Barriers to Exercise in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: A Patient Survey.

Background: Although adequate physical activity is an essential component of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD), the majority of people with MASLD do not engage in regular exercise and lead sedentary lifestyles. We aimed to identify perceived barriers to exercise and to examine awareness about the role of exercise in the treatment of MASLD. Methods: Individuals aged 18 years and above were recruited from a hepatology outpatient clinic. MASLD severity was assessed using controlled attenuation parameter (CAP) and transient elastography (TE) determined liver stiffness measurement (LSM) for the severity of hepatic steatosis and fibrosis, respectively. An online questionnaire was administered to record self-reported exercise patterns, barriers to exercise, and knowledge regarding effectiveness of different types of exercise for MASLD. Results: Eighty-one participants (57% female) with a mean age of 55.3 ± 13.4 years and a mean body mass index (BMI) of 33.8 ± 6.4 answered the questionnaire. The mean CAP score was 335.7 ± 47.8 dB/m, and the median LSM was 12.45 kPa. While most patients (83%) considered MASLD to be a serious health concern, 73% did not achieve the recommended exercise levels of ≥ 150 min of moderate-intensity physical activity per week, and 54% were unsure about the role of exercise in the treatment of MASLD. Commonly reported barriers to exercise included physical and mental health issues (57%), lack of time (43%), lack of enjoyment in exercising (31%), fatigue caused by exercise (24%), and others (25%). Conclusions: Most participants with MASLD were unaware of the role of exercise as a potential treatment option and were not achieving recommended exercise levels. Inadequate time, physical and mental health problems, lack of enjoyment in exercise, and fatigue were major barriers.

Cancer stem cell metabolism: a potential target for cancer therapy.

Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to dysregulation in glucose metabolism, fatty acid synthesis, and glutaminolysis. To propagate their lethal effects and maintain survival, tumour cells alter their metabolic requirements to ensure optimal nutrient use for their survival, evasion from host immune attack, and proliferation. It is now evident that cancer cells metabolise glutamine to grow rapidly because it provides the metabolic stimulus for required energy and precursors for synthesis of proteins, lipids, and nucleic acids. It can also regulate the activities of some of the signalling pathways that control the proliferation of cancer cells.This review describes the key metabolic pathways required by CSCs to maintain a survival advantage and highlights how a combined approach of targeting cellular metabolism in conjunction with the use of chemotherapeutic drugs may provide a promising strategy to overcome therapeutic resistance and therefore aid in cancer therapy.

Persistent pain following lumbar disc replacement.

BACKGROUND: Pain patterns associated with the facet and sacroiliac joints following lumbar total disc replacement correlate with biomechanical modeling observations, such as load transfer to the posterior spinal elements in total disc replacement with an artificial disc. When conventional treatment options are exhausted, spinal cord stimulation (SCS) offers clinically favorable outcomes to treat intractable pain. OBJECTIVES: To contribute to the literature on neuroaugmentive techniques and on pain following disc replacement, and to highlight recent advances and forward-thinking concepts for nonsurgical intradiscal therapies. RESULTS: Three years of injection therapies and physical therapy did not significantly alleviate the patient's pain. A trial period of SCS rather than reoperation (fusion surgery) was elected. A constant-current multiple source SCS system was implanted. At 12-month follow-up for this system, the patient's pain had been reduced by more than 75%, and the patient reported improved quality of life, including a return of restful sleep. CONCLUSIONS: SCS is a viable technique to control pain associated with artificial disc implant.

Spinal cord stimulation to treat postthoracotomy neuralgia: non-small-cell lung cancer: a case report.

Surgery is the mainstay of therapy for resectable-type tumors associated with non-small-cell lung cancer. Today, thoracotomy and video-assisted thoracotomy are surgical options. The prevalence of chronic pain with neuropathic symptoms is relatively high after thoracotomy. Spinal cord stimulation to treat such pain has received limited attention in the literature. The aim of this article is to report on the use of spinal cord stimulation in a single case of neuralgia after thoracotomy with lobectomy to treat non-small-cell lung cancer. At 24 months after implantation of the spinal cord stimulation system, the patient reported >75% pain relief, an overall improvement in quality of life-described as less pain with breathing, and improved functional ability pertaining to arm movements-and improved sleep patterns. This detailed case presentation provides a qualitatively weighted investigation into spinal cord stimulation for postthoracotomy neuralgia against the backdrop of oncologic care. Further investigations relying on quantitative assessment tools are necessary to further explore this form of therapy in this patient population. In the single case reported here, the use of spinal cord stimulation suppressed intractable pain targeted at the T6 and T7 dermatomes of the chest wall in the manifestation of postthoracotomy neuralgia.

