Regenerative potential of mesoporous silica nanoparticles scaffold on dental pulp and root maturation in immature dog's teeth: a histologic and radiographic study.

OBJECTIVE: To evaluate histologically and radiographically the potential of dog's immature roots with apical periodontitis to regenerate after regenerative endodontic treatment using mesoporous silica nanoparticles (MSNs) with/without bone morphogenic protein (BMP-2) as scaffolds. METHODS: In 4 mongrel dogs, 56 immature teeth with 96 roots were infected, resulting in necrotic pulps and periapical pathosis. According to the evaluation time (Group I = 30 days and Group II = 90 days), 90 roots were divided into two equal groups (45 roots each) and 6 roots used to replace any lost root during the procedure. The two main groups were further divided according to treatment protocol into 5 subgroups (9 roots each): blood clot (BC subgroup), mesoporous silica nanoparticles scaffold only (MSNs subgroup), mesoporous silica nanoparticles impregnated with BMP2 (MSNs + BMP2 subgroup), infected teeth without treatment (+ ve control subgroup) and normal untouched teeth (-ve control subgroup). All teeth surfaces were coated with Tincture iodine and calcium hydroxide was applied prior to treatment protocols. Then, teeth were restored with glass ionomer filling to seal the remaining part of the access cavity. Radiography evaluation of the increase in root length, root thickness and occurrence of apical closure were performed. Following the sacrifice of the two dogs at each time of evaluation, histopathological analysis was performed and included the inflammatory cells count, bone resorption, tissue ingrowth, deposition of hard tissue, and closure of the apical part. All data were statistically analyzed. RESULTS: Compared to BC subgroup, MSNs and MSNs + BMP-2 subgroups exhibited significant higher increase in root length and thickness as well as higher vital tissue in-growth and new hard tissue formation in group II (P < 0.05). MSNs + BMP-2 subgroup had significant higher increase in root length and thickness as well as significant lower inflammatory cell count than MSNs subgroup in both groups (P < 0.05). There were no significant differences between MSNs and MSNs + BMP-2 subgroups regarding new hard tissue formation in both groups and apical closure in group I (P > 0.05). CONCLUSION: MSNs with/without BMP-2 scaffolds enabled the continuing growth of roots in immature teeth with necrotic pulps and periapical pathosis. Addition of BMP-2 to MSNs scaffold improved its outcome in regenerative endodontics. CLINICAL RELEVANCE: MSNs with/without BMP-2 scaffolds may alternate blood clot for regenerative endodontic treatment of immature teeth with necrotic pulps.

Ultrafast intraoperative parathyroid hormone monitoring system: prospective, multicentre, clinical validity study.

BACKGROUND: Intraoperative parathyroid hormone (PTH) monitoring is a proven and reliable adjunct to parathyroid surgery, able to improve the outcomes and efficiency of the diagnostic and therapeutic pathway for patients with primary hyperparathyroidism. This study evaluated the innovative, compact, fully automated NBCL CONNECT Analyzer, which can measure whole-blood PTH in 5 min. METHODS: A prospective multicentre study was conducted in stages: results reviews, recommendations, and implementation of improvements to the mechanical design, components of cartridges, calibration, and sampling protocols. Patients undergoing parathyroidectomy had PTH levels measured on the Analyzer and main laboratory platforms, either Roche or Abbott. The Miami criterion of a 50% drop in PTH concentration was used to define biochemical cure during surgery, and normal postoperative calcium level as cure of primary hyperparathyroidism. Measurements on the Analyzer were done by laboratory staff in London and nurses in Stuttgart. The Pearson coefficient (R) and Wilcoxon test were used for statistical analysis. RESULTS: Some 234 patients (55 male, 179 female) with a median age of 58.5 (age full range 15-88) years underwent parathyroidectomy (195 minimally invasive, 38 bilateral neck exploration, 1 thoracoscopic; 12 conversions) for primary hyperparathyroidism between November 2021 and July 2022. Primary hyperparathyroidism was cured in 225 patients (96.2%). The sensitivity, specificity, and overall accuracy of the Analyzer assay in predicting biochemical cure were 83.9, 100, and 84.8% in phase 1; 91.2, 100, and 91.3% in phase 2; and 98.6, 100, and 98.6% in phase 3. There were no false-positive results (positive predictive value 100%). Correlations between Analyzer measurements and those obtained using the Roche device were very strong (R = 0.98, P < 0.001 in phase 1; R = 0.92, P < 0.001 in phase 2; R = 0.94, P < 0.001 in phase 3), and correlations for Analyzer readings versus those from the Abbott platform were strong (R = 0.82, P < 0.001; R = 0.89, P < 0.001; R = 0.91, P < 0.001). The Analyzer showed continued good mechanical performance, with stable and repeatable operations (calibrations, quality controls). Introducing a stricter sampling protocol and improvements in the clot-detecting system led to a decrease in the number of clotted samples and false-negative results. Outcomes were not affected by measurements performed either by nurses or laboratory staff. CONCLUSION: Intraoperative PTH monitoring during parathyroid surgery can be done accurately, simply, and quickly in whole blood using the Analyzer.

