Acquired Idiopathic Stiffness After Contemporary Total Knee Arthroplasty: Incidence,Risk Factors,and Results Over 25 Years

BackgroundAcquired idiopathic stiffness (AIS) remains a common failure mode of contemporary total knee arthroplasties (TKAs). The present study investigated the incidence of AIS and manipulation under anesthesia (MUA) at a single institution over time, determined outcomes of MUAs, and identified risk factors associated with AIS and MUA.MethodsWe identified 9771 patients (12,735 knees) who underwent primary TKAs with cemented, modular metal-backed, posterior-stabilized implants from 2000 to 2016 using our institutional total joint registry. Mean age was 68 years, 57% were female, and mean body mass index was 33 kg/m². Demographic, surgical, and comorbidity data were investigated via univariate Cox proportional hazard models and fit to an adjusted multivariate model to access risk for AIS and MUA. Mean follow-up was 7 years.ResultsDuring the study period, 456 knees (3.6%) developed AIS and 336 knees (2.6%) underwent MUA. Range of motion (ROM) increased a mean of 34° after the MUA; however, ROM for patients treated with MUA was inferior to patients without AIS at final follow-up (102° vs 116°, P < .0001). Significant risk factors included younger age (HR 2.3, P < .001), increased tourniquet time (HR 1.01, P < .001), general anesthesia (HR 1.3, P = .007), and diabetes (HR 1.5, P = .001).ConclusionAcquired idiopathic stiffness has continued to have an important adverse impact on the outcomes of a subset of patients undergoing primary TKAs. When utilized, MUA improved mean ROM by 34°, but patients treated with MUA still had decreased ROM compared to patients without AIS. Importantly, we identified several significant risk factors associated with AIS and subsequent MUA.Level of EvidenceLevel III, retrospective comparative study.     

Sex differences in circadian timing systems: Implications for disease

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.     

Immediate, preferential prolactin release after discrete brain lesions in male rats

Adult male rats under pentobarbital anesthesia received electrolytic lesions in various sites within the preoptic-hypothalamic complex. Anodic direct current (500 μA, 30 s) was delivered through platinum electrodes. Blood samples were taken before and after the lesions, at 30-min intervals. LH, TSH, and prolactin were measured by RIA procedures in the same plasma sample. LH and TSH mean values did not show any significant increase after discrete lesions in several brain regions. On the contrary, prolactin increased significantly 30 min after a lesion in a region encompassing the dorsal preoptic area and bed nucleus of the stria terminalis. Lesions placed in other preoptic-hypothalamic regions (excluding the arcuate nucleus-median eminence region) did not result in prolactin release. A common effective region for the control of the preferential release of pituitary prolactin in the male rat seemed to include neural elements within the dorsal preoptic area and/or the bed nucleus of the stria terminalis which probably projected caudally and ventrally toward the arcuate nucleus-median eminence region. Whether this contribution is locally generated within the dorsal preoptic area-bed nucleus stria terminalis region and/or is mediated by incoming fibers remains to be established. Results are discussed in terms of possible local effects of the induced lesion, i.e., activation vs. suppression.     

Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem

Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway. Combinatorial photothermal effects and BRAF knockdown by FA-GNR-siBRAF effectively killed tumor cells through apoptosis, with enhanced efficiency than individual treatments. Therefore, the FA-GNR-siBRAF simultaneously induced BRAF gene silencing and photothermal effects which achieved synergistic efficacy in the treatment of melanoma, paving a new path for developing clinical treatment methods for melanoma.     

Single-cell and multiunit activity in freely moving rats after corticosterone administration

With the purpose of correlating possible electrophysiologic changes in the brain with the negative feedback effect of glucocorticoids on neuroendocrine functions, the effects of corticosterone on multiunit (MUA) and single-cell activity in freely moving rats were studied in the hypothalamus, amygdala, and midbrain reticular formation. The hormone changed the MUA in all regions studied causing mainly an increase in the rate of firing. In the hypothalamus there was a predominance in overall inhibition, when the sensory responsiveness to acoustic stimulation was compared before and after corticosterone administration. No such effect was observed in the amygdala and midbrain reticular formation. The hormonally induced changes in MUA in the hypothalamus were confirmed by analysis of single-cell activity in the freely moving rats which showed also changes in the pattern of firing, as demonstrated by autocorrelations. These findings in the hypothalamus are significant and may represent the electrophysiologic correlates of changes in corticotrophin releasing factor in this region.     

Excitability of auditory neurons in the dorsal and ventral cochlear nuclei of DBA2 and C57BL6 mice

Extracellular response properties were studied in neurons of the dorsal and ventral divisions of the cochlear nucleus (DCN and VCN, respectively) of $\text{DBA}\text{2}$ (DBA) and $\text{C57BL}\text{6}$ (C57) mice. Mice of the former inbred strain show susceptibility to audiogenic seizures and have severe high frequency hearing loss when young; mice of the latter strain do not. Whereas afterdischarges had been readily observed in the inferior colliculus of DBA mice in a previous study, they were never observed in the cochlear nucleus. The incidence of nonmonotonic intensity functions, the slopes of intensity functions, and the incidence of inhibition in response areas indicated that inhibition was diminished in the DCN of DBA mice. However, in the VCN, these response properties did not differ between the two strains. There appeared to be an “amplification” of excitability (i.e., attenuation of inhibition) from VCN to DCN to inferior colliculus in DBA mice.     

