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.

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.

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.

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.

Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations.

BACKGROUND: Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. AIM: In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. CONCLUSIONS: Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents.

A Pathophysiological Insight into Sepsis and Its Correlation with Postmortem Diagnosis.

BACKGROUND: Sepsis is among the leading causes of death worldwide and is the focus of a great deal of attention from policymakers and caregivers. However, sepsis poses significant challenges from a clinical point of view regarding its early detection and the best organization of sepsis care. Furthermore, we do not yet have reliable tools for measuring the incidence of sepsis. Methods based on analyses of insurance claims are unreliable, and postmortem diagnosis is still challenging since autopsy findings are often nonspecific. AIM: The objective of this review is to assess the state of our knowledge of the molecular and biohumoral mechanisms of sepsis and to correlate them with our postmortem diagnosis ability. CONCLUSION: The diagnosis of sepsis-related deaths is an illustrative example of the reciprocal value of autopsy both for clinicians and for pathologists. A complete methodological approach, integrating clinical data by means of autopsy and histological and laboratory findings aiming to identify and demonstrate the host response to infectious insults, is mandatory to illuminate the exact cause of death. This would help clinicians to compare pre- and postmortem findings and to reliably measure the incidence of sepsis.

Physical exercise for late-life major depression.

BACKGROUND: Interventions including physical exercise may help improve the outcomes of late-life major depression, but few studies are available. AIMS: To investigate whether augmenting sertraline therapy with physical exercise leads to better outcomes of late-life major depression. METHOD: Primary care patients (465 years) with major depression were randomised to 24 weeks of higher-intensity, progressive aerobic exercise plus sertraline (S+PAE), lower-intensity, non-progressive exercise plus sertraline (S+NPE) and sertraline alone. The primary outcome was remission (a score of ≤10 on the Hamilton Rating Scale for Depression). RESULTS: A total of 121 patients were included. At study end, 45% of participants in the sertraline group, 73% of those in the S+NPE group and 81% of those in the S+PAE group achieved remission (P = 0.001). A shorter time to remission was observed in the S+PAE group than in the sertraline-only group. CONCLUSIONS: Physical exercise may be a safe and effective augmentation to antidepressant therapy in late-life major depression.

DOES TOTAL KNEE REPLACEMENT MODIFY FLEXION AXIS OF THE KNEE ON FRONTAL AND AXIAL PLANE REGARDLESS FROM LIMB ALIGNMENT?

The optimal reference for rotational positioning of femoral component in total knee replacement (TKR) is debated. Navigation has been suggested for intra-op acquisition of patient’s specific kinematics and functional flexion axis (FFA). The main purpose of the present study is to prospectively investigate whether pre-operative FFA in patients with osteoarthritis (OA) and varus alignment changes after TKR and whether a correlation exists between post-op FFA and pre-op alignment. A navigated TKR was performed in 108 patients using a specific software to acquire passive joint kinematics before and after TKR. The knee was cycled through three passive range of motions (PROM), from 0° to 120°. FFA was computed using the mean helical axis algorithm. The angle between FFA and surgical TEA was determined on frontal (αf) and axial (αa) plane. The pre- and post-op hip-knee-ankle angle (HKA) was determined. Post-op FFA was different from pre-op FFA only on frontal plane. No significant difference was found on axial plane. No correlation was found between HKA-pre and αA-pre. A significant correlation was found between HKA-pre and αF–pre. The study concluded that TKR modifies FFA only on frontal plane. No difference was found on axial plane. Pre-op FFA is in a more varus position respect to TEA. The position of FFA on frontal plane is dependent on limb alignment. The present study has demonstrated TKR modifies the position of FFA only on frontal plane. The position of FFA on axial plane is not dependent on the amount of varus deformity and is not influenced by TKR. Level of evidence, IV, case series.

Use of contrast media in diagnostic imaging: medico-legal considerations.

