Bosentan effect on echocardiographic systolic pulmonary arterial pressure in systemic sclerosis-related pulmonary hypertension: a systematic review and metanalysis.

OBJECTIVES: Bosentan is a dual endothelin receptor antagonist approved for the treatment of SSc digital ulcers (DU) and pulmonary arterial hypertension (PAH). Systolic pulmonary arterial pressure (sPAP) is a relevant parameter for the follow-up and prognosis of SSc-PAH. The therapeutic magnitude of bosentan in SSc-PAH is not fully understood, thus we aim to establish the degree of sPAP reduction in bosentan treated SSc-PAH patients. METHODS: We performed a systematic literature review in three databases from January 2000 to June 2023, involving sPAP measurement at transthoracic echocardiography of SSc patients before and after starting bosentan. Following the study quality assessment and data extraction, we performed random-effects meta-analysis and Egger's test for publication bias. Stratified analysis was performed for mono-/combination therapy, follow up duration (≤1 year), indication for bosentan therapy (PAH or DU/mixed). RESULTS: In the 11 selected manuscripts, sPAP mean difference before and after bosentan therapy was - 5.63mmHg (CI95% -9.79 to -1.48, p=0.0078). In stratified analysis, sPAP mean was significantly different before and after bosentan therapy only for studies considering < 1 year of follow-up (p=0.0020), monotherapy (p=0.0140) and the strict indication for PAH (p=0.0002). CONCLUSIONS: Bosentan significantly decreases sPAP, a relevant prognostic marker, especially in overt SSc-PAH. However, bosentan did not decrease sPAP when started for DU/mixed indication nor for follow-up>1 year. The burden of publication bias was significant. Therefore, further studies are required to assess bosentan's haemodynamic effect in high-risk patients for SSc-PAH.

Synthesis of Imidazolidin-2-ones and Imidazol-2-ones via Base-Catalyzed Intramolecular Hydroamidation of Propargylic Ureas under Ambient Conditions.

The first organo-catalyzed synthesis of imidazolidin-2-ones and imidazol-2-ones via intramolecular hydroamidation of propargylic ureas is reported. The phosphazene base BEMP turned out to be the most active organo-catalyst compared with guanidine and amidine bases. Excellent chemo- and regioselectivities to five-membered cyclic ureas have been achieved under ambient conditions, with a wide substrate scope and exceptionally short reaction times (down to 1 min). A base-mediated isomerization step to an allenamide intermediate is the most feasible reaction pathway to give imidazol-2-ones, as suggested by DFT studies.

Analytical Criticalities Associated to Different Immunological Methods for Serum Free Light Chain Detection in Plasma Cell Dyscrasias: A Description of Particular Clinical Cases.

Current criteria for differential diagnosis of multiple myeloma (MM), Monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM) are included in the 2003 guidelines by the International Myeloma Working Group (IMWG). An updated version was then published in 2014, highlighting the importance of serum free light chain (sFLC) detection, as well as the κ/λ ratio as excellent indicators of clonality. At present, two commercial assays for sFLC quantification are available: the Freelite™ assay and the N-Latex assay. The first was developed by The Binding Site based on a mixture of polyclonal antibodies directed against a variety of FLC epitopes. It may be run on a wide range of nephelometers, as well as on turbidimeters. The second method was developed by Siemens and runs exclusively on Siemens instruments. It employs a probe mixture of mouse monoclonal antibodies. The aim of our study was to evaluate sFLC measurement and calculated κ/λ ratio in 85 patients with monoclonal gammopathies (MGs) in order to compare methods. We demonstrated that there is only a moderate concordance between the two FLC assays. In particular, in one case, we observed no qualitative alterations of the serum protein pattern, and in the absence of a Freelite™ assay, sFLC measurement would not have been possible to highlight the increase of λ FLC.

The impact of body mass index on the pregnancy outcomes and risk of perinatal depression: Findings from a multicenter Italian study.

BACKGROUND: Body Mass Index (BMI) is an informative factor on body fatness which has been associated to higher levels of Perinatal Depression (PD) and complications during pregnancy. We aimed to explore the impact of pre-pregnancy and postnatal BMI on the risk of Perinatal Depression and pregnancy outcomes among women recruited at their third trimester of pregnancy. METHODS: We report on findings from a large multi-centre study conducted in the South of Italy and involving 1611 women accessing three urban gynaecological departments from July to November 2020. Pregnant women were assessed at their third trimester of pregnancy (T0) and after the childbirth (T1) ;The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time (T0 and T1) as well as other standardized measures for neuroticism, resilience, and quality of life at baseline. BMI (T0 and T1) and other socio-demographic and clinical characteristics have been collected. RESULTS: Over-weight and obesity (higher levels of BMI) were associated with higher risk of PD (higher scores of EPDS), higher neuroticism and poorer subjective psychological well-being among enrolled women. Also, obesity and over-weight were associated with lower education, higher number of physical comorbidities, medical treatments and complications during pregnancy. CONCLUSIONS: Over-weight and obesity may impact on mental health and pregnancy outcome of women enrolled. Psycho-educational interventions aimed to improve the management of physical and emotional issues may reduce the risk of PD and complications during pregnancy.