Leflunomide-induced cardiac injury in adult male mice and bioinformatic approach identifying Nrf2/NF-κb signaling interplay.

Leflunomide (LFND) is an immunosuppressive and immunomodulatory disease-modifying antirheumatic drug (DMARD) that was approved for treating rheumatoid arthritis. LFND-induced cardiotoxicity was not fully investigated since its approval. We investigated the cardiac injury in male mice and identified the role of nuclear factor erythroid 2-related factor 2/nuclear factor-κ B (Nrf2/NF-κB) signaling. Male albino mice were assigned into five groups as control, vehicle, and LFND (2.5, 5, and 10 mg/kg). We investigated cardiac enzymes, histopathology, and the mRNA expression of Nrf2, NF-κB, BAX, and tumor necrosis factor-α (TNF-α). The bioinformatic study identified the interaction between LFND and Nrf2/NF-κB signaling; this was confirmed by amelioration in mRNA expression (0.5- to 0.34-fold decrease in Nrf2 and 2.6- to 4.61-fold increases in NF-κB genes) and increased (1.76- and 2.625-fold) serum creatine kinase (CK) and 1.38- and 2.33-fold increases in creatine kinase-MB (CK-MB). Histopathological results confirmed the dose-dependent effects of LFND on cardiac muscle structure in the form of cytoplasmic, nuclear, and vascular changes in addition to increased collagen deposits and apoptosis which were increased compared to controls especially with LFND 10 mg/kg. The current study elicits the dose-dependent cardiac injury induced by LFND administration and highlights, for the first time, dysregulation in Nrf2/NF-κB signaling.

Comparing the Efficacy of Local Corticosteroid Injection, Platelet-Rich Plasma, and Extracorporeal Shockwave Therapy in the Treatment of Pes Anserine Bursitis: A Prospective, Randomized, Comparative Study.

Background: Pes anserine bursitis (PAB) is one of the most common causes of painful knee syndromes. This study aimed at examining the efficacy of local corticosteroid injection, platelet-rich plasma (PRP) injection, and extracorporeal shock wave therapy (ESWT) as different modalities to alleviate pain and enhance function in patients with pes anserine bursitis (PAB). Methods: A prospective, randomized, comparative study was conducted on 180 patients diagnosed with chronic PAB. They were equally divided into three groups as follows: Group I received a local corticosteroid injection of 40 mg of methylprednisolone acetate/1 ml; Group II received a PRP injection; and in Group III, ESWT was used. Outcome measures included the visual analog scale (VAS), Western Ontario and McMaster Universities (WOMAC) pain score, WOMAC physical function score, and Ritchie articular index (RAI) for tenderness, which were recorded at the baseline, after 1 week, and after 8 weeks. Results: Before the application of procedures, there was a statistically significant increase in the WOMAC pain score in the local corticosteroid group compared to the PRP group and the ESWT group (P < 0.001). After the application of procedures, there was a statistically significant improvement in the 1-week and 8-week WOMAC pain score, WOMAC physical function score, and VAS in the local corticosteroid group in comparison to the PRP group and the ESWT group. (P < 0.001). Moreover, RAI for tenderness shows statistically significant improvement at 8 weeks in the local corticosteroid groups compared to the PRP groups (P < 0.001) and ESWT groups (P < 0.001). Similarly, a statistically significant difference was found between the PRP and ESWT groups (P=0.023). Conclusion: Our data suggest that in patients with PAB, local corticosteroid injection is more efficient than PRP injection and ESWT for reducing pain and enhancing function.

