Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism.

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.

Emergency department reorganisation to cope with COVID-19 outbreak in Milan university hospital: a time-sensitive challenge.

BACKGROUND: In March 2020 we faced a huge spread of the epidemic of SARS-CoV2 in northern Italy; the Emergency Departments (ED) and the Emergency Medical Services (EMS) were overwhelmed by patients requiring care. The hospitals were forced to reorganize their services, and the ED was the focal point of this challenge. As Emergency Department in a metropolitan area of the region most affected, we saw an increasing number of patients with COVID-19, and we made some structural and staff implementations according to the evolution of the epidemic. METHODS: We analysed in a narrative way the weaknesses and the point of strength of our response to COVID-19 first outbreak, focusing point by point on main challenges and minor details involved in our ED response to the pandemics. RESULTS: The main stems for our response to the pandemic were: use of clear and shared contingency plans, as long as preparedness to implement them; stockage of as much as useful material can be stocked; training of the personnel to be prepared for a fast response, trying to maintain divided pathway for COVID-19 and non-COVID-19 patients, well-done isolation is a key factor; preparedness to de-escalate as soon as needed. CONCLUSIONS: We evaluated our experience and analysed the weakness and strength of our first response to share it with the rest of the scientific community and colleagues worldwide, hoping to facilitate others who will face the same challenge or similar challenges in the future. Shared experience is the best way to learn and to avoid making the same mistakes.

Use of platelet rich plasma in human infertility.

Successful embryo implantation requires good quality embryo but also needs a receptive endometrium site. In our clinical practice, we daily verify that an adequate endometrial growth is reached for successful implantation. To understand whether platelet rich plasma (PRP) can improve endometrium thickness and performance, PRP treatment was carried out after at least three of the classic medical protocols currently in use had been unsuccessfully adopted. Eight patients with more than 3 cryo-transfers cancelled because of failure of endometrial growth, defined as endometrium less than 6 mm, with negative hysteroscopic screening for endometrial pathology, and with negative bacteriologic screening, before present and all previous treatment, were selected to undergo PRP treatment. In 7 out of 8 treatments, an endometrial thickness greater than 6.5 mm (mean 6.9 mm) was reached, with endometrial three-layer pattern, before progesterone administration and embryo transfer was performed. In 6 out of 7 patients, who underwent embryo transfer, beta-HCG were positive, with 2 biochemical abortions, one miscarriage at 6-week pregnancy, two babies born and one drop-out. In this study, 8 patients had extraordinarily poor endometrial quality, and the endometrium was non-responsive to conventional estrogenic therapy, resulting in cycle cancellation. After application of PRP, the endometrial thickness was satisfactory in all the patients except one. Of these, beta-HCG was positive in 6 women, the pregnancy was progressing normally in 2 women, and one had an early miscarriage. We can suppose that the multiple implantation failures were caused by inefficient expression adhesion molecules, which can hypothetically be more represented after PRP application.

Postoperative complications in cirrhotic pediatric deceased donor liver transplantation: Focus on transfusion therapy.

Intraoperative transfusions seem associated with patient death and graft failure after PLTx. A retrospective analysis of recipients' and donors' characteristics and transplantation data in a cohort of patients undergoing PLTx from 2002 to 2009 at the Bergamo General Hospital was performed. A two-stage hierarchical Cox proportional hazard regression with forward stepwise selection was used to identify the main risk factors for major complications. In addition, propensity score analysis was used to adjust risk estimates for possible selection biases in the use of blood products. Over the 12-year period, 232 pediatric cirrhotic patients underwent PLTx. One-year patient and graft survival rates were 92.3% and 83.7%, respectively. The Kaplan-Meier shows that the main decrease in both graft and patient survival occurs during the first months post-transplantation. At the same time, it appears that most of the complications occur during the first month post-transplantation. One-month and 1-year patient complication-free survival rates were 24.8% and 12.1%, respectively. Our study shows that intraoperative red blood cells and platelet transfusions are independent risk factors for developing one or more major complications in the first year after PLTx. Decreasing major complications will improve the health status and overall long-term patient survival after pediatric PLTx.

Shrimp Allergy: Analysis of Commercially Available Extracts for In Vivo Diagnosis.