Acquired Hemophilia A After SARS-CoV-2 Infection: A Case Report.

Acquired hemophilia A is a rare autoimmune coagulation disorder associated to the development of neutralizing antibodies directed towards coagulation factor VIII, known as factor VIII inhibitors, in subjects with previous normal clotting system homeostasis and personal and family history negative for bleeding episodes. This condition, although variable in severity and clinical presentation, may lead to severe and life-threatening hemorrhages which can be either spontaneous or associated with traumatic events and invasive procedures. Here we report the case of a 53-year-old woman who was admitted to our Internal Medicine Unit "Cesare Frugoni", Policlinico di Bari, in July 2021, and diagnosed with acquired hemophilia A. We aim to raise awareness about this rare condition, its clinical presentation and therapeutic management options in order to obtain a quick diagnosis and an effective therapeutic intervention.

Perinatal depression screening and prevention: Descriptive findings from a multicentric program in the South of Italy.

Introduction: Perinatal depression (PD) is a cluster of clinical depressive symptoms occurring globally during pregnancy or after childbirth, with a prevalence of 11.9%. Risk factors for PD among pregnant women may include personality traits of neuroticism, low personal resilience, higher anxiety, avoidance in close relationships, as well as dysfunctional coping strategies. Methods: We report on descriptive findings of a screening/prevention program aimed to detect depressive symptoms and associated risk factors in a large sample of women (N = 1,664) accessing the gynecological departments of the Regione Puglia (South of Italy) from July to November 2020. Pregnant women were assessed in their third trimester of pregnancy (T0), after childbirth (T1), and those at risk for PD within 1 year from delivery (T2-T4); The Edinburgh Postnatal Depression Scale (EPDS) has been employed for the screening of PD over time as well as other standardized measures for neuroticism, resilience, coping strategies, and quality of life. Results: Of 1,664, n = 1,541 were tested at T1, and 131 scored ≥ 12 at EPDS (14.6 ± 2.95), showing a higher risk for PD. They were followed over time at 1, 6, and 12 months after childbirth (T2-T4), and 15 of them scored ≥ 12 (EPDS) at T4. Women with a higher risk of PD also reported higher levels of neuroticism, lower levels of personal resilience, more anxiety and avoidance in close relationships, higher employment of dysfunctional coping strategies (e.g., denial, self-blame, etc.), and lower quality of life (0.0008 < all p < 0.0001). Conclusion: This study confirmed the benefit of screening programs for the early detection of PD among pregnant women. We may suggest a set of risk factors to be considered in the clinical assessment of PD risk as well as the promotion of similar programs to improve depressive outcomes and pathways to care for PD on the basis of a more accurate assessment and referral.

Antiphospholipid syndrome: a case report with an unusual wide spectrum of clinical manifestations.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis, and the detection of circulating antiphospholipid antibodies. The classification criteria for definite APS are actually met when at least one clinical criterion (thrombosis or pregnancy morbidity) is present in association of one laboratory criterion (LAC, aCL antibody or aß2GPI antibody present on two or more occasions, at least 12 weeks a part), and thrombosis should be confirmed by objective validated criteria. The average age of primary APS patients has been reported to be about 35-40 years and the disease is more common in women than in men. CASE PRESENTATION: In this report, we described a rare case of an adult male who presented over a period of 9 years with a wide spectrum of clinical manifestations involving different organs that were not initially diagnosed as APS. Dizziness and syncope were his first clinical symptoms, and a non-bacterial thrombotic endocarditis (NBTE) involving the mitral valve was at first diagnosed. Subsequently, the patient also presented with generalized seizures and subsequent head injury. When the patient was admitted to our clinic with bilateral epistaxis and fever, thrombocytopenia was revealed. Moreover, laboratory examinations showed acute pancreatitis with an increase of levels of inflammation markers. CONCLUSION: Based on the patient's medical history and all the examination results, it was possible to make a diagnosis of primary APS and, starting from diagnosis of thrombocytopenia, we were allowed to conclude that all of manifestation were epi-phenomena of a unique clinical entity, rather than unrelated diseases. Though APS is one of the most common thrombocytophilias, unfortunately, it is not recognized often enough. The lack of prevention in undiagnosed patients may cause severe complications which can in turn result in the death of those patients.

