Persistent Gastrointestinal Bleeding after Aortic Valve Replacement in Heyde's Syndrome.

Heyde's syndrome (HS) represents an association between aortic stenosis and intestinal angiodysplasias, and it has been demonstrated that acquired von Willebrand disease plays a pivotal role in the pathophysiology of this syndrome. In patients with HS, von Willebrand factor deficiency represents an additional risk factor, further contributing to the risk of bleeding and anemia. We present the case of an 86-year-old patient diagnosed with HS and von Willebrand deficiency in 2018. Four years prior, the patient underwent surgical aortic valve replacement. Since then, she has been receiving chronic oral anticoagulation therapy with a vitamin K antagonist. The patient was admitted to the Internal Medicine Clinic due to semi-solid dark stools, diffuse abdominal pain, and asthenia. Upon examination, the patient presented with an altered general status and clinical signs suggestive of anemia. Laboratory findings revealed anemia with elevated INR and aPTT values. Colonic angiodysplasias were identified during a colonoscopy, although no sources of active bleeding were detected. On the 9th day of hospitalization, the patient experienced an episode of lower gastrointestinal bleeding. The pharmacological management was adjusted, and argon plasma coagulation was recommended. Following treatment of the angiodysplastic lesions, the patient's clinical evolution was favorable, with the correction of the anemia.

Drug Survival, Effectiveness and Safety of Secukinumab in Axial Spondyloarthritis up to 4 Years: A Real-Life Single Center Experience.

(1) Objective: The main aims of our study were to explore the drug survival and effectiveness of secukinumab in patients with axial spondyloarthritis (axSpA). (2) Methods: We underwent a retrospective analysis of consecutive axSpA treated with secukinumab as a first line of biologics or at switch in a biologic-experienced population. Efficacy data, indicating improvement in inflammation parameters (such as C-reactive protein and erythrocyte sedimentation rate) and disease activity scores (such as Ankylosing Spondylitis Disease Activity Score [ASDAS-CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and patient-reported outcomes (pain), were assessed at 6, 12, 24, 36 and 48 months. The drug survival rate, dropout rate and discontinuation reasons (efficacy versus safety) of secukinumab were assessed in subgroup analysis (axSpA with and without exposure to biologics). (3) Results: In total, 46 patients were exposed to the IL-17A inhibitor secukinumab. The drug survival for axSpA patients 59.7% at 12 months and 31.3% at 24 months. There were no statistically significant differences in the median drug survival between biologic-naïve versus biologic-experienced subgroups. (4) Conclusions: Secukinumab has demonstrated effectiveness and safety in treating a cohort of axSpA patients in real-world settings, with a notable retention rate of the drug.

Two Cases of Congenital Hypothyroidism Revealing Thyroid Agenesis.

Congenital hypothyroidism (CH) may have major detrimental effects on growth and neurological development, but early intervention leads to excellent outcomes. CH is classified as transient or permanent, primary or secondary, with primary CH being the most common neonatal endocrine disorder. Most patients with CH do not present any typical signs and symptoms of hypothyroidism shortly after birth, partly due to transplacental maternal thyroid hormone transfer and residual neonatal thyroid function. This paper reports on two CH cases. During the initial Neonatal Intensive Care Unit (NICU) admission phase, CH was not suspected due to nonspecific signs. The distinct characteristics of our cases are as follows: both infants were admitted to the NICU for respiratory distress syndrome, requiring invasive mechanical ventilation, and both were born to diabetic mothers. Following extubation, they both showed similar neurological issues, including reduced muscle tone and feeding difficulties. Initially, those symptoms were attributed to delayed clearance of analgesic and sedative medication. However, symptoms progressively worsened over time. Subsequent tests revealed both meeting CH diagnostic criteria: an unusual ultrasound indicating thyroid agenesis and abnormal hormone levels. Guided by the pediatric endocrinology team, prompt hormonal treatment was started with improvements in neurocognitive function and feeding. Usually, CH screening involves blood samples from healthy newborns at 2-3 days of life. Abnormal results require confirmation, prompting treatment within two weeks. Certain NICU-admitted infants face higher diagnosis delays, as seen in those two cases where CH screening was postponed. Thus, for all neonates with persistent pathologies unresponsive to standard etiological treatment, conducting a comprehensive anamnestic evaluation of the medical history, along with maternal preconceptional and prenatal nutrition, is recommended.

Polyurethane Degradable Hydrogels Based on Cyclodextrin-Oligocaprolactone Derivatives.

Polymer networks based on cyclodextrin and polyethylene glycol were prepared through polyaddition crosslinking using isophorone diisocyanate. The envisaged material properties are the hydrophilic character, specific to PEG and cyclodextrins, and the capacity to encapsulate guest molecules in the cyclodextrin cavity through physical interactions. The cyclodextrin was custom-modified with oligocaprolactone to endow the crosslinked material with a hydrolytically degradable character. SEM, DTG, and FTIR characterization methods have confirmed the morphology and structure of the prepared hydrogels. The influence of the crosslinking reaction feed was investigated through dynamic rheology. Further, thermal water swelling and hydrolytic degradation in basic conditions revealed the connectivity of the polymer network and the particular influence of the cyclodextrin amount in the crosslinking reaction feed on the material properties. Also, levofloxacin was employed as a model drug to investigate the drug loading and release capacity of the prepared hydrogels.

