Prevalence and Characterization of External Cervical Resorption Using Cone Beam Computed Tomography.

INTRODUCTION: The aim of this study was to assess the prevalence of external cervical resorption (ECR) and characterize the cases of ECR using cone beam computed tomography (CBCT). METHODS: High-resolution CBCT scans of 6216 patients (2280 males and 3936 females), consecutively acquired during the period July 2021 to March 2022, were analyzed. Identified cases of ECR were characterized by 3 evaluators regarding lesion height, circumferential spread, portal of entry proximity to root canal, stage, location, and width. RESULTS: In a total of 38 patients and 40 teeth, ECR cases demonstrated an incidence of 0.61%. The median age of the patients was 39 years. Prevalence of ERC was 0.78% among males and 0.50% among females. The most affected teeth were the maxillary incisors and canines. The most frequent characteristics of the lesion were: extension up to the cervical third (47.5%), more than 270° circumferential spread (42.55%), probable pulpal involvement (57.5%), progressive stage (65%), supracrestal (52.1%) and mesial (34.7%) localization of >1 mm in size (52.1%) portals of entry. Cases with greater longitudinal involvement also showed greater circumferential progression (P = .008). There was no association between portal of entry location and bone crest or ECR reparative phase (P = .42). Inter-rater agreement ranged from good to very good. No association between portal of entry and ECR progression was observed. CONCLUSIONS: ECR showed low prevalence in the Brazilian population, affecting mostly anterior maxillary teeth of patients within a wide age range. CBCT allowed characterization of ECR lesions with good interobserver agreement.

Management of teeth with dens invaginatus and apical periodontitis: A case series.

BACKGROUND: Dens invaginatus is a dental anomaly that can predispose the tooth to pulp and periapical pathology. CASE DESCRIPTION: Different endodontists treated 6 maxillary incisors with dens invaginatus associated with apical periodontitis. Cone-beam computed tomography was used to help with diagnosis and treatment planning in most patients. Four patients received diagnoses of Oehlers type II dens invaginatus and the other 2 as type III. In some patients with type II, the invagination had to be perforated to permit access to the apical part of the true root canal. Both the true canal and the invagination (pseudocanal) were treated in all cases using an antimicrobial regimen based on chemomechanical preparation with sodium hypochlorite irrigation and supplementary disinfection approaches. Calcium hydroxide medication was used in all but 1 case. The root canal and invagination were often filled using thermoplasticized gutta-percha techniques, sometimes using an apical plug with a bioceramic material in teeth with large apical openings. All treated patients had favorable clinical and radiographic outcomes. PRACTICAL IMPLICATIONS: Regardless of the complex anatomic variations, common strategic therapeutic approaches were identified that might serve as recommendations for proper management of teeth with dens invaginatus and apical periodontitis. These approaches include cone-beam computed tomographic planning, aggressive disinfection using sodium hypochlorite ultrasonic or sonic activation and calcium hydroxide intracanal medication, and thermoplasticized gutta-percha obturation of both the root canal and invagination.

Effects of Endodontic Infections on the Maxillary Sinus: A Case Series of Treatment Outcome.

This article shows the follow-up of several cases of maxillary sinusitis of dental (usually endodontic) origin, with different manifestations, diagnostic challenges, and outcomes.Cases from 14 patients from 3 countries and treated by 7 different endodontists are presented, all of them with inflammatory sinus changes represented by mucositis, osteoperiostitis, and/or partial/full obstruction. All cases showed dental and/or sinus signs/symptoms that resolved after dental management. In 13 cases, the sinus condition had an endodontic origin, 4 of them concurrently with periodontal involvement. In 1 case, sinusitis was caused by trauma to the face. All cases but 1 had a satisfactory response of the periradicular tissues and maxillary sinus to treatment that consisted of root canal therapy, root amputation, extraction, or trauma management.The successful management of most cases reported in this article emphasizes the importance of endodontics as a specialty engaged in saving teeth and promoting health not only in the oral cavity but also in other areas that may be affected by infections of endodontic origin, including the maxillary sinus.

