[Translated article] In vitro elution of local anaesthetics from PMMA bone cement.

BACKGROUND AND AIM: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterize the elution profile of two local anaesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. MATERIAL AND METHODS: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anaesthetic in the liquid was analyzed by liquid chromatography. RESULTS: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). CONCLUSIONS: Local anaesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anaesthetic blocks.

[Translated article] In vitro elution of local anaesthetics from PMMA bone cement.

BACKGROUND AND AIM: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterise the elution profile of two local anaesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. MATERIAL AND METHODS: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anaesthetic in the liquid was analysed by liquid chromatography. RESULTS: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). CONCLUSIONS: Local anaesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anaesthetic blocks.

In vitro elution of local anesthetics from PMMA bone cement. / Estudio in vitro de elución de anestésicos locales en cemento óseo de PMMA.

BACKGROUND AND AIM: Currently, we do not have a gold standard for pain management after total knee arthroplasty. We may use one of more drug delivery systems, none of which are ideal. An ideal depot delivery system would provide therapeutic, nontoxic, doses of drug at the surgical side, especially during 72h postoperatively. The bone cement used in arthroplasties has been used as a drug delivery system, especially antibiotics, since 1970. Based on this principle, we developed this study with the aim to characterize the elution profile of two local anesthetics (lidocaine hydrochloride and bupivacaine hydrochloride) from PMMA (polymethilmethacrylate) bone cement. MATERIAL AND METHODS: Palacos® R+G bone cement and lidocaine hydrochloride or bupivacaine hydrochloride specimens were obtained depending on the study group. These specimens were immersed in PBS (phosphate buffered saline) and removed from the solution at different set times. Subsequently, the concentration of local anesthetic in the liquid was analyzed by liquid chromatography. RESULTS: The percentage of lidocaine eluted from PMMA bone cement in this study was 9.74% of the total lidocaine content per specimen at 72h and 18.73% at 336h (14 days). In case of bupivacaine, the elution percentage was 2.71% of the total bupivacaine content per specimen at 72h and 2.70% at 336h (14 days). CONCLUSIONS: Local anesthetics elute in vitro from PMMA bone cement, reaching doses at 72h close to the doses used in anesthetic blocks.

[Translated article] Current situation of robotics in knee prosthetic surgery: A technology that has come to stay?

Robotic surgery is a surgical technique that is on the rise. The goal of robotic-assisted total knee arthroplasty (RA-TKA) is to provide the surgeon with a tool to accurately execute bone cuts according to previous surgical planning to restore knee kinematics and balance of soft tissue, being able to precisely apply the type of alignment that we choose. In addition, RA-TKA is a very useful tool for training. Within the limitations, there is the learning curve, the need for specific equipment, the high cost of the devices, the increase in radiation in some systems and that each robot is linked to a specific type of implant. Current studies show, with RA-TKA, variations in the alignment of the mechanical axis are reduced, postoperative pain is improved and earlier discharge is facilitated. On the other hand, there are no differences in terms of range of motion, alignment, gap balance, complications, surgical time or functional results.

Validity and acceptance of self vs conventional sampling for the analysis of human papillomavirus and Pap smear.

