Efficacy of new active viscosupplements on the behavior of an experimental model of osteoarthritis. / Eficacia de nuevos viscosuplementos activos en el comportamiento de un modelo experimental de osteoartritis.

OBJECTIVE: To evaluate with an animal model of osteoarthritis (New Zealand rabbits) the effectiveness of treatment with active viscosupplements (hyaluronic acid loaded with nanoparticles (NPs) that encapsulate anti-inflammatory compounds or drugs. MATERIAL AND METHODS: Experimental study composed of 5 groups of rabbits in which section of the anterior cruciate ligament and resection of the internal meniscus were performed to trigger degenerative changes and use it as a model of osteoarthritis. The groups were divided into osteoarthrosis without treatment (I), treatment with commercial hyaluronic acid (HA) (II), treatment with HA with empty nanoparticles (III), treatment with HA with nanoparticles encapsulating dexamethasone (IV) and treatment with HA with nanoparticles that encapsulate curcumin (V). In groups II to V, the infiltration of the corresponding compound was carried out spaced one week apart. Macroscopic histological analysis was performed using a scale based on the Outerbridge classification for osteoarthritis. RESULTS: We observed that this osteoarthritis model is reproducible and degenerative changes similar to those found in humans are observed. The groups that were infiltrated with hyaluronic acid with curcumin-loaded nanoparticles (V), followed by the dexamethasone group (IV) presented macroscopically less fibrillation, exposure of subchondral bone and sclerosis (better score on the scale) than the control groups (I) (osteoarthritis without treatment), group (II) treated with commercial hyaluronic acid and hyaluronic acid with nanoparticles without drug (III). CONCLUSIONS: The use of active viscosupplements could have an additional effect to conventional hyaluronic acid treatment due to its antioxidant and anti-inflammatory effect. The most promising group was hyaluronic acid with nanoparticles that encapsulate curcumin and the second group was the one that encapsulates dexamethasone.

Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Lesiones osteolíticas multifocales / Multifocal osteolytic lesions

A 79-year-old woman with multiple pathologies and multiple osteolytic lesions during the Covid-19 pandemic. Histopathological and radiological differential diagnosis of injuries. (AU)

Impact of COVID-19 in nutritional and functional status of survivors admitted in intensive care units during the first outbreak. Preliminary results of the NUTRICOVID study.

BACKGROUND & AIMS: COVID-19 patients present a high hospitalization rate with a high mortality risk for those requiring intensive care. When these patients have other comorbid conditions and older age, the risk for severe disease and poor outcomes after ICU admission are increased. The present work aims to describe the preliminary results of the ongoing NUTRICOVID study about the nutritional and functional status and the quality of life of adult COVID-19 survivors after ICU discharge, emphasizing the in-hospital and discharge situation of this population. METHODS: A multicenter, ambispective, observational cohort study was conducted in 16 public hospitals of the Community of Madrid with COVID-19 survivors who were admitted to the ICU during the first outbreak. Preliminary results of this study include data retrospectively collected. Malnutrition and sarcopenia were screened at discharge using MUST and SARC-F; the use of healthcare resources was measured as the length of hospital stay and requirement of respiratory support and tracheostomy during hospitalization; other study variables were the need for medical nutrition therapy (MNT); and patients' functional status (Barthel index) and health-related quality of life (EQ-5D-5L). RESULTS: A total of 176 patients were included in this preliminary analysis. Most patients were male and older than 60 years, who suffered an average (SD) weight loss of 16.6% (8.3%) during the hospital stay, with a median length of stay of 53 (27-89.5) days and a median ICU stay of 24.5 (11-43.5) days. At discharge, 83.5% and 86.9% of the patients were at risk of malnutrition and sarcopenia, respectively, but only 38% were prescribed MNT. In addition, more than 70% of patients had significant impairment of their mobility and to conduct their usual activities at hospital discharge. CONCLUSIONS: This preliminary analysis evidences the high nutritional and functional impairment of COVID-19 survivors at hospital discharge and highlights the need for guidelines and systematic protocols, together with appropriate rehabilitation programs, to optimize the nutritional management of these patients after discharge.

Maximum adenoma diameter, regardless of uni- or bilaterality, is a risk factor for autonomous cortisol secretion in adrenal incidentalomas.

