Should patients with complex febrile seizure be admitted for further management?

Background and aims

Children with first complex febrile seizure (CFS) are often admitted for observation. The goals of this study were 1) to assess the risk of seizure recurrence during admission, 2) to determine whether early EEG affects acute management.

Intensity discrimination deficits cause habituation changes in middle-aged Caenorhabditis elegans

The ability to learn and remember is critical for all animals to survive in the ever-changing environment. As we age, many of our biological faculties decay and of these, decline in learning and memory can be the most distressing. To carefully define age-dependent changes in learning during reproductive age in the nematode Caenorhabditis elegans, we performed a parametric behavioral study of habituation to nonlocalized mechanical stimuli (petri plate taps) over a range of intensities in middle-aged worms. We found that as worms age (from the onset of reproduction to the end of egg laying), response probability habituation increases (at both 10- and 60-second interstimulus intervals) and that these age-related changes were associated with a decrease in the discrimination between stimuli of different intensities. We also used optogenetics to investigate where these age-dependent changes occur. Our data suggest that the changes occur upstream of mechanosensory neuron depolarization. These data support the idea that declines in stimulus intensity discrimination abilities during aging may be one variable underlying age-related cognitive deficits.     

SARS-CoV-2-induced immunodysregulation and the need for higher clinical suspicion for co-infection and secondary infection in COVID-19 patients

Cases of co-infection and secondary infection emerging during the current Coronavirus Disease-19 (COVID-19) pandemic are a major public health concern. Such cases may result from immunodysregulation induced by the SARS-CoV-2 virus. Pandemic preparedness must include identification of disease natural history and common secondary infections to implement clinical solutions.     

Patients at elevated risk of major adverse events following endarterectomy for asymptomatic carotid stenosis

Background

Carotid endarterectomy (CEA) as treatment in patients with asymptomatic carotid stenosis is the subject of much debate.

Methods

The National Surgical Quality Improvement Program database from 2005 to 2012 was queried. Patients undergoing CEA for asymptomatic carotid stenosis were identified. Preoperative risk factors and patient demographics were compared using chi-square analysis and logistic regression to determine their relation with stroke and death.

Results

During an 8-year period, 24,211 CEAs performed for asymptomatic carotid stenosis were identified. Patients with dependent functional status (12.5%), recent myocardial infarction (6.3%), chronic heart failure (5.0%), hypoalbuminemia (4.8%), angina (4.1%), dialysis dependence (3.4%), steroid dependence (3.4%), chronic obstructive pulmonary disease (3.3%), and American Society of Anesthesiologists > 3 (3.2%) had a clinically significant increase in risk of stroke and death. Patients with none of the above risk factors had a stroke and death rate of 1.08%, which was significantly less than the overall stroke and death rate (P < .001).

Conclusions

A high-risk subset of patients undergoing CEA for asymptomatic carotid stenosis can be identified. If patient selection is optimized and perioperative morbidity and mortality are minimized, CEA will continue to play an important role in stroke prevention for those with significant asymptomatic carotid stenosis.     

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

Background

Intervertebral disc degeneration is a common condition with few inexpensive and effective modes of treatment, but current investigations seek to clarify the underlying process and offer new treatment options. It will be important for physicians to understand the molecular basis for the pathology and how it translates to developing clinical treatments for disc degeneration. In this review, we sought to summarize for clinicians what is known about the molecular processes that causes disc degeneration.

Results

A healthy disc requires maintenance of a homeostatic environment, and when disrupted, a catabolic cascade of events occurs on a molecular level resulting in upregulation of proinflammatory cytokines, increased degradative enzymes, and a loss of matrix proteins. This promotes degenerative changes and occasional neurovascular ingrowth potentially contributing to the development of pain. Research demonstrates the molecular changes underlying the harmful effects of aging, smoking, and obesity seen clinically while demonstrating the variable influence of exercise. Finally, oral medications, supplements, biologic treatments, gene therapy, and stem cells hold great promise but require cautious application until their safety profiles are better outlined.

Conclusions

Intervertebral disc degeneration occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians because it may help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.     

MDX‐1097 induces antibody‐dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide

MDX‐1097 is an antibody specific for a unique B cell antigen called kappa myeloma antigen (KMA) that consists of cell membrane‐associated free kappa light chain (κFLC). KMA was detected on kappa human multiple myeloma cell lines (κHMCLs), on plasma cells (PCs) from kappa multiple myeloma (κMM) patients and on κPC dyscrasia tissue cryosections. In primary κMM samples, KMA was present on CD38+ cells that were CD138 and CD45 positive and/or negative. MDX‐1097 exhibited a higher affinity for KMA compared to κFLC and the latter did not abrogate binding to KMA. MDX‐1097‐mediated antibody‐dependent cellular cytotoxicity (ADCC) and in vitro exposure of target cells to the immunomodulatory drug lenalidomide resulted in increased KMA expression and ADCC. Also, in vitro exposure of peripheral blood mononuclear cells (PBMCs) to lenalidomide enhanced MDX‐1097‐mediated ADCC. PBMCs obtained from myeloma patients after lenalidomide therapy elicited significantly higher levels of MDX‐1097‐mediated ADCC than cells obtained prior to lenalidomide treatment. These data establish KMA as a relevant cell surface antigen on MM cells that can be targeted by MDX‐1097. The ADCC‐inducing capacity of MDX‐1097 and its potentiation by lenalidomide provide a powerful rationale for clinical evaluation of MDX‐1097 alone and in combination with lenalidomide.     

Ratio of hepatic arterial flow to recipient body weight predicts biliary complications after deceased donor liver transplantation

ObjectivesAdequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation.MethodsA retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg (n = 884) and ≥5 ml/min/kg (n = 1800).ResultsPatients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001).ConclusionsA ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications.