Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple / Nicolau syndrome due to self-injectable drugs in multiple sclerosis

Introducción y objetivos: El síndrome de Nicolau, o embolia cutis medicamentosa, es una complicación cutánea infrecuente de los fármacos inyectados que se ha descrito escasamente en relación con los fármacos empleados en la esclerosis múltiple. Pacientes y métodos: Es un estudio retrospectivo de pacientes afectos de síndrome de Nicolau que reciben fármacos autoinyectables para la esclerosis múltiple desde 2010 hasta octubre de 2022. Resultados: Desde enero de 2010 hasta octubre de 2022 se ha seguido en nuestra consulta de patología desmielinizante a 449 pacientes con fármacos autoinyectables –317 con interferón beta y 132 con acetato de glatiramer (AG)–. En este período de tiempo se han recogido 10 episodios de síndrome de Nicolau en siete pacientes (seis hombres y una mujer) que recibían AG, lo que supone un 5,3% del total de pacientes bajo ese tratamiento. Las zonas más afectadas fueron el glúteo (n = 4) y el brazo (n = 3). Tres pacientes (42,8%) sufrieron un segundo episodio. Conclusión: El síndrome de Nicolau es una complicación exclusiva del AG y más frecuente en hombres en nuestra cohorte de pacientes con esclerosis múltiple. La recurrencia de esta complicación cutánea es frecuente en un mismo paciente, lo que es un factor que hay que tener en cuenta en la decisión de mantener el fármaco o cambiar a otra estrategia terapéutica.(AU)

Introduction and aims: Nicolau syndrome, or embolia cutis medicamentosa, is a rare cutaneous complication of drug injection that has been rarely described in relation to medication used in multiple sclerosis. Patients and methods: We conducted a retrospective study of patients with Nicolau syndrome receiving self-injectable multiple sclerosis medication from 2010 to October 2022. Results: From January 2010 to October 2022, 449 patients were followed up in our demyelinating pathology unit with self-injectable drugs - 317 with beta interferons and 132 with glatiramer acetate (GA). In this period of time, 10 episodes of Nicolau syndrome were recorded in seven patients (six men and one woman) receiving GA, which represents 5.3% of the total number of patients receiving this treatment. The most commonly affected areas were the buttocks (n = 4) and the arms (n = 3). Three patients (42.8%) suffered a second episode. Conclusion: Nicolau syndrome is a complication unique to GA and more frequent in men in our cohort of multiple sclerosis patients. This cutaneous complication frequently recurs in the same patient, which is a factor to be taken into account in the decision to maintain the drug or switch to another therapeutic strategy.(AU)

[Nicolau syndrome due to self-injectable drugs in multiple sclerosis]. / Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple.

INTRODUCTION AND AIMS: Nicolau syndrome, or embolia cutis medicamentosa, is a rare cutaneous complication of drug injection that has been rarely described in relation to medication used in multiple sclerosis. PATIENTS AND METHODS: We conducted a retrospective study of patients with Nicolau syndrome receiving self-injectable multiple sclerosis medication from 2010 to October 2022. RESULTS: From January 2010 to October 2022, 449 patients were followed up in our demyelinating pathology unit with self-injectable drugs - 317 with beta interferons and 132 with glatiramer acetate (GA). In this period of time, 10 episodes of Nicolau syndrome were recorded in seven patients (six men and one woman) receiving GA, which represents 5.3% of the total number of patients receiving this treatment. The most commonly affected areas were the buttocks (n = 4) and the arms (n = 3). Three patients (42.8%) suffered a second episode. CONCLUSION: Nicolau syndrome is a complication unique to GA and more frequent in men in our cohort of multiple sclerosis patients. This cutaneous complication frequently recurs in the same patient, which is a factor to be taken into account in the decision to maintain the drug or switch to another therapeutic strategy.