BACKGROUND AND OBJECTIVE: Skin prick testing (SPT) with commercial extracts is the first step in the diagnosis of shrimp allergy, although its clinical efficiency is unknown. Objective: To analyze the clinical usefulness of all commercial crustacean extracts available for SPT in Italy. METHODS: We performed a multicenter study of 157 shrimp-allergic patients who underwent SPT with 5 commercial crustacean extracts and with house dust mite (HDM) extract. Commercial extracts were analyzed using SDS-PAGE and compared with a freshly prepared in-house shrimp extract. IgE to Pen a 1/Pen m 1, Pen m 2, and Pen m 4 was determined, and immunoblot analysis was performed on a large number of sera. RESULTS: The skin reactions caused by commercial crustacean extracts were extremely heterogeneous, resulting in 32 clinical profiles, with marked differences in protein content and missing proteins at molecular weights corresponding to those of major shrimp allergens. Only strong Pen a 1/Pen m 1 reactors reacted to both HDM and all 5 commercial extracts in SPT. Most patients, including those who were tropomyosin-negative, reacted to HDM. Patients reacted to a large and variable array of proteins, and IgE reactivity was common at high molecular weights (>50 kDa). CONCLUSIONS: The in vivo diagnosis of shrimp allergy must continue to be based on SPT with fresh material. Shrimp-allergic patients frequently react to a number of ill-defined high-molecular-weight allergens, thus leaving currently available materials for component-resolved diagnosis largely insufficient. Mites and crustaceans probably share several allergens other than tropomyosin.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Histamine release positive test associates with disease remission in chronic spontaneous urticaria: a proof-of-concept study.

SUMMARY: Background. Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU). Objectives and methods. Twenty CSU patients unresponsive to antihistamine treatment were enrolled in order to evaluate the correlations between HR test results and demographic features, quality of life, disease activity, clinical course, and autologous serum and plasma skin tests (ASST and APST). Results. All patients with positive HR test (9/9, 100%) had a more severe disease activity at onset (urticaria activity score, UAS > 2) when compared to negative HR test patients (5/11; p = 0.04). Quality of life questionnaire's results were not substantially different between HR positive and negative subgroups at baseline (p > 0.05), and results of HR test and ASST/APST did not co-segregate (p > 0.05). After 12 months, patients with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0.027). Conclusions. Positive HR test may predict spontaneous CSU remission at 12 months.

Cost-benefit of reflectance confocal microscopy in the diagnostic performance of melanoma.

BACKGROUND: The sub-optimal diagnostic accuracy for melanoma leads to excise a high number of benign lesions, with consequent costs. Reflectance confocal microscopy (RCM) improves diagnostic specificity, thus possibly inducing a reduction in unnecessary excisions and related costs. OBJECTIVE: To estimate the influence of RCM on number of benign lesions needed to excise (NNE) a melanoma, in term of clinical outcomes and costs per patient. PATIENTS AND METHODS: Skin neoplasms excised by the dermatology public service in the Province of Modena were retrieved form centralized pathology database. Differences in NNE between the territorial service (using dermoscopy only) and the University Hospital (adding also RCM to the patients' workflow) were calculated and cost analysis was performed through a micro-costing approach. RESULTS: A large reduction in benign lesions excised at University Hospital was evident, leading to NNE of 6.25 for University Hospital, compared to 19.41 for Territorial Dermatology. Since 4320 unnecessary excisions can be saved every million inhabitants, an overall yearly saving of over 280,000 Eur can be expected from the use of RCM. CONCLUSIONS: The systematic use of RCM was dramatically affecting the number of benign lesions excised, and this can be translated in a significant cost-benefit advantage.

Patients with breakthrough reactions to iodinated contrast media have low incidence of positive skin tests.