Corticosteroids for Acute and Recurrent Idiopathic Pericarditis: Unexpected Evidences.

Pericarditis is a common disease, often postviral or "idiopathic," diagnosed in about 5% of emergency room visits for non-ischemic chest pain. Although pericarditis often occurs as a benign and self-limiting disease, it may present recurrences. The first-line therapy includes aspirin/nonsteroidal anti-inflammatory drugs (ASA/NSAIDs) plus colchicine. Steroids especially at high-dose have been associated with a higher recurrence rate. In this retrospective study, we evaluated efficacy and safety of ASA/NSAIDs and prednisone in the treatment of acute or recurrent idiopathic pericarditis (colchicine was off-label in the period of the study). The cohort included 276 patients diagnosed with acute idiopathic pericarditis. Mean age was 45.4 ± 12.7 years, and males were significantly higher in number and younger than females. Sixty-one patients (22.1%) were treated with prednisone and 215 with ASA/NSAIDs (77.9%). 171 patients experienced at least one recurrence (62%). No difference in recurrence rate was observed (p=0.257) between the groups treated with prednisone (55.7%) vs. ASA/NSAIDs (63.7%). The recurrences were treated with steroids at low doses and very gradual tapering, and the dose reduction was slower as the number of relapses was higher. Steroids alone were administered to about 80% of patients, while in the remaining 20% of cases, they were associated with ASA/NSDAIDs or colchicine. Approximately 90% of patients had a very favorable course, that is no more than 2 relapses and no patients presented serious side effects. Steroids at low dose, did not act, surprisingly, as an independent risk factor for recurrences and therefore may be considered a successful and safe treatment for acute and recurrent idiopathic pericarditis.

Policies for reirradiation of recurrent high-grade gliomas: a survey among Italian radiation oncologists.

PURPOSE: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach. METHODS: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach. RESULTS: A total of 37 of 210 questionnaires were returned (18% of all centers): 16 (43%) from nonacademic hospitals, 14 (38%) from academic hospitals, 5 (13%) from private institutions, and 2 (6%) from hadron therapy centers. The majority of responding centers (59%) treated ≤5 cases per year. Performance status at the time of recurrence, along with a target diameter <5 cm and an interval from primary radiation ≥6 months, were the prevalent predictive factors considered for reRT. Sixty percent of reirradiated patients had already received a salvage therapy, either chemotherapy (40%) or reoperation (20%). The most common approach for reRT was fractionated stereotactic radiotherapy to a mean (photon) dose of 41.6 Gy. CONCLUSIONS: Although there were wide variations in the clinical practice of reRT across the 37 centers, the core activities were reasonably consistent. These findings provide a basis for encouraging a national collaborative study to develop, implement, and monitor the use of reRT in this challenging clinical setting.

Presurgical promestriene therapy in postmenopausal women with stress urinary incontinence.

OBJECTIVE: Our study was aimed at evaluating the efficacy of therapy with promestriene, a synthetic diethyl-ether of estradiol with no distal hormonal effects, in patients undergoing surgical correction for stress urinary incontinence (SUI). MATERIALS AND METHODS: Ninety-eight healthy, postmenopausal women, non-users of hormone replacement therapy, with a diagnosis of SUI and vulvovaginal dystrophy, were recruited and openly randomized into two main groups. Group I (48 patients) received promestriene 10 mg daily, by vaginal capsule, for 21 days before the operation. Group II (50 patients) underwent the surgical procedure with TVT (Tension-free Vaginal Tape) directly, without pharmacological preparation. The results were collected and analyzed using SAS software (version 8). RESULTS: The two groups were homogeneous in terms of age, parity and body mass index. There were no significant differences between the two groups with respect to the time required to accomplish the TVT, blood loss, length of hospital stay, blood component measurements and postoperative subjective symptoms. There were slight differences postoperatively in problems during intercourse and the appearance of new genital symptoms, but again they were not shown to be statistically significant. CONCLUSIONS: Our results, although preliminary and subjective, confirm the efficacy of remedial surgical treatment of SUI with TVT. Preoperative administration of promestriene seems to favor trophism and vascularization of the whole muscular and fascial support of the pelvic floor and facilitates performance of the operation, but is not supported statistically.

Hemophagocytic Lymphohistiocytosis, an Unclear Nosologic Entity: Case Report of an Adult Man with Rising of Amylase and Lipase and Spinal Cord Infiltration.

