The Importance of Molecular Testing for the Diagnosis of Fabry Disease Manifested by Cornea Verticillata Only

Aims: To describe a Fabry disease, that it’s diagnosis was only possible through the molecular test Presentation of Case: L.A.P. female, 42 years old, lawyer, seen by the ophthalmology department for routine consultation only with refractive complaints. Fundus of the eye: Mild narrowing with increased vascular brightness and presence of pathological arteriovenous crossings. The rest of the exam was within normal limits. Therefore, a genetic test with the dosage of the α-Gal enzyme was requested, which evidenced the alteration in it, confirming the diagnosis of Fabry disease. Discussion: A Fabry Disease (FD) is an inborn error of glycosphingolipid (GL) metabolism, resulting from deficient activity of the enzyme alpha-galactosidase A (α -Gal). It has X-chromosome-linked inheritance, affecting mainly males, with an estimated prevalence of 1:40,000 males. The expression of the disease in heterozygous female patients can vary from an asymptomatic condition to a severe systemic disease, like that which occurs in men. Conclusions: The ophthalmological examination played an important role in the diagnosis, as this change is highly suggestive of the disease, in order to avoid erroneous and late diagnoses that can cause consequences for patients with this condition.

What is beyond Salmonella gastroenteritis? A case of acute pancreatitis complicating Salmonella infection in a child: a case report and literature review

Background Salmonella infection presents itself in a wide variety of ways, ranging from mild self-limited illness to severe systemic disease with multiorgan involvement. Acute pancreatitis (AP) is a very rare complication that is associated with Salmonella infection, especially among the pediatric population. Case presentation A five-year-old boy presented with a two-day fever and experienced vomiting, diarrhea, and abdominal pain. The boy was admitted as a case of acute gastroenteritis, and Salmonella was found in his stool culture. The severity of his abdominal pain during his hospital stay indicated the possibility of AP. A clinical examination and blood workup were performed and showed significant elevation in amylase and lipase, which confirmed the diagnosis of AP. Conclusion Although abdominal pain is a common presentation of Salmonella infection, the possibility of AP must be considered when the pain is severe and the characteristics of the pain are suggestive of AP. Herein, we report a case of AP complicating Salmonella infection in an immunocompetent child.

The additional use of methylene blue has a decatecholaminisation effect on cardiac vasoplegic syndrome after cardiac surgery

Background Postoperative vasoplegia with minimal responsiveness to vasopressors is common after cardiac surgery. Called cardiac vasoplegic syndrome (CVS), it is caused by multiple factors. Treating CVS involves a high dose of fluids and catecholamines, however high doses of catecholamines and fluids are associated with serious side effects. There is evidence that new therapeutic strategies can lead to a reduction in norepinephrine doses and mortality in CVS. Specifically, the use of non-adrenergic vasopressors such as methylene blue (MB) can be beneficial. Methods We retrospectively analyzed the electronic records of 8716 adult cardiac surgery patients from November 2008 to December 2016. Medication, hemodynamic and outcome parameter data were analyzed for CVS until discharge. We determined CVS according to the following parameters: a postoperative onset of ≤24 h, a reduced mean arterial pressure (MAP) of < 70 mmHg, a dose of norepinephrine ≥0.8 mg*h− 1 and a continuously increasing need for catecholamine, without ventricular dysfunction. Results We identified 513 patients with CVS. Perioperative risk factors were higher in patients treated with methylene blue (MB). Before MB administration patients had a significantly higher dose of norepinephrine, and MAP increased after MB administration. Norepinephrine could be reduced after MB administration and MAP remained stable at the same level even after the reduction of norepinephrine. Conclusions CVS patients have a severe systemic disease accompanied by significant operative stress and a high catecholamine requirement. The administration of MB in addition to standard treatment for CVS in the first 24 h was accompanied by an increase in MAP followed by a decrease in vasopressor requirement, indicating that early MB administration can be beneficial.

Analysis of the care complexity in the surgical area: Persiceto’s score

Introduction: In Italy a new way of thinking about hospitals is emerging. It involves the articulation of care and resources according to the intensity and the complexity of care; patients acquire a central role and are no longer grouped by medical disciplines but by high, medium or low care complexity. Purpose of this study is to test a tool that detects care complexity in the areas of intervention, calculating and analyzing the care complexity of surgical patients in their first day after surgery. Methods: adoption of the Swot method to specify the Persiceto's Score tool, adapted to the Alexandrian context. The Persiceto tool consists of scores obtained from three elements: type of surgery, state of health/concurrent disease condition, autonomy level of the patient in various activities. Results: In an evaluation period of about 60 days the Persiceto tools completed on the first day after surgery were 80. The state of health and concurrent disease condition of the 80 patients was constituted by 43 with moderate systemic disease, 22 with severe systemic disease, 13 in good health and 2 in threatening health conditions. The level of care dependency that emerged from the IDA assessment of the 80 patients was 56 with low care dependency, 23 with average and 1 with high care dependency. Conclusions: This study has shown that a simple, effective and replicable tool can be useful during the reorganization of care intensity during post-surgery to obtain a precise classifications of care complexity.