TITLE: Síndrome de Nicolau por fármacos autoinyectables en la esclerosis múltiple.Introducción y objetivos. El síndrome de Nicolau, o embolia cutis medicamentosa, es una complicación cutánea infrecuente de los fármacos inyectados que se ha descrito escasamente en relación con los fármacos empleados en la esclerosis múltiple. Pacientes y métodos. Es un estudio retrospectivo de pacientes afectos de síndrome de Nicolau que reciben fármacos autoinyectables para la esclerosis múltiple desde 2010 hasta octubre de 2022. Resultados. Desde enero de 2010 hasta octubre de 2022 se ha seguido en nuestra consulta de patología desmielinizante a 449 pacientes con fármacos autoinyectables ­317 con interferón beta y 132 con acetato de glatiramer (AG)­. En este período de tiempo se han recogido 10 episodios de síndrome de Nicolau en siete pacientes (seis hombres y una mujer) que recibían AG, lo que supone un 5,3% del total de pacientes bajo ese tratamiento. Las zonas más afectadas fueron el glúteo (n = 4) y el brazo (n = 3). Tres pacientes (42,8%) sufrieron un segundo episodio. Conclusión. El síndrome de Nicolau es una complicación exclusiva del AG y más frecuente en hombres en nuestra cohorte de pacientes con esclerosis múltiple. La recurrencia de esta complicación cutánea es frecuente en un mismo paciente, lo que es un factor que hay que tener en cuenta en la decisión de mantener el fármaco o cambiar a otra estrategia terapéutica.

Voice Quality and Laryngeal Findings in Patients With Suspected Lung Cancer.

OBJECTIVE: To describe laryngeal findings and voice quality in patients with suspected lung cancer, relative to voice quality and possible laryngeal pathology. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary care center. METHODS: Patients with known or suspected lung cancer were approached before planned thoracic surgery, and they completed acoustic analysis, the Voice-Related Quality of Life (V-RQOL) questionnaire, and stroboscopy. The prevalence of dysphonia, V-RQOL and Cepstral Spectral Index of Dysphonia (CSID) scores, and laryngeal findings were examined and compared between patients ultimately found to have lung cancer and those without cancer. RESULTS: Sixty-one patients (45 cancer, 16 noncancer) were analyzed. Patients with cancer were older than those without (mean ± SD, 72.3 ± 9.94 vs 62.6 ± 9.30 years; P = .001). Otherwise, the distribution of stroboscopy findings, acoustic measures, and self-reported voice handicap were similar between the cancer and noncancer cohorts. Prior to surgery, no patients had vocal cord paralysis or obvious neoplasm, though 4 (6.56%) had leukoplakia and 28 (45.9%) had vocal fold movement asymmetry on stroboscopy. Overall, 21 patients (35.0%) had average CSID scores >19, and 13 (21.7%) had CSID scores >24; however, only 4 self-described their voice as not working as it should, and only 2 had a V-RQOL score <85. CONCLUSION: Patients with suspected lung cancer have moderate dysphonia on acoustic measures, though self-reported impact on quality of life is low. While leukoplakia was seen in 4 patients, obvious neoplasm and occult paralysis were not seen in this cohort. Together, these findings suggest that patients with suspected lung cancer should be assessed for subjective voice dysfunction, but routine laryngeal screening may otherwise be unnecessary.

Physical Exercise for Late-Life Major Depression.

(Reprinted with permission from Br J Psychiatry 2005; 207: 235-242).

Küntscher nails with static cement spacer: A simple technique in periprosthetic knee infections with massive bone loss and instability.

BACKGROUND: Two-stage revision for periprosthetic knee infection is challenging in cases of massive bone loss and instability. The present study aims to describe our experience with an alternative technique of reinforced cement spacer, usually necessary in these situations, focusing on its advantages and clinical results. METHODS: We retrospectively identified all patients who underwent a two-stage revision for periprosthetic knee infection using two intramedullary Küntscher nails as reinforcement from January 2010 to September 2018. From each medical record, we extracted the type of explanted prosthesis, isolated micro-organism, number of cement spacers before index procedure (and related episodes of spacer dislocation) and final treatment. RESULTS: Twelve patients were identified, mean age of 64.0 years (range 39-85). In four of them, the reinforced spacer was used twice for persistent infection, with a total of 16 procedures performed and no cases of dislocation. Ten patients were finally treated with reimplantation or arthrodesis with intramedullary nails, whereas an above-knee amputation was necessary for two patients. Infection was eradicated in 10 patients out of 12 (83%) at a mean follow up of 34.3 months (range 10-62). CONCLUSIONS: This technique is an effective alternative to traditional spacers in cases of massive bone loss, producing a mechanically stable joint and preserving adequate tissue tensions. The construct is technically easy to perform and, not less importantly, to remove during stage 2. Further studies, with larger groups, are necessary to determine its validity.