Polyethylene Glycol-Isophorone Diisocyanate Polyurethane Prepolymers Tailored Using MALDI MS.

The reaction of diols with isocyanates, leading to mono-functional and di-functional prepolymers may be investigated using various characterization methods which show the overall conversion of isocyanate monomers. On the other hand, matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) polymer characterization can be employed to identify the monomer units, the end-group functionalities, molecular weight averages, and to determine the copolymer sequence. Herein, we focus on prepolymer synthesis using isophorone diisocyanate (IPDI), a widely used diisocyanate for prepolymers preparation, especially in waterborne polyurethane materials. Thus, the reaction between polyethylene glycol diol and IPDI was in-depth investigated by mass spectrometry to determine the influence of the reaction parameters on the prepolymer's structure. The relative content of the different functional oligomer species at given reaction times was determined in the reaction mixture. More specifically, the offline analysis revealed the influence of reaction parameters such as reaction temperature, the concentration of reactants, and the amount of dibutyltin dilaurate catalyst. The established MALDI MS analysis involved measurements of samples, first, directly collected from the reaction mixture and secondly, following derivatization with methanol. The obtained results revealed the effects of reaction parameters on the functionalization reaction with isocyanates, allowing to achieve a better reaction control.

Respiratory pathology in late preterm infants conceived by in vitro fertilization.

This study aimed to identify the incidence of in vitro fertilization (IVF) in late preterm infants and the presence of respiratory pathology in this premature category compared with those conceived naturally. This retrospective study was performed over 6 months, including newborns with a gestational age between 34-36 weeks and 6 days in the Department of Obstetrics, Gynecology and Neonatology, Alessandrescu-Rusescu National Institute of Mother and Child Health. The following variables were assessed: infants' gestational age, delivery mode, respiratory morbidity, and the need for respiratory support. During the mentioned period, 112 late preterm infants were born, out of whom 9.8% represented late preterm infants conceived by in vitro fertilization. The delivery mode of late preterm infants conceived by in vitro fertilization was exclusively by C-section (100%) compared to those conceived spontaneously (44.5%). 18.1% of IVF late preterm infants developed transient tachypnea of the newborn. In the non-IVF group, respiratory distress syndrome was present in 5.9% and transient tachypnea in 33.6% of cases. No IVF late preterm infant required hospitalization in neonatal intensive care for more than 3 days, compared to 19.8% of naturally conceived late preterm infants. Respiratory distress syndrome very seldom occurs in late preterm IVF infants due to prenatal prophylactic treatment with corticosteroids. Respiratory pathology is rarely present due to very careful monitoring during pregnancy, the presence of a neonatal team in the delivery room for possible resuscitation, and providing proper care according to the good state of health during the short, one-week hospitalization.

Practical Significance of Biomarkers in Axial Spondyloarthritis: Updates on Diagnosis, Disease Activity, and Prognosis.

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that can lead to ankylosis by secondary ossification of inflammatory lesions, with progressive disability and a significant impact on quality of life. It is also a risk factor for the occurrence of comorbidities, especially cardiovascular diseases (CVDs), mood disorders, osteoporosis, and malignancies. Early diagnosis and treatment are needed to prevent or decrease functional decline and to improve the patient's prognosis. In respect of axSpA, there is an unmet need for biomarkers that can help to diagnose the disease, define disease activity and prognosis, and establish personalized treatment approaches. The aim of this review was to summarize the available information regarding the most promising biomarkers for axSpA. We classified and identified six core categories of biomarkers: (i) systemic markers of inflammation; (ii) molecules involved in bone homeostasis; (iii) HLA-B27 and newer genetic biomarkers; (iv) antibody-based biomarkers; (v) microbiome biomarkers; and (vi) miscellaneous biomarkers. Unfortunately, despite efforts to validate new biomarkers, few of them are used in clinical practice; however, we believe that these studies provide useful data that could aid in better disease management.

The Influence of the Hydroxyl Type on Crosslinking Process in Cyclodextrin Based Polyurethane Networks.

The influence of the hydroxyl groups (OH) type on the polyaddition processes of isocyanates represents a critical approach for the design of multicomponent polyurethane systems. Herein, to prove the effect of hydroxyl nature on both the isocyanate-OH polyaddition reactions and the structure/properties of the resulting networks, two structurally different cyclodextrins in terms of the primary and secondary groups' ratio were analyzed, namely native ß-cyclodextrin (CD) and its derivative esterified to the primary hydroxyl groups with oligolactide chains (CDLA). Thus, polyurethane hydrogels were prepared via the polyaddition of CD or CDLA to isophorone diisocyanate polyethylene glycol-based prepolymers (PEG-(NCO)2). The degradable character of the materials was induced by intercalating oligolactide short sequences into the polymer chains composing the polymer network. In order to establish the influence of the OH type, the synthesis of polyurethane hydrogels was analyzed by a rheological investigation of the overall system reactivity. Materials properties such as swelling behavior, thermal properties and hydrolytic degradation were influenced by the reaction feed. Specifically, the presence of primary OH groups leads to more compact networks with similar water uptake, disregarding the CD content, while the predominance of secondary OH groups together with the presence of oligolactide spacers leads to the fine tuning of the water swelling properties.

Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review.

BACKGROUND: Systemic sclerosis (SSc) is a chronic multisystem autoimmune condition defined by a complex pathobiology, comprising excessive fibrosis of skin and internal organs, peripheral vasculopathy with endothelial cell dysfunction, inadequate vascular repair and neovascularization, and aberrant immunity. Vitamin D is a steroid hormone with pleiotropic effects beyond its traditional role in calcium and bone homeostasis. Since vitamin D has immunomodulatory, cardioprotective, and antifibrotic properties, it could potentially interfere with SSc pathogenesis. Suboptimal vitamin D levels are classically recognized in scleroderma, irrespective of clinical and serological phenotype. AIM: This systematic review is aimed at investigating and clarifying the role of vitamin D in SSc and emphasizing the association of vitamin D status with different clinical settings. METHODS AND RESULTS: A systematic online search was performed, using PubMed databases to collect articles on the topic of vitamin D in SSc. The final analysis included 40 eligible articles. CONCLUSIONS: Hypovitaminosis D is common in SSc patients and could be associated with clinical and serologic patterns of the disease. Intervention for low serum vitamin D levels in SSc pathogenesis remains controversial, as well as the significance of vitamin D supplementation in such patients.

Diagnosing HIV-associated cerebral diseases - the importance of Neuropathology in understanding HIV.

The study aims to compare two aspects concerning the diagnosis of acquired immune deficiency syndrome (AIDS)-associated central nervous system (CNS) pathology (neuroAIDS): clinical diagnoses issued ante mortem with pathology results issued post mortem. The group of 39 human immunodeficiency virus (HIV)-positive patients was created over 23 years and is limited by marked heterogeneity. The enrolled cases were treated at the "Prof. Dr. Matei Bals" National Institute for Infectious Diseases, Bucharest, Romania, deceased due to AIDS-related complications and underwent brain necropsies performed in the Pathology Laboratory at the "Colentina" Clinical Hospital, Bucharest. The level of superposition between clinical and the necroptic diagnoses of neurological AIDS-associated diseases was: 60% for progressive multifocal leukoencephalopathy (PML), 50% for cerebral cryptococcosis, 33% for cerebral toxoplasmosis, 20% for cerebral lymphoma, null for cerebral tuberculosis, HIV encephalopathy (HIVE), neurosyphilis and cytomegalovirus cerebral infection. Half of the cases without an AIDS-associated CNS lesion were previously clinically overdiagnosed. We observed that the rate of overdiagnosis concerning an AIDS-associated cerebral illness has risen from 36% in 1993 to 124% in 2015, an elevation with statistical relevance [p=0.037, confidence interval (CI) 95%]. The rate of underdiagnosis has slowly risen from 24% in 1993 to 40% in 2015, however, with no statistical relevance. The rate of clinical confirmation has been stagnant in linear regression from 1993 to 2015. The results of our study reveal a gap between ante mortem and post mortem diagnoses, with many instances of overdiagnosis and underdiagnosis of several major AIDS-associated CNS illnesses, highlighting the need for a more detailed, multidisciplinary approach of neuroAIDS.

Hepatopulmonary syndrome: an unusual cause of dyspnea in the pulmonology ward - case presentation.

Hepatopulmonary syndrome is one of the possible complications of chronic liver disease, defined clinically by impaired oxygenation. The underlying cause of the respiratory failure is the presence of intrapulmonary shunting, as a result of abnormal vascular dilatations in the lungs. We report the case of 52-year-old male, exsmoker, with a history of pulmonary TB and also of heavy drinking, who was admitted to the pulmonology ward for dyspnea at rest and limb cyanosis. His clinical exam was suggestive of liver cirrhosis, with signs of pneumonia, but also chronic lung disease. Variations in SaO2 with posture were noted: platypnea and orthodeoxia. Arterial gas assessment revealed severe hypoxemia, only partially corrected by high-flow oxygen therapy, while plethysmography showed only a mild obstructive syndrome, but with severely impaired alveolar-capillary diffusion. The suspicion of a hepatopulmonary syndrome was raised and a contrast echocardiography confirmed the diagnosis by revealing the presence of an intrapulmonary shunt. Although it is believed to be a fairly common complication of chronic liver disease, it is possible for a case of hepatopulmonary syndrome to be admitted solely for respiratory symptoms. The patient's poor socio-economic status is the main reason for both the lack of proper followup for his liver disease and the limited therapeutic options. Keywords: Hepatopulmonary syndrome, liver cirrhosis, respiratory failure, contrast echocardiography