The newest high-risk human papillomavirus (HPV) detection techniques were included for cervical cancer primary screening under the Spanish National Health System in 2019. These analyses allow changing population approaches to foster adherence to screening. Therefore, the validity of self versus conventional sampling for HPV and cytology analyses was appraised. Women's preferences concerning samples and devices were also evaluated. This is a diagnostic accuracy cross-sectional study among 120 women recruited from a colposcopy clinic at a general hospital in Illes Balears, Spain. Participants were given written information and asked for a self-sample. One of two sets containing two devices each were handed. One set was transported dry and the second in liquid medium. Next, clinicians collected vaginal samples that were our gold standards. The agreement between both techniques was examined with the Kappa coefficient (κ). Self-sampling evaluation and preferences for different vaginal devices were also surveyed. The agreement between self and conventional samples concerning HPV positivity was very good (κ 0.86 for Mía by XytoTest® and 0.83 for Viba-Brush®) or reasonable (κ 0.73 for Iune and 0.68 for viscose swab). Pap smears from self-samples exhibited moderate agreement (κ 0.41 for Mía® and 0.51 for Viba-Brush® respectively) for negative versus ASC-US and worse results. Most of the participants considered self-sampling as beneficial (110 or 91.7%) and the advantages were, in decreasing order, scheduling, comfort, intimacy and less fear for pain or disturbance. The priority of choice for the devices was Mía® and viscose swab (chosen in first or second place) in opposition to Iune and Viba-Brush® (chosen in third or fourth place). If Viba-Brush® was to collect the best quality samples, 108 women (94.7%) switched their decisions. Our agreement between self and conventional samples was very good or reasonable for HPV, with the best values for devices in a liquid medium, and moderate for cytology. Even so, reflex cytology on self-samples is a valuable tool in promoting adherence. Self-sampling was widely accepted for smooth and thin devices. However, there is no resistance to change to others if a higher quality of the sample is obtained.

Current situation of robotics in knee prosthetic surgery, a technology that has come to stay? / Situación actual de la robótica en cirugía protésica de rodilla, ¿una tecnología que ha venido para quedarse?

Robotic surgery is a surgical technique that is on the rise. The goal of robotic-assisted total knee arthroplasty (RA-TKA) is to provide the surgeon with a tool to accurately execute bone cuts according to previous surgical planning to restore knee kinematics and balance of soft tissue, being able to precisely apply the type of alignment that we choose. In addition, RA-TKA is a very useful tool for training. Within the limitations, there is the learning curve, the need for specific equipment, the high cost of the devices, the increase in radiation in some systems and that each robot is linked to a specific type of implant. Current studies show, with RA-TKA, variations in the alignment of the mechanical axis are reduced, postoperative pain is improved and earlier discharge is facilitated. On the other hand, there are no differences in terms of range of motion, alignment, gap balance, complications, surgical time or functional results.

Corpus callosum size by neurosonography in fetuses with congenital heart defect and relationship with expected pattern of brain oxygen supply.

OBJECTIVE: To evaluate corpus callosum (CC) size by neurosonography (NSG) in fetuses with an isolated major congenital heart defect (CHD) and explore the association of CC size with the expected pattern of in-utero oxygen supply to the brain. METHODS: A total of 56 fetuses with postnatally confirmed isolated major CHD and 56 gestational-age-matched controls were included. Fetuses with CHD were stratified into two categories according to the main expected pattern of cerebral arterial oxygen supply: Class A, moderately to severely reduced oxygen supply (left outflow tract obstruction and transposition of the great arteries) and Class B, near normal or mildly impaired oxygenated blood supply to the brain (other CHD). Transvaginal NSG was performed at 32-36 weeks in all fetuses to evaluate CC length, CC total area and areas of CC subdivisions in the midsagittal plane. RESULTS: CHD fetuses had a significantly smaller CC area as compared to controls (7.91 ± 1.30 vs 9.01 ± 1.44 mm2 ; P < 0.001), which was more pronounced in the most posterior part of the CC. There was a significant linear trend for reduced CC total area across the three clinical groups, with CHD Class-A cases showing more prominent changes (controls, 9.01 ± 1.44 vs CHD Class B, 8.18 ± 1.21 vs CHD Class A, 7.53 ± 1.33 mm2 ; P < 0.05). CONCLUSIONS: Fetuses with major CHD had a smaller CC compared with controls, and the difference was more marked in the CHD subgroup with expected poorer brain oxygenation. Sonographic CC size could be a clinically feasible marker of abnormal white matter development in CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Validation of the Spanish Wound-QoL Questionnaire. / Validación de la versión española del cuestionario Wound-QoL.