A transition clinic model for inflammatory bowel disease between two tertiary care centers: outcomes and predictive factors.

OBJECTIVE: Few models of transition have been proposed for inflammatory bowel disease (IBD). The aim of the present study is to evaluate the feasibility of a transition model and the predictive factors for success/failure. PATIENTS AND METHODS: Patients with low activity or remission IBD were enrolled. Proposed model: three meetings every four-six weeks: the first one in the pediatric center (Bambino Gesù Children's Hospital); the second one, in the adult center (Foundation Polyclinic University A. Gemelli), with pediatric gastroenterologists; the last one, in the adult center, with adult gastroenterologists only. Questionnaires included anxiety and depression clinical scale, self-efficacy, quality of life, visual-analogic scale (VAS). Transition was considered successful if the three steps were completed. RESULTS: Twenty patients were enrolled (range 18-25 years; M/F: 12/8; Ulcerative Colitis/Crohn's Disease 10/10); eight accepted the transition program, four delayed the process and eight refused. Patients who completed transition generated higher scores on the resilience scale, better scores on well-being perception, and had lower anxiety scores. Patients who failed transition were mostly women. The perceived utility of the transition program was scored 7.3 on a VAS scale. CONCLUSIONS: The proposed transition program seems to be feasible. Psychological scores may help in selecting patients and predicting outcomes.

Two-dimensional transvaginal sonography vs saline contrast sonohysterography for diagnosing endometrial polyps: systematic review and meta-analysis.