Non-alcoholic fatty liver disease is associated with decreased bone mineral density in upper Egyptian patients.

Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (- 2.29 ± 0.4 vs. - 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348-0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.

Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC. DESIGN: Analyse SGPL1 expression impact on patient survival and adrenal cancer cell phenotype. We analysed two ACC cohorts with survival and corresponding transcriptomic data, focusing on SGPL1 and sphingolipid pathway genes. In vitro, we generated SGPL1-knockout and overexpressing H295R adrenocortical cells to investigate the role of SGPL1 in cell signalling in ACCs. RESULTS: We found increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1 correlated with reduced patient survival in both cohorts. Overexpression of SGPL1 in the H295R cell line increased proliferation and migration while reducing apoptosis, while SGPL1 knockout had the opposite effect. RNA-seq revealed a global increase in the expression of genes in the electron transport chain in overexpressing cells, correlating with increased aerobic respiration and glycolysis. Furthermore, the opposite phenotype was seen in cells lacking SGPL1. We subsequently found the increased proliferation is linked to metabolic substrate availability and increased capacity to use different fuel sources, but particularly glucose, in overexpressing cells. CONCLUSIONS: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.

Silent Lupus Nephritis: Renal Histopathological Profile and Early Detection with Urinary Monocyte Chemotactic Protein 1.

Objective: Lupus nephritis (LN) affects almost half of all individuals with systemic lupus erythematosus (SLE). Overt LN (OLN) symptoms might vary from asymptomatic microscopic hematuria to renal failure. However, when there are no clinical or laboratory indicators of renal involvement, some people with silent LN (SLN) may have pathological evidence of renal involvement identified by renal biopsy. Monocyte Chemotactic Protein 1 (MCP-1) is a chemotactic factor that promotes leukocyte migration to the kidney. MCP-1 urine levels (uMCP-1) have been demonstrated to be high in individuals with active LN. The purpose of this study was to discover the occurrence of SLN, as well as the possible variations between overt LN (OLN) and SLN across SLE patients based on the histopathological assessment, as well as the role of uMCP-1 in the early detection of SLN. Methods: An overall of 144 patients with SLE were included in the current research. Patients were subsequently divided into two groups: individuals who did not have clinical evidence of LN (84 patients) and those with OLN (60 patients). All the patients were subjected to the following investigations: uMCP-1, erythrocyte sedimentation rate (ESR), complement C3 (C3), complement C4 (C4), creatinine, albumin/creatinine ratio (uACR), creatinine clearance, quantitative assessment of proteinuria by 24-hour urine proteinuria (24hr UP) and percutaneous renal biopsy. Results: Sixty patients from group I (71.4%) showed glomerular lesions on renal biopsy (SLN), and class II was the predominant class. uMCP-1 had a sensitivity of 95.2% and a specificity of 98% in the detection of SLN, and uMCP-1 values were markedly higher in patients with OLN in comparison to SLN. Conclusion: The actual frequency of SLN may be higher than expected. High levels of uMCP-1 may have warranted the early activity of LN. uMCP-1 can be used as a non-invasive, useful tool for the prediction of LN.

Circulating microRNAs and Clinicopathological Findings of Papillary Thyroid Cancer: A Systematic Review.