BACKGROUND: The term "breakthrough reactions" designates repeated hypersensitivity reactions to iodinated contrast media (ICM) despite premedication with glucocorticoids and antihistamines. We aimed to retrospectively evaluate the rate of positive skin test (STs) in our cohort of patients with previous breakthrough reactions to different ICMs. METHODS: A series of 35 patients, who experienced at least one breakthrough reaction to ICM and who underwent STs within 6 months from the reaction were studied, and results were compared to a control group of patients with a first hypersensitivity reaction occurred without premedication. Skin prick tests (SPT), intradermal tests (IDT) and patch tests (PT) at different dilutions, with a set of three to four ICM were performed. RESULTS: Of the 35 patients with prior breakthrough reactions, 57% had an immediate reaction (IR) and 43% had a non-immediate reaction (NIR). Patients who experienced the first hypersensitivity IR or NIR, later had one or more breakthrough IR or NIR, respectively. Overall, 29% (10/35) of patients with prior breakthrough reactions resulted positive to STs compared to 57% (16/28) of the control group (p < 0.05). No significant difference in allergy history, age, sex, other clinical / demographic features nor chronic use of ACE-inhibitor, beta-blockers or NSAIDs was observed. CONCLUSION: This preliminary finding suggests that patients with prior breakthrough reactions have significantly lower immunologically proven ICM reactions (positive STs) if compared to non-breakthrough patients. According to that, a considerable number of breakthrough reactions seems to be non-allergic hypersensitivity reactions or reactions which could be mostly prevented by a proper, well-timed skin testing. Larger prospective studies are needed to confirm these results, with a more careful analysis of patients' risk factors, a laboratory assessment that includes an in vitro allergy diagnostics, and hopefully a drug provocation test for selected cases.

Human recombinant follicle stimulating hormone (rFSH) compared to urinary human menopausal gonadotropin (HMG) for ovarian stimulation in assisted reproduction: a literature review and cost evaluation.

BACKGROUND: Gonadotropins are protein hormones which are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. There is still a lively debate on which type of gonadotropin medication should be used, either human menopausal gonadotropin or recombinant follicle-stimulating hormone. The objective of the study was to perform a systematic review of the recent literature to compare recombinant follicle-stimulating hormone to human menopausal gonadotropin with the aim to assess any differences in terms of efficacy and to provide a cost evaluation based on findings of this systematic review. METHODS: The review was conducted selecting prospective, randomized, controlled trials comparing the two gonadotropin medications from a literature search of several databases. The outcome measure used to evaluate efficacy was the number of oocytes retrieved per cycle. In addition, a cost evaluation was performed based on retrieved efficacy data. RESULTS: The number of oocytes retrieved appeared to be higher for human menopausal gonadotropin in only 2 studies while 10 out of 13 studies showed a higher mean number of oocytes retrieved per cycle for recombinant follicle-stimulating hormone. The results of the cost evaluation provided a similar cost per oocyte for both hormones. CONCLUSIONS: Recombinant follicle-stimulating hormone treatment resulted in a higher oocytes yield per cycle than human menopausal gonadotropin at similar cost per oocyte.

Proposal of a skin tests based approach for the prevention of recurrent hypersensitivity reactions to iodinated contrast media.

The purpose of the present work is to evaluate the efficacy of an approach that combines clinical history, skin tests results, and premedication, in preventing recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin Prick tests, Intradermal tests, and Patch tests were performed in 36 patients with a previous reaction to ICM. All patients underwent a second contrast enhanced radiological procedure with an alternative ICM selected on the basis of the proposed approach. After alternative ICM re-injection, only one patient presented a mild NIR. The proposed algorithm, validated in clinical settings where repeated radiological exams are needed, offers a safe and practical approach for protecting patients from recurrent hypersensitivity reactions to ICM.

Interobserver reliability to interpret intrapartum electronic fetal heart rate monitoring: Does a standardized algorithm improve agreement among clinicians?

Our aim was to investigate the accuracy in predicting intrapartum fetal acidaemia and the interobserver reproducibility of a mathematical algorithm for the interpretation of electronic fetal heart rate (FHR) monitoring throughout labour. Eight physicians (blinded to the clinical outcomes of the deliveries) evaluated four randomly selected intrapartum FHR tracings by common visual interpretation, trying to predict umbilical artery base excess at birth. They subsequently were asked to re-evaluate the tracings using a mathematical algorithm for FHR tracing interpretation. Common visual interpretation allowed a correct estimation of the umbilical artery base excess in 34.4% of cases, with a poor interobserver reproducibility (Kappa correlation coefficient = 0.24). After implementation of the algorithm, the proportion of correct estimates significantly increased to 90.6% (p < 0.001), with excellent inter-clinician agreement (κ: 0.85). To conclude, incorporation of a standardised algorithm reduces the interobserver variability and allows a better estimation of fetal acidaemia at birth.

Illness perception, mood and coping strategies in allergic rhinitis: are there differences among ARIA classes of severity?