OBJECTIVE: To compare the diagnostic performance of two-dimensional transvaginal sonography (TVS) and saline contrast sonohysterography (SCSH) for the diagnosis of endometrial polyps in studies that used both tests in the same group of patients. METHODS: This was a systematic review and meta-analysis. An extensive search was conducted of Medline (PubMed), Cochrane Library and Web of Science, for studies comparing the diagnostic performance of TVS and SCSH for identifying endometrial polyps, published between January 1990 and December 2019, that reported a definition of endometrial polyp on TVS and SCSH and used pathologic analysis as the reference standard. Quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. A random-effects model was used to determine pooled sensitivity, specificity and positive and negative likelihood ratios of TVS and SCSH in the detection of endometrial polyps. Subanalysis according to menopausal status was performed. RESULTS: In total, 1278 citations were identified; after exclusions, 25 studies were included in the meta-analysis. In the included studies, the risk of bias evaluated using QUADAS-2 was low for most of the four domains, except for flow and timing, which had an unclear risk of bias in 13 studies. Pooled sensitivity, specificity and positive and negative likelihood ratios for TVS in the detection of endometrial polyps were 55.0% (95% CI, 46.0-64.0%), 91.0% (95% CI, 86.0-94.0%), 5.8 (95% CI, 3.9-8.7) and 0.5 (95% CI, 0.41-0.61), respectively. The corresponding values for SCSH were 92.0% (95% CI, 87.0-95.0%), 93.0% (95% CI, 91.0-95.0%), 13.9 (95% CI, 9.9-19.5) and 0.08 (95% CI, 0.05-0.14), respectively. Significant differences were found when comparing the methods in terms of sensitivity (P < 0.001), but not for specificity (P = 0.0918). Heterogeneity was high for TVS and moderate for SCSH. On subanalysis according to menopausal status, SCSH was found to have higher diagnostic accuracy in both pre- and postmenopausal women; sensitivity and specificity did not differ significantly between the groups for either TVS or SCSH. CONCLUSION: Given that SCSH has better diagnostic positive and negative likelihood ratios than does TVS in both pre- and postmenopausal women, those with clinical suspicion of endometrial polyps should undergo SCSH if TVS findings are inconclusive. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Ecografía transvaginal bidimensional vs histerosonografía con contraste salino para el diagnóstico de pólipos endometriales: revisión sistemática y metaanálisis OBJETIVO: Comparar el desempeño del diagnóstico de la ecografía transvaginal bidimensional (TVS, por sus siglas en inglés) y la histerosonografía con contraste salino (SCSH, por sus siglas en inglés) para el diagnóstico de pólipos endometriales en estudios que utilizaron ambas pruebas en el mismo grupo de pacientes. MÉTODOS: Este estudio fue una revisión sistemática y metaanálisis. El estudio realizó una extensa búsqueda en Medline (PubMed), Cochrane Library y Web of Science de estudios en los que se había comparado el desempeño del diagnóstico de la TVS y la SCSH para identificar pólipos endometriales, publicados entre enero de 1990 y diciembre de 2019, que incluyeran una definición de pólipo endometrial en la TVS y la SCSH y utilizaran el análisis patológico como estándar de referencia. La calidad de los estudios incluidos se evaluó mediante la herramienta de Evaluación de Calidad de los Estudios de Precisión en el Diagnóstico-2 (QUADAS-2, por sus siglas en inglés). Se utilizó un modelo de efectos aleatorios para determinar la sensibilidad combinada, la especificidad, los cocientes de verosimilitud positivos y negativos de la TVS y la SCSH en la detección de pólipos endometriales. Se realizó un subanálisis en función del estatus de la menopausia. RESULTADOS: Se identificaron un total de 1278 citas, de las cuales se incluyeron 25 estudios en el metaanálisis. En los estudios incluidos, el riesgo de sesgo evaluado mediante QUADAS-2 fue bajo para la mayoría de los cuatro dominios, excepto para el flujo y el tiempo, que tuvieron un riesgo de sesgo poco claro en 13 estudios. La sensibilidad combinada, la especificidad y los cocientes de verosimilitud positivos y negativos para la TVS en la detección de pólipos endometriales fueron del 55,0% (IC 95%, 46,0-64,0%), 91,0% (IC 95%, 86,0-94,0%), 5,8 (IC 95%, 3,9-8,7) y 0,5 (IC 95%, 0,41-0,61), respectivamente. Los valores correspondientes para la SCSH fueron 92,0% (IC 95%, 87,0-95,0%), 93,0% (IC 95%, 91,0-95,0%), 13,9 (IC 95%, 9,9-19,5) y 0,08 (IC 95%, 0,05-0,14), respectivamente. Se encontraron diferencias significativas al comparar los métodos respecto a la sensibilidad (P<0,001), pero no respecto a la especificidad (P=0,0918). La heterogeneidad fue alta para la TVS y moderada para la SCSH. En el subanálisis según el estado menopáusico, se determinó que la SCSH tenía una mayor precisión en el diagnóstico en las mujeres pre- y posmenopáusicas, mientras que la sensibilidad y la especificidad no difirieron significativamente entre ambos grupos, tanto para la TVS como para la SCSH. CONCLUSIÓN: Dado que la SCSH tiene mejores coeficientes de verosimilitud positivos y negativos de diagnóstico que la TVS en las mujeres pre- y posmenopáusicas, las mujeres con sospecha clínica de pólipos endometriales deberían someterse a una SCSH si los hallazgos de la TVS no son concluyentes.

In soil radon anomalies and volcanic activity on Mt. Etna (Italy).

We present here the first attempt to understand the fast dynamics of an active basaltic volcano, namely Mt. Etna using soil gas radon measured in some sites located in strategic places around the volcano. Data were measured continuously from July 2015 to February 2017 and the raw signals were treated in order to filter out all possible periodic components that are normally due to non-volcanic factors, applying a method that does not require acquisition of other parameters, which are not always available. The residual signals highlighted seven anomalous changes, with radon values reaching levels from 2 to 5 times higher than the normal background. In six out of seven cases, anomalies were almost contemporaneous in all or almost all of the sites, indicating a common source for the observed radon variations. The pattern of anomalies suggests a transient wave-like propagation in the space/time domain, compatible with pressure-induced displacement of the gas. The observed patterns are most probably caused by the rapid upward motion of gas-rich magma into the volcano conduits, as almost all anomalies precede or accompany major volcanic events. In some cases, an alternative explanation could be the strong and sudden strain releases through earthquakes swarms, with consequent variations in the permeability of rocks at a large scale, given the apparent correlation between those anomalies and intense seismicity.