BACKGROUND AND AIMS: The Wound-QoL is a validated and feasible questionnaire for measuring disease-specific health-related quality of life in chronic wounds, originally developed for use in German. The objective of this study was to translate the Wound-QoL for use in clinical care and in clinical trials in Spain and to validate this version. MATERIALS AND METHODS: Two independent fourth- and back translations of the Wound-QoL from the original German version were conducted, followed by an expert consensus of the resulting versions. After refinement, the final tool was piloted in N=10 patients and then used in the validation study. RESULTS: A total of 115 patients were recruited. Mean age was 69.5 (SD 14.5) years, 60.0% were female. The Spanish version of Wound-QoL showed high internal consistency (Cronbach's alpha>0.8 in all scales). Factor analysis resulted in the same scales as the original version. There were satisfactory distribution characteristics of the global score and the subscales. Construct validity and convergent validity with other outcomes (generic QoL, healing rate) were satisfactory. The vast majority of patients considered the Wound-QoL a simple and feasible tool. Mean time needed for completing the questionnaire was 5minutes. Overall, 99.1% of the participants found it easy to understand the questions and 94.7% stated that the questionnaire suits the personal situation. CONCLUSIONS: The Spanish version of the Wound-QoL shows good validity in clinical practice. It can be recommended for use in clinical routine and trials.

Strain-engineering Mott-insulating La2CuO4.

The transition temperature Tc of unconventional superconductivity is often tunable. For a monolayer of FeSe, for example, the sweet spot is uniquely bound to titanium-oxide substrates. By contrast for La2-xSrxCuO4 thin films, such substrates are sub-optimal and the highest Tc is instead obtained using LaSrAlO4. An outstanding challenge is thus to understand the optimal conditions for superconductivity in thin films: which microscopic parameters drive the change in Tc and how can we tune them? Here we demonstrate, by a combination of x-ray absorption and resonant inelastic x-ray scattering spectroscopy, how the Coulomb and magnetic-exchange interaction of La2CuO4 thin films can be enhanced by compressive strain. Our experiments and theoretical calculations establish that the substrate producing the largest Tc under doping also generates the largest nearest neighbour hopping integral, Coulomb and magnetic-exchange interaction. We hence suggest optimising the parent Mott state as a strategy for enhancing the superconducting transition temperature in cuprates.

Syphilis Maligna: A Presentation to Bear in Mind. / Sífilis maligna, una presentación de sífilis a tener en cuenta.

Malignant syphilis is an uncommon form of secondary syphilis associated with HIV infection. Clinically, it is characterized by necrotic nodules and generalized ulcerated lesions. We present 4 cases of malignant syphilis diagnosed after evaluating syphilis cases diagnosed at our hospital between 2012 and 2016. We describe the epidemiologic, clinical, histiopathologic, and serologic characteristics of malignant syphilis and explore its response to treatment and association with HIV infection. Although malignant syphilis is uncommon, there has been an increase in the number of cases published in recent years, particularly in young HIV-positive patients. Malignant syphilis must be contemplated in the differential diagnosis of HIV patients with ulcerated, necrotic lesions.

Description of Patients Treated with Biologic Drugs as First-Line Systemic Therapy in the BIOBADADERM Registry Between 2008 and 2016. / Descripción de los pacientes que reciben biológicos como primer tratamiento sistémico en el registro BIOBADADERM durante el periodo 2008-2016.

INTRODUCTION AND OBJECTIVES: Biologic drugs are usually prescribed as second-line treatment for psoriasis, that is, after the patient has first been treated with a conventional psoriasis drug. There are, however, cases where, depending on the characteristics of the patient or the judgement of the physician, biologics may be chosen as first-line therapy. No studies to date have analyzed the demographics or clinical characteristics of patients in this setting or the safety profile of the agents used. The main aim of this study was to characterize these aspects of first-line biologic therapy and compare them to those observed for patients receiving biologics as second-line therapy. MATERIAL AND METHOD: We conducted an observational study of 181 patients treated in various centers with a systemic biologic drug as first-line treatment for moderate to severe psoriasis between January 2008 and November 2016. All the patients were registered in the Spanish Registry of Adverse Events Associated with Biologic Drugs in Dermatology. RESULTS: The characteristics of the first- and second-line groups were very similar, although the patients receiving a biologic as first-line treatment for their psoriasis were older. No differences were observed for disease severity (assessed using the PASI) or time to diagnosis. Hypertension, diabetes, and liver disease were all more common in the first-line group. There were no differences between the groups in terms of reasons for drug withdrawal or occurrence of adverse effects. CONCLUSIONS: No major differences were found between patients with psoriasis receiving biologic drugs as first- or second-line therapy, a finding that provides further evidence of the safety of biologic therapy in patients with psoriasis.