Here we present the case of a 57-years old patient affected by hemophagocytic lymphohistiocytosis (HLH), a rare disease characterized by an uncontrolled immune activation, resulting in clinical and biochemical manifestations of extreme inflammation. In a previous hospitalization, the patient showed fever, hepato-splenomegaly, pancytopenia, hyperferrtitinemia, lymphadenopathy and cholestasis. No diagnosis was done, however, he totally recovered after splenectomy. Eight months later, he relapsed, showing also hypofibrinogenemia, hypertriglyceridemia, hemophagocytic signs in bone marrow, cholestatic jaundice, high LDH and high PT-INR. Interestingly, he presented increased levels of amylase and lipase in absence of radiologic signs of pancreatitis. He was treated with Dexamethasone and Cyclosporine according to HLH-2004 guidelines. The clinical and biochemical manifestations disappeared in a few weeks, but he was newly hospitalized for lower limbs hypotonia caused by a hemophagocytic lesion of the cauda equina and lumbar cord. The death occurred in a few days, despite the immunosuppressive treatment.

Temozolomide and radiotherapy as first-line treatment of high-grade gliomas.

AIMS AND BACKGROUND: Temozolomide, a novel alkylating agent, has shown promising results in the treatment of patients with high-grade gliomas, when used as single agent as well as in combination with radiation therapy. MATERIALS AND METHODS: In this report we retrospectively reviewed the clinical outcome of 128 consecutive patients with a diagnosis of high-grade gliomas referred to our Institutions from April 1994 to November 2001. The first 64 patients were treated with radiotherapy alone and the other 64 with a combination of radiotherapy and temozolomide (31 with radiotherapy and adjuvant temozolomide and 33 with radiotherapy and concomitant temozolomide followed by adjuvant temozolomide). RESULTS: Grade 3 hematological toxicity was scored in 9% of 64 patients treated with radiotherapy and temozolomide. No grade 4 hematological toxicity was reported, and the other acute side effects observed were mild or easily controlled with medications. Age, histology and administration of temozolomide were statistically significant prognostic factors associated with better 2-year overall survival. In contrast, we did not observe a significant difference in overall survival between adjuvant and concomitant/adjuvant temozolomide administration. CONCLUSIONS: We report the favorable results of a schedule combining radiotherapy and temozolomide in the treatment of patients with high-grade gliomas. The literature data and above all the findings of the phase III EORTC-NCIC 26981 trial suggest that actually the schedule can be used routinely in clinical practice. Further clinical studies, using temozolomide in combination with other agents, are required.

An unusual association of three autoimmune disorders: celiac disease, systemic lupus erythematosus and Hashimoto's thyroiditis.

Autoimmune disorders are known to be more frequent in women and often associated each others, but it is rare to see multiple autoimmune diseases in a single patient. Recently, the concept of multiple autoimmune syndrome has been introduced to describe patients with at least three autoimmune diseases. We describe a case of a young man with a clinical history of psychiatric symptoms and celiac disease (CD) who was diagnosed to have other two autoimmune disorders: systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. This case is unusual upon different patterns: the rare combination of the three autoimmune diseases, their appearance in a man and the atypical onset of the diseases with psychiatric symptoms likely to be related either to CD or to SLE.

Temozolomide and radiotherapy versus radiotherapy alone in high grade gliomas: a very long term comparative study and literature review.

UNLABELLED: Temozolomide (TMZ) is the first line drug in the care of high grade gliomas. The combined treatment of TMZ plus radiotherapy is more effective in the care of brain gliomas then radiotherapy alone. Aim of this report is a survival comparison, on a long time (>10 years) span, of glioma patients treated with radiotherapy alone and with radiotherapy + TMZ. MATERIALS AND METHODS: In this report we retrospectively reviewed the outcome of 128 consecutive pts with diagnosis of high grade gliomas referred to our institutions from April 1994 to November 2001. The first 64 pts were treated with RT alone and the other 64 with a combination of RT and adjuvant or concomitant TMZ. RESULTS: Grade 3 (G3) haematological toxicity was recorded in 6 (9%) of 64 pts treated with RT and TMZ. No G4 haematological toxicity was observed. Age, histology, and administration of TMZ were statistically significant prognostic factors associated with 2 years overall survival (OS). PFS was for GBM 9 months, for AA 11. CONCLUSIONS: The combination of RT and TMZ improves long term survival in glioma patients. Our results confirm the superiority of the combination on a long time basis.

Automatic evaluation of progression angle and fetal head station through intrapartum echographic monitoring.

