Long-term results of arthroscopic repair of type II SLAP lesions in sports: assessment of return to pre-injury playing level and critical risk factors for complication.

PURPOSE: The management of isolated SLAP lesions is still debated especially in athletes. Aims of the study were: 1. to analyse our algorithm to treat SLAP lesions starting from the selection of patients for surgery and 2. to correlate the familiarity for diabetes and hypothyroid disorders with post-operative results. METHODS: Seventy-eight patients with isolated SLAP lesion were arthroscopically treated using knotless anchors and microfractures. All patients had a pre-operative and post-operative clinical examination according to Walch-Duplay, Constant, Rowe and Dash scores and interviewed for familiarity to diabetes and hypothyroid disorders. RESULTS: About 68.8% of patients solved pain with rehabilitation. About 29% of patients returned to the sports activities. About 32% of patients were no responder to physiotherapy and were arthroscopically treated. About 53.9% of patients responded excellent, 34.7% good, 3.8% medium and 7.6% poor results according to Walch-Duplay score. The Constant score increased from 64 to 95, the Rowe score from 48 to 96. The outcomes were significantly worse in patients with familiarity for diabetes. CONCLUSIONS: Microfractures and knotless anchor give long-term good results for the treatment of SLAP lesions in athletes. The familiarity for diabetes is an important risk factor that can lead to decreased outcomes.

Inhibition of C5aR1 as a promising approach to treat taxane-induced neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several antitumor agents resulting in progressive and often irreversible damage of peripheral nerves. In addition to their known anticancer effects, taxanes, including paclitaxel, can also induce peripheral neuropathy by activating microglia and astrocytes, which release pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1ß), and chemokine (C-C motif) ligand 2 (CCL-2). All these events contribute to the maintenance of neuropathic or inflammatory response. Complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling was very recently shown to play a crucial role in paclitaxel-induced peripheral neuropathy. Our recent findings highlighted that taxanes have the previously unreported property of binding and activating C5aR1, and that C5aR1 inhibition by DF3966A is effective in preventing paclitaxel-induced peripheral neuropathy (PIPN) in animal models. Here, we investigated if C5aR1 inhibition maintains efficacy in reducing PIPN in a therapeutic setting. Furthermore, we characterized the role of C5aR1 activation by paclitaxel and the CIPN-associated activation of nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. Our results clearly show that administration of the C5aR1 inhibitor strongly reduced cold and mechanical allodynia in mice when given both during the onset of PIPN and when neuropathy is well established. C5aR1 activation by paclitaxel was found to be a key event in the induction of inflammatory factors in spinal cord, such as TNF-α, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP). In addition, C5aR1 inhibition significantly mitigated paclitaxel-induced inflammation and inflammasome activation by reducing IL-1ß and NLRP3 expression at both sciatic and dorsal root ganglia level, confirming the involvement of inflammasome in PIPN. Moreover, paclitaxel-induced upregulation of C5aR1 was significantly reduced by DF3966A treatment in central nervous system. Lastly, the antinociceptive effect of C5aR1 inhibition was confirmed in an in vitro model of sensory neurons in which we focused on receptor channels usually activated upon neuropathy. In conclusion, C5aR1 inhibition is proposed as a therapeutic option with the potential to exert long-term protective effect on PIPN-associated neuropathic pain and inflammation.

KCTD1 is a new modulator of the KCASH family of Hedgehog suppressors.