BACKGROUND: This study was designed to assess if illness perception, mood state and coping strategies differ according to allergic rhinitis (AR) persistence and severity. METHODS: Illness perception, mood profiles, coping behaviors and rhinitis symptoms were assessed by means of validated tools inpatients classified according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines. RESULTS: Two hundred and thirty-one patients underwent data analysis. No difference in age, sex, socio-economic status, smoking habits was detected comparing patients according to AR severity, duration or 4 ARIA classes. Patients with intermittent AR reported higher scores than those with persistent AR in confusion-bewilderment of Profile of Mood States (POMS); patients with moderate/severe rhinitis had significantly higher scores than those with mild rhinitis in TSSS, Identity and Consequences. No differences were detected in all assessed outcomes in the 4 ARIA classes. CONCLUSIONS: The patient's perspective about AR is independent of persistence and severity of symptoms. This may explain why AR remains under-diagnosed and under-treated, even in its most severe forms. Self-management plans should consider the patient's perspective.

Role of single nucleotide polymorphism rs2383206 on coronary artery disease risk among Saudi Population: a case-control study.

OBJECTIVE: We aim to investigate the relationship between genetic variation and biological function on a genomic scale, focusing on identifying genes responsible for complex diseases using single nucleotide polymorphisms. Specifically, the study explores the association between the rs2383206 gene located on chromosome 9p21.3 and the development of coronary artery disease (CAD) in a specific Saudi population. PATIENTS AND METHODS: This case-control study was conducted between September 2013 and May 2015 at King Abdullah Medical City (KAMC) and Al-Noor Specialist Hospital targeting the Saudi Population residing in the western region of Saudi Arabia. The study enrolled 315 cases with documented CAD and 205 controls with normal coronary arteries on coronary angiography. Genomic DNA was extracted from peripheral blood samples of both groups, and genotyping of rs2383206 was performed using the tetra-primer amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) method. RESULTS: In this study, the prevalence of the GG genotype in rs2383206 was found to be higher in patients with CAD than in controls, with an odds ratio of 1.997 [95% confidence interval (CI): 1.176-3.394, p = 0.007]. Additionally, individuals with the GG genotype who had sedentary lifestyles, hyperlipidemia, and smoked were found to be at a higher risk for developing CAD (p = 0.003, 0.009, and 0.003, respectively). The G allele also increased the risk of CAD with an odds ratio of 1.413 (95% CI: 1.099-1.817; p = 0.004). CONCLUSIONS: In conclusion, this study demonstrated a significant association between the rs2383206 variant located on chromosome 9p21 and the development of CAD. The findings of this study provide valuable insights into the genetic susceptibility to CAD and highlight the potential of this variant as a target for future functional studies.

Shrimp allergy in Italian adults: a multicenter study showing a high prevalence of sensitivity to novel high molecular weight allergens.

BACKGROUND: Shrimp is a frequent cause of food allergy worldwide. Besides tropomyosin, several allergens have been described recently. OBJECTIVE: We investigated which allergens are involved in Italian shrimp-allergic adults. METHODS: Sera from 116 shrimp-allergic patients selected in 14 Italian allergy centers were studied. Skin prick tests with house dust mite (HDM) as well as measurements of IgE to Pen a 1 (shrimp tropomyosin) and whole shrimp extract were performed. All sera underwent shrimp immunoblot analysis, and inhibition experiments using HDM extract as inhibitor were carried out on some Pen a 1-negative sera. RESULTS: Immunoblots showed much variability. IgE reactivity at about 30 kDa (tropomyosin) was found in <50% of cases, and reactivity at about 67 kDa and >90 kDa was frequent. Further reactivities at 14-18, 25, 43-50, about 60 and about 80 kDa were detected. Most subjects had a history of shrimp-induced systemic symptoms irrespective of the relevant allergen protein. IgE to Pen a 1 were detected in sera from 46 (41%) patients. Skin reactivity to HDM was found in 43/61 (70%) Pen 1-negative subjects and inhibition studies showed that pre-adsorption of sera with HDM extract induced a marked weakening of the signal at >67 kDa. CONCLUSIONS: Several allergens other than tropomyosin are involved in shrimp allergy in adult Italian patients. Some hitherto not described high molecular weight allergens seem particularly relevant in this population and their cross-reactivity with HDM allergens makes them novel potential panallergens of invertebrates.