Oxytocin Controls Chondrogenesis and Correlates with Osteoarthritis.

This study investigated the relationship of oxytocin (OT) to chondrogenesis and osteoarthritis (OA). Human bone marrow and multipotent adipose-derived stem cells were cultured in vitro in the absence or presence of OT and assayed for mRNA transcript expression along with histological and immunohistochemical analyses. To study the effects of OT in OA in vivo, a rat model and a human cohort of 63 men and 19 women with hand OA and healthy controls, respectively, were used. The baseline circulating OT, interleukin-6, leptin, and oestradiol levels were measured, and hand X-ray examinations were performed for each subject. OT induced increased aggrecan, collagen (Col) X, and cartilage oligomeric matrix protein mRNA transcript levels in vitro, and the immunolabelling experiments revealed a normalization of Sox9 and Col II protein expression levels. No histological differences in lesion severity were observed between rat OA groups. In the clinical study, a multivariate analysis adjusted for age, body mass index, and leptin levels revealed a significant association between OA and lower levels of OT (odds ratio = 0.77; p = 0.012). Serum OT levels are reduced in patients with hand OA, and OT showed a stimulatory effect on chondrogenesis. Thus, OT may contribute to the pathophysiology of OA.

Presepsin versus other biomarkers to predict sepsis and septic shock in patients with infection defined by Sepsis-3 criteria: the PREDI study of diagnostic accuracy. / Capacidad diagnóstica de presepsina comparada con otros biomarcadores para predecir sepsis y shock séptico en pacientes con infección siguiendo la definición Sepsis-3 (estudio PREDI).

OBJECTIVES: An accurate diagnosis of sepsis in the emergency department must be made before appropriate treatment can be started. Many biomarkers that are potentially useful have been studied. The main aim of this study was to compare the diagnostic accuracy of blood levels of presepsin, lactate, C-reactive protein (CRP), and procalcitonin (PCT) for predicting sepsis as defined by the Sepsis-3 criteria. The secondary aim was to evaluate the diagnostic accuracy of these biomarkers for predicting bacteremia whether or not sepsis or septic shock was present. MATERIAL AND METHODS: Single-center, prospective, observational cohort study in the emergency department of a university hospital. Consecutive patients suspected of having infection were enrolled prospectively if they had at least 2 criteria for systemic inflammatory response syndrome. We measured presepsin, PCT, CRP, and lactate in blood extracted on admission. RESULTS: Blood samples from 359 patients were analyzed; 228 (63.5%) met the criteria for sepsis and 20 (5.6%) met the criteria for septic shock. PCT and presepsin levels were the best predictors of sepsis and septic shock with areas under the receiver operating characteristic curve (AUC) of 0.711 (95% CI, 0.660-0.758) and 0.709 (95% CI, 0.658- 0.756), respectively (P <.001, both comparisons). The AUCs for CRP and lactate concentrations were, respectively, 0.63 (95% CI, 0.58-0.69) and 0.61 (95% CI, 0.56-0.66) (P <.05, both comparisons). On applying the diagnostic cut points of 0.25 ng/mL for PCT and 500 pg/mL for presepsin, the odds ratios were 2.51 (95% CI, 1.53-4.12) for PCT and 3.19 (95% CI, 1.91-5.31) for presepsin. The diagnostic accuracy of the combination of presepsin and PCT results (AUC, 0.71; 95% CI 0.66-0.76; P <.001) was no better than the accuracy of PCT alone. The most accurate predictor of bacteremia was PCT (AUC, 0.835; 95% CI, 0.79-0.87; P <.001). CONCLUSION: Presepsin and PCT seem to be the best predictors of a diagnosis of sepsis or septic shock in emergency department patients.