The Sonic Hedgehog (Hh) signal transduction pathway plays a critical role in many developmental processes and, when deregulated, may contribute to several cancers, including basal cell carcinoma, medulloblastoma, colorectal, prostate, and pancreatic cancer. In recent years, several Hh inhibitors have been developed, mainly acting on the Smo receptor. However, drug resistance due to Smo mutations or non-canonical Hh pathway activation highlights the need to identify further mechanisms of Hh pathway modulation. Among these, deacetylation of the Hh transcription factor Gli1 by the histone deacetylase HDAC1 increases Hh activity. On the other end, the KCASH family of oncosuppressors binds HDAC1, leading to its ubiquitination and subsequent proteasomal degradation, leaving Gli1 acetylated and not active. It was recently demonstrated that the potassium channel containing protein KCTD15 is able to interact with KCASH2 protein and stabilize it, enhancing its effect on HDAC1 and Hh pathway. KCTD15 and KCTD1 proteins share a high homology and are clustered in a specific KCTD subfamily. We characterize here KCTD1 role on the Hh pathway. Therefore, we demonstrated KCTD1 interaction with KCASH1 and KCASH2 proteins, and its role in their stabilization by reducing their ubiquitination and proteasome-mediated degradation. Consequently, KCTD1 expression reduces HDAC1 protein levels and Hh/Gli1 activity, inhibiting Hh dependent cell proliferation in Hh tumour cells. Furthermore, analysis of expression data on publicly available databases indicates that KCTD1 expression is reduced in Hh dependent MB samples, compared to normal cerebella, suggesting that KCTD1 may represent a new putative target for therapeutic approaches against Hh-dependent tumour.

The data project: a shared approach between stakeholders of the healthcare system in definition of a therapeutic algorithm for inflammatory arthritis.

Rheumatic musculoskeletal diseases or RMD [rheumatoid arthritis (RA) and spondyloarthritis (SpA)] are systemic inflammatory diseases for which there are no biomarkers capable of predicting treatments with a higher likelihood of response in naive patients. In addition, the expiration of the anti-TNF blocking drugs' patents has resulted in the availability of anti-TNF biosimilar drugs with the same efficacy and safety than originators but at significantly reduced prices. To guarantee a personalized therapeutic approach to RMD treatment, a board of rheumatologists and stakeholders from the Campania region, Italy, developed a clinically applicable arthritis therapeutic algorithm to guide rheumatologists (DATA project). The general methodology relied on a Delphi technique forecast to produce a set of statements that summarized the experts' consensus. Selected clinical scenarios were discussed in light of the available evidence, and there were two rounds of voting on the therapeutic approaches. Separate discussions were held regarding rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The decision-making factors for each disease were clinical presentation, demographics, and comorbidities. In this paper, we describe a virtuous process between rheumatologists and healthcare system stakeholders that resulted in the development of a shared therapeutic algorithm for RMD patients naive to bDMARDs.

MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Posterior component separation with TAR: lessons learned from our first consecutive 52 cases.

Patients with complex incisional hernia (IH) is a growing and challenging category that surgeons are facing in daily practice and represent indeed a technical challenge for most of them. The posterior component separation with TAR (PCS-TAR) has become the procedure of choice to repair most complex abdominal wall defects, including those with loss of domain, subxiphoid, subcostal, parastomal or after trauma and sepsis treated initially with "open abdomen" and in those scenarios in which the fascia closure was not performed to avoid an abdominal compartment syndrome. Most recent studies showed that the PCS-TAR represents a valid procedure in recurrent IH. The purpose of our study is to evaluate the reproducibility of the PCS-TAR, describing our experience, our surgical technique and the rate of postoperative complications and recurrences in a cohort of consecutive patients. 52 consecutive patients with complex IH, who underwent PCS-TAR at "Betania Hospital and Ospedale del Mare Hospital" in Naples between May 2014 and November 2019 were identified from a prospectively maintained database and reviewed retrospectively. There were 36 males (69%) and 16 females (31%) with a mean age of 57.88 (range 39-76) and Body mass index (BMI kg/m2) of 31.2 (24-45). More than half of patients (58%) were active smokers. Mean defect width was 13.6 cm (range 6-30) and mean defect area was about 267.9 cm2. Mean operative time was 228 min. Posterior fascial closure was reached in all cases, while anterior fascial closure only in 29 cases (56%). Mean hospital stay was 5.7 days. 27% of patients developed minor complications (Clavien-Dindo grade I-II) and one case (1.9%) major complication (Clavien-Dindo III). Seroma was registered in 23% of cases. SSI was reported to be 3.8% with no deep wound infection. Recurrence rate was 1.9% in a mean follow-up of 28 months. In Univariate analysis Bio-A surface > 600 cm2 and drain removal at discharge were significantly associated with major complications, while in a multivariate analysis only Bio-A surface > 600 cm2 was related. Considering univariate analysis for recurrences, number of drains, SSO, Clavien-Dindo score > 2 and defect area were significantly associated with recurrence, while in a multivariate analysis no variables were related. PCS-TAR is an indispensable tool in managing complex ventral hernias associated with a low rate of SSO and recurrence. Tobacco use, obesity and comorbidities cannot be considered absolute contraindications to PCS-TAR. Peri and postoperative management of complications and drainages have an impact on short term outcomes. Based on these outcomes, posterior component separation with transversus abdominis release has become our method of choice for the management of patients with complex ventral hernia requiring open hernia repair in selected patients.