Feasibility of combined epicranial temporal and occipital neurostimulation: treatment of a challenging case of headache.

BACKGROUND: Evidence of a paradigm shift towards epicranial neurostimulation treatment techniques aimed at the site of headache pain is beginning to populate the literature. This is most apparent by 2 recently published reports describing alternative approaches to peripheral nerve stimulation techniques for refractory migraine, including hemiplegic migraine. OBJECTIVES: To contribute to the emerging literature on epicranial-based neuroaugmentative approaches which target site-specific areas of distinct, but relatively diffuse, headache pain. Specifically, we describe the feasibility of a novel neurostimulation technique: occipital nerve stimulation, combined with bilateral subcutaneous electrical stimulation over the temporal region, to treat a patient dually diagnosed with "complicated migraine" and occipital neuralgia. Integral to this report, key stimulation programming data are also presented to better distinguish the role of this form of therapy in migraine, or other headache forms, from both the clinical and biomedical perspectives. METHODS: Case presentation with literature review. RESULTS: At 24-month follow-up, headache onset had been reduced by more than 50%, including cessation of neurologic deficits that accompanied the patient's migraines. No complications or adverse side effects are reported. The programming data reported here supports a proposed mechanism of action concerning stimulation of the auriculotemporal nerve distribution/anterior temporal region for management of refractory pain in migraine. LIMITATIONS: Case presentation provides only initial assessment of treatment safety, not conclusive evidence of treatment effectiveness. Future studies which consider "follow-the-path" epicranial approaches to peripheral nerve stimulation techniques for refractory headache pain are needed to better quantify outcomes and mechanisms of action. CONCLUSIONS: In the single case reported here, the feasibility of a novel neurostimulation technique (occipital nerve stimulation/bilateral subcutaneous temporal region stimulation) to treat headache is presented. At the 24-month follow-up, no complications (such as loss of coverage due to lead displacement or lead fracture or erosion) or adverse side effects were reported. Finally, inclusion of fundamental programming data in reports on neuroaugmentative approaches to headache care will complement initiatives in research from the clinical and biomedical communities involved in this field.

Radiation exposure in percutaneous spinal cord stimulation mapping: a preliminary report.

BACKGROUND: The utilization of spinal cord stimulation (SCS) to treat intractable pain has increased substantially in recent years. Integral to this therapy, the fluoroscope assists with requisite mapping protocols during trialing procedures to identify topographical dermatomal representations of spinal segments, and its use demands measurements of radiation exposure. However, such data is not found in the literature. PURPOSE: The aim of this study was to report on radiation exposure during percutaneous SCS trialing procedures. DESIGN: An observational study. SETTING: A non-university out-patient Interventional Pain Management practice in the United States. METHODS: Fluoroscopy time from 110 SCS trialing procedures performed in a non-university, outpatient setting was studied retrospectively. Summary statistics were reported for all procedures collectively, as well as for lead arrangement and location. The interventional spine team carried out all procedural cases with the same mobile C-arm fluoroscopy system. Incident air kerma was evaluated by simplistic modeling. RESULTS: Mean total fluoroscopy time was 133.4 s with a standard deviation of 84.8 s, and the mean percentage of time allocated to pulsed fluoroscopy was 31.9%. Fluoroscopy time for the most common lead arrangement/location, neural canal dual leads/low-thoracic (n=87), ranged from 28.5 s to 387.4 s. Incident air kerma was 1.8-43.7 mGy. LIMITATIONS: A preliminary report with a sample size of 110. CONCLUSION: Various lead placement options are available to the spinal interventionalist to treat pain with SCS. Our data set provides first steps to obtain benchmark reference estimates on fluoroscopy times and radiation exposure during SCS trialing procedures/spinal segment mapping. Fluoroscopy times for such interventions may be considerable when compared to more commonly performed pain medicine procedures; however, skin injury is improbable.

The use of self-interaction chromatography in stable formulation and crystallization of proteins.