PURPOSE: To evaluate differences between patients with unilateral and bilateral adrenal incidentalomas (AIs) in the prevalence of autonomous cortisol secretion (ACS) and related comorbidities. METHODS: In this multicentre retrospective study, AIs ≥ 1 cm without overt hormonal excess were included in the study. ACS was defined by a post-dexamethasone suppression test (DST) serum cortisol ≥ 5.0 µg/dl, in the absence of signs of hypercortisolism. For the association of ACS with the prevalence of comorbidities, post-DST serum cortisol was also analysed as a continuous variable. RESULTS: Inclusion criteria were met by 823 patients, 66.3% had unilateral and 33.7% bilateral AIs. ACS was demonstrated in 5.7% of patients. No differences in the prevalence of ACS and related comorbidities were found between bilateral and unilateral AIs (P > 0.05). However, we found that tumour size was a good predictor of ACS (OR = 1.1 for each mm, P < 0.001), and the cut-off of 25 mm presented a good diagnostic accuracy to predict ACS (sensitivity of 69.4%, specificity of 74.1%). During a median follow-up time of 31.2 (IQR = 14.4-56.5) months, the risk of developing dyslipidaemia was increased in bilateral compared with unilateral AIs (HR = 1.8, 95% CI = 1.1-3.0 but, this association depended on the tumour size observed at the end of follow-up (HR adjusted by last visit-tumour size = 0.9, 95% CI = 0.1-16.2). CONCLUSIONS: Tumour size, not bilaterality, is associated with a higher prevalence of ACS. During follow-up, neither tumour size nor bilaterality were associated with the development of new comorbidities, yet a larger tumour size after follow-up explained the association of bilateral AIs with the risk of dyslipidaemia.

Sonographic evolution of the superficial vein thrombosis of the lower extremity.

BACKGROUND: Superficial venous thrombosis (SVT) is a common clinical problem across various treatment settings. SVT shares risk factors with deep venous thrombosis (DVT) and carries a risk of thromboembolic complications, greater than previously expected. Little is known about the pathophysiology, resolution and recurrence of this disease. OBJECTIVES: The objective of the present study was to describe the natural course of SVT, and factors correlated with the progression or resolution of the thrombus. METHODS: We included 218 patients with a recent diagnosis of SVT that were consecutively referred to a thrombosis clinic from the Emergency Department (ED) between January 2016 and April of 2018. RESULTS: The resolution of the thrombus prior to discharge was correlated to gender (female 73.8% vs. male 57.5%, p = 0.015), presence of varicose veins (62.4% vs. 46.4, p = 0.026), absence of family or personal history of thrombosis (98% vs. 91.3%, p = 0.021). The factor most correlated to thrombus resolution prior to discharge was the result of the 2nd ultrasound (improvement 83.9% vs. 16.1%, p < 0.001) immediately after initiation of heparin treatment. In the multivariate analysis, a high thrombus burden in the early follow-up ultrasound was the most significant predictive variable with prior to discharge recanalization (B = 20.9, 95% CI 9.8-44.7; p < 0.001). CONCLUSION: The follow-up of SVT with duplex lower extremity ultrasound allows us to monitor the evolution and early identify residual thrombosis, as a marker of hypercoagulability and recurrence. This study offers new perspectives for future research, necessary to improve the management of this disease, to reduce long-term complications.

Mesenchymal hamartoma and undifferentiated embryonal sarcoma: diagnostic keys that radiologists need to know. / Hamartoma mesenquimatoso y sarcoma embrionario indiferenciado: claves diagnósticas que el radiólogo debe conocer.

OBJECTIVE: Hepatic tumors are uncommon in pediatric patients. Among the most common of these uncommon tumors are mesenchymal hamartoma and undifferentiated embryonal sarcoma, which have different origins but similar appearance on imaging studies. This paper reviews the characteristic findings and differential diagnosis of these entities. Ultrasonography is the first-line imaging test to study these tumors. Magnetic resonance imaging and computed tomography are useful for further characterizing the tumors and planning surgery. CONCLUSION: Radiologists need to be familiar with the imaging findings of the different disease entities and to evaluate them together with the patient's age, personal history, and bloodwork.

Myofibroblasts and increased angiogenesis contribute to periapical cystic injury containment and repair.