BACKGROUND/AIM: Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a rising incidence. There is a need for a non-invasive preoperative test to enable better patient counselling. The aim of this systematic review was to investigate the potential role of circulating microRNAs (miRNAs) in the diagnosis and prognosis of PTC. MATERIALS AND METHODS: A systematic literature search was performed using MEDLINE, Cochrane, and Scopus databases (last search date was December 1, 2021). Studies investigating the expression of miRNAs in the serum or plasma of patients with PTC were deemed eligible for inclusion. RESULTS: Among the 1,533 screened studies, 39 studies met the inclusion criteria. In total, 108 miRNAs candidates were identified in the serum, plasma, or exosomes of patients suffering from PTC. Furthermore, association of circulating miRNAs with thyroid cancer-specific clinicopathological features, such as tumor size (13 miRNAs), location (3 miRNAs), extrathyroidal extension (9 miRNAs), pre- vs. postoperative period (31 miRNAs), lymph node metastasis (17 miRNAs), TNM stage (9 miRNAs), BRAF V600E mutation (6 miRNAs), serum thyroglobulin levels (2 miRNAs), 131I avid metastases (13 miRNAs), and tumor recurrence (2 miRNAs) was also depicted in this study. CONCLUSION: MiRNAs provide a potentially promising role in the diagnosis and prognosis of PTC. There is a correlation between miRNA expression profiles and specific clinicopathological features of PTC. However, to enable their use in clinical practice, further clinical studies are required to validate the predictive value and utility of miRNAs as biomarkers.

Evaluating Gender Differences in Egyptian Fibromyalgia Patients Using the 1990, 2011, and 2016 ACR Criteria.

Background: Fibromyalgia (FM) is a common rheumatic illness distinguished by chronic pain, fatigue, cognitive problems, and functional disability. However, the differences between men and women have not yet been comprehensively studied, especially after the development of the last 2016 American College of Rheumatology (ACR) criteria. The aim of this study was to evaluate the gender differences in symptom characteristics, cognitive dysfunction, and disease severity in Egyptian FM patients considering both the ACR 1990, 2011, and the last 2016 ACR diagnostic criteria. Methods: This is a prospective cross-sectional study that was carried out on 352 patients with FM in the Rheumatology Department, Al-Azhar University Hospital in Egypt, in the period between January 1, 2020, and June 1, 2021. In addition to the number of tender points (TPC), data was collected on age, gender, body mass index (BMI), marital status, disease onset, duration, and diagnostic delay. The widespread pain index (WPI), the symptom severity scale (SSS), fatigue, cognitive dysfunction, sleep disturbance, awakening unrefreshed, headache, abdominal pain, and depression were evaluated and scored according to 2010 and 2016 ACR criteria. A visual analog scale (VAS) for pain, fatigue, stiffness, anxiety, and depression is included in the questionnaire. The total score ranges were produced using total score ranges ranging from 0 to 80 (excluding job items), with higher scores indicating a stronger negative effect and/or intensity of symptoms. The polysymptomatic distress scale (PDS) has been calculated by the summation of the SSS with the WPI. The Revised FM impact questionnaire (FIQR) has also been evaluated. Results: The study shows that females have a significantly higher prevalence of fatigue, cognitive dysfunction, sleep disturbance, headache, and abdominal pain (p < 0.05). Also, females showed significantly higher scores than males regarding WPI, SSS, and mean TPC (p = 0.004, 0.027, and 0.001, respectively). While there was no difference regarding the FIQR (p=0.93), PDS was significantly higher in women (p= 0.001). Conclusion: Female patients with FM had greater disease severity scores, symptomatology, and number of tender points. Whatever the criteria applied, the prevalence and intensity of the disease features are higher in females, which may underestimate the disease in male patients.

Macrophage activation syndrome triggered by systemic lupus erythematosus flare: successful treatment with a combination of dexamethasone sodium phosphate, intravenous immunoglobulin, and cyclosporine: a case report.

BACKGROUND: Macrophage activation syndrome is classified as a secondary form of hemophagocytic lymphohistiocytosis. It is a hyperinflammatory complication observed to be comorbid with a variety of autoimmune diseases, including adult-onset Still's disease and systemic juvenile idiopathic arthritis. Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus, which, if untreated, can be fatal, though determining the optimum treatment strategy is still a challenge. CASE PRESENTATION: Herein, we report a case of macrophage activation syndrome in a 33-year-old Egyptian female as an unusual complication of a systemic lupus erythematosus flare in adult patients. Our patient was initially treated with a combination of intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy, which was followed by a course of oral prednisolone and oral cyclosporine with little response. Switching from oral prednisone to intravenous dexamethasone sodium phosphate showed a more favorable clinical and biochemical response. CONCLUSION: Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus. Our case demonstrates that dexamethasone sodium phosphate can be a successful alternative treatment for patients with systemic lupus erythematosus complicated by macrophage activation syndrome in whom the response to pulse methylprednisolone was inadequate to manage their illness, proving to be remarkably effective in a relatively short time frame.