In vitro and in vivo pharmacological characterization of the synthetic opioid MT-45.

MT-45 is a synthetic opioid that was developed in the 1970s as an analgesic compound. However, in recent years MT-45 has been associated with multiple deaths in Europe and has been included in the class of novel psychoactive substances known as novel synthetic opioids (NSOs). Little is known about the pharmaco-toxicological effects of MT-45. Therefore, we used a dynamic mass redistribution (DMR) assay to investigate the pharmacodynamic profile of this NSO in vitro compared with morphine. We then used in vivo studies to investigate the effect of the acute systemic administration of MT-45 (0.01-15 mg/kg i.p.) on motor and sensorimotor (visual, acoustic and tactile) responses, mechanical and thermal analgesia, muscle strength and body temperature in CD-1 male mice. Higher doses of MT-45 (6-30 mg/kg i.p.) were used to investigate cardiorespiratory changes (heart rate, respiratory rate, SpO2 saturation and pulse distention). All effects of MT-45 were compared with those of morphine. In vitro DMR assay results demonstrated that at human recombinant opioid receptors MT-45 behaves as a potent selective mu agonist with a slightly higher efficacy than morphine. In vivo results showed that MT-45 progressively induces tail elevation at the lowest dose tested (0.01 mg/kg), increased mechanical and thermal antinociception (starting from 1 to 6 mg/kg), decreased visual sensorimotor responses (starting from 3 to 6 mg/kg) and reduced tactile responses, modulated motor performance and induced muscle rigidity at higher doses (15 mg/kg). In addition, at higher doses (15-30 mg/kg) MT-45 impaired the cardiorespiratory functions. All effects were prevented by the administration of the opioid receptor antagonist naloxone. These findings reveal the risks associated with the ingestion of opioids and the importance of studying these drugs and undertaking more clinical studies of the current molecules to better understand possible therapeutic interventions in the case of toxicity.

Pathophysiology of hypoxic-ischemic encephalopathy: a review of the past and a view on the future.

Hypoxic-ischemic encephalopathy, also referred as HIE, is a type of brain injury or damage that is caused by a lack of oxygen to the brain during neonatal period. The incidence is approximately 1.5 cases per 1000 live births in developed countries. In low and middle-income countries, the incidence is much higher (10‒20 per 1000 live births). The treatment for neonatal HIE is hypothermia that is only partially effective (not more than 50% of the neonates treated achieve an improved outcome). HIE pathophysiology involves oxidative stress, mitochondrial energy production failure, glutaminergic excitotoxicity, and apoptosis. So, in the last years, many studies have focused on peptides that act somewhere in the pathway activated by severe anoxic injury leading to HIE. This review describes the pathophysiology of perinatal HIE and the mechanisms that could be the target of innovative HIE treatments.

Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains.

Optimal autophagic activity is crucial to maintain muscle integrity, with either reduced or excessive levels leading to specific myopathies. LGMD2H is a muscle dystrophy caused by mutations in the ubiquitin ligase TRIM32, whose function in muscles remains not fully understood. Here, we show that TRIM32 is required for the induction of muscle autophagy in atrophic conditions using both in vitro and in vivo mouse models. Trim32 inhibition results in a defective autophagy response to muscle atrophy, associated with increased ROS and MuRF1 levels. The proautophagic function of TRIM32 relies on its ability to bind the autophagy proteins AMBRA1 and ULK1 and stimulate ULK1 activity via unanchored K63-linked polyubiquitin. LGMD2H-causative mutations impair TRIM32's ability to bind ULK1 and induce autophagy. Collectively, our study revealed a role for TRIM32 in the regulation of muscle autophagy in response to atrophic stimuli, uncovering a previously unidentified mechanism by which ubiquitin ligases activate autophagy regulators.

Pelvic floor rehabilitation for defecation disorders.

Pelvic floor rehabilitation is frequently recommended for defecation disorders, in both constipation and fecal incontinence. However, the lack of patient selection, together with the variety of rehabilitation methods and protocols, often jeopardize the results of this approach, causing difficulty in evaluating outcomes and addressing proper management, and above all, in obtaining scientific evidence for the efficacy of these methods for specific indications. The authors represent different gastroenterological and surgical scientific societies in Italy, and their aim was to identify the indications and agree on treatment protocols for pelvic floor rehabilitation of patients with defecation disorders. This was achieved by means of a modified Delphi method, utilizing a working team (10 members) which developed the statements and a consensus group (15 members, different from the previous ones) which voted twice also suggesting modifications of the statements.