OBJETIVO: El diagnóstico correcto de la sepsis en urgencias es clave para iniciar el tratamiento de forma adecuada. Para ello, se han estudiado múltiples biomarcadores que podrían ser de utilidad. El objetivo principal de este estudio fue evaluar la capacidad diagnóstica de presepsina en sangre, en comparación con procalcitonina (PCT), proteína C reactiva (PCR) y lactato, para predecir sepsis o shock séptico según la definición de Sepsis-3. El objetivo secundario fue valorar la capacidad de estos biomarcadores para predecir bacteriemia, independientemente del diagnóstico final de sepsis o shock séptico. METODO: Estudio prospectivo de cohorte observacional, realizado en un único servicio de urgencias (SU) de un hospital universitario. Se incluyeron pacientes con sospecha clínica de infección y al menos dos criterios de síndrome de respuesta inflamatoria sistémica. En todos los pacientes se determinó en sangre presepsina, PCT, PCR y lactato en el momento de la visita en el SU. RESULTADOS: Se analizaron 359 pacientes, de los que 228 (63,5%) presentaban criterios de sepsis y 20 (5,6%) de shock séptico. PCT y presepsina fueron los mejores biomarcadores para predecir la sepsis/shock séptico con un área bajo la curva (ABC) de la capacidad operativa del receptor (ROC) de 0,711 (IC 95% 0,660-0,758; p < 0,001) y 0,709 (IC 95% 0,658-0,756; p < 0,001). La PCR obtuvo una ABC de 0,635 (IC 95% 0,582-0,686; p < 0,05), y el lactato una ABC de 0,61 (IC 95% 0,556-0,661; p < 0,05). Se utilizó un punto de decisión de 0,25 ng/ml para PCT y de 500 pg/ ml para presepsina. La odds ratio de presepsina para predecir sepsis fue de 3,19 (IC 95% 1,91-5,31) y para PCT de 2,51 (IC 95% 1,53-4,12). El diagnóstico de sepsis/shock séptico no mejoró al combinar presepsina y PCT (el ABC-ROC fue de 0,714, IC 95% 0,66-0,76; p < 0,001) en comparación con PCT aislada. La PCT fue el predictor más preciso de bacteriemia en pacientes con infección con un ABC-ROC de 0,835 (IC 95% 0,79-0,87; p < 0,001). CONCLUSIONES: La presepsina y la PCT son los biomarcadores con mejor rendimiento para el diagnóstico de sepsis y shock séptico en el SU.

Capacidad diagnóstica de presepsina comparada con otros biomarcadores para predecir sepsis y shock séptico en pacientes con infección siguiendo la definición Sepsis-3 (estudio PREDI) / Presepsin versus other biomarkers to predict sepsis and septic shock in patients with infection defined by Sepsis-3 criteria: the PREDI study of diagnostic accuracy

Objetivos. El diagnóstico correcto de la sepsis en urgencias es clave para iniciar el tratamiento de forma adecuada. Para ello, se han estudiado múltiples biomarcadores que podrían ser de utilidad. El objetivo principal de este estudio fue evaluar la capacidad diagnóstica de presepsina en sangre, en comparación con procalcitonina (PCT), proteína C reactiva (PCR) y lactato, para predecir sepsis o shock séptico según la definición de Sepsis-3. El objetivo secundario fue valorar la capacidad de estos biomarcadores para predecir bacteriemia, independientemente del diagnóstico final de sepsis o shock séptico. Método. Estudio prospectivo de cohorte observacional, realizado en un único servicio de urgencias (SU) de un hospital universitario. Se incluyeron pacientes con sospecha clínica de infección y al menos dos criterios de síndrome de respuesta inflamatoria sistémica. En todos los pacientes se determinó en sangre presepsina, PCT, PCR y lactato en el momento de la visita en el SU. Resultados. Se analizaron 359 pacientes, de los que 228 (63,5%) presentaban criterios de sepsis y 20 (5,6%) de shock séptico. PCT y presepsina fueron los mejores biomarcadores para predecir la sepsis/shock séptico con un área bajo la curva (ABC) de la capacidad operativa del receptor (ROC) de 0,711 (IC 95% 0,660-0,758; p < 0,001) y 0,709 (IC 95% 0,658-0,756; p < 0,001). La PCR obtuvo una ABC de 0,635 (IC 95% 0,582-0,686; p < 0,05), y el lactato una ABC de 0,61 (IC 95% 0,556-0,661; p < 0,05). Se utilizó un punto de decisión de 0,25 ng/ml para PCT y de 500 pg/ml para presepsina. La odds ratio de presepsina para predecir sepsis fue de 3,19 (IC 95% 1,91-5,31) y para PCT de 2,51 (IC 95% 1,53-4,12). El diagnóstico de sepsis/shock séptico no mejoró al combinar presepsina y PCT (el ABC-ROC fue de 0,714, IC 95% 0,66-0,76; p < 0,001) en comparación con PCT aislada. La PCT fue el predictor más preciso de bacteriemia en pacientes con infección con un ABC-ROC de 0,835 (IC 95% 0,79-0,87; p < 0,001). Conclusión. La presepsina y la PCT son los biomarcadores con mejor rendimiento para el diagnóstico de sepsis y shock séptico en el SU

