Simulation of the Interaction Between Muscle Fiber Conduction Velocity and Instantaneous Firing Rate

In this study, the relationships between the early and late afterpotentials and velocity and amplitude recovery functions (VRF and ARF) in skeletal muscle were examined using model simulation. A mathematical model of the muscle fiber action potential, that incorporated a tubular slow potassium conductance, was developed and used to simulate muscle fiber action potentials at a range of interpulse intervals. The slow potassium conductance produced an afterhyperpolarization which resulted in supernormal action potential conduction velocity and amplitude for interpulse intervals >7 ms. Increasing the number of conditioning stimuli caused a further increase in conduction velocity and amplitude, and an additional phase of supernormality, with a peak at approximately 100 ms. Positive correlations between instantaneous firing rate and both conduction velocity and amplitude were also observed during simulation of repetitive stimulation of the muscle fiber. The relationships were eliminated when the slow potassium conductance channel was removed from the model. The results suggest that an afterhyperpolarization, possibly due to a slow tubular potassium conductance, could cause the VRF and ARF observed in muscle. They additionally suggest that the positive correlations between instantaneous firing rate, conduction velocity, and amplitude are directly related to the VRF and ARF.     

Postoperative thyroid hormone supplementation rates following thyroid lobectomy

BackgroundThyroid lobectomy is performed for symptomatic benign nodules, indeterminate nodules, or low-risk well differentiated thyroid cancer. We aimed to determine factors associated with thyroid stimulating hormone over goal (TH) following lobectomy.MethodsWe performed a retrospective single-institution cohort study of patients undergoing thyroid lobectomy from January 2016 to December 2017. TH was defined as need for thyroid hormone in accordance with guidelines. Univariate and multivariate logistic regression analysis was performed.ResultsOne hundred patients were included and 47% developed.TH73% of those with cancer, 38% with benign pathology (p = 0.002). Patients with TH were more likely to have thyroiditis 26% versus 3.8% (p = 0.002); higher preoperativeTSHmean 1.88mIU/L (SD 1.17) versus 1.16mIU/L (SD 0.77) (p = 0.0002), and smaller remnant thyroid lobe adjusted for body surface area 2.99ml/m2 versus 3.72ml/m2 (p = 0.003).ConclusionsAfter thyroid lobectomy, TH is associated with preoperative TSH level, thyroiditis, remnant thyroid volume, and malignancy. The majority of patients with final pathology of carcinoma will require thyroid hormone supplementation to achieve TSH goal.     

Effects of Anesthetic Agents on Focal Adhesion Kinase (pp125FAK) Tyrosine Phosphorylation in Rat Hippocampal Slices

Background: Tyrosine protein kinase proteins exert a prominent control on signaling pathways and may couple rapid events, such as action potential and neurotransmitter release, to long-lasting changes in synaptic strength and survival. Whether anesthetics modulate tyrosine kinase activity remains unknown. The aim of the current study was therefore to examine the effects of intravenous and volatile anesthetics on the phosphorylation of focal adhesion kinase (pp125FAK), a functionally important nonreceptor tyrosine kinase, in the rat hippocampus.

Methods: Phosphorylation of pp125FAK was examined in hippocampal slices by immunoblotting with both antiphosphotyrosine and specific anti-pp125FAK antibodies. Experiments were performed in the absence (control) or presence of various concentrations of pharmacologic or anesthetic agents or both.

Results: Clinically relevant concentrations of thiopental, propofol, etomidate, isoflurane, sevoflurane, and desflurane induced a concentration-related increase in tyrosine phosphorylation. In contrast, ketamine (up to 100 [mu]m) and the nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane, 25 [mu]m) did not significantly affect pp125FAK phosphorylation. The anesthetic-induced increase in pp125FAK phosphorylation was blocked by GF 109203X, RO 318220, and chelerythrin (100 [mu]m), three structurally distinct inhibitors of protein kinase C and U 73122 (50 [mu]m), an inhibitor of phospholipase C. The propofol- and isoflurane-induced increase in pp125FAK phosphorylation was reversible and showed nonadditivity of effects with phorbol 12-myristate 13-acetate (an activator of protein kinase C, 0.1 [mu]m). In contrast, ketamine (up to 100 [mu]m), MK801 (10 [mu]m, an N-methyl-d-aspartate receptor antagonist), bicuculline (10 [mu]m, a [gamma]-aminobutyric acid type A receptor antagonist), and dantrolene (30 [mu]m, an inhibitor of the ryanodine receptor) were ineffective in blocking anesthetic-induced activation of tyrosine phosphorylation.     

Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Chronic idiopathic orofacial pain. A long‐term follow‐up study

Patients suffering facial pain that does not fit with the traditional diagnostic criteria and which does not respond to dental treatment constitute a clinical problem. These patients lack a proper diagnosis and are frequently exposed to excessive and inadequate invasive treatment. The aim of this investigation was to study the long‐term development of pain and the result of treatment in a cohort of patients suffering chronic idiopathic facial pain. The 74 patients referred to the Facial Pain Diagnostic Group at the Karolinska Institute School of Dentistry between 1981 and 1992 were invited to take part in a follow‐up study. As 16 subjects were unwilling or unable to take part in the study and 13 had died, the remaining 45 were interviewed either in accordance with a standard protocol or by filling out a questionnaire mailed to them. The interview revealed that 10 were free of orofacial pain, but only 2 were totally free of pain. Over the 9–19 years' follow‐up period the relationship between facial pain and pain in the rest of the body had changed substantially. Of 14 patients and more than 100 extractions, permanent pain relief was felt by only 3 patients. It is concluded that a diagnosis was given in only 2 cases. The distribution of the pain has changed dramatically. The low success rate of invasive treatments suggests that such therapeutic methods are to be considered contraindicated in patients suffering from idiopathic orofacial pain.     

Liver transplantation and waitlist mortality for HCC and non‐HCC candidates following the 2015 HCC exception policy change

Historically, exception points for hepatocellular carcinoma (HCC) led to higher transplant rates and lower waitlist mortality for HCC candidates compared to non‐HCC candidates. As of October 2015, HCC candidates must wait 6 months after initial application to obtain exception points; the impact of this policy remains unstudied. Using 2013‐2017 SRTR data, we identified 39  350 adult, first‐time, active waitlist candidates and compared deceased donor liver transplant (DDLT) rates and waitlist mortality/dropout for HCC versus non‐HCC candidates before (October 8, 2013‐October 7, 2015, prepolicy) and after (October 8, 2015‐October 7, 2017, postpolicy) the policy change using Cox and competing risks regression, respectively. Compared to non‐HCC candidates with the same calculated MELD, HCC candidates had a 3.6‐fold higher rate of DDLT prepolicy (aHR = _3.49 3.69 _3.89) and a 2.2‐fold higher rate of DDLT postpolicy (aHR = _2.09 2.21 _2.34). Compared to non‐HCC candidates with the same allocation priority, HCC candidates had a 37% lower risk of waitlist mortality/dropout prepolicy (asHR = _0.54 0.63 _0.73) and a comparable risk of mortality/dropout postpolicy (asHR = _0.81 0.95 _1.11). Following the policy change, the DDLT advantage for HCC candidates remained, albeit dramatically attenuated, without any substantial increase in waitlist mortality/dropout. In the context of sickest‐first liver allocation, the revised policy seems to have established allocation equity for HCC and non‐HCC candidates.     

Living donor program crisis management plans: Current landscape and talking point recommendations

Although minimized by expert evaluation, operative technique, and postoperative care, the extremely low risk of perioperative mortality following living kidney or liver donation will never be eliminated. Furthermore, anticipation of poor donor outcome may simultaneously be a source of anxiety for physicians and programs and also be a circumstance for which they are unprepared. We conducted a national survey of US transplant surgeons to understand experiences with and systemic preparedness for the event of a living donor death. Respondents represented 87 unique transplant programs (71 kidney and 16 liver donor programs). Perioperative deaths were rare, as expected. Although most respondents (N = 57, 64% of total respondents; 88% of liver programs) reported being moderately to extremely concerned about a future living donor death at their institution, only 30 (33% of total program respondents) had a written plan available in the case of such an event; 63% of programs would find guidance and recommendations useful. To help address this gap, the American Society of Transplantation Live Donor Community of Practice (AST LDCOP) developed Living Donor Crisis Management Plan Talking Points suitable to guide crisis plan development at transplant programs.     

Distance traveled to undergo revision shoulder arthroplasty is impacted by patient demographics and exceeds that of primary shoulder arthroplasty

BackgroundPrevious research has highlighted disparities in access to and outcomes following shoulder arthroplasty. The purpose of this study is to compare travel distance for primary vs. revision surgery and to determine the relationships between travel distance to undergo revision shoulder arthroplasty and patient demographics and postoperative adverse outcomes. We hypothesized that older patients, those with increased medical comorbidities, and those with greater financial resources would travel farther for surgery.MethodsThe Healthcare Cost and Utilization Project, American Hospital Association, and UnitedStatesZipCodes.org Enterprise data sets were compiled to collect data on patient demographics, operation performed, and postoperative adverse outcomes. Population-weighted zip code centroid points of patients’ residences as well as hospital coordinates were used to approximate the distance traveled to undergo shoulder arthroplasty. Kruskal-Wallis tests and logistic regression analyses were used to analyze the relationship between travel distance and patients’ demographics and postoperative outcomes.ResultsPatients traveled farther to undergo revision shoulder arthroplasty than to undergo primary shoulder arthroplasty (P = .0001). Among patients who underwent revision operations, older age (P = .0001) and increased medical comorbidities (P = .003) were associated with decreased travel distance. White patients and those with commercial insurance traveled farther to receive care (P = .0001). There were no clinically significant associations between postoperative outcomes following revision surgery and travel distance.ConclusionPatients may travel farther to undergo revision surgery owing to patient preferences or because these complex operations are performed at fewer centers. Younger and healthier patients, white patients, and those with commercial insurance plans traveled farther to receive care. Future work is needed to determine the underlying causes of these disparities and whether it is patient preferences or systemic factors such as hospital density or access to high-quality health insurance that are influencing access to this specialized surgical care.