Transapical off-pump mitral valve repair with NeoChord implantation: A systematic review.

INTRODUCTION: Mitral valve repair (MVr) is the gold standard for the treatment of degenerative mitral valve regurgitation (MR). The recently introduced NeoChord DS1000 has gained increasing recognition as a feasible, potentially safe, and effective procedure with minor complications and promising outcomes. This study aims to conduct a systematic review of the published literature that discusses the technical feasibility and outcome of transapical off-pump MVr with NeoChord DS1000 device implantation in the treatment of degenerative MR. METHODS: This review was performed according to the PRISMA statement. Databases searched in this review included Pubmed, Web of Science, Scopus, and Cochrane databases for systematic reviews. All English articles on humans reporting isolated MVr using NeoChord DS1000 device were included provided that basic preoperative data, operative specifications, and postoperative mortality and morbidity were reported. RESULTS: This review included six studies comprised 249 patients who had NeoChord mitral procedure. Almost all patients included had severe MR (243/249, 97.6%). Operative success was achieved in 241 out of the 249 patients (96.8%). No intraoperative mortality was reported. Intraoperative arrhythmia was reported in six patients (2.4%) and significant bleeding was reported in eight patients (3.2%). CONCLUSION: Awaiting more evidence, NeoChord mitral procedure appears to be a promising procedure that can be considered in selected cases.

Investigating the structure-activity relationship of marine natural polyketides as promising SARS-CoV-2 main protease inhibitors.

Since its first report in December 2019, the novel coronavirus virus, SARS-CoV-2, has caused an unprecedented global health crisis and economic loss imposing a tremendous burden on the worldwide finance, healthcare system, and even daily life. Even with the introduction of different preventive vaccines, there is still a dire need for effective antiviral therapeutics. Nature has been considered as the historical trove of drug discovery and development, particularly in cases of worldwide crises. Herein, a comprehensive in silico investigation of a highly focused chemical library of 34 pederin-structurally related marine compounds, belonging to four polyketides families, was initiated against the SARS-CoV-2 main protease, Mpro, being the key replicating element of the virus and main target in many drugs development programs. Two of the most potent SARS-CoV-2 Mpro co-crystallized inhibitors, O6K and N3, were added to the tested database as reference standards. Through molecular docking simulation, promising compounds including Pederin (1), Dihydro-onnamide A (11), Onnamide C (14), Pseudo-onnamide A (17), and Theopederin G (29) have been identified from different families based on their superior ligand-protein energies and relevant binding profiles with the key Mpro pocket residues. Thermodynamic behaviors of the identified compounds were investigated through 200 ns all-atom molecular dynamics simulation illustrating their significant stability and pocket accommodation. Furthermore, structural activity preferentiality was identified for the pederin-based marine compounds highlighting the importance of the terminal guanidine and cyclic hemiacetal linker, and the length of the sidechain. Our findings highlight the challenges of targeting SARS-CoV-2 Mpro as well as recommending further in vitro and in vivo studies regarding the examined marine products either alone or in combination paving the way for promising lead molecules.

Treating papillary and follicular thyroid cancer in children and young people: Single UK-center experience between 2003 and 2018.