Objectives. An accurate diagnosis of sepsis in the emergency department must be made before appropriate treatment can be started. Many biomarkers that are potentially useful have been studied. The main aim of this study was to compare the diagnostic accuracy of blood levels of presepsin, lactate, C-reactive protein (CRP), and procalcitonin (PCT) for predicting sepsis as defined by the Sepsis-3 criteria. The secondary aim was to evaluate the diagnostic accuracy of these biomarkers for predicting bacteremia whether or not sepsis or septic shock was present. Methods. Single-center, prospective, observational cohort study in the emergency department of a university hospital. Consecutive patients suspected of having infection were enrolled prospectively if they had at least 2 criteria for systemic inflammatory response syndrome. We measured presepsin, PCT, CRP, and lactate in blood extracted on admission. Results. Blood samples from 359 patients were analyzed; 228 (63.5%) met the criteria for sepsis and 20 (5.6%) met the criteria for septic shock. PCT and presepsin levels were the best predictors of sepsis and septic shock with areas under the receiver operating characteristic curve (AUC) of 0.711 (95% CI, 0.660-0.758) and 0.709 (95% CI, 0.658-0.756), respectively (P<.001, both comparisons). The AUCs for CRP and lactate concentrations were, respectively, 0.63 (95% CI, 0.58-0.69) and 0.61 (95% CI, 0.56-0.66) (P<.05, both comparisons). On applying the diagnostic cut points of 0.25 ng/mL for PCT and 500 pg/mL for presepsin, the odds ratios were 2.51 (95% CI, 1.53-4.12) for PCT and 3.19 (95% CI, 1.91-5.31) for presepsin. The diagnostic accuracy of the combination of presepsin and PCT results (AUC, 0.71; 95% CI 0.66-0.76; P<.001) was no better than the accuracy of PCT alone. The most accurate predictor of bacteremia was PCT (AUC, 0.835; 95% CI, 0.79-0.87; P<.001). Conclusion. Presepsin and PCT seem to be the best predictors of a diagnosis of sepsis or septic shock in emergency department patients

Isolated follicle-stimulating hormone (FSH) deficiency in two infertile men without FSH ß gene mutation: Case report and literature review.

OBJECTIVE: Congenital FSH deficiency is an exceptional cause of male infertility most often attributed to FSH ß gene mutations. The few published cases report azoospermia, severe testicular hypotrophy and normal testosterone levels associated with normal virilization. We report the exploration of two young men aged 26 and 27 years with severe sperm abnormalities, moderate testicular hypotrophy and isolated FSH deficiency. METHODS: Several FSH, LH, total testosterone and inhibin B assays and FSH ß gene sequencing were performed. RESULTS: FSH was almost undetectable at baseline and poorly responsive to GnRH test, whereas LH was normal at baseline and increased after GnRH test. Testosterone levels were within the adult range, while inhibin B levels were upper-normal to high. No FSH ß gene mutations were found. Exogenous FSH treatment was followed by spontaneous pregnancy in one case and required intra-cytoplasmic sperm injection (ICSI) in the other. CONCLUSIONS: The paradoxical high levels of inhibin B reflect the presence of functional Sertoli cells and may explain the isolated FSH deficiency. An intra-gonadal factor stimulating inhibin B secretion is discussed.

