients with refractory schizophrenia, thus accounting for its frequent use. Despite its effectiveness, this drug is not without its adverse effects. The most well known is agranulocytosis. There are, however, many others, such as myocarditis, aspiration pneumonia, ileus, fever, hyperglycemia, hyperlipidemia, hypertriglycemia, tachycardia, and weight gain, among others (Bruijnzeel et al. Asian J Psychiatr 2014;11:3-7). Fever induced by clozapine is a common phenomenon (Lowe et al. Ann Pharmacother 2007;41:1700-1704), which usually occurs in the first 4 weeks of treatment, and its prevalence oscillates from 0.5% and 55%, depending on the study (Jeong et al. Schizophr Res 2002;56:191-193; Young et al. Schizophr Bull 1998;24:381-390). The fever lasts for 2.5 days on average, and unless the treatment is discontinued, it generally abates between day 8 and 16 of treatment (Kohen et al. Ann Pharmacother 2009;43:143-146). There are several different theories about the physiopathological mechanism; it could be a variation of malignant neuroleptic syndrome, an infection secondary to neutropenia, and allergic reaction or the emergence of the immunomodulating effect of clozapine. Some case reports in the bibliography have shown that patients in treatment with clozapine can develop a mild leukocytosis, but the presence of other concurrent symptoms, which indicate infection, is not common (Tham and Dickson. J Clin Psychiatry 2002;63:880-884). The theory of an allergic reaction is unsupported because of the fact that the fever does not recur after reintroducing clozapine. So we question, "What would be the attitudes to follow when we find clozapine-induced fever (Nielsen et al. J Clin Psychiatry 2013;74:603-613)?" The management of patients with clozapine-induced fever should include a complete blood picture, liver and renal function tests, a creatine kinase test urine culture, and a chest x-ray. A nasopharyngeal aspirate can also be useful to exclude infection (Pui-yin Chung et al. Can J Psychiatry 2008;53:857-862). On the other hand, some drugs have been suggested for treatment of fever induced by clozapine. The use of acetaminophen, in the treatment of the fever induced by clozapine, is supported by many studies (Jeong et al. Schizophr Res 2002;56:191-193). In one of these, clozapine was suspended and restarted successfully after 1 week. However, in some studies, such as the case report of Tremeau et al (Clin Neuropharmacol 1997;20:168-170), clozapine was reduced instead of discontinued. In other studies, the recommendation is continuating clozapine treatment (Martin and Williams. J Psychiatry Neurosci 2013;38:E9-E10).

Background The knowledge of the individual genetic “status” in the prenatal era is particularly relevant in the case of positive family history for genetic diseases, in advanced maternal age and in the general screening for foetal abnormalities. In this context, here, we report an innovative molecular assay which utilizes the cell-free foetal DNA (cffDNA) as a source for the early and fast detection of the foetal sex. The study involved 132 pregnant women in their first 3 months of pregnancy, who agreed to give a blood sample. All the collected samples were immediately subjected to the separation of the plasma, which was utilized for the extraction of the cffDNA. Successively, the extracted cffDNA was analysed by a quantitative PCR (qPCR) method based on Plexor-HY chemistry, which is able to simultaneously identify, quantify and discriminate the autosomal DNA from the sex-linked DNA. Results Overall, the Plexor-HY assay demonstrated to be sensitive and specific for the determination of low-template DNA, such as the cffDNA. In fact, the Plexor-HY assay has been successfully performed in all the samples, identifying 70 males and 62 females. As the foetal sex can be provided in 120 min just by utilizing a maternal blood sample as cffDNA source, the assay represents a very fast, safe and non-invasive prenatal method. Conclusions The possibility of determining the foetal sex in the early prenatal life consents the application of our assay as a helpful screening test for subjects and families at risk of sex-linked disorders. Moreover, the early knowledge of the foetal sex may be of great help even for the specialist, who might promptly advise the patients concerning the foetal risk of inheriting sex-linked disorders and the clinical utility of performing an invasive prenatal diagnosis. Electronic supplementary material The online version of this article (doi:10.1186/s40246-016-0066-2) contains supplementary material, which is available to authorized users.