AIM: Differentiated thyroid cancer (DTC) in children and adolescents is rare and data about its presentation and management are not well known. The aim of this study was to provide evidence of the current practice in the United Kingdom before the launch of the Rare National Paediatric Endocrine Tumours Guidelines (to be published in 2020). METHODS: Seventy-two children and adolescents with DTC (<18 years) who were treated at our institution between 2003 and 2018 were identified and their presentation, treatment and outcomes were reviewed. RESULTS: Median age at presentation was 12.7 years [range: 1-18] and fifty-two (72%) were girls. Fifty (69.4%) children and adolescents presented with a thyroid nodule. Thirteen (18%) had cervical adenopathy and seven of them (54%) underwent an excision biopsy under GA. Eight patients (11%) had evidence of lung metastases at presentation. Twenty-four patients (33%) underwent a hemithyroidectomy and 22 of those had a completion thyroidectomy subsequently, ten (14%) a total thyroidectomy alone and 37 (51%) a total thyroidectomy with lymph nodes dissection. Seventy patients (97%) underwent adjuvant RAI at our institution. The median number of children and adolescents managed per year was five [range: 0-10]. After an overall median follow-up of 40 months, eight patients (11%) had developed recurrent disease. The 1- and 5-year recurrence-free-survival-rates were 93% and 87%, respectively. Overall survival was 100%, with eight children and adolescents (11%) being alive with disease. CONCLUSION: This study confirms that DTC in children and adolescents is uncommon, is frequently advanced at presentation and has considerable recurrence rates. Despite this, overall survival is excellent. Although the work-up was generally appropriate (image-guided cytology), open biopsy for the diagnosis of lymph node involvement was still employed. The introduction of a specific UK guideline for this age-group will likely result in more tailored-made treatment-pathways and thereby hopefully improve quality and outcomes even further. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level IV.

Supplement With Calcium or Alendronate Suppresses Osteopenia Due to Long Term Rabeprazole Treatment in Female Mice: Influence on Bone TRAP and Osteopontin Levels.

BACKGROUND AND PURPOSE: Rabeprazole, a proton pump inhibitor (PPIs) is much endorsed to patients with increased gastric acidity. PPIs were accused to have osteoporotic effects on patients who chronically use them. The point of the current investigation was to decide the impact of rabeprazole on osteoporosis and to explore the modulatory effects of dietary calcium or alendronate on this side effect. METHODS: 80 female mice were alienated into four groups maintained for 18 weeks: [1] Vehicle group: given distilled water in 12 ml/kg, P.O. [2] Rabeprazole control group: given rabeprazole in a dose equals 10 mg/kg every 48 h, P.O. [3] Rabeprazole + calcium: given rabeprazole (10 mg/kg every 48 h) along with calcium supplement. [4] Rabeprazole + alendronate: given rabeprazole (10 mg/kg every 48 h) and alendronate (1 mg/kg per week, i.p.). Serum calcium, phosphorus and parathyroid hormone were measured. Both femurs were kept in paraformaldehyde, and then the right one was used for X-ray examination with analysis by Digora software and the left one for histopathological examination (H&E) and immunohistochemical stains for osteopontin and tartrate resistant acid phosphatase (TRAP). RESULTS: Calcium supplementation or administration of alendronate along with rabeprazole significantly restored the mean bone density as shown by X-ray analysis. Femurs from mice received rabeprazole showed widely separated, thin-walled bone trabeculae and increased number of osteoclasts. Calcium or alendronate with rabeprazole showed thick bone trabeculae without full recovery from rabeprazole induced damage. Adding calcium supplementation to rabeprazole did not affect the histological abnormalities related to osteoclasts meanwhile alendronate produced inactivation of osteoclasts. Both calcium and alendronate decreased the rabeprazole-induced increment in the femur osteopontin level. CONCLUSION: Calcium or alendronate can be recommended for female patients on PPI therapy who are at risk of osteopenia.

Late Recovery of Parathyroid Function after Total Thyroidectomy in Children and Adults: Is There a Difference?

BACKGROUND: Parathyroid failure after total thyroidectomy is the commonest adverse event amongst both children and adults. The phenomenon of late recovery of parathyroid function, especially in young patients with persistent hypoparathyroidism, is not well understood. This study investigated differences in rates of parathyroid recovery in children and adults and factors influencing this. METHODS: A joint dual-centre database of patients who underwent a total thyroidectomy between 1998 and 2018 was searched for patients with persistent hypoparathyroidism, defined as dependence on oral calcium and vitamin D supplementation at 6 months. Demographic, surgical, pathological, and biochemical data were collected and analysed. Parathyroid Glands Remaining in Situ (PGRIS) score was calculated. RESULTS: Out of 960 patients who had total thyroidectomy, 94 (9.8%) had persistent hypoparathyroidism at 6 months, 23 (24.5%) children with a median [range] age 10 [0-17], and 71 (75.5%) adults aged 55 [25-82] years, respectively. Both groups were comparable regarding sex, indication, extent of surgery, and PGRIS score. After a median follow-up of 20 months, the parathyroid recovery rate was identical for children and adults (11 [47.8%] vs. 34 [47.9%]; p = 0.92). Sex, extent, and indication for surgery had no effect on recovery (all p > 0.05). PGRIS score = 4 (HR = 0.48) and serum calcium >2.25 mmol/L (HR = 0.24) at 1 month were associated with a decreased risk of persistent hypoparathyroidism on multivariate analysis (p < 0.05). CONCLUSION: Almost half of patients recovered from persistent hypoparathyroidism after 6 months; therefore, the term persistent instead of permanent hypoparathyroidism should be used. Recovery rates of parathyroid function in children and adults were similar. Regardless of age, predictive factors for recovery were PGRIS score = 4 and a serum calcium >2.25 mmol/L at 1 month.