Oral sodium butyrate supplementation ameliorates paclitaxel-induced behavioral and intestinal dysfunction.

Paclitaxel (PTX) is one of the most broadly used chemotherapeutic agents for the treatment of several tumor types including ovarian, breast, and non-small cell lung cancer. However, its use is limited by debilitating side effects, involving both gastrointestinal and behavioral dysfunctions. Due to growing evidence showing a link between impaired gut function and chemotherapy-associated behavioral changes, the aim of this study was to identify a novel therapeutic approach to manage PTX-induced gut and brain comorbidities. Mice were pre-treated with sodium butyrate (BuNa) for 30 days before receiving PTX. After 14 days, mice underwent to behavioral analysis and biochemical investigations of gut barrier integrity and microbiota composition. Paired evaluations of gut functions revealed that the treatment with BuNa restored PTX-induced altered gut barrier integrity, microbiota composition and food intake suggesting a gut-to-brain communication. The treatment with BuNa also ameliorated depressive- and anxiety-like behaviors induced by PTX in mice, and these effects were associated with neuroprotective and anti-inflammatory outcomes. These results propose that diet supplementation with this safe postbiotic might be considered when managing PTX-induced central side effects during cancer therapy.

Evaluation of the immunomodulatory activity of thalidomide on tumor-associated macrophages in the 4T1 murine metastatic breast cancer model / [Avaliação do efeito imunomodulador da talidomida em macrófagos associados a tumores no modelo murino de câncer de mama metastático 4T1]

The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)

No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)

Diagnosis and treatment of dens invaginatus with open apex in a young adult patient by using cone-beam computed tomography and operative microscope.

BACKGROUND: Dens invaginatus is a developmental anomaly that can affect both deciduous and permanent dentition. The anomaly is caused by the invagination of the enamel organ into the dental papilla prior to the calcification of the dental tissues. The treatment option changes according to the classification, from the simple filling of the invaginated enamel area to root canal treatment with or without retrograde surgery, intentional re-implantation, or the extraction of the affected tooth. CASE REPORT: In this study we report a case of a maxillary lateral incisor invaginatus in a young adult patient. The periapical endoral X-ray showed the presence of a periapical radiolucency in tooth 22, that had a structure similar to a tooth inside it and an immature apex. Cold thermal testing showed that it was not a vital tooth. CBCT confirmed the diagnosis of Oehler Class II dens invaginatus. The treatment plan involved root canal treatment of both the "true" and the "invaginated" canal using calcium hydroxide-based intermediate medication. Then, after removing the hard internal structure with the aid of an operative microscope, MTA was used to close the immature apex. Finally, the large endodontic space was filled with self-etching, self-adhesive, dual curing resin cement. The patient was included in a follow-up programme to monitor and verify the complete healing of the periapical bone of the affected tooth. CONCLUSION: The use of technology and of special materials allowed an adequate management and resolution of the case reported.

The recommended lifetime immunization schedule from the board of vaccination calendar for life in Italy: A continuing example of impact on public health policies.