BACKGROUND: Myofibroblasts (MF) and angiogenesis are important factors in the development and expansion of cystic lesions, where these cells secrete growth factors and proteases, stimulating angiogenesis, matrix deposition and cell migration, affecting the growth of these periapicopathies. The present study aimed to evaluate the immunohistochemical expression of CD34 and α-SMA in radicular cysts (RC) and residual radicular cysts (RRC), with the purpose of contributing to a better understanding of the expansion and progression of these periapical lesions. MATERIAL AND METHODS: The present study os a descriptive, quantitative and comparative analysis of positive CD34 and α-SMA immunohistochemical expressions in 30 RC and 30 RRC specimens. α-SMA expression was evaluated in the fibrous capsule of the lesions, at 100x magnification below the epithelial lining. A total of 10 higher immunostaining fields were selected and subsequently, positive cells were quantified at 400x magnification, averaged per field. Regarding the angiogenic index, immuno-labeled microvessel counts for the anti-CD34 antibody were performed in 10 fields at 200x magnification. RESULTS: Statistically significant differences regarding α-SMA immunostaining were observed (p = 0.035), as well as a correlation between α-SMA versus CD34 (p = 0.004) in RRC. However, the angiogenic index obtained by immunostaining for CD34 indicated no statistical difference between lesions. Intense inflammatory infiltrates were predominant in RC, while mild and moderate degrees were more commonly observed in RRC (p <0.001). Intense inflammatory infiltrates were also more often noted in larger RRC (p = 0.041). Inflammatory infiltrates showed no significant correlation with α-SMA and CD34 immunostaining. CONCLUSIONS: The results indicate that the significant correlation found between the presence of MF and the angiogenic index are related to the repair process in RRC.

Maintenance treatment in metastatic colorectal cancer: in search of the best strategy.

Over the last 2 decades, the standard fluoropyrimidine-based chemotherapy backbone for metastatic colorectal cancer has been complemented by the addition of novel biological agents, achieving impressive increases in 5-year survival rates. Nonetheless, these new combinations have also entailed increases in toxicity, leading to evaluation of de-escalated chemotherapy regimens and "drug holiday" periods in attempts to reduce side effects and optimise quality of life without impairing efficacy. Here, we review the current and emerging evidence for maintenance schedules with chemotherapy and targeted agents, versus continuous treatment after induction treatment, in metastatic colorectal cancer patients.

Neutrophil-to-lymphocyte ratio and mesenteric ischemia: can it predict the etiology of mesenteric ischemic at computed tomography?

OBJECTIVES: To assess the usefulness of the neutrophil-to-lymphocyte ratio (NLR) as a predictive factor of acute mesenteric ischemia (AMI) in patients presenting at the emergency department (ED) with acute abdominal pain. METHODS: This is a retrospective case-control study of patients older than 16 years admitted to the ED with acute abdominal pain with CT and histologic confirmation. The study group corresponded to patients with abdominal CT with radiological signs of AMI. The control group corresponded to patients with non-AMI findings in abdominal CT. Association measurements of NLR with radiological signs were compared with a paired-sample t test, and multivariate regression performed to analyze potential correlations. To assess the diagnosis capacity of NLR, ROC curves were calculated. RESULTS: A total of 61 patients were included (32 cases and 29 controls). The cases of AMI showed higher mortality (43.8% vs 6.9%, p < 0.01) and higher NLR on the limit of statistical significance (13.8 vs 8.7, p = 0.053). Patients with AMI due to occlusion of the superior mesenteric artery (SMA) showed a higher NLR (8.3 vs 22.3, p < 0.001). The area under the curve (AUC) of the NLR for AMI due to occlusion of the SMA was 0.88 (95% CI 0.7-1.0, p = 0.001). No patient with NLR < 5 presented AMI due to occlusion of the SMA. An NLR of 12.8 showed a sensitivity of 92% and a specificity of 74% for AMI due to occlusion of SMA. CONCLUSIONS: The NLR is a useful parameter of AMI of arterial origin due to occlusion of the SMA; it can help the clinician to raise suspicion of this diagnosis and the interpreting radiologist in the acquisition protocol for the CT study and would alert for an early surgical treatment.

Store-independent Orai1-mediated Ca2+ entry and cancer.

Ca2+ channels play an important role in the development of different types of cancer, and considerable progress has been made to understand the pathophysiological mechanisms underlying the role of Ca2+ influx in the development of different cancer hallmarks. Orai1 is among the most ubiquitous and multifunctional Ca2+ channels. Orai1 mediates the highly Ca2+-selective Ca2+ release-activated current (ICRAC) and participates in the less Ca2+-selective store-operated current (ISOC), along with STIM1 or STIM1 and TRPC1, respectively. Furthermore, Orai1 contributes to a variety of store-independent Ca2+ influx mechanisms, including the arachidonate-regulated Ca2+ current, together with Orai3 and the plasma membrane resident pool of STIM1, as well as the constitutive Ca2+ influx processes activated by the secretory pathway Ca2+-ATPase-2 (SPCA2) or supported by physical and functional interaction with the small conductance Ca2+-activated K+ channel 3 (SK3) or the voltage-dependent Kv10.1 channel. This review summarizes the current knowledge concerning the store-independent mechanisms of Ca2+ influx activation through Orai1 channels and their role in the development of different cancer features.