Magnetic coupling to the advanced Virgo payloads and its impact on the low frequency sensitivity.

We study the electromagnetic coupling of the Advanced Virgo (AdV) input mirror payload in response to a slowly time-varying magnetic field. As the problem is not amenable to analytical solution, we employ and validate a finite element (FE) analysis approach. The FE model is built to represent as faithfully as possible the real object, and it has been validated by comparison with experimental measurements. The intent is to estimate the induced currents and the magnetic field in the neighbourhood of the payload. The procedure found 21 equivalent electrical configurations that are compatible with the measurements. These have been used to compute the magnetic noise contribution to the total AdV strain noise. At the current stage of development, AdV seems to be unaffected by magnetic noise, but we foresee a non-negligible coupling once AdV reaches the design sensitivity.

New CACNA1A deletions are associated to migraine phenotypes.

BACKGROUND: Familial hemiplegic migraine type 1 (FHM1) is a form of migraine with aura caused by heterozygous mutations in 4 genes: CACNA1A, ATP1A2, SNC1A and PRRT2, but further heterogeneity is expected. Here have been described clinical and molecular features in patients suffering from migraine with Aura (MA), without (MO) and hemiplegic migraine attacks. Next Generation Sequencing by TruSeq Custom Amplicon for CACNA1A and ATP1A2 gene has been performed. All genetic variants have been confirmed by Sanger sequencing and all samples were also analyzed with MLPA assay for ATP1A2-CACNA1A genes to detect duplication or deletion. All MLPA data were verified by Real Time PCR. RESULTS: Sequencing analysis showed 3 point mutations, two novel variants and one already described in literature. Moreover, MLPA analysis showed 3 deletions in 9 sporadic hemiplegic migraine (18%), in 3 patients with non-hemiplegic migraine (4.1%) and in 3 patients affected by episodic ataxia (20%). Two sporadic patients showed a deletion in exons 41-43, while the rest of HM patients (5) showed a deletion in the terminal part of the CACNA1A gene. About episodic ataxia, we have identified deletions in exon 12-15 and in exon 47. Finally, in migraine patients, we have found different subjects affected by different phenotypes deleted in exon 47. CONCLUSION: This work highlights the importance to complement analysis as direct sequencing with quantitative analysis (MLPA). In fact, intragenic CACNA1A rearrangements have been detected. Our work demonstrated that deletions in CACNA1A gene may be associated also to different migraine phenotypes.

Anterior cruciate ligament revision with Achilles tendon allograft in young athletes.

BACKGROUND: Return to sport after revision ACL reconstruction is a controversial topic, several studies reported the results of different techniques and graft in sportsman, presenting an incredibly wide range of return to the same pre-injury activity level, from 0% to 100%. The purpose of this study was to evaluate the clinical outcomes and return to sport rate in young athletes after non anatomic double-bundle revision ACL reconstruction with Achilles allograft. HYPOTHESIS: The present revision technique was effective in terms of stability, return to sport and functional outcomes. MATERIAL AND METHODS: All the athletes undergone Revision ACL reconstruction with non-irradiated Achilles tendon allograft with a non-anatomical double-bundle technique were included in the study. A split Achilles tendon allograft was used to reproduce the anteromedial (AM) bundle using the over-the-top position, while the posterolateral (PL) bundle was reconstructed through a femoral tunnel located in the anatomical PL footprint. Sport activity, knee function with Lysholm score, knee laxity and re-injury or re-operations were evaluated. RESULTS: Twenty-six athletes (23 males, three females) with a mean age of 23.4±3.6 years were evaluated at a mean follow-up of 6.0±1.6 years. Overall 69% of patients returned to sport both at elite (44%) or county level (56%) after a mean 6.7±1.5 (3-9 range) months. The mean Lysholm score showed a significant improvement from 64.4±8.1 at pre-operative status to 83.8±11.3 at final follow-up (P<.0001). Seven patients (30%) were rated as excellent, nine (39%) as good, five (22%) as fair and 2 (9%) as poor. Three patients (12%) experienced a further graft rupture after a mean 2.6 years, (3.5 months-48 months range) and two had >5mm side-to-side difference at KT-1000. Therefore, the overall survival rate at mean six years follow-up was 81%. CONCLUSION: The ACL revision with a double-bundle technique using Achilles tendon allograft was successful in 81% of athletes at six years mean follow-up. TYPE OF STUDY AND LEVEL OF EVIDENCE: Retrospective case series, level IV.

