Tumor Lysis Syndrome in Patients With Hepatocellular Carcinoma: A Systematic Review of Published Case Reports.

Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. It is characterized by massive tumor cell death leading to metabolic derangements and multiple organ failure. It is a rare complication of hepatocellular carcinoma (HCC) with only a few cases have been reported in the literature to date. We collected and summarized published case reports of tumor lysis syndrome in patients with HCC. We also reported one additional case who developed TLS after sorafenib therapy and wrote a clinical vignette. A comprehensive and current search for relevant articles was conducted in Medline and EMbase through May 2018. A systematic review was performed following the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).  A total of 28 cases of TLS associated with HCC were enrolled in our review. The median age of included cases was 55.5 years with a male to female ratio of 25:3. The two most common attributed factors of TLS were transcatheter arterial chemoembolization (TACE) (12 cases, 42.9 %) and sorafenib (nine cases, 32.1%). Among enrolled cases, the diameter of the largest tumor was 12 cm. Regarding Barcelona Clinic Liver Cancer (BCLC) staging, seven cases were at least stage A (22.6%), 11 cases were at least stage B (35.5%), and 10 cases were at least stage C (32.3%). The median time of onset of TLS was three days. As for uric acid-lowering agents, nine cases (32.1%) used allopurinol and four cases (14.3%) used rasburicase. Ten cases (35.7%) did not specify the medication prescribed. The overall mortality rate of this cohort was 67.9%. Compared with patients developing TLS following TACE, patients who had TLS following sorafenib therapy had a later onset of TLS (two days versus seven days, p < 0.001) and a more advanced stage of HCC (p = 0.002). There was a trend toward increased mortality of patients in the sorafenib group in comparison with those in the TACE group (77.8% versus 41.7%, p = 0.18). The results of this current review suggest that TLS rarely occurs in HCC but carries significantly higher mortality compared to TLS occurring in hematologic malignancies. It may occur shortly after TACE or with a delayed onset following sorafenib therapy. Considering the kaleidoscope of novel therapies and diverse pathogenesis of HCC, it is crucial for clinicians to recognize the clinicolaboratory derangements suggestive of TLS and initiate appropriate management. The present review highlights the need for clinicians to consider TLS within differentials when caring for patients with HCC.

Use of high-flow nasal cannula in obese patients receiving colonoscopy under intravenous propofol sedation: A case series.

Intravenous sedation during colonoscopy has become the standard practice in the United States given its higher patient satisfaction and procedural quality. This practice is not free of side effects as a significant proportion of patients undergoing this procedure tend to have respiratory depression and desaturation events. Obesity, as it relates to higher levels of body mass index (BMI) has a positive correlation with the incidence of hypoxemia. During colonoscopy High flow nasal cannula (HFNC) may potentially improve oxygen performance in patients receiving colonoscopy under intravenous sedation. Here we present 3 cases of patients undergoing adjunctive oxygen therapy with HFNC during colonoscopy with intravenous sedation. We found patients to have lower number of desaturation events and were satisfied with their experience.

Hopping isn't always about the legs: forelimb muscle activity patterns during toad locomotion.

Although toads are not known for their jumping ability, they are excellent at landing, using their forelimbs to stabilize and decelerate the body as they transition between hops. Forelimb muscles must play important roles during this landing behavior, but to date our understanding of forelimb muscle function during jumping in anurans, particularly after takeoff, is quite limited. Here, we use simultaneous high-speed video and electromyography to characterize the timing and intensity of electrical activity patterns of six muscles that act at the shoulder or elbow joints in the cane toad, Bufo marinus. In particular, we aim to address the importance of these muscles with respect to various potential roles during hopping (e.g. contributing to propulsion during takeoff, resisting impact forces during landing). Five of the six recorded muscles exhibited their highest average intensities during the aerial phase of the hop, with the most intense activity present near forelimb touchdown. In contrast, no muscles exhibited high levels of activity in the initial phase of takeoff. We interpret these data to indicate that the forelimb muscles studied here are likely unimportant in augmenting force production during takeoff, but are critical for both mid-air forelimb positioning and resisting the forces associated with impact. The onset timing of elbow extensors seems to occur at a nearly fixed interval before impact, regardless of hop length, suggesting that these muscles are particularly tuned to resisting impact.

Do toads have a jump on how far they hop? Pre-landing activity timing and intensity in forelimb muscles of hopping Bufo marinus.

During jumping or falling in humans and various other mammals, limb muscles are activated before landing, and the intensity and timing of this pre-landing activity are scaled to the expected impact. In this study, we test whether similarly tuned anticipatory muscle activity is present in hopping cane toads. Toads use their forelimbs for landing, and we analysed pre-landing electromyographic (EMG) timing and intensity in relation to hop distance for the m. coracoradialis and m. anconeus, which act antagonistically at the elbow, and are presumably important in stabilizing the forelimb during landing. In most cases, a significant, positive relationship between hop distance and pre-landing EMG intensity was found. Moreover, pre-landing activation timing of m. anconeus was tightly linked to when the forelimbs touched down at landing. Thus, like mammals, toads appear to gauge the timing and magnitude of their impending impact and activate elbow muscles accordingly. To our knowledge these data represent the first demonstration of tuned pre-landing muscle recruitment in anurans and raise questions about how important the visual, vestibular and/or proprioceptive systems are in mediating this response.

Disruption of the axon initial segment cytoskeleton is a new mechanism for neuronal injury.

Many factors contribute to nervous system dysfunction and failure to regenerate after injury or disease. Here, we describe a previously unrecognized mechanism for nervous system injury. We show that neuronal injury causes rapid, irreversible, and preferential proteolysis of the axon initial segment (AIS) cytoskeleton independently of cell death or axon degeneration, leading to loss of both ion channel clusters and neuronal polarity. Furthermore, we show this is caused by proteolysis of the AIS cytoskeletal proteins ankyrinG and betaIV spectrin by the calcium-dependent cysteine protease calpain. Importantly, calpain inhibition is sufficient to preserve the molecular organization of the AIS both in vitro and in vivo. We conclude that loss of AIS ion channel clusters and neuronal polarity are important contributors to neuronal dysfunction after injury, and that strategies to facilitate recovery must preserve or repair the AIS cytoskeleton.