Diagnostic approach to subcutaneous nodules in patients with neuroendocrine tumours treated with depot somatostatin analogs: a cross-sectional study.

BACKGROUND: The presence of cutaneous nodules in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs) receiving depot somatostatin analogs (SSAs) is a diagnostic challenge as differential diagnosis between injection site reactions and metastases is essential. OBJECTIVE: To characterize the clinical, radiological, cytological and histopathological features of subcutaneous nodules in patients with GEP-NETs treated with SSAs. MATERIALS AND METHODS: Retrospective, cross-sectional study of patients with GEP-NETs treated with SSAs in whom subcutaneous nodules were detected on routine abdominal computed tomography (CT) scans. High resolution and colour Doppler ultrasonography was performed. Those patients with inconclusive radiological studies went through fine-needle aspiration cytology (FNAC) and/or biopsy. RESULTS: Twelve patients (five males, seven females) were included (six midgut carcinoid NETs, six pancreatic NETs). Three patients received intramuscular depot octreotide, seven subcutaneous lanreotide, and two both treatments. CT scan findings were nonspecific. Sonography revealed a hyperechoic pattern in recent injections, and a hypoechoic pattern with a characteristic hyperechoic peripheral rim in long-term injections (more than 3 months after injection). On colour Doppler sonography, nodules showed no signs of intralesional vascularity. Fine-needle aspiration cytology (FNAC) was performed in five patients, revealing a characteristic acellular proteinaceous material. Biopsy in four patients showed different reactional infiltrates around the acellular material. CONCLUSIONS: High resolution and colour Doppler ultrasonography may be very useful for the differential diagnosis of subcutaneous nodules in patients with GEP-NETs treated with SSAs. FNAC and a biopsy are useful tests for confirmation of the diagnosis in patients with inconclusive findings. We propose a management algorithm.

Immunoexpression of tryptase-positive mast cells in periapical granulomas and radicular cysts.

AIM: To evaluate and compare the immunoexpression of tryptase in samples of periapical granulomas (PGs) and radicular cysts (RCs) correlating it with the type of lesion, localization, intensity of the inflammatory infiltrate and thickness of the cystic epithelial lining, in order to gain insight into the phlogistic role of these cells in the lesions studied. METHODOLOGY: Twenty-five PGs and twenty-five RCs obtained from human teeth without endodontic treatment were submitted to morphological and immunohistochemical analysis using anti-tryptase antibody. Mast cells were identified and counted in three regions: intra-epithelial, central/superficial and deep portions. The data were analysed using the Mann-Whitney U-test (P < 0.05). RESULTS: In comparison with RCs, PGs exhibited higher immunoexpression of tryptase-positive mast cells located in both central/superficial and deep regions (P < 0.001 and P < 0.001, respectively). When considering the total number of mast cells and disregarding the location, the number of tryptase-positive mast cells increased gradually from RCs to PGs (P < 0.001). Lesions with inflammatory infiltrate grade III had greater number of tryptase-positive mast cells located in both central/superficial and deep regions than lesions with inflammatory infiltrates grade II (P = 0.045 and P = 0.025). When the location was ignored, the lesions with inflammatory infiltrate grade III also exhibited higher immunostaining of tryptase-positive mast cells (P = 0.01). CONCLUSIONS: Tryptase-positive mast cells were present in chronic periapical lesions in a larger number in periapical granulomas than in radicular cysts, in both central/superficial and deep regions.

Hiperfosfatasemia transitoria de la infancia: actualización / No disponible

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[Synchronous metastases of the spermatic cord from papillary renal cell carcinoma]. / Carcinoma renal papilar con metástasis sincr6nica en el cordón espermático.

Papillary renal cell carcinoma has been related with higher survival rate and lower metastatic cancer mortality rate than clear renal cell carcinoma. We present an aggressive case related to unusual features for this histological type, like a tumor size higher than ten cm, great perirrenal fat and suprarenal gland infiltration, tumoral thrombosis of the infrahepatic cava vein, retroperitoneal adenopatic tumoral infiltration, high nuclear grade and synchronous solitary distant organ metastases of the right spermatic cord, finding three previous cases in the literature with this last feature. Prognostic implication of the papillary renal cell carcinoma type is unclear in cases like this, so probably we need better molecular and cytogenetic studies to get a correct classification of this histological type.