This paper reviews the basic principles of the recently developed self-interaction chromatography (SIC) technique with regard to protein solution stability and protein crystallization. It gives experimental protocols for both normal-scale and micro-scale SIC experiments and reviews recent developments and current applications of this novel technique in the biopharmaceutical area. This paper aims to be a benchmark in the further proliferation of this highly effective and fast technology for the rational design of stable aqueous formulations of therapeutic proteins and the determination of solution conditions favoring protein crystallization.

Protein self-interaction chromatography on a microchip.

This paper presents the development of a novel miniaturized experimental procedure for the measurement of protein-protein interactions through Self-Interaction Chromatography (SIC) on a microchip, without the use of chromatographic resins. SIC was recently demonstrated to be a relatively easy method to obtain quantitative thermodynamic information about protein-protein interactions, like the osmotic second virial coefficient B(22), which relates to protein phase behavior including protein crystallization. This successful miniaturization to microchip level of a measurement device for protein self-interaction data is a first key step to a complete microfluidic screening platform for the rational design of protein crystallizations, using substantially less expensive protein and experimentation time.

Spinal cord stimulation for pain management in ankylosing spondylitis: a case report.

Introduction. The classic presentation of ankylosing spondylitis not only impairs spinal mobility but also imposes functional limitations, and fatigue is common. Methods. We report here the outcomes of spinal cord stimulation (SCS) in the case of a 47-year-old man with low back and hip/thigh pain due to ankylosing spondylitis, with failed responses to conservative therapies aimed at treating this pain. Results. Spinal cord stimulation induced axial low back and bilateral hip paresthesia resulting in complete subjective pain relief, cessation of analgesic medications, reduced fatigue, and improved sleep patterns. SCS also resulted in improved socioeconomic outcomes with a return to work. Conclusions. With further research in patients with broader presentations of the disease, SCS may prove efficacious in suppressing intractable pain symptoms due to ankylosing spondylitis, thus improving quality of life measures.

Surviving severe acute respiratory distress syndrome: utility of open-lung biopsy and large doses of dexamethasone.

The etiology of acute respiratory distress syndrome is wide and mortality is extremely high. We describe a patient dying from severe acute respiratory distress syndrome who had a tremendous recovery after receiving dexamethasone (1 g daily). This patient required positive end-expiratory pressure (up to 18 mm/Hg) and fractional inspiratory oxygen (up to 100%). Thirty-six hours after the large dose of corticosteroids, the respiratory mechanics and oxygenation were acceptable for extubation. Acute respiratory distress syndrome was proven and other etiologies of respiratory failure were ruled out by a bedside open-lung biopsy. The biopsy proven acute respiratory distress syndrome dramatically resolved with this salvage therapy. High-dose usage of corticosteroids for acute respiratory distress syndrome has tremendous potential.

The incidence of infectious complications of central venous catheters at the subclavian, internal jugular, and femoral sites in an intensive care unit population.

OBJECTIVE: The objective was to assess the risk of central venous catheter infection with respect to the site of insertion in an intensive care unit population. The subclavian, internal jugular, and femoral sites were studied. DESIGN: An epidemiologic, prospective, observational study. SETTING: The setting is a well-functioning intensive care unit under a unified critical care medicine division in a university teaching hospital. Critical care medicine attendings and fellows covered on site 17 and 24 hrs per day, respectively. PATIENTS: Patients were critically ill. All patients were triaged into the intensive care unit by on-site critical care medicine fellows. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In an intensive care unit population, we prospectively studied the incidence of central venous catheter infection and colonization at the subclavian, internal jugular, and femoral sites. The optimal insertion site for each individual patient was selected by experienced intensive care physicians (critical care medicine attendings and fellows). All of the operators were proficient in inserting catheters at all three sites. Confounding factors were eliminated; there were a limited number of experienced operators inserting the catheters, a uniform protocol stressing strict sterile insertion was enforced, and standardized continuous catheter care was provided by dedicated intensive care nurses proficient in all aspects of central venous catheter care. Two groups of patients were analyzed. Group 1 was patients with one catheter at one site, and group 2 was patients with catheters at multiple sites. Group 1 was the primary analysis, whereas group 2 was supporting.A total of 831 central venous catheters and 4,735 catheter days in 657 patients were studied. The incidence of catheter infection (4.01/1,000 catheter days, 2.29% catheters) and colonization (5.07/1,000 catheter days, 2.89% catheters) was low overall. In group 1, the incidence of infection was subclavian: 0.881 infections/1,000 catheter days (0.45%), internal jugular: 0/1,000 (0%), and femoral: 2.98/1,000 (1.44%; p = .2635). The incidence of colonization was subclavian: 0.881 colonization/1,000 catheter days (0.45%), internal jugular: 2.00/1,000 (1.05%), and femoral: 5.96/1,000 (2.88%, p = .1338). There was no statistically significant difference in the incidence of infection and colonization or duration of catheters (p = .8907) among the insertion sites. In group 2, there was also no statistically significant difference in the incidence of infection and colonization among the three insertion sites. CONCLUSION: In an intensive care unit population, the incidence of central venous catheter infection and colonization is low overall and, clinically and statistically, is not different at all three sites when optimal insertion sites are selected, experienced operators insert the catheters, strict sterile technique is present, and trained intensive care unit nursing staff perform catheter care.