Pro-inflammatory M1/Th1 type immune network and increased expression of TSG-6 in the eutopic endometrium from women with endometriosis.

OBJECTIVE: The study aimed to explore the type 1 and type 2 cytokines expression in the endometrium from women affected by endometriosis compared to controls. The expression of TSG-6, a multifunctional protein involved in several inflammatory disease, was also evaluated. Study Design SETTING: Experimental clinical study. PATIENTS: 10 patients affected by endometriosis and 11 controls. INTERVENTIONS: Patients underwent to an ultrasound transvaginal examination and a diagnostic hysteroscopy in order to exclude any uterine abnormality. All patients underwent endometrial biopsy using a Novak's curette. MAIN OUTCOME MEASURES: The endometrial expression of type 1 (IL- 1 ß TNF-α, IL-8) and type 2 (IL-10) cytokines, and of TSG-6 was evaluated by immunohistochemistry and by real time PCR. The expression of TSG-6 was confirmed by western blot. RESULTS: Results of PCR analysis and of immunohistochemistry revealed an increased expression of IL-1ß, TNF-α, IL-8 and of TSG-6 in the endometrium of endometriosic patients. IL-10 expression did not show any difference. CONCLUSIONS: An increased expression of pro-inflammatory type 1 cytokines was demonstrated in the endometrium from endometriosic patients, suggesting an endometrial environment harmful for implantation due to the prevalence of Th1 related immunity. An increased expression of TSG-6 was also demonstrated for the first time. Our findings concur to better define the inflammatory imbalance and the abnormal endometrial receptivity, reported in literature, of the eutopic endometrium of women affected by endometriosis.

Concurrent femoral and tibial osteotomies versus soft tissue balance in total knee arthroplasty: A technical case report.

This case report outlines some of the challenges as well as limitations in correction of osteoarthritis of the knee in combination with extra-articular deformities,and provides a novel and straightforward surgical solution in overcoming these challenges. We describe the case of a 37-year-old male who suffered from advanced bilateral tri-compartmental knee arthritis due to untreated bloodstream-sourced osteomyelitis after birth. Radiographs and surgery confirmed extremely severe deformities. We performed two different surgical techniques in order to correct extra-articular deformities (one-stage approach of concurrent tibial and femoral osteotomy and total knee arthroplasty on one side, and soft tissue balancing with "pie-crusting technique" plus total knee arthroplasty on the other side), with description of subsequent results at 36-months follow-up.

Precision Continuous Renal Replacement Therapy and Solute Control.

Continuous renal replacement therapy (CRRT) remains the dominant form of renal support among critically ill patients worldwide. Current clinical practice on CRRT prescription mostly relies on high quality studies suggesting no impact of CRRT dose on critically ill patients' outcomes. Recent clinical practice guidelines have been developed based on these studies recommending a static prescribed CRRT dose of 20-25 ml/kg/h. There is a rationale for renewed attention to CRRT prescription/practice based on the concept of dynamic solute control adapted to the changing clinical needs of critically ill patients. In response, Acute Disease Quality Initiative convened a 17th consensus meeting centered on re-evaluation of CRRT. This work group developed 4 themes focused specifically on CRRT dose prescription, delivery and solute control that were summarized in a series of consensus statements, along with the identification of critical knowledge gaps. CRRT dose prescription and delivery can be based on effluent flow rate. Delivered dose should be routinely monitored to ensure coherence with prescribed dose. CRRT dose should be dynamic, in recognition of between- and within-patient variation in targeted solute control or unintended solute clearance. Quality measures specific for monitoring delivered CRRT dose have been proposed that require further validation, prior to implementation, into the practice of guiding optimal CRRT dosage.