Aspirin hypersensitivity: a practical guide for cardiologists.

Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.

The largest caucasian kindred with dentatorubral-pallidoluysian atrophy: A founder mutation in italy.

BACKGROUND: Dentatorubral-pallidoluysian atrophy is a hereditary neurodegenerative disease prevalently reported in Japan but rare in Caucasians. The objective of this study was to reconstruct the pedigree of Italian dentatorubral-pallidoluysian atrophy familial cases describing their clinical features. METHODS: We investigated 6 apparently unrelated dentatorubral-pallidoluysian atrophy families comprising a total of 51 affected individuals: 13 patients were clinically examined, and for 38 patients clinical data were collected from clinical sources. The dentatorubral-pallidoluysian atrophy diagnosis was genetically confirmed in 18 patients. Genealogical data from historical archives were analyzed. RESULTS: All 6 families were unified in a large pedigree deriving from a founder couple originating from Monte San Giuliano (Italy) in the late 1500s, with 51 affected subjects over the last 4 generations. Wide phenotypical variability in age at onset and clinical features was confirmed. Epilepsy was more frequent in juvenile cases than in late adults, with cognitive/psychiatric and motor disorders observed regardless of age at onset. CONCLUSIONS: We have described the largest Caucasian dentatorubral-pallidoluysian atrophy pedigree from a single founder couple. The introduction of the dentatorubral-pallidoluysian atrophy gene in Italy could have arisen as a result of trade relationships between the Spanish or Portuguese and the Japanese in the 1500s. © 2019 International Parkinson and Movement Disorder Society.

Laparoscopic Assisted Percutaneous Anterior Gastropexy for the Management of Acute and Chronic Gastric Volvulus in Infants.

Acute and chronic gastric volvulus (ACGV) is a rare event in infants and children. Its prompt treatment is needed to avoid gastric ischemia and perforation. A laparotomy or a laparoscopic/endoscopic reduction with or without the gastrostomy formation has been described to treat this condition. We wanted to report our experience and describe the surgical technique used to perform the percutaneous laparoscopic assisted anterior gastropexy in neonates presenting with this condition. We perform a retrospective review of a single institution's experience with laparoscopic assisted percutaneous anterior gastropexy over a seven-year period (2015-2022). Procedures were performed under general anesthesia and the anterior gastropexy was performed using a modified extracorporeal knotting technique as described for the laparoscopic assisted repair of inguinal hernias via percutaneous internal ring suturing. Thirteen patients underwent surgery for ACGV at our institution over a seven-year period. The median age at diagnosis was 57 days, 7/13 patients presented with acute vomiting and regurgitation (54%), 1/13 (8%) presented with mainly feeding difficulties and 1/13 (8%) presented with acute abdominal distension. Data were not available for 4/13 patients. All of the patients underwent laparoscopic assisted anterior gastropexy using extracorporeal knotting technique; no gastrostomy insertion was needed. The median operative time was 50 min (40-95 min). No intraoperative complications were reported. Post-operatively patients were started on feeds on day 3 (2-5 days). Only one patient (8%) developed a postoperative complication: subcutaneous granuloma at the extracorporeal knot site. Although rare, acute GV is an important cause of gastric outlet obstruction with a detrimental outcome if not promptly recognized and treated. Laparoscopic assisted percutaneous anterior gastropexy is an attractive and safe alternative for the management of this condition in both infants and older children. This technique does not require gastrostomy placement and it has a very low morbidity rate with no mortality reported.

Altered cytoskeletal structure of smooth muscle cells in ureteropelvic junction obstruction.

PURPOSE: Ureteropelvic junction obstruction is one of the most common causes of hydronephrosis in children. A malfunction of smooth muscle cells is believed to be the underlying mechanism causing obstruction. We investigated the expression of some integrins, talin and ß-dystroglycan, considered the main compound of smooth muscle cell cytoskeleton, and active caspase 3 at the level of the ureteropelvic junction obstruction. MATERIALS AND METHODS: Specimens were obtained at pyeloplasty in 12 children with ureteropelvic junction obstruction. Six control specimens were obtained during organ explantation. Specimens were divided into renal pelvis, ureteropelvic junction and ureter below the obstruction. Western blot analysis of active caspase 3, and immunofluorescence and polymerase chain reaction analysis were performed for α7A, ß1A, α7B and ß1D integrins, talin and ß-dystroglycan. RESULTS: Talin and ß-dystroglycan were slightly impaired in ureteropelvic junction obstruction, while α7B and ß1D integrins were severely reduced, and α7A, ß1A and active caspase 3 were significantly enhanced compared to controls. CONCLUSIONS: We demonstrated activation of apoptosis and a critical alteration of cytoskeleton that might explain the altered function and the increased apoptosis in smooth muscle cells in ureteropelvic junction obstruction. The delayed rearrangement of the cytoskeleton of smooth muscle cells in ureteropelvic junction obstruction might be linked to a postnatal splicing from α7A and ß1A to α7B and ß1D integrins, respectively. This relationship could explain the common clinical scenario of spontaneous improvement of hydronephrosis in children with suspected ureteropelvic junction obstruction.

Movements execution in amnestic mild cognitive impairment and Alzheimer's disease.

We evaluated the relationship between motor and neuropsychological deficits in subjects affected by amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer's Disease (AD). Kinematics of goal-directed movement of aMCI and AD subjects were compared to those of age-matched control subjects. AD showed a slowing down of motor performance compared to aMCI and controls. No relationships were found between motor and cognitive performances in both AD and aMCI. Our results suggest that the different motor behaviour between AD and aMCI cannot be related to memory deficits, probably reflecting the initial degeneration of parietal-frontal circuits for movement planning. The onset of motor dysfunction in early AD could represent the transition from aMCI to AD.

Activation of adenosine A2A receptors by polydeoxyribonucleotide increases vascular endothelial growth factor and protects against testicular damage induced by experimental varicocele in rats.

In rat experimental varicocele, polydeoxyribonucleotide (PDRN) induces vascular endothelial growth factor (VEGF) production, thereby enhancing testicular function. This may point to a new therapeutic approach in human varicocele.