Absent pericardium and lung hypoplasia in a child with severe mitral regurgitation.

An 8-year-old girl with severe mitral regurgitation presented with symptoms of heart failure. Clinical investigations did not raise suspicion of an absent left pericardium. Congenital defects of the pericardium are rare and frequently associated with other cardiac lesions. We describe a case of severe mitral regurgitation in a child in whom an absent left-sided pericardium with hypoplasia of left lung was found incidentally during surgery to repair the mitral valve. We believe such associations with other heart diseases is usually circumstantial but can influence the perioperative morbidity, length of hospital stay, and even alter the surgical management.

Children are at a high risk of hypocalcaemia and hypoparathyroidism after total thyroidectomy.

PURPOSE: Disruption of calcium homeostasis is the most common complication after total thyroidectomy in adults. We explored the incidence and risk factors of hypocalcaemia and hypoparathyroidism after total thyroidectomy in children (≤18 years of age). METHODS: One hundred six children underwent total thyroidectomy. Patient, operative and outcome data were collected and analyzed. RESULTS: The indication for surgery was Graves' disease in 52 children (49.1%), Multiple Endocrine Neoplasia type-2 in 36 (33.9%), multinodular goiter in 3 (2.8%) and follicular/papillary thyroid carcinoma in 15 (14.2%). Neck dissection was performed in 23 children (18.9%). In 14 children (13.2%), autotransplantation was performed; in 31 (29.2%), ≥1 glands were found in the specimen. Hypocalcaemia within 24 h of thyroidectomy was observed in 63 children (59.4%) and 52 (49.3%) were discharged on supplements. Hypoparathyroidism at 6 months persisted in 23 children (21.7%). The ratios of all forms of calcium-related-morbidity were larger among children with less than four parathyroid glands remaining in situ: hypocalcaemia within 24 h of thyroidectomy (54.0% versus 47.5%; p = 0.01), hypoparathyroidism on discharge (64.4% versus 37.7%; p = 0.004) and long-term hypoparathyroidism (31.1% versus 14.8%; p = 0.04). CONCLUSION: The incidence of postoperative hypocalcaemia and hypoparathyroidism among children undergoing total thyroidectomy is considerable. The inability to preserve the parathyroid glands in situ during surgery seems an important factor. For optimal outcomes, the parathyroid glands should be preserved in situ. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level IV.

DLK1/PREF1 marks a novel cell population in the human adrenal cortex.

The adrenal cortex governs fundamental metabolic processes though synthesis of glucocorticoid, mineralocorticoids and androgens. Studies in rodents have demonstrated that the cortex undergoes a self-renewal process and that capsular/subcapsular stem/progenitor cell pools differentiate towards functional steroidogenic cells supporting the dynamic centripetal streaming of adrenocortical cells throughout life. We previously demonstrated that the Notch atypical ligand Delta-like homologue 1 (DLK1)/preadipocyte factor 1 (PREF1) is expressed in subcapsular Sf1 and Shh-positive, CYP11B1-negative and CYP11B2-partially positive cortical progenitor cells in rat adrenals, and that secreted DLK1 can modulate GLI1 expression in H295R cells. Here we show that the human adrenal cortex remodels with age to generate clusters of relatively undifferentiated cells expressing DLK1. These clusters (named DLK1-expressing cell clusters or DCCs) increased with age in size and were found to be different entities to aldosterone-producing cell clusters, another well-characterized and age-dependent cluster structure. DLK1 was markedly overexpressed in adrenocortical carcinomas but not in aldosterone-producing adenomas. Thus, this data identifies a novel cell population in the human adrenal cortex and might suggest a yet-to be identified role of DLK1 in the pathogenesis of adrenocortical carcinoma in humans.