First family case of haemoglobinopathy Titusville in France and literature overview.

Normal haemoglobin is a tetramer molecule, consisting of two α and ß haemoglobin chains. Haemoglobinopathies occur when abnormalities in these proteins are present. More than 1000 naturally occurring human haemoglobin variants with single amino acid substitution throughout the molecule have been identified and can be discovered through their clinical and biological manifestations. Here, we report the case of a 60-year-old woman for whom no oximetry results were obtained during blood gas analysis (BGA) and the values of oxygen saturation obtained from pulse oximetry (73%) and co-oximetry (90%) differed. Haemoglobin analysis demonstrated the presence of a variant in the alpha chain. Clinical history of the patient and her family revealed they carry a haemoglobin variant (Titusville type), thus representing the first French family case reported. Those results raised the question whether the presence of this variant could be the cause of the errors encountered during BGA.

Is interstitial 8p23 microdeletion responsible of 46,XY gonadal dysgenesis? One case report from birth to puberty.

BACKGROUND: Chromosome 8p deletions are associated with a variety of conditions, including cardiac abnormalities, mental, behavioral problems with variable morphotype and genitourinary anomalies in boys. METHODS: We describe the follow-up over almost 15 years of a boy who initially presented with perineal hypospadias with a micropenis and cryptorchidism with 46,XY DSD. RESULTS: Imaging, pathology, and hormonal exploration suggested gonadal dysgenesis. Further genetic studies were deemed necessary during follow-up. The child's further development recommended further genetic analyses. High-resolution analysis showed an interstitial deletion on the short arm of a chromosome 8: 46,XY,del(8)(p23.1p23.1). We reviewed the literature and found 102 cases including 54 boys: 62.7% had mental problems, 50.9% a dysmorphic disorder, 55.9% cardiac anomalies, and 46.3% of the boys had genitourinary anomalies. Our patient's genital abnormalities can be explained by the haploinsufficiency of the genes, such as GATA4 (OMIM 600576) that are included in the deleted area. CONCLUSION: This case of severe 46,XY DSD raises the question of the role played by 8p23 microdeletion in gonadal dysgenesis. Clinicians are encouraged to look for this anomaly on chromosome 8 in cases of unexplained gonadal dysgenesis even when few signs suggestive of this anomaly are present.

Blood lactate measurement within the emergency department: A two-year retrospective analysis.

We evaluate in this retrospective cohort, the clinical situations leading emergency physicians to take a blood lactate sample, the prevalence of hyperlactatemia and its impact on short-term adverse outcome. ED patients requiring a blood lactate measurement (BLM) during a two-year period were included. Early patients' outcomes were extracted and discharge diagnoses were classified into 12 diagnostic categories. A total of 118,737 patients were analyzed. A BLM was carried out in 13,089 of them. Surprisingly, the proportion of patients having a BLM was higher in those admitted for seizure (31.4%) than in those admitted for infection (27.9%). Ten percent of patients who had a blood lactate test had a lactate level >4 mmol/l (1,315). Among them, 23.2% were admitted for infections, 20% for seizures, and 11% for cardiovascular diseases. After excluding the patients older than 75 years from the analysis in order to prevent a selection bias, the patient's severity was independently associated to an age over 65 years (OR: 1.26), an arterial blood sampling (OR: 2.77) and the blood lactate level (OR: 1.31). The blood lactate level was very informative to detect the sicker patients in the infection group whereas its interest was poor in the group of patients admitted for seizures. In conclusion, blood lactate testing has become routine in emergency departments and a large proportion of patients have abnormal blood lactate levels. The most frequent causes of high blood lactate in the ED are infection and seizures but the prognostic value of blood lactate seems to be different from one diagnostic category to the other.

Association of abdominal aortic aneurysm diameter with insulin resistance index.

