A case of oncogenic osteomalacia due to occult nasal sinus tumor.

This paper shows a case of oncogenic osteomalacia in a 35-year-old man who presented with a 2-year history of generalized pain and progressive weakness of lower limbs, eventually became bed bound. At admission he had severe hip pain resulting from atraumatic femoral neck fractures. Laboratory investigations revealed hypophosphatemia, hyperphosphaturia, normocalcemia, elevated alkaline phosphatase, and normal serum levels of parathormone and 25-hydroxyvitamin D. Serum FGF-23 was elevated. Imaging showed osteoporosis and insufficiency fractures of the femoral neck. Whole body functional imaging failed to reveal any areas of increased activity. However, on computed tomography (CT) and magnetic resonance (MR) imaging, a tumor was discovered at left nasal cavity. The patient was treated with phosphate supplements and vitamin D, but his hypophosphatemia persisted. The tumor was surgically removed. Histologically, the tumor was diagnosed as variant of a sinonasal hemangiopericytoma-like tumor. After surgery, his symptoms were relieved and biochemical parameters normalized.

Non-alcoholic fatty liver disease in type 2 diabetes: Emerging evidence of benefit of peroxisome proliferator-activated receptors agonists and incretin-based therapies.

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, affecting more than half of the people living with type 2 diabetes (T2D). The relationship between NAFLD and T2D is bidirectional and the presence of one perpetuates the other, which significantly increases the hepatic as well as extrahepatic complications. Until recently, there was no approved pharmacological treatment for NAFLD/ nonalcoholic steatohepatitits (NASH). However, there is evidence that drugs used for diabetes may have beneficial effects on NAFLD. Insulin sensitizers acting through peroxisome proliferator-activated receptor (PPAR) modulation act on multiple levels of NAFLD pathogenesis. Pioglitazone (PPARγ agonist) and saroglitazar (PPARα/γ agonist) are particularly beneficial and recommended by several authoritative bodies for treating NAFLD in T2D, although data on biopsy-proven NASH are lacking with the latter. Initial data on elafibanor (PPAR α/δ agonist) and Lanifibranor (pan PPAR agonist) are promising. On the other hand, incretin therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA) and dual- and triple-hormone receptor co-agonists reported impressive weight loss and may have anti-inflammatory and antifibrotic properties. GLP-1 RAs have shown beneficial effects on NAFLD/NASH and more studies on potential direct effects on liver function by dual- and triple-agonists are required. Furthermore, the long-term safety of these therapies in NAFLD needs to be established. Collaborative efforts among healthcare providers such as primary care doctors, hepatologists, and endocrinologists are warranted for selecting patients for the best possible management of NAFLD in T2D.

Type 2 diabetes in children and adolescents: Exploring the disease heterogeneity and research gaps to optimum management.

Over the past 20 years, the incidence and prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents have increased, particularly in racial and ethnic minorities. Despite the rise in T2DM in children and adolescents, the pathophysiology and progression of disease in this population are not clearly understood. Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM. Furthermore, the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients, mostly due to the challenges of implementing clinical trials. A better understanding of the mechanisms underlying the de-velopment and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies. This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.

A Novel Nutraceutical Supplement Lowers Postprandial Glucose and Insulin Levels upon a Carbohydrate-Rich Meal or Sucrose Drink Intake in Healthy Individuals-A Randomized, Placebo-Controlled, Crossover Feeding Study.