Midodrine and albumin as a possible "winning pair" in managing paracentesis-induced circulatory dysfunction: a clinical case report.

BACKGROUND: Paracentesis-induced circulatory dysfunction (PICD) is a "silent killer syndrome" occurring after large volume paracenteses (LVPs). We here report an unusual case of PICD induced by right heart failure recognized and managed successfully. CASE PRESENTATION: A 60-year-old woman was admitted to our Emergency Department for worsening dyspnea and hypoxia. Her medical history enclosed a chronic heart failure with reduced ejection fraction and post-stroke dysarthria associated to right hemiplegia. Clinical and laboratory examination defined a severe right-heart failure unresponsive to high-dose diuretic therapy. Diagnostic and therapeutic paracentesis was thus performed determining, initially, a progressive normalization of the abdominal volume, followed, subsequently, by a severe hypotension associated with an acute kidney injury (AKI) combined with severe hyponatremia associated with a normal cardiac output. In the hypothesis of a PICD, abdominal drainage and diuretic therapy were interrupted, reninemia sampling was performed, resulting in diagnostic, and treatment with albumin and norepinephrine was started. The latter was tapered and then replaced with Midodrine that conferred the possibility to reach clinical and laboratory stability, allowing relocation in a cardiological rehabilitation. PICD represents an independent predictor of mortality. Midodrine's prophylactic use in PICD has been suggested as a cheaper alternative to albumin, as it appears to improve renal perfusion and reduce ascites with better clinical handling, as demonstrated in our patient. CONCLUSIONS: Our clinical case wants to show how not all PICDs are secondary to hepatic dysfunctions with Midodrine playing a possible therapeutic role by counteracting the pathophysiological mechanism in a rapid and non-invasive way, representing a valid therapeutic option in adjunction to albumin.

The complexity of immunology: a rare adverse event following a Pfizer-BioNTech vaccine booster shot.

OBJECTIVE: Several mRNA vaccines have been developed to tackle the global pandemic. Despite their remarkable clinical efficacy, they are not devoid of severe short- and long-term adverse events. CASE PRESENTATION: In this paper, we describe a rare delayed adverse event (arterial and venous renal thrombosis with myocardial injury) in an otherwise healthy adult female, which occurred three months after she received a booster shot of Pfizer COVID-19 vaccine.  The patient was successfully treated for subacute renal ischemia with intra-arterial urokinase, and her myocardial injury was diagnosed with imaging (contrast-enhanced thoracic CT and cardiac magnetic resonance) and percutaneous coronary intervention. Deferred post-vaccine myocarditis was diagnosed and resolved with steroid therapy. CONCLUSIONS: In this paper, we report a useful clinical case for the pharmacovigilance database. Although scientific evidence confirms that the benefits of vaccination far outweigh the risk of adverse events, we would like to point out how important watchful observation is in the medium and long term, especially when the subject belongs to a specific risk category.

Microscopic colitis, a forgotten condition: a clinical case and review of the literature.

OBJECTIVE: Microscopic colitis is a not uncommon chronic inflammatory disease of the colon, characterized by watery, non-bloody diarrhea, which is often forgotten and misdiagnosed. CASE PRESENTATION: In this paper, we present a puzzling case of relapsing chronic diarrhea triggered by non-steroidal anti-inflammatory drug (NSAID) abuse, smoking, inappropriate antibiotic use, and secondary Clostridium Difficilis infection. Several tests were performed during hospitalization, all of which were negative apart from fecal calprotectin (> 6,000 mg/kg, normal values < 50 mg/kg) and a positive Clostridium Difficilis toxin test. Since Vancomycin treatment did not bring about the expected response, colonoscopy was performed, which led to diagnosis, targeted therapy, and clinical resolution. Targeted therapy with budesonide and probiotics was initiated leading to resolution of the diarrhea. CONCLUSIONS: This case study shows how actual diagnosis may be delayed not only due to having to perform differential diagnosis with chronic inflammatory diseases, but also because certainty can only come from histological evidence, which takes time to obtain, especially when the disease's multifactorial nature is considered (smoking, NSAID abuse, oral proton pump inhibitors, inappropriate antibiotic use, and Clostridium difficilis infection).