Clinical, Radiographic, and Patient-Reported Outcomes of First Metatarsophalangeal Interposition Arthrodesis Using Porous Titanium Wedges.

BACKGROUND: First metatarsophalangeal (MTP) arthrodesis is a common surgical procedure for addressing hallux MTP pathology. In the setting of revision procedures with significant bone loss, porous titanium wedges may provide an alternative to structural bone autograft or allograft. OBJECTIVE: The purpose of this study is to report the clinical and radiographic outcomes achieved in first MTP interposition arthrodesis using porous titanium wedges. METHODS: A retrospective analysis of 9 patients with a mean age 65.4 years (45-82 years) who underwent first MTP interposition arthrodesis with the use of porous titanium wedges from February 2014 to September 2017 was performed. Outcomes were assessed using both plain-film radiographs and computed tomography (CT) scans, as well as patient-reported outcome measures, including Foot and Ankle Ability Measure (FAAM) (Sports and Activities of Daily Living), pain Visual Analogue Scale (VAS), and 36-Item Short Form Survey (SF-36). Average follow-up time was 34.2 months (14-72 months). RESULTS: At final follow-up, the average FAAM score was 91.1 ± 14.7 (75.1 ± 5.3 FAAM Activities of Daily Living; 17.9 ± 9.9 FAAM Sports). Average pain VAS score was 1.9 ± 1.7. Postoperative computed tomography (CT) imaging was obtained for 5 patients, all of which demonstrated good bony apposition or osseous integration of the wedge. Four patients underwent subsequent surgical procedures, including 3 isolated dorsal fixation revisions, and 1 complete MTP arthrodesis revision. CONCLUSION: To our knowledge, this study represents the first reported clinical and radiographic outcomes in patients undergoing first MTP interposition arthrodesis with use of porous titanium wedges. While we found this technique to be a viable alternative to bone grafting for this difficult problem, further research should focus on comparative data with other commonly performed operative techniques. LEVEL OF EVIDENCE: Level IV: Case series.

The Course of Tarsal Tunnel Syndrome after Ultrasound-Guided Injections.

BACKGROUND: Local ultrasound (US)-guided injections of anesthetics with corticosteroids are commonly performed for the conservative treatment of tarsal tunnel syndrome (TTS). OBJECTIVE: This retrospective study aimed to investigate the outcomes of TTS after US-guided injections. METHODS: The study included patients who were diagnosed with TTS and received US-guided injections as part of their initial treatment. The pain levels were noted on a scale between zero and ten before and after each injection. The patients were divided into non-surgical and surgical groups. The nonsurgical group included patients who had received US-guided injections and did not proceed to surgical treatment, and the surgical group included those who received US-guided injections and ultimately underwent tarsal tunnel release (TTR). The two groups were compared in terms of age, post-injection follow-up time, and the amount of pain reduction immediately after injection (ΔPN). In the surgical group, outcomes of surgical treatment were also assessed. RESULTS: A total of 218 patients were diagnosed with TTS and received US-guided injections. After the injections, 169 patients (77.5%) did not go on to TTR (nonsurgical group) and 49 patients (22.5%) underwent TTR (surgical group). The average ages for the nonsurgical and surgical groups were 53.8 and 48.9 years (P = 0.03). The average time between the injection and final follow-up for the nonsurgical group was 339 days. The average time between the injection and TTR for the surgical group was 145 days. There were no differences in pain relief after the injections between the nonsurgical and surgical groups (mean ΔPN: 3.6 and 3.8, respectively). The average post-surgical follow-up time was 117 days. At final follow-up, 41 patients (84%) in the surgical group had complete resolution of pain and neurological symptoms. CONCLUSION: US-guided injection can be an effective conservative treatment option for patients with TTS. Younger patients may be more likely to proceed to TTR. Level of Evidence: Level III.

Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents.

Copper (Cu) plays a pivotal role in cancer progression by acting as a co-factor that regulates the activity of many enzymes and structural proteins in cancer cells. Therefore, Cu-based complexes have been investigated as novel anticancer metallodrugs and are considered as a complementary strategy for currently used platinum agents with undesirable general toxicity. Due to the high failure rate and increased cost of new drugs, there is a global drive towards the repositioning of known drugs for cancer treatment in recent years. Disulfiram (DSF) is a first-line antialcoholism drug used in clinics for more than 65 yr. In combination with Cu, it has shown great potential as an anticancer drug by targeting a wide range of cancers. The reaction between DSF and Cu ions forms a copper diethyldithiocarbamate complex (Cu(DDC)2 also known as CuET) which is the active, potent anticancer ingredient through inhibition of NF-κB and ubiquitin-proteasome system as well as alteration of the intracellular reactive oxygen species (ROS). Importantly, DSF/Cu inhibits several molecular targets related to drug resistance, stemness, angiogenesis and metastasis and is thus considered as a novel strategy for overcoming tumour recurrence and relapse in patients. Despite its excellent anticancer efficacy, DSF has proven unsuccessful in several cancer clinical trials. This is likely due to the poor stability, rapid metabolism and/or short plasma half-life of the currently used oral version of DSF and the inability to form Cu(DDC)2 at relevant concentrations in tumour tissues. Here, we summarize the scientific rationale, molecular targets, and mechanisms of action of DSF/Cu in cancer cells and the outcomes of oral DSF ± Cu in cancer clinical trials. We will focus on the novel insights on harnessing the immune system and hypoxic microenvironment using DSF/Cu complex and discuss the emerging delivery strategies that can overcome the shortcomings of DSF-based anticancer therapies and provide opportunities for translation of DSF/Cu or its Cu(DDC)2 complex into cancer therapeutics.