Incidence of intravascular uptake during fluoroscopically guided lumbar disc injections: a prospective observational study.

BACKGROUND: Although there are many in vivo studies evaluating lumbar disc injections, no studies have described the occurrence of intravascular uptake of contrast on discography. This phenomenon, however, has been well documented for other fluoroscopically-guided, contrast-enhanced spinal injections. OBJECTIVES: To document the phenomenon and incidence of intravascular uptake during fluoroscopically-guided, contrast-enhanced lumbar disc injections. DESIGN: A prospective, observational, community-based study. METHODS: The incidence of fluoroscopically-confirmed intravascular uptake of contrast material was documented in 160 patients representing a subset of individuals presenting to a small private community hospital for evaluation and treatment of lower back pain. These patients underwent fluoroscopically-guided lumbar disc injections for therapeutic and/or diagnostic purposes. RESULTS: A total of 280 discs from L1-2 to L5-S1 were studied. The degree of disc degeneration of the evaluated discs was scored using the Adams' scoring criteria for intervertebral disc degeneration. The incidence of intravascular uptake as well as any correlation between stage of disc degeneration and intravascular uptake was statistically evaluated. A total of 40 out of 280 discs (14.3%) demonstrated intravascular uptake. Detection of intravascular uptake usually required real-time fluoroscopy. There was no statistical correlation between the degree of disc degeneration and the incidence of intravascular uptake. No disc infections or other adverse sequelae occurred. CONCLUSION: This is the first study, to our knowledge, that addresses the incidence of intravascular uptake during lumbar disc injections in patients with low back pain. The presence of intravascular uptake may have implications both clinically and diagnostically in regards to interpretation of lumbar discography and adverse events related to loss of injected medications into the vascular system.

Liver failure, transplantation, and critical care.

The management of patients for end-stage liver disease in the ICU mandates a multidisciplinary approach and intense monitoring. Orthotopic liver transplantation still remains the only definitive therapy. Given the increasing disparity between the number of potential recipients and available cadaver organs, the current challenge is to optimize outcome with the limited resource. In recent years, considerable progress has been made in developing specific and supportive medical measures. Future research should target a better understanding of mechanisms responsible for liver cell death and liver regeneration, as well as developments in xenotransplantation, hepatocyte transplantation, and liver-directed gene therapy.

Length-normalized pulse photoplethysmography: a noninvasive method to measure blood hemoglobin.

To determine whether blood hemoglobin concentration ([Hb]) could be measured noninvasively as the ratio of pulsatile changes in attenuation (absorbance plus scatter) of light (D) across a body part to changes in light path length (l), we measured transmission of near-infrared light (905 +/- 10 nm) through a finger, using a modified pulse oximeter, and simultaneously monitored fingertip diameter, using a sonomicrometer. In 25 subjects with [Hb] ranging from 3.1 to 18.2 gm/dl, and with normal oxygenation, average D/l ratio over 30-60 s correlated strongly with [Hb] measured by Coulter counter (r = 0.84, p << 0.001), though with considerable scatter, with absolute value of differences averaging 17% of the mean. Using 12 gm/dl and 0.75 mm(-1) as the lower limits of normal for [Hb] and D/l, respectively, two of nine normals had low (D/l) (78% specificity), and only one of 16 anemic subjects had borderline normal (D/l) (94%-100% sensitivity). The positive predictive value of a low (D/l) was 88% and the negative predictive value was 87.5%. With further development, this technique may reduce the need for phlebotomy, thereby reducing risks and costs and improving the experience of being a patient.