INTRODUCTION: Epidemiological studies have highlighted a negative association between diabetes and abdominal aortic aneurysm (AAA). The aim of this study was to investigate the association between insulin resistance and AAA size. MATERIALS AND METHODS: This prospective cross sectional monocentric study analysed fasting blood samples from 55 patients with AAA eligible for surgical repair. They were divided into 2 groups according to the median AAA diameter: diameter < 50 mm (N = 28) and diameter > 50 mm (N = 27). The median ages were respectively 73 years (62 - 79) and 72 years (67 - 81). Glucose and fructosamine concentrations were determined by spectrophotometry; insulin and C-peptide using chemiluminescent technology. Homeostasis model assessment 2 calculator was used to estimate insulin resistance index (HOMA2 IR). RESULTS: There was no significant difference for fasting glucose concentration between the groups (6.1 vs. 5.9 mmol/L, P = 0.825). C-peptide and insulin concentrations, as well as HOMA2 IR index were significantly higher in patients with AAA > 50 mm (0.82 vs. 0.54 nmol/L, P = 0.012; 9 vs. 5 mU/L, P = 0.019 and 1.72 vs. 1.26, P = 0.028, respectively). No linear correlation was identified between AAA diameter and HOMA2 IR. Fructosamine concentration was lower in patients with AAA > 50 mm (225.5 vs. 251 µmol/L, P = 0.005) and negatively correlated with AAA diameter (r = - 0.54, P < 0.001). CONCLUSION: This study evidenced an association between AAA diameter and insulin resistance. Further studies are required to determine a causal link between insulin resistance and AAA development.

Positive Association of High Leptin Level and Abdominal Aortic Calcification in Men　- The Prospective MINOS Study.

BACKGROUND: Severe abdominal aortic calcification (AAC) points to high cardiovascular risk and leptin stimulates arterial calcification; however, clinical data on their association are scarce. We studied the link between serum leptin and AAC severity and progression, and the effect of smoking and lipid levels, on this association in men. Methods and Results: At baseline, 548 community-dwelling men aged 50-85 years underwent blood collection and lateral lumbar spine radiography. In 448 men, X-ray was repeated after 3 and 7.5 years. AAC was assessed using Kauppila's semiquantitative score. In multivariable models, high leptin was associated with higher odds of severe AAC (odds ratio [OR]=1.71 per SD, 95% confidence interval [CI]: 1.22-2.40). The odds of severe AAC were the highest in men who had elevated leptin levels and either were ever-smokers (OR=9.22, 95% CI: 3.43-24.78) or had hypertriglyceridemia (vs. men without these characteristics). Higher leptin was associated with greater AAC progression (OR=1.34 per SD, 95% CI: 1.04-1.74). The risk of AAC progression was the highest in men who had elevated leptin levels and either were current smokers or had high low-density lipoprotein-cholesterol levels (OR=5.91, 95% CI: 2.46-14.16 vs. men without these characteristics). These links remained significant after adjustment for baseline AAC and in subgroups defined according to smoking and low-density lipoprotein-cholesterol levels. CONCLUSIONS: In older men, high leptin levels are associated with greater severity and rapid progression of AAC independent of smoking, low-density lipoprotein-cholesterol or triglycerides.

Endocrine Disrupting Chemicals Interfere With Leydig Cell Hormone Pathways During Testicular Descent in Idiopathic Cryptorchidism.

Cryptorchidism, a frequent genital malformation in male newborn, remains in most cases idiopathic. On the basis of experimental, epidemiological, and clinical data, it has been included in the testicular dysgenesis syndrome and believed to be influenced, together with genetic and anatomic factors, by maternal exposure to endocrine disrupting chemicals (EDCs). Here, we analyze how EDCs may interfere with the control of testicular descent, which is regulated by two Leydig cell hormones, testosterone, and insulin like peptide 3 (INSL3).

Decreased serum glicentin concentration in patients with severe and morbid obesity.