The holding temperature of blood during a delay to processing can affect serum and plasma protein measurements.

Accurate blood-borne biomarkers are sought for diagnosis, prognosis and treatment stratification. Consistent handling of blood is essential for meaningful data interpretation, however, delays during processing are occasionally unavoidable. We investigated the effects of immediately placing blood samples on ice versus room temperature for 1 h (reference protocol), and holding samples on ice versus room temperature during a 3 h delay to processing. Using Luminex multi-plex assays to assess cytokines (n = 29) and diabetes-associated proteins (n = 15) in healthy subjects, we observed that placing blood samples immediately on ice decreased the serum levels of several cytokines, including PAI-1, MIP1-ß, IL-9, RANTES and IL-8. During a delay to processing, some analytes, e.g. leptin and insulin, showed little change in serum or plasma values. However, for approximately half of the analytes studied, a delay, regardless of the holding temperature, altered the measured levels compared to the reference protocol. Effects differed between serum and plasma and for some analytes the direction of change in level varied across individuals. The optimal holding temperature for samples during a delay was analyte-specific. In conclusion, deviations from protocol can lead to significant changes in blood analyte levels. Where possible, protocols for blood handling should be pre-determined in an analyte-specific manner.

The Selective Progesterone Receptor Modulator Ulipristal Acetate Inhibits the Activity of the Glucocorticoid Receptor.

CONTEXT: The selective progesterone modulator ulipristal acetate (ulipristal) offers a much-needed therapeutic option for the clinical management of uterine fibroids. Although ulipristal initially passed safety evaluations in Europe, postmarketing analysis identified cases of hepatic injury and failure, leading to restrictions on the long-term use of ulipristal. One of the factors potentially contributing to significant side effects with the selective progesterone modulators is cross-reactivity with other steroid receptors. OBJECTIVE: To determine whether ulipristal can alter the activity of the endogenous glucocorticoid receptor (GR) in relevant cell types. DESIGN: Immortalized human uterine fibroid cells (UtLM) and hepatocytes (HepG2) were treated with the synthetic glucocorticoid dexamethasone and/or ulipristal. Primary uterine fibroid tissue was isolated from patients undergoing elective gynecological surgery and treated ex vivo with dexamethasone and/or ulipristal. In vivo ulipristal exposure was performed in C57Bl/6 mice to measure the effect on basal gene expression in target tissues throughout the body. RESULTS: Dexamethasone induced the expression of established glucocorticoid-target genes period 1 (PER1), FK506 binding protein 51 (FKBP5), and glucocorticoid-induced leucine zipper (GILZ) in UtLM and HepG2 cells, whereas cotreatment with ulipristal blocked the transcriptional response to glucocorticoids in a dose-dependent manner. Ulipristal inhibited glucocorticoid-mediated phosphorylation, nuclear translocation, and DNA interactions of GR. Glucocorticoid stimulation of PER1, FKBP5, and GILZ was abolished by cotreatment with ulipristal in primary uterine fibroid tissue. The expression of glucocorticoid-responsive genes was decreased in the lung, liver, and uterus of mice exposed to 2 mg/kg ulipristal. Interestingly, transcript levels of Fkbp5 and Gilz were increased in the hippocampus and pituitary. CONCLUSIONS: These studies demonstrate that ulipristal inhibits endogenous glucocorticoid signaling in human fibroid and liver cells, which is an important consideration for its use as a long-term therapeutic agent.

Multiple equilibrium states in a micro-vascular network.

We use a simple model of micro-vascular blood flow to explore conditions that give rise to multiple equilibrium states in a three-node micro-vascular network. The model accounts for two primary rheological effects: the Fåhraeus-Lindqvist effect, which describes the apparent viscosity of blood in a vessel, and the plasma skimming effect, which governs the separation of red blood cells at diverging nodes. We show that multiple equilibrium states are possible, and we use our analytical and computational tools to design an experiment for validation.

Transmission of high-data-rate optical signals through a micrometer-scale silicon ring resonator.

The effects of a micrometer-scale silicon ring resonator with a FWHM of 0.078 nm (9.6 GHz) on a nonreturn to zero amplitude-modulated optical signal with a modulation rate of 10 Gbps are experimentally investigated. By transmitting the optical signal through the device, significant spectral distortion and side band attenuation is introduced, as characterized by amplitude Bode plots, and a power penalty of 0.8 dB is observed. Carrier wavelengths within the transmission resonance, but detuned from the center wavelength, are investigated as well. Numerical simulations further support the experimental results.

On cascades of resonators for high-bandwidth integrated optical interconnection networks.

The power penalty characteristics of high-speed optical signals transmitted through a variety of filters based on multiple microring resonator devices are analyzed by numerical simulation. The technique used here has been verified with single-ring experimental measurements. Butterworth and Chebyshev filters are investigated, as are serial cascades of resonant devices. Although the power penalty is generally not prohibitive, it is a parameter which cannot be ignored for the design of complex high-bandwidth photonic interconnect systems that utilize microring resonators as filters and switches.