The Vaccination Calendar for Life is an alliance of scientific and professional societies of public health physicians, paediatricians and general practitioners in Italy which provides a periodical update on the ideal, scientifically driven vaccination calendar throughout lifetime. Since 2012, the Lifetime Immunization Schedule has represented a benchmark for Regional and National Authorities to set up the updated list of vaccines provided actively and free of charge to infants, children, adolescents, adults and the elderly by inclusion in the Triennial National Vaccination Plan (TNVP), and in the Essential Levels of Care (LEA). The impact of the different editions of the Lifetime Immunization Schedule on the TNVP was deep, representing the inspiring source for the present vaccination policy. The 2019 edition called for more attention to pregnant women immunization; risk groups vaccination; uniform high coverage with the MMRV vaccine; extension of Meningococcal B vaccination also at adolescent age; use of quadrivalent conjugate meningococcal vaccine also at 1 year of life; progressive decrease of the age of free-of-charge offer of influenza to ≥ 60 and then to ≥ 50 year-old population; implementation of flu immunization ages 6 months-6 years; HPV vaccination also offered to 25-year old women at the time of the first screening (gender neutral immunization already offered); sequential PCV13-PPV23 pneumococcal vaccination in 65 year-old subjects; increased coverage with rotavirus vaccine in infants and zoster vaccine in the elderly.

Steroidal saponins from the roots of Solanum sisymbriifolium Lam. (Solanaceae) have inhibitory activity against dengue virus and yellow fever virus

Dengue is the most important arthropod-borne viral disease worldwide. Infection with any of the four dengue virus (DENV) serotypes can be asymptomatic or lead to disease with clinical symptoms ranging from undifferentiated and self-limiting fever to severe dengue disease, which can be fatal in some cases. Currently, no specific antiviral compound is available for treating DENV. The aim of this study was to identify compounds in plants from Paraguayan folk medicine with inhibitory effects against DENV. We found high virucidal activity (50% maximal effective concentration (EC50) value of 24.97 µg/mL) against DENV-2 in the ethanolic extract of the roots of Solanum sisymbriifolium Lam. (Solanaceae) without an evident cytotoxic effect on Vero E6 cells. Three saponins isolated from the root extract showed virucidal effects (EC50 values ranging from 24.9 to 35.1 µg/mL) against DENV-2. Additionally, the saponins showed inhibitory activity against yellow fever virus (EC50 values ranging from 126 to 302.6 µg/mL), the prototype virus of the Flavivirus genus, suggesting that they may also be effective against other members of this genus. Consequently, these saponins may be lead compounds for the development of antiviral agents.

Ten-Year Efficacy and Safety of Once-Daily Tacrolimus in Kidney Transplant: A Prospective Cohort Study.

Tacrolimus is a cornerstone in the immunosuppressive therapy of kidney transplantation. The once-daily formulation of tacrolimus has been shown to improve adherence of patients without affecting short-term efficacy. However, long-term proof of once-daily tacrolimus efficacy and safety is still lacking. From January 2009 to November 2013, 170 clinically stable kidney transplant patients were offered to change from the ongoing twice-daily tacrolimus (TDT) formulation to a once-daily tacrolimus (ODT) regimen. Kidney transplant recipients agreeing to the change to be treated with an ODT regimen (n = 105, estimated glomerular filtration rate [eGFR] 57.1 ± 1.6 mL/min/1.73 m2) and patients continuing on a TDT formulation (n = 65, eGFR 52.0 ± 2.2 mL/min/1.73 m2) were prospectively followed (median follow-up time 10.4 and 12.6 years in the ODT and TDT groups, respectively, P = not significant). At the end of the follow-up, patients in both groups experienced similar eGFR (50.4 ± 2.2 vs 48.0 ± 2.7 mL/min/1.73 m2 in the ODT and TDT groups, respectively, P = not significant). No differences were observed in biopsy-proven acute rejection, overall graft survival, doubling of serum creatinine, and new onset of proteinuria. The 2 groups also had a comparable rate of death, sepsis, and neoplasia. In conclusion, ODT appears safe and effective in stable kidney graft recipients even 10 years after transplantation. These findings support the use of ODT as a primary tacrolimus formulation in patients with kidney transplantation.

Colonic transit in patients after anterior resection: prospective, comparative study using single-photon emission CT/CT scintigraphy.

BACKGROUND: Bowel dysfunction after anterior resection is well documented, but its pathophysiology remains poorly understood. No study has assessed whether postoperative variation in colonic transit contributes to symptoms. This study measured colonic transit using planar scintigraphy and single-photon emission CT (SPECT)/CT in patients after anterior resection, stratified according to postoperative bowel function. METHODS: Symptoms were assessed using the low anterior resection syndrome (LARS) score. Following gallium-67 ingestion, scintigraphy was performed at predefined time points. Nine regions of interest were defined, and geometric centre (GC), percentage isotope retained, GC velocity index and colonic half-clearance time (T½ ) determined. Transit parameters were compared between subgroups based on LARS score using receiver operating characteristic (ROC) curve analyses. RESULTS: Fifty patients (37 men; median age 72·6 (range 44·4-87·7) years) underwent planar and SPECT scintigraphy. Overall, 17 patients had major and nine had minor LARS; 24 did not have LARS. There were significant differences in transit profiles between patients with major LARs and those without LARS: GCs were greater (median 5·94 (range 2·35-7·72) versus 4·30 (2·12-6·47) at 32 h; P = 0·015); the percentage retained isotope was lower (median 53·8 (range 6·5-100) versus 89·9 (38·4-100) per cent at 32 h; P = 0·002); GC velocity indices were greater (median 1·70 (range 1·18-1·92) versus 1·45 (0·98-1·80); P = 0·013); and T½ was shorter (median 38·3 (17·0-65·0) versus 57·0 (32·1-160·0) h; P = 0·003). Percentage tracer retained at 32 h best discriminated major LARS from no LARS (area under curve (AUC) 0·828). CONCLUSION: Patients with major LARS had accelerated colonic transit compared with those without LARS, which may help explain postoperative bowel dysfunction in this group. The percentage tracer retained at 32 h had the greatest AUC value in discriminating such patients.

ANTECEDENTES: La disfunción intestinal después de la resección anterior (anterior resection, AR) está bien documentada, pero su fisiopatología sigue siendo poco conocida. Ningún estudio ha evaluado si la variación postoperatoria en el tránsito colónico contribuye a los síntomas. Este estudio midió el tránsito colónico mediante gammagrafía planar con SPECT/CT en pacientes después de una AR, estratificados según la función intestinal postoperatoria. MÉTODOS: Los síntomas se evaluaron mediante el sistema de puntuación del síndrome de resección anterior baja (low anterior resection syndrome, LARS). Después de la administración oral de galio-67, se realizó una gammagrafía en tiempos predefinidos. Se establecieron nueve regiones de interés y se midió/calculó las siguientes variables: (i) centro geométrico (geometric centre, GC); (ii) porcentaje de isótopo retenido; (iii) velocidad del GC; y (iv) semivida de aclaramiento del colon (T1/2). Se compararon los parámetros de tránsito en diferentes subgrupos de pacientes de acuerdo con su puntuación LARS utilizando análisis de curva ROC RESULTADOS: La gammagrafía planar con SPECT se realizó en 50 pacientes con AR seleccionados al azar (37 varones, media de 72,3 años (DE 9,0)). En total, 17 pacientes presentaban un LARS mayor, 9 tenían un LARS menor y 24 no presentaban LARS. En comparación con los pacientes sin LARS, los pacientes con LARS mayor tenían perfiles de tránsito significativamente diferentes: a las 32 horas, (i) los GC fueron mayores (mediana 5,94 (rango 2,35-7,72) versus 4,30 (2,12-6,47), P = 0,015)); (ii) el porcentaje de isótopo retenido fue menor (mediana 53,8% (error estándar de la media 6,5) versus 89,9% (3,4), P = 0,002)); (iii) las velocidades del GC fueron mayores (1,70 (1,18-1,92) versus 1,45 (0,98-1,80), P = 0,013)); y (iv) las semividas T1/2 fueron más cortas (38,3 horas (17,0-65,0) versus 57,0 (32,1-160), P = 0,003)). El porcentaje de isótopo retenido a las 32 horas fue el parámetro que mejor discriminó los pacientes con LARS mayor de los pacientes sin LARS (AUC 0,828). CONCLUSIÓN: Los pacientes con LARS mayor presentaron un tránsito colónico acelerado en comparación con los pacientes sin LARS, lo que puede contribuir a explicar la disfunción intestinal postoperatoria en dichos pacientes. El marcador de porcentaje de isótopo retenido a las 32 horas tenía un valor de AUC más elevado en la discriminación de estos pacientes.

