Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.

Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.

Nature Genetics

Miller Fisher syndrome (MFS) is considered a rare variant of Guillain-Barr&#xe9; syndrome (GBS), a group of acute-onset immune-mediated neuropathies characterized by the classic triad of ataxia, areflexia, and ophthalmoparesis. The present review aimed to provide a detailed and updated profile of all aspects of the syndrome through a collection of published articles on the subject, ranging from the initial description to recent developments related to COVID-19.

We searched PubMed, Scopus, EMBASE, and Web of Science databases and gray literature, including references from the identified studies, review studies, and conference abstracts on this topic. We used all MeSH terms pertaining to "Miller Fisher syndrome," "Miller Fisher," "Fisher syndrome," and "anti-GQ1b antibody."

An extensive bibliography was researched and summarized in the review from an initial profile of MFS since its description to the recent accounts of diagnosis in COVID-19 patients. MFS is an immune-mediated disease with onset most frequently following infection. Anti-ganglioside GQ1b antibodies, detected in ~85% of patients, play a role in the pathogenesis of the syndrome. There are usually no abnormalities in MFS through routine neuroimaging. In rare cases, neuroimaging shows nerve root enhancement and signs of the involvement of the central nervous system. The most consistent electrophysiological findings in MFS are reduced sensory nerve action potentials and absent H reflexes. Although MFS is generally self-limited and has excellent prognosis, rare recurrent forms have been documented.

This article gives an updated narrative review of MFS with special emphasis on clinical characteristics, neurophysiology, treatment, and prognosis of MFS patients.

Miller Fisher syndrome: an updated narrative review.

Frontiers in Neurology

Midline incisional hernia guidelines: the European Hernia Society.

British Journal of Surgery

The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. We hypothesized that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium.

103,094 hospitalized adults undergoing general anesthesia for non-cardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts, USA were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within seven days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied.

78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery. 770 patients (0.8%) developed delirium within seven days. The median (interquartile range [IQR]) total intraoperative dose of phenylephrine was 1.0 (0.2-3.3) mg and 10.0 (10.0-20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within seven days (adjusted odds ratio [ORadj] 1.35; 95%CI 1.06-1.71; adjusted absolute risk difference [ARDadj] 0.2%; 95%CI 0.1%-0.3%; p=0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence 3.2%, ORadj 1.88; 95%CI 1.49-2.37; p&lt;0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient 0.08; 95%CI 0.02-0.14; p=0.013, per each mcg/kg increase in the cumulative phenylephrine dose).

The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on our data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Intraoperative use of phenylephrine versus ephedrine and postoperative delirium: A multicenter retrospective cohort study.

Anesthesiology

Multiple myeloma (MM) is a hematologic malignancy characterized by the abnormal clonal proliferation of plasma cells that may result in focal bone lesions, renal failure, anemia, and/or hypercalcemia. Recently, the diagnosis and treatment of MM have evolved due to a better understanding of disease pathophysiology, improved risk stratification, and new treatments. The incorporation of new drugs, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies and high-dose chemotherapy followed by hematopoietic stem cell transplantation, has resulted in a significant improvement in patient outcomes and QoL. In this review, we summarize differential diagnoses and therapeutic advances in MM.

Differential Diagnosis and Therapeutic Advances in Multiple Myeloma: A Review Article.

Blood and Lymphatic Cancer : Targets and Therapy

Use of renin-angiotensin-aldosterone system (RAAS) inhibiting medications is critical in the prevention of cardiovascular disease and kidney function decline in patients with chronic kidney disease (CKD); however, these agents can lead to hyperkalemia, an electrolyte disorder associated with risk of arrythmia, conduction disorders, and increased overall mortality. Discontinuation, or reduction of dose, of RAAS inhibitor therapy in hyperkalemic patients with CKD can lead to loss of kidney and cardiovascular protection afforded by these medications. Given the high prevalence of hyperkalemia among patients with CKD utilizing RAAS inhibitors, clear management principles are critical to minimize risk and maximize benefit when facing this clinical dilemma.

Strategies to mitigate hyperkalemia that do not interfere with optimal RAAS inhibitor therapy should be prioritized when managing potassium elevation in patients with CKD. These strategies include discontinuing non-RAAS inhibitor medications known to cause hyperkalemia, correction of metabolic acidosis, and maximization of medication therapies that lower serum potassium, including diuretics and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Initiation of potassium exchange resins should also be considered to allow for sustained RAAS inhibitor utilization. An approach which employs multiple strategies concurrently is important to mitigate hyperkalemia and maintain long-term use of RAAS-inhibitors. Persistence of RAAS inhibitor use in patients with CKD is important to slow kidney function decline, delay onset of dialysis or the need for kidney transplant, and prevent adverse cardiovascular outcomes. When hyperkalemia develops among patients with CKD utilizing a RAAS inhibitor, a deliberate effort to reduce serum potassium levels using an approach that allows for continuation of maximally dosed RAAS inhibitor therapy is important. Patient education and engagement in the potassium management process is important for sustained success.

Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.

Full text links

For the best experience, use the Read mobile app

Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome.

Full text links

Trending Papers

For the best experience, use the Read mobile app