Dwarfs and Giants of Parathyroid Adenomas-No Difference in Outcome After Parathyroidectomy.

BACKGROUD: This study compares the outcome of parathyroidectomy for primary hyperparathyroidism (PHPT) in patients whose adenomas' weights were at the extremes of the distribution curve. As the size of parathyroid adenomas influences the success rate of localization studies for PHPT, it is possible that a difference in cure rate could be observed between subgroups of patients. MATERIALS AND METHODS: Data were retrieved from a prospective database maintained in a large university hospital. RESULTS: From a cohort of 519 patients who underwent parathyroidectomy for PHPT, two subgroups of patients were identified based on the extreme 10% of the distribution curve for adenomas' weight: adenomas <300 mg ("dwarfs", n = 100, median 200 mg) and >3000 mg ("giants", n = 56, median 4300 mg). In comparison with giant adenomas, dwarf adenomas were associated with less severe hypercalcemia (median 2.84 versus 3.00 mmol/L, P < 0.001) and lower PTH (median 11.7 versus 25.6 pmol/L, P < 0.001). The occurrence of dwarf adenomas showed no trend during the study period (23/173 [13%] in 2000-2004 versus 36/217 [17%] in 2007-2011). Scan-directed parathyroidectomy was feasible in more patients with giant adenomas (59% versus 38%). Persistent disease was diagnosed in three patients with dwarf adenomas. Patients with giant adenomas had no recurrence during a follow-up of 40 mo even though eight patients had histological features suggestive of atypical/malignant tumors. CONCLUSIONS: Preoperative biochemistry is a poor predictor of adenomas' size even at the extremes of the distribution curve. Cure can be achieved in all patients with "dwarf" adenomas. Even in the presence of suspicious histological features, "giant" adenomas did not show malignant behavior.

Impact of intraoperative parathyroid hormone monitoring on the management of patients with primary hyperparathyroidism.

BACKGROUND/OBJECTIVE: Intraoperative parathyroid hormone (IOPTH) monitoring during surgery for primary hyperparathyroidism (PHPT) could improve cure rate and simplify current care pathways. This study assesses the performance of US, MIBI and IOPTH monitoring and their impact on outcomes and perioperative strategy. DESIGN: This is a retrospective study of a prospectively maintained database of patients who underwent parathyroidectomy guided by preoperative US, MIBI and IOPTH monitoring. Test performance (sensitivity, specificity, PPV, NPV, accuracy) and IOPTH added value (percentage of patients in whom test contributed to achieving cure) were calculated. RESULTS: A total of 617 patients (median age 59 years, 75% females), 603 (97.7%) of them cured, were included in analysis. Sensitivity of US was higher than MIBI (78.2% vs 70%, P < 0.05), but both were inferior to IOPTH (98.6%, P < 0.05). US and MIBI were more sensitive at detecting single gland disease (SGD) than multigland disease (MGD) (85% vs 55% and 77.5% vs 45.5%, respectively, P < 0.05), while IOPTH performed well in both situations (98.8% vs 96.7%, P > 0.05). In 41 patients with incorrect US predictions, MIBI gave correct result only in 12 (29.3%) cases, while IOPTH gave correct predictions in all but one patient (97.6%). Minimally invasive parathyroidectomy (MIP) was completed in 409 patients, with a similar completion rate regardless whether both or one scan was positive. IOPTH added value was significant in whole cohort (14%) and in subgroups of patients with concordant vs discordant scans, minimally invasive vs conventional surgery, and initial vs reoperative surgery. CONCLUSIONS: Intraoperative parathyroid hormone monitoring is more accurate at predicting cure than US and MIBI are at identifying abnormal glands in patients undergoing parathyroidectomy for PHPT and significantly contributes to cure rate in range of clinical scenarios. This implies that its routine use could facilitate successful surgery in patients with single positive imaging and increase number of MIPs while maintaining high cure rate.