BACKGROUND: Alkaloid- and polyphenol-rich white mulberry leaf and apple peel extracts have been shown to have potential glucose-lowering effects, benefitting the control of postprandial blood glucose levels. This study aimed to determine the effect of the combination of Malus domestica peel and Morus alba leaf extracts (GLUBLOCTM) on postprandial blood glucose and insulin-lowering effects in healthy adults after a carbohydrate-rich meal or sucrose drink intake. METHODS: This study was designed as a randomized, crossover, single-blinded clinical trial. Out of 116 healthy participants, 85 subjects (aged 18-60 years) completed the day 1 and 5 crossover study. On day 1, subjects were supplemented with a placebo or GLUBLOCTM tablet 10 min before the carbohydrate-rich meal (300 g of tomato rice) or sucrose drink intake (75 g of sucrose dissolved in 300 mL water). On day 5, the treatments were crossed over, and the same diet was followed. Postprandial blood glucose and insulin levels were measured on days 1 and 5 (baseline 0, post-meal 30, 60, 90, and 120 min). Differences in iAUC, Cmax, and Tmax were determined between the placebo and GLUBLOCTM-treated cohorts. RESULTS: Significant changes in total iAUC (0-120 min), Cmax, and Tmax of postprandial blood glucose and insulin levels were noticed upon GLUBLOCTM supplementation. The percentage reduction in the iAUC of blood glucose levels was 49.78% (iAUC0-60min) and 43.36% (iAUC0-120min), respectively, compared with the placebo in the sucrose drink intake study. Similarly, there was a 41.13% (iAUC0-60min) and 20.26% (iAUC0-120min) glucose-lowering effect compared with the placebo in the carbohydrate-rich meal intake study. CONCLUSIONS: Premeal supplementation with GLUBLOCTM significantly reduced the postprandial surge in blood glucose and insulin levels after a carbohydrate-rich meal or sucrose drink intake over 120 min in healthy individuals. This study proves that GLUBLOCTM can manage steady postprandial blood glucose levels.

Gastric volvulus through morgagni hernia: an easily overlooked emergency.

BACKGROUND: Intractable vomiting in an elderly patient is an emergency condition requiring prompt diagnosis and intervention. Acute gastric outlet obstruction due to gastric volvulus through Morgagni-type diaphragmatic hernia is an exceedingly rare cause of this nonspecific complaint. OBJECTIVE: Our aim was to highlight that Morgagni hernia, although rare in adults, should be suspected in the appropriate clinical setting, and that a clue toward diagnosis often comes from routine chest and abdominal x-ray studies. In addition, we emphasize the atypical radiological findings and importance of emergency surgical intervention in such a case. CASE REPORT: We describe the case of a 78-year-old woman who presented to the Emergency Department with a 4-day history of intractable vomiting, and with no definitive clue to the diagnosis on examination. Her routine chest and abdomen x-ray studies suggested abnormal air-fluid level at right hemithorax, which prompted a computed tomography (CT) scan of the abdomen and an upper gastrointestinal contrast study. Gastric volvulus through a foramen of Morgagni was diagnosed and transthoracic reduction of the contents was performed, along with repair of the defect. CONCLUSIONS: A symptomatic Morgagni hernia in adults, although rare, can present with a variety of symptoms ranging from nonspecific complaints of bloating and indigestion to the more severe complaint of intestinal obstruction. Gastric volvulus and obstructive features are less frequently reported as acute complications of these hernias, which need early identification and intervention.

Randomised placebo-controlled double blind multicentric trial on efficacy and safety of Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12 for prevention of antibiotic-associated diarrhoea.

AIMS: To evaluate the effectiveness, safety and tolerability of a probiotic formulation containing Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12 in the prevention of antibiotic associated diarrhoea (AAD). METHODS AND MATERIAL: A double-blind randomised placebo controlled multicentric trial was conducted in adults who were prescribed a seven-day course of oral antibiotic (either cefadroxil or amoxycillin) for a documented indication. The effectiveness of a 14-day therapy (concomitant with antibiotic course and seven days thereafter) of the probiotic formulation in preventing AAD was evaluated. Safety profile was assessed by monitoring of all treatment emergent adverse events and tolerability on a global well being scale. RESULTS: The incidence of AAD in the probiotic group was 10.8% compared to 15.6% in the placebo group, the difference being statistically non-significant (p = 0.19). The relative risk for AAD was 0.7 with the 95% CI being 0.4 to 1.2. The diarrhoea duration in the probiotic group was two days with an interquartile range of 1- 3 days and was significantly less (p = 0.01) than the placebo group which was four days with an