Contrast media (CM) are used in imaging techniques to enhance the differences between body tissues on images. The ideal contrast medium should achieve very high concentration in the tissues without producing any adverse effects. Unfortunately, this has not been possible so far and all CM have adverse effects. The increasing use of CM is likely to give rise to a wide range of pitfalls, including compliance with and appropriateness of indications for the use of CM themselves, the choice of the 'best' contrast agent, off-label use, evaluation of special populations of patients, and competence to tackle emergency scenarios following the administration of CM. Even more prominent, and potentially more important, is the issue of informed consent which brings with it a duty to inform patients awaiting the administration of CM with regard to the nature of the procedure, the existence of alternative procedures, the extent of the risks relating to the use of CM and, finally, the risks relating to refusal of the procedure. All these issues may give rise to concerns about liability for failure to offer adequate information to patients or to carefully evaluate and balance the potential risks and benefits of the procedure or, finally, for being unprepared in the event of adverse reactions to CM, especially when these are severe and life-threatening. Educational and training programmes for radiologists are likely to shape change in the medical liability environment in the coming years.

[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.

Retrospective analysis of anaesthesia-related deaths during a 12-year period: looking at the data from a forensic point of view.

Anaesthesia-related death is one of the most complex events to be studied in forensic pathology because of its rarity and its doubtful presentation. Particularly, the difficulties in assessing the cause of deaths in such circumstances are underlined. A scale must be considered in order to determine the causal role of anaesthesia in the process leading to death. Indeed, beyond deaths exclusively explained by anaesthetic care, there are deaths that are not anaesthesia-related and deaths explained by surgery and co-morbidities in which the role of anaesthetic care has to be carefully investigated. A retrospective analysis of 3138 autopsies is presented with the aim of better understanding the patho-physiological process of anaesthesia-related mortality and to determine the causal role of anaesthesiological care in the process leading to death, thus assessing the real incidence of deaths due to anaesthesia (0.16%). In the present study, the number of deaths generically anaesthesia-related (33 cases) accounts for 2.06% of autopsies due to medical malpractice claims and 1.05% of all autopsies. The number of deaths totally related to anaesthesic care is rather low with 0.32% of autopsies due to medical malpractice claims and 0.16% of all autopsies. Anaesthesia-related deaths were due to lack of or delay in intubation (2 cases), acute cardio-respiratory failure (2 cases) and anaesthetic-induced hepatotoxicity (1 case). The importance of a careful forensic investigation (clinical and familial history, medical records, complete autopsy and toxicology), which can lead to a clear understanding of anaesthesia-related deaths, is also stressed.

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.

High mean fluorescence intensity donor-specific anti-HLA antibodies associated with chronic rejection Postliver transplant.

In contrast to kidney transplantation where donor-specific anti-HLA antibodies (DSA) negatively impact graft survival, correlation of DSA with clinical outcomes in patients after orthotopic liver transplantation (OLT) has not been clearly established. We hypothesized that DSA are present in patients who develop chronic rejection after OLT. Prospectively collected serial serum samples on 39 primary OLT patients with biopsy-proven chronic rejection and 39 comparator patients were blinded and analyzed for DSA using LABScreen(®) single antigen beads test, where a 1000 mean fluorescence value was considered positive. In study patients, the median graft survival was 15 months, 74% received ≥ one retransplant, 20% remain alive and 87% had ≥ one episode of acute rejection. This is in contrast to comparator patients where 69% remain alive, and no patient needed retransplant or experienced rejection. Thirty-six chronic rejection patients (92%) and 24 (61%) comparator patients had DSA (p = 0.003). Chronic rejection versus comparator patients had higher mean fluorescence intensity (MFI) DSA. Although a further study with larger numbers of patients is needed to identify clinically significant thresholds, there is an association of high-MFI DSA with chronic rejection after OLT.

Limiting hepatitis C virus progression in liver transplant recipients using sirolimus-based immunosuppression.

Hepatitis C virus (HCV) causes progressive liver fibrosis in liver transplant recipients and is the principal cause of long-term allograft failure. The antifibrotic effects of sirolimus are seen in animal models but have not been described in liver transplant recipients. We reviewed 1274 liver recipients from 2002 to 2010 and identified a cohort of HCV recipients exposed to sirolimus as primary immunosuppression (SRL Cohort) and an HCV Control Group of recipients who had never received sirolimus. Yearly protocol biopsies were done recording fibrosis stage (METAVIR score) with biopsy compliance of >80% at both year one and two. In an intent-to-treat analysis, the SRL Cohort had significantly less advanced fibrosis (stage ≥2) compared to the HCV Control Group at year one (15.3% vs. 36.2%, p < 0.0001) and year two (30.1% vs. 50.5%, p = 0.001). Because sirolimus is sometimes discontinued for side effects, the SRL Cohort was subgroup stratified for sirolimus duration, showing progressively less fibrosis with longer sirolimus duration. Multivariate analysis demonstrated sirolimus as an independent predictor of minimal fibrosis at year one, and year two. This is the first study among liver transplant recipients with recurrent HCV to describe the positive impact of sirolimus in respect of reduced fibrosis extent and rate of progression.

Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver.

Liver toxicity is one of the consequences of ecstasy (3,4-methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported after MDMA consumption. Various factors probably play a role in ecstasy-induced hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive hepatic metabolism that involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-α can promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-κB, Bcl-2) proteins. The aim of the present study was to obtain evidence for the oxidative stress mechanism and apoptosis involved in ecstasy-induced hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration. Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment included decrease of GR and GPx activities (29% and 25%, respectively) and GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy administration compared to control rats. Liver cytosolic level of AA was increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong positive reaction for TNFα (p<0.001) in hepatocytes and a diffuse apoptotic process in the liver specimens (p<0.001). There was correlation between immunohistochemical results and Western blotting which were quantitatively measured by densitometry, confirming the strong positivity for TNF-α (p<0.001) and NF-κB (p<0.001); weak and intense positivity reactions was confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The results obtained in the present study suggest that MDMA induces loss of GSH homeostasis, decreases antioxidant enzyme activities, and lipoperoxidation that causes an oxidative stress that accompaines the MDMA-induced apoptosis in liver cells.

Clinical, morphological and genetic studies in a cohort of 21 patients with myofibrillar myopathy.

The term myofibrillar myopathies (MFM) refers to uncommon neuromuscular disorders that pathologically are characterized by myofibrillar degeneration and ectopic expression of several proteins. MFM are partly caused by mutations in genes that encode mainly Z-disk-related proteins (desmin, alphaB-crystallin, myotilin, ZASP, filamin C and BAG3). We reviewed clinical, light and electron microscopy, immunohistochemistry, immunoblotting and genetic findings of 21 patients with MFM (15 unrelated patients and three pairs of brothers) investigated at our neuromuscular center. MFM patients begin to show symptoms at any age, from juvenile to late adult life and present a different distribution of muscle weakness. Cardiac involvement and peripheral neuropathy are common. Typical histological features include focal areas with reduction/loss of ATPase and oxidative enzyme activity, and amorphous material (eosinophilic on hematoxylin and eosin and dark blue on Engel-Gomori trichrome) in these abnormal fiber areas. Electron microscopy shows disintegration of myofibrils starting from the Z-disk and accumulation of granular and filamentous material among the myofilaments. Immunohistochemical studies demonstrate focal accumulation of desmin, alphaB-crystallin and myotilin in abnormal muscle fibers while immunoblot analysis does not highlight differences in the expression of these proteins also including ZASP protein. Therefore, unlike immunoblot, immunohistochemistry together with light and electron microscopy is a useful diagnostic tool in MFM. Finally three of our 21 patients have missense mutations in the desmin gene, two brothers carry missense mutations in the gene encoding myotilin, one has a missense mutation in alphaB-crystallin, and none harbour pathogenic variations in the genes encoding ZASP and BAG3.

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.

Physical Exercise for Late-Life Major Depression.

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

C3a, TNF-alpha and interleukin myocardial expression in a case of fatal sudden cardiac failure during clinic reactivation of systemic lupus erythematosus.

Isolated myocarditis, or dilated cardiomyopathy, is a rare and usually late clinical manifestation of systemic lupus erythematosus (SLE). Increased levels of complement split products are associated with disease activity. Injury of the vascular endothelium due to complement activation and immune complexes may contribute to the vasculopathy in SLE. We present a case of sudden cardiac failure and death in a 28-year-old Caucasian man, during reactivation of SLE. To explain the sudden cardiac failure, we looked for anti-tumour necrosis factor (TNF)- proportional, variant and anti-interleukin (IL) expression in cardiac cells, and anti-complement (anti-C)3a in small cardiac vessels. The immunohistochemical examination of heart specimens revealed a strong positive reaction in cardiac myocytes for antibodies anti-TNF- proportional, variant and IL-8, and a milder positive reaction for antibodies anti-IL-15 and IL-10. A strong positive reaction of C3a in small cardiac vessels was observed in all specimens. Furthermore, the expression of CD4 and CD8 showed a strong positive reaction in pericardium and valvular endocardium, and a lesser positivity in myocardial specimens. TNF appears to have played a major proinflammatory role in this fatal case.