Cardiac magnetic resonance imaging-indeterminate/negative cardiac sarcoidosis revealed by 18F-fluorodeoxyglucose-positron emission tomography: two case reports and a review of the literature.

BACKGROUND: Sarcoidosis is an inflammatory disorder of immune dysregulation characterized by non-caseating granulomas that can affect any organ. Cardiac sarcoidosis is an under-recognized entity that has a heterogeneous presentation and may occur independently or with any severity of systemic disease. Diagnosing cardiac sarcoidosis remains problematic with endomyocardial biopsies associated with a high risk of complications. Several diagnostic algorithms are currently available that rely on histopathology or clinical and radiological measures. The dominant mode of diagnostic imaging to date for cardiac sarcoidosis has been cardiac magnetic resonance imaging with gadolinium enhancement. CASE PRESENTATIONS: We report the cases of two adult patients: case 1, a 50-year-old white man who presented with severe congestive cardiac failure; and case 2, a 37-year-old white woman who presented with complete heart block. Both patients had a background of untreated pulmonary sarcoidosis. Cardiac magnetic resonance imaging did not show evidence of sarcoidosis in either patient and both proceeded to 18F-fluorodeoxyglucose-positron emission tomography scans that were highly suggestive of cardiac sarcoidosis. Both patients were systemically immunosuppressed with orally administered prednisone and methotrexate and had subsequent improvement by clinical and nuclear medicine imaging measures. CONCLUSIONS: Current consensus guidelines recommend all patients with sarcoidosis undergo screening for occult cardiac disease, with thorough history and examination, electrocardiogram, and transthoracic echocardiogram. If any abnormalities are detected, advanced cardiac imaging should follow. While cardiac magnetic resonance imaging identifies the majority of cardiac sarcoidosis, early disease may not be detected. These cases demonstrate 18F-fluorodeoxyglucose-positron emission tomography is warranted following an indeterminate or normal cardiac magnetic resonance imaging if clinical suspicion remains high. Unidentified and untreated cardiac sarcoidosis risks significant morbidity and mortality, but early detection can facilitate disease-modifying immunosuppression and cardiac-specific interventions.

Effect of lifelong football training on the expression of muscle molecular markers involved in healthy longevity.

PURPOSE: We investigated whether lifelong football training affects the expression of healthy longevity-related muscle molecular markers. METHODS: Biopsies were collected from the vastus lateralis muscle of 10 lifelong football-trained men (68.2 ± 3.0 years) and of 10 active untrained healthy men (66.7 ± 1.3 years). Gene and protein expression was measured by RTqPCR on RNA and by western blotting on protein extracts from muscle biopsies, respectively. RESULTS: The expression of AMPKα1/α2, NAMPT, TFAM and PGC1α, which are markers of oxidative metabolism, and MyHC ß isoform expression was higher in the muscle of football-trained men vs untrained men. Also citrate synthase activity was higher in trained than in untrained men (109.3 ± 9.2 vs 75.1 ± 9.2 mU/mg). These findings were associated with a healthier body composition in trained than in untrained men [body weight: 78.2 ± 6.5 vs 91.2 ± 11.2 kg; body mass index BMI: 24.4 ± 1.6 vs 28.8 ± 4.0 kg m-2; fat%: 22.6 ± 8.0 vs 31.4 ± 5.0%)] and with a higher maximal oxygen uptake (VO2max: 34.7 ± 3.8 vs 27.3 ± 4.0 ml/min/kg). Also the expression of proteins involved in DNA repair and in senescence suppression (Erk1/2, Akt and FoxM1) was higher in trained than in untrained men. At BMI- and age-adjusted multiple linear regression analysis, fat percentage was independently associated with Akt protein expression, and VO2max was independently associated with TFAM mRNA and with Erk1/2 protein expression. CONCLUSIONS: Lifelong football training increases the expression of key markers involved in muscle oxidative metabolism, and in the DNA repair and senescence suppression pathways, thus providing the molecular basis for healthy longevity.