Effectiveness of Nonsurgical Interventions for Managing Adhesive Capsulitis in Patients With Diabetes: A Systematic Review

Objective

This systematic review evaluated the effectiveness of nonsurgical interventions for managing adhesive capsulitis (AC) in patients with diabetes on pain, function, and range of motion.

Effect of carbachol “push-pull” perfusion in the reticular formation on alumina cream-induced focal motor seizures in cats

The effect of carbachol perfusion in pontine (PRF) and mesencephalic reticular formations (MRF) on type B and C focal motor seizures induced by alumina cream was studied in a group of cats, in an attempt to reproduce (totally or partially) that observed under spontaneous sleep-waking states and state transitions. During carbachol perfusion in the PRF, there was a pure hypotonic response: significant decrease in mean tonic and phasic electromyographic multiple-unit activities (MUAs) with no changes in number of electroencephalogram (EEG) type B spikes and duration of type C paroxysmal discharges. This response lasted 60 to 80 min and was followed by a slow-wave-sleep-like response: further significant decrease in mean tonic and phasic electromyographic MUA and increase in number of EEG type B spikes and duration of type C paroxysmal discharges, which lasted until 180 min after carbachol perfusion. During carbachol perfusion in the MRF, there was an arousal-like response: significant increase in type B mean tonic and phasic electromyographic MUA and decrease in number of EEG spikes and prevention of occurrence of electroencephalogram-electromyogram patterns of type C seizures. This response lasted 60 to 80 min after perfusion and was followed by a paradoxical-sleep-like response: significant decrease in type B mean tonic and phasic electromyographic MUA and number of EEG spikes and delay of type C phasic electromyographic MUA and decreased duration of EEG paroxysmal discharges.     

Understanding rates,risk factors,and complications associated with manipulation under anesthesia after total knee arthroplasty (TKA): An analysis of 100,613 TKAs

BackgroundConsidering the growing adoption of technology-assisted total knee arthroplasties (TKA), previous database studies evaluating post-operative stiffness may be outdated. The present study aimed to: (1) evaluate the incidence of manipulation under anesthesia (MUA) after primary TKA; (2) determine independent risk factors for MUA; and (3) assess complications after MUA.MethodsPrimary TKAs, with at least 6-month follow-up, were identified from the Florida State Inpatient Database (January 2016–June 2018) and linked to outpatient records from the Florida State Ambulatory Surgery and Services Database. Multivariable regression analyses were performed to compare patient factors and complications (e.g., mechanical, non-mechanical, infectious) associated with MUA, while adjusting for baseline demographics, comorbidities, use of robotic- and computer-technologies, time to MUA (0–3, 3–12, or >12 months), and need for repeat MUA (one-time vs >1).ResultsThe MUA rate was 2.8% (2821 of 100,613). Being younger, a woman, Black or Hispanic; having private or self-pay insurance; and conventional TKA were associated with significantly higher odds of undergoing MUA. Higher rates of mechanical complications and acute posthemorrhagic anemia were observed in the MUA cohort. Time to MUA, repeat MUA, and baseline demographics were not associated with complication rates among the MUA cohort.ConclusionOverall, 1 in 36 patients underwent MUA after primary TKA. Several non-modifiable patient characteristics, such as Black or Hispanic race, female sex, and younger age were associated with an increased risk of MUA. However, technology-assisted TKA might help to decrease the risk of MUA.     

Effects of morphine on spontaneous multiple-unit activity: possible relation to mechanisms of analgesia and reward.

The effects of morphine (15 mg/kg) on multiple-unit activity in the awake rat were investigated at brain sites previously characterized by their ability to support stimulation-produced analgesia (SPA) and intracranial self-stimulation (ICSS). Of the SPA and SPA + ICSS sites, most of which were located in the periaqueductal gray matter, 91% showed increased multiple-unit activity after morphine administration (median increase = 80%). In contrast, only 50% of the ICSS-only sites, most of which were located in the lateral hypothalamus, and only 29% of sites supporting neither behavior showed this effect. All increases in multiple-unit activity were at least partly reversed by naloxone (1 mg/kg). Latencies to their onset and to analgesia measured by the tail-flick method were significantly correlated. A significant negative correlation was found between ICSS current thresholds and increases in multiple-unit activity after morphine at ICSS-only sites. These data lend further support to the suggestion that morphine exerts its analgesic action by activating an endogenous analgesic system and that the periaqueductal gray constitutes an important part of such a system. Furthermore, it is suggested that morphine's excitatory effect at self-stimulation loci may reflect its rewarding properties.