Neurologic and Neuroscientific Evidence in Aged COVID-19 Patients

The COVID-19 pandemic continues to prevail as a catastrophic wave infecting over 111 million people globally, claiming 2. 4 million lives to date. Aged individuals are particularly vulnerable to this disease due to their fraility, immune dysfunction, and higher rates of medical comorbidities, among other causes. Apart from the primary respiratory illness, this virus is known to cause multi-organ dysfunction including renal, cardiac, and neurologic injuries, particularly in the critically-ill cohorts. Elderly patients 65 years of age or older are known to have more severe systemic disease and higher rates of neurologic complications. Morbidity and mortality is very high in the elderly population with 6–930 times higher likelihood of death compared to younger cohorts, with the highest risk in elderly patients ≥85 years and especially those with medical comorbidities such as hypertension, diabetes, heart disease, and underlying respiratory illness. Commonly reported neurologic dysfunctions of COVID-19 include headache, fatigue, dizziness, and confusion. Elderly patients may manifest atypical presentations like fall or postural instability. Other important neurologic dysfunctions in the elderly include cerebrovascular diseases, cognitive impairment, and neuropsychiatric illnesses. Elderly patients with preexisting neurologic diseases are susceptibility to severe COVID-19 infection and higher rates of mortality. Treatment of neurologic dysfunction of COVID-19 is based on existing practice standards of specific neurologic condition in conjunction with systemic treatment of the viral illness. The physical, emotional, psychologic, and financial implications of COVID-19 pandemic have been severe. Long-term data are still needed to understand the lasting effects of this devastating pandemic.

COVID-19 as a systemic disease

COVID-19 usually manifests by respiratory symptoms. However, it would be an erroneous simplification to consider it as a local respiratory disease. The nervous system and intestines are often involved even in patients with mild infection, although the risk of dissemination of the infectious process and the development of severe systemic disease is mainly associated with lung damage. The addition of infectious thrombotic microvasculitis (endothelitis) to bronchopneumonia-alveolitis not only forms a substrate for respiratory failure, but also increases a risk of viruses entry into the bloodstream. Viral sepsis develops, whereas inflammatory thrombosis damages new areas of the vascular bed. These mechanisms or direct viral invasion can result in involvement of many tissues and organs in the pathological process. This review examines the molecular, cellular and clinical manifestations and complications of the new coronavirus disease.

Conserved tandem arginines for PbgA/YejM allow Salmonella to regulate LpxC and control lipopolysaccharide biogenesis during infection

ABSTRACTSalmonella enterica serovar Typhimurium uses PbgA/YejM, a conserved multi-pass transmembrane protein with a soluble periplasmic domain (PD), to balance the glycerophospholipid (GPL) and lipopolysaccharide (LPS) concentrations within the outer membrane (OM). The lipid homeostasis and virulence defects of pbgAΔ191-586 mutants, which are deleted for the PD, can be suppressed by substitutions in three LPS regulators, LapB/YciM, FtsH, and LpxC. We reasoned that S. Typhimurium uses the PbgA PD to regulate LpxC through functional interactions with LapB and FtsH. In the stationary phase of growth, pbgAΔ191-586 mutants accumulated LpxC and overproduced LPS precursors, known as lipid A-core molecules. Trans-complementation fully decreased the LpxC and lipid A-core levels for the mutants, while substitutions in LapB, FtsH, and LpxC variably reduced the concentrations. PbgA binds lipid A-core, in part, using dual arginines, R215 and R216, which are located near the plasma membrane. Neutral, conservative, and non-conservative substitutions were engineered at these positions to test whether the side-chain charges for residues 215 and 216 influenced LpxC regulation. Salmonellae that expressed PbgA with dual alanines or aspartic acids overproduced LpxC, accumulated lipid A-core and short-LPS molecules, and were severely attenuated in mice. Bacteria that expressed PbgA with tandem lysines were fully virulent in mice and yielded LpxC and lipid A-core levels that were similar to the wild type. Thus, S. Typhimurium uses the cationic charge of PbgA R215 and R216 to down-regulate LpxC and decrease lipid A-core biosynthesis in response to host stress and this regulatory mechanism enhances their virulence during bacteremia.IMPORTANCESalmonella enterica serovar Typhimurium causes self-limiting gastroenteritis in healthy individuals and severe systemic disease in immunocompromised humans. The pathogen manipulates the immune system of its host by regulating the lipid, protein, and polysaccharide content of the outer membrane (OM) bilayer. Lipopolysaccharides (LPS) comprise the external leaflet of the OM, and are essential for establishing the OM barrier and providing gram-negative microbes with intrinsic antimicrobial resistance. LPS molecules are potent endotoxins and immunomodulatory ligands that bind host-pattern receptors, which control host resistance and adaptation during infection. Salmonellae use the cationic charge of dual arginines for PbgA/YejM to negatively regulate LPS biosynthesis. The mechanism involves PbgA binding to an LPS precursor and activating a conserved multi-protein signal transduction network that cues LpxC proteolysis, the rate-limiting enzyme. The cationic charge of the tandem arginines is critical for the ability of salmonellae to survive intracellularly and to cause systemic disease in mice.