Labor progression is routinely assessed through transvaginal digital inspections, meaning that the clinical decisions taken during the most delicate phase of pregnancy are subjective and scarcely supported by technological devices. In response to such inadequacies, we combined intrapartum echographic acquisitions with advanced tracking algorithms in a new method for noninvasive, quantitative, and automatic monitoring of labor. Aim of this work is the preliminary clinical validation and accuracy evaluation of our automatic algorithm in assessing progression angle (PA) and fetal head station (FHS). A cohort of 10 parturients underwent conventional labor management, with additional translabial echographic examinations after each uterine contraction. PA and FHS were evaluated by our automatic algorithm on the acquired images. Additionally, an experienced clinical sonographer, blinded regarding the algorithm results, quantified on the same acquisitions of the two parameters through manual contouring, which were considered as the standard reference in the evaluation of automatic algorithm and routine method accuracies. The automatic algorithm (mean error ± 2SD) provided a global accuracy of 0.9 ± 4.0 mm for FHS and 4° ± 9° for PA, which is far above the diagnostic ability shown by the routine method, and therefore it resulted in a reliable method for earlier identification of abnormal labor patterns in support of clinical decisions.

Sonographic markers for early diagnosis of fetal malformations.

Fetal malformations are very frequent in industrialized countries. Although advanced maternal age may affect pregnancy outcome adversely, 80%-90% of fetal malformations occur in the absence of a specific risk factor for parents. The only effective approach for prenatal screening is currently represented by an ultrasound scan. However, ultrasound methods present two important limitations: the substantial absence of quantitative parameters and the dependence on the sonographer experience. In recent years, together with the improvement in transducer technology, quantitative and objective sonographic markers highly predictive of fetal malformations have been developed. These markers can be detected at early gestation (11-14 wk) and generally are not pathological in themselves but have an increased incidence in abnormal fetuses. Thus, prenatal ultrasonography during the second trimester of gestation provides a "genetic sonogram", including, for instance, nuchal translucency, short humeral length, echogenic bowel, echogenic intracardiac focus and choroid plexus cyst, that is used to identify morphological features of fetal Down's syndrome with a potential sensitivity of more than 90%. Other specific and sensitive markers can be seen in the case of cardiac defects and skeletal anomalies. In the future, sonographic markers could limit even more the use of invasive and dangerous techniques of prenatal diagnosis (amniocentesis, etc.).

A prospective study of pelvic floor dysfunctions related to delivery.

OBJECTIVE: To estimate the prevalence and impact on quality of life of urinary incontinence (UI) and anal incontinence (AI) three months after first delivery; to identify risk factors involved in UI or AI; to evaluate possible changes in sexual behaviour and anatomical modifications of pelvic floor after childbirth. STUDY DESIGN: A multicenter prospective study, in six Italian Ob/Gyn departments, of nulliparous women who delivered at term (37-42 weeks of gestation) between April and September 2005. A structured questionnaire investigated several maternal and obstetric variables. UI and AI were assessed by administration of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and according to Wexner's Continence Grading Scale, at 2-3 days post-partum and at 3 months after delivery. Changes in sexual behaviour, and pelvic floor condition after delivery, were also recorded. Statistical analysis included comparison of means (Mann-Whitney or Student's t-test) and proportions (Chi-square test). Multiple logistic regression analysis was performed including variables that were significant in univariate comparisons. RESULTS: Of 960 enrolled women, 744 were evaluated 3 months after delivery and included in final analysis. The prevalences of UI and AI at that time were 21.6% and 16.3%, respectively. Onset of incontinence during pregnancy was an independent predictor for persistent UI (Odds Ratio (OR) 4.6, Confidence Interval (CI) 3.1-6.8, p<0.001) and AI (OR 3.6, CI 2.2-6.1, p<0.001). Family history of urinary or anal incontinence were respectively associated with UI (OR 2.6, CI 1.6-4.0, p<0.001) and AI (OR 2.4, CI 1.4-4.0, p<0.001) 3 months after delivery. Among obstetric factors, vaginal delivery was a strong risk factor for UI (OR 3.3, CI 2.0-5.3, p<0.001). The sexual score improved 3 months after delivery in 72.4% of women. Urogynaecological evaluation showed a significant association between grade 1-2 anterior prolapse, urethral hypermobility and UI. CONCLUSION: New onset of UI or AI during pregnancy, positive family history and vaginal delivery are independent risk factors for the persistence of symptoms of UI and AI in the early postpartum period. Adequate counselling and the implementation of targeted strategies to prevent or early identify these conditions are therefore mandatory to improve the patient's quality of life.