Rare-earth nickelates RNiO3: thin films and heterostructures.

This review stands in the larger framework of functional materials by focussing on heterostructures of rare-earth nickelates, described by the chemical formula RNiO3 where R is a trivalent rare-earth R = La, Pr, Nd, Sm, …, Lu. Nickelates are characterized by a rich phase diagram of structural and physical properties and serve as a benchmark for the physics of phase transitions in correlated oxides where electron-lattice coupling plays a key role. Much of the recent interest in nickelates concerns heterostructures, that is single layers of thin film, multilayers or superlattices, with the general objective of modulating their physical properties through strain control, confinement or interface effects. We will discuss the extensive studies on nickelate heterostructures as well as outline different approaches to tuning and controlling their physical properties and, finally, review application concepts for future devices.

Multiple Supersonic Phase Fronts Launched at a Complex-Oxide Heterointerface.

Selective optical excitation of a substrate lattice can drive phase changes across heterointerfaces. This phenomenon is a nonequilibrium analogue of static strain control in heterostructures and may lead to new applications in optically controlled phase change devices. Here, we make use of time-resolved nonresonant and resonant x-ray diffraction to clarify the underlying physics and to separate different microscopic degrees of freedom in space and time. We measure the dynamics of the lattice and that of the charge disproportionation in NdNiO_{3}, when an insulator-metal transition is driven by coherent lattice distortions in the LaAlO_{3} substrate. We find that charge redistribution propagates at supersonic speeds from the interface into the NdNiO_{3} film, followed by a sonic lattice wave. When combined with measurements of magnetic disordering and of the metal-insulator transition, these results establish a hierarchy of events for ultrafast control at complex-oxide heterointerfaces.

Determination of adalimumab and etanercept trough levels and drug antibodies in long-term psoriasis treatment: a single-centre cohort study.

BACKGROUND: An algorithm based on measurement of a serum tumour necrosis factor antagonists (anti-TNF) and antidrug antibodies (ADA) has been proposed previously to guide dose escalation or therapy switching in the early (i.e. the first months of) treatment of psoriasis by anti-TNF. In long-term treatment of responding patients with psoriasis, it is usual to empirically reduce standard doses of anti-TNF to reduce exposure while maintaining clinical response. The relationship between serum anti-TNF, ADA levels and clinical efficacy in long-term treated patients with psoriasis has not yet been determined, so the potential role of these parameters in guiding dose escalation in this scenario is unknown. AIMS: To evaluate the relationship between drug/ADA levels and clinical efficacy in a group of patients with psoriasis undergoing long-term treatment with adalimumab or etanercept. METHODS: This was a single-centre, prospective, cohort study of patients with psoriasis receiving adalimumab or etanercept for a minimum of 48 weeks. All patients were started on the standard dose, but some adalimumab users had a reduced frequency of administration. Clinical efficacy was measured using the Psoriasis Area and Severity Index. Serum concentrations were measured by ELISA. Clinical assessment and blood sample collection were carried out simultaneously within 24 h before the next drug administration. RESULTS: In total, 21 patients were enrolled (67 simultaneous clinical and serum determinations: 38 receiving adalimumab, 29 receiving etanercept). We did not find any association between serum anti-TNF levels and clinical response. None of the patients developed ADA. CONCLUSIONS: ADA and anti-TNF levels are not related to clinical effectiveness in patients with psoriasis undergoing long-term treatment with adalimumab or etanercept.