Background Proglucagon-derived hormones represent a family of peptides mainly produced in the pancreas and the intestine. While several proglucagon-derived peptides play key roles in metabolic diseases, little is known about glicentin. The aim of the present study was to investigate serum glicentin concentrations in individuals with adult obesity and to study its potential link with various metabolic parameters. Methods Fifty-two individuals with normal body mass index (BMI < 25 kg/m2) and 39 patients with severe or morbid obesity (BMI > 35 kg/m2) were prospectively included at the University Hospital of Nice between January 2014 and April 2016. Clinical data were recorded, and a fasting blood sample was collected to measure glicentin, glucose, insulin, C-peptide, total cholesterol, triglyceride, LDL and HDL-cholesterol. In addition, a homeostasis model assessment for insulin resistance (HOMA2-IR) was also calculated. Results Patients with severe and morbid obesity had significantly higher plasma glucose, together with higher serum concentrations of insulin, C-peptide, HOMA2-IR, triglyceride, LDL-cholesterol and lower serum concentrations of HDL-cholesterol compared with individuals with a normal body mass index. The obese patients displayed significantly lower fasting serum concentrations of glicentin compared with subjects with a normal body mass index (12 pmol/L vs. 24 pmol/L, P < 0.0001). In the total population, fasting glicentin concentrations did not correlate with BMI, glycaemic parameters (glucose, insulin, C-peptide, HOMA-IR) or lipid parameters (total cholesterol, triglyceride, LDL and HDL-cholesterol). Conclusion To the best of our knowledge, this is the first study reporting serum glicentin concentrations in healthy lean and obese adult subjects. We found that fasting serum glicentin concentrations are decreased in patients with severe or morbid obesity suggesting the potential interest of this peptide in obesity and metabolic-related disorders.

Is Inappropriate Response to Cosyntropin Stimulation Test an Indication of Corticosteroid Resistance in Septic Shock?

We recently published a comparison of two hydrocortisone dosage regimens in patients with septic shock. We compare the results conferred by the two regimens as a function of the response to cosyntropin stimulation test (CST). Patients with septic shock were treated by one of two hydrocortisone regimens: either a 50-mg intravenous bolus every 6 h during 7 days (200 mg group; n = 49), or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300 mg group; n = 50). Nonresponders was defined as a CST response of 9 µg/dL or less. Nonresponders had more severe septic shock, greater fluid resuscitation needs, and greater vasopressor dependence than responders. When analyzed only as a function of CST results, there was no difference in survival between responders and nonresponders. However, analyses crossing CST results and the treatment regimens showed that patients who were responders and in the 300 mg group had significantly less intensive care unit mortality compared with responders in the 200 mg group (respective mortality of 24% vs. 55% [relative risk 0.43, 95% confidence interval, 0.20 to 0.94, P = 0.018]). Multivariate analysis identified baseline blood cortisol as an independent prognostic factor for 28-day mortality in all groups (hazard ratio 1.002, 95% confidence interval, 1.001 to 1.002, P ≤ 0.0001). The results suggest that in patients who respond to CST, hydrocortisone can provide a dose-dependent benefit. In contrast, nonresponse may indicate corticosteroid resistance. This heterogeneity of response to hydrocortisone may explain the difficulties encountered when trying to demonstrate its benefit in septic shock.

Insights on glicentin, a promising peptide of the proglucagon family.

Glicentin is a proglucagon-derived peptide mainly produced in the L-intestinal cells. While the roles of other members of the proglucagon family including glucagon-like peptide 1, glucagon-like peptide 2 and oxyntomodulin has been well studied, the functions and variation of glicentin in human are not fully understood. Experimental and clinical studies have highlighted its role in both intestinal physiology and glucose metabolism, pointing to its potential interest in a wide range of pathological states including gastrointestinal and metabolic disorders. Due to its structure presenting many similarities with the other proglucagon-derived peptides, its measurement is technically challenging. The recent commercialization of specific detection methods has offered new opportunities to go further in the understanding of glicentin physiology. Here we summarize the current knowledge on glicentin biogenesis and physiological roles. In the limelight of clinical studies investigating glicentin variation in human, we discuss future directions for potential applications in clinical practice.

Platelet-rich plasma respectively reduces and promotes adipogenic and myofibroblastic differentiation of human adipose-derived stromal cells via the TGFß signalling pathway.