Arthroscopic Bankart repair associated with subscapularis augmentation (ASA) versus open Latarjet to treat recurrent anterior shoulder instability with moderate glenoid bone loss: clinical comparison of two series.

PURPOSE: The treatment of chronic anterior shoulder instability with glenoid bone loss is still debated. The purpose of this study is to compare short-term results of two techniques treating chronic shoulder instability with moderate glenoid bone loss: bone block according to open Latarjet-Patte procedure and arthroscopic Bankart repair in association with subscapularis augmentation. METHODS: Ninety-one patients with moderate anterior glenoid bone loss underwent from 2011 to 2015. From these patients, two groups of 20 individuals each have been selected. The groups were homogeneous in terms of age, gender, dominance and glenoid bone loss. In group A, an open Latarjet procedure has been performed, and in group B, an arthroscopic Bankart repair associated with subscapularis augmentation has been performed. The mean follow-up in group A was 21 months (20-39 months), while in group B was 20 months (15-36 months). QuickDash score, Constant and Rowe shoulder scores, were used for evaluations of results. RESULTS: The mean preoperative rate of QuickDash score was 3.6 for group A and 4.0 for group B; Rowe Score was 50.0 for group A and 50.0 for group B. Preoperative mean Constant score was 56.2 for Latarjet-Patte and 55.2 for Bankart plus ASA. Postoperative mean QuickDash score was in group A 1.8 and 1.7 in group B; Rowe Score was 89.8 and 91.6; Constant Score was 93.3 and 93.8. No complications related to surgery have been observed for both procedures. Not statistically significant difference was reported between the two groups (p > .05). Postoperatively, the mean deficit of external rotation in ER1 was -9° in group A and -8 in group B; In ER2, the mean deficit was -5° in both groups (p = .0942). CONCLUSIONS: Arthroscopic subscapularis augmentation of Bankart repair is an effective procedure for the treatment of recurrent anterior shoulder instability with glenoid bone loss without any significant difference in comparison with the well-known open Latarjet procedure.

MiR-16 mediates trastuzumab and lapatinib response in ErbB-2-positive breast and gastric cancer via its novel targets CCNJ and FUBP1.

ErbB-2 amplification/overexpression accounts for an aggressive breast cancer (BC) subtype (ErbB-2-positive). Enhanced ErbB-2 expression was also found in gastric cancer (GC) and has been correlated with poor clinical outcome. The ErbB-2-targeted therapies trastuzumab (TZ), a monoclonal antibody, and lapatinib, a tyrosine kinase inhibitor, have proved highly beneficial. However, resistance to such therapies remains a major clinical challenge. We here revealed a novel mechanism underlying the antiproliferative effects of both agents in ErbB-2-positive BC and GC. TZ and lapatinib ability to block extracellular signal-regulated kinases 1/2 and phosphatidylinositol-3 kinase (PI3K)/AKT in sensitive cells inhibits c-Myc activation, which results in upregulation of miR-16. Forced expression of miR-16 inhibited in vitro proliferation in BC and GC cells, both sensitive and resistant to TZ and lapatinib, as well as in a preclinical BC model resistant to these agents. This reveals miR-16 role as tumor suppressor in ErbB-2-positive BC and GC. Using genome-wide expression studies and miRNA target prediction algorithms, we identified cyclin J and far upstream element-binding protein 1 (FUBP1) as novel miR-16 targets, which mediate miR-16 antiproliferative effects. Supporting the clinical relevance of our results, we found that high levels of miR-16 and low or null FUBP1 expression correlate with TZ response in ErbB-2-positive primary BCs. These findings highlight a potential role of miR-16 and FUBP1 as biomarkers of sensitivity to TZ therapy. Furthermore, we revealed miR-16 as an innovative therapeutic agent for TZ- and lapatinib-resistant ErbB-2-positive BC and GC.