Carcinoma renal papilar con metástasis sincrónica en el cordón espermático / Synchronous metastases of the spermatic cord from papillary renal cell carcinoma

El carcinoma de células renales papilar (CCRP) se ha relacionado con porcentajes de supervivencia superiores y tasas de mortalidad por cáncer metastático inferiores respecto al carcinoma de células renales convencional. Presentamos un caso de comportamiento agresivo de acuerdo a la suma de características infrecuentes para esta variante histológica, como el tamaño tumoral superior a 10 cm, la infiltración severa de la grasa perirrenal y de la glándula suprarrenal homolateral, la trombosis tumoral de la vena renal y de la vena cava infradiafragmática, la afectación adenopática retroperitoneal, un alto grado nuclear y la asociación en el momento del diagnóstico de una metástasis a distancia única sincrónica en el cordón espermático derecho, habiéndose comunicado esta última circunstancia en tres casos previos. La diferenciación pronóstica de la variante papilar resulta controvertida ante casos de este tipo, planteando la necesidad de obtener mejores perfiles diferenciales citogenéticos y moleculares para la clasificación de esta entidad histológica

Papillary renal cell carcinoma has been related with higher survival rate and lower metastatic cancer mortality rate than clear renal cell carcinoma. We present an aggressive case related to unusual features for this histological type, like a tumor size higher than ten cm, great perirrenal fat and suprarenal gland infiltration, tumoral thrombosis of the infrahepatic cava vein, retroperitoneal adenopatic tumoral infiltration, high nuclear grade and synchronous solitary distant organ metastases of the right spermatic cord, finding three previous cases in the literature with this last feature. Prognostic implication of the papillary renal cell carcinoma type is unclear in cases like this, so probably we need better molecular and cytogenetic studies to get a correct classification of this histological type

A community outbreak of Legionnaires' disease: evidence of a cooling tower as the source.

A community outbreak of Legionella pneumonia in the district of Cerdanyola, Mataró (Catalonia, Spain) was investigated in an epidemiological, environmental and molecular study. Each patient was interviewed to ascertain personal risk-factors and the clinical and epidemiological data. Isolates of Legionella from patients and water samples were subtyped by pulsed-field gel electrophoresis. Between 7 August and 25 August 2002, 113 cases of Legionella pneumonia fulfilling the outbreak case definition criteria were reported, with 84 (74%) cases being located within a 500-m radius of the suspected cooling tower source. In this area, the relative risk of being infected was 54.6 (95% CI 25.3-118.1) compared with individuals living far from the cooling tower. Considering the population residing in the Cerdanyola district (28,256 inhabitants) as a reference population, the attack rate for the outbreak was 399.9 cases/100,000 inhabitants, and the case fatality rate was 1.8%. A single DNA subtype was observed among the ten clinical isolates, and one of the subtypes from the cooling tower matched exactly with the clinical subtype. Nine days after closing the cooling tower, new cases of pneumonia caused by Legionella ceased to appear. The epidemiological features of the outbreak, and the microbiological and molecular investigations, implicated the cooling tower as the source of infection.

[Primary hepatic actinomycosis]. / Actinomicosis hepática primaria.

Primary hepatic actinomycosis is a rare infection that can clinically be confused with hepatic pyogenous abscesses or neoproliferative processes. We present the case of a 71-year-old man who had previously undergone total gastrectomy for gastric adenocarcinoma. After 4 years of favorable clinical course he presented a space-occupying lesion in the right hepatic lobe. Diagnostic tests were nonspecific and the diagnosis was confirmed by histological study of a biopsy of the lesion obtained through laparotomy. Prolonged antibiotic treatment produced a complete response. The etiopathogenesis and diagnostic-therapeutic options of hepatic actinomycosis are reviewed.

Splenic and adrenal lymphangiomatosis.

Lymphangiomatosis is a rare syndrome that can affect different organs, although simultaneous splenic and adrenal involvement is exceptional. We report the case of a young female with a symptomatic massive splenomegaly and no-nhypersecreating bilateral adrenal masses incidentally discovered that represented a diagnostic challenge. The management of adrenal incidentalomas is controversial, as the presence of large sized bilateral masses are highly indicative of malignancy. Despite the different diagnostic techniques available, it is sometimes impossible to reach an accurate preoperative diagnosis. Elective splenectomy and left adrenalectomy were performed, preserving the functioning of the right adrenal gland, radiologically similar to the left one, to prevent the development of definitive adrenal insufficiency. Postoperative evolution has been favourable without initial increase of the size of the right adrenal lesion. However, the persistence of this mass obligated long-term follow-up and shall assist us in better understanding the behavior of this bening lesion.