Autologous fat grafting is a gold standard therapy for soft tissue defects, but is hampered by unpredictable postoperative outcomes. Fat graft enrichment with adipose-derived stromal cell (ASCs) was recently reported to enhance graft survival. Platelet-rich plasma (PRP) has also emerged as a biologic scaffold that promotes fat graft viability. Combined ASC/PRP fat grafting enrichment is thus a promising new regenerative medicine approach. The effects of PRP on ASC proliferation are well documented, but the impact of PRP on ASC differentiation has yet to be investigated in depth to further elucidate the PRP clinical effects. Here we analyzed the human ASC fate upon PRP treatment. PRP was found to sharply reduce the potential of ASCs to undergo differentiation into adipocytes. Interestingly, the PRP anti-adipogenic effect was accompanied by the generation of myofibroblast-like cells. Among the various factors released from PRP, TGFß pathway activators played a critical role in both the anti-adipogenic and pro-myofibroblastic PRP effects. Overall, these data suggest that PRP participates in maintaining a pool of ASCs and in the repair process by promoting ASC differentiation into myofibroblast-like cells. TGFß may provide an important target pathway to improve PRP clinical outcomes.

Fasting Circulating Glicentin Increases After Bariatric Surgery.

INTRODUCTION: Bariatric surgery including the Roux-en-Y gastric bypass (RYGB) and the laparoscopic sleeve gastrectomy (LSG) is a well-established therapeutic option for patients with morbid or severe obesity. Metabolic modifications observed after bariatric surgery are thought to be, at least partly, linked to hormonal changes. While variation of several proglucagon-derived peptides during bariatric surgery is well documented, little is known about glicentin. The aim of this study was to investigate circulating glicentin variations after bariatric surgery. MATERIAL AND METHODS: Thirty patients eligible for bariatric surgery (18 RYGB and 12 LSG procedures) were prospectively included in the University Hospital of Nice. Clinical data and fasting biological parameters were recorded preoperatively, at 3, 6, and 12 months after bariatric surgery. RESULTS: The median age of patients was 51 years (35-56) with 33.3% men. Fasting glicentin concentration increased progressively after bariatric surgery from 6 months and was more marked at 12 months (14 ± 3.6 pmol/L at baseline vs 19.7 ± 2.7 pmol/L at 12 months for RYGB and 12.5 ± 1.4 vs 16.4 ± 1.8 pmol/L for LSG, respectively). Compared to preoperative values, the fold increase of glicentin at 12 months was 2 ± 0.2 in the RYGB group and 1.6 ± 0.3 in the LSG group. Glicentin variation after surgery did not correlate with anthropometric, glycemic, or lipid parameter modifications. CONCLUSION: Fasting glicentin level increases after bariatric surgery suggesting the potential interest of this peptide as a player and/or a marker of physiological changes after bariatric surgery.

Accuracies of fecal calprotectin, lactoferrin, M2-pyruvate kinase, neopterin and zonulin to predict the response to infliximab in ulcerative colitis.

BACKGROUND: Fecal markers might predict the response to anti-TNFα in ulcerative colitis (UC). AIMS: To compare the performance of fecal calprotectin (fCal), lactoferrin (fLact), M2-PK (fM2-PK), neopterin (fNeo), and zonulin (fZon) to predict the response to therapy in active UC patients. METHODS: Disease activity from 31 consecutive patients with an active UC, treated with infliximab (IFX) was assessed by the Mayo score at baseline and at week 14 and by the partial Mayo score at W52 and stool samples collected for fecal marker measurements at W0, W2, and W14. RESULTS: At W14, 19 patients (61%) were responders to IFX induction. The median levels of fCal, fLact and fM2-PK drop dramatically from baseline to W14 in clinical responders. At W2, fM2-PK, fLact and fCal levels predicted accurately the response to IFX induction. At W14, fLact, fCal, and fM2-PK were individually reliable markers to predict sustained response at W52. The performances of fNeo and fZon were weaker in this setting. CONCLUSIONS: The performance of fM2-PK at W2 to predict response to induction therapy with IFX was superior to that of fLact and fCal, whereas monitoring fLact was the best tool to predict adequately the course of the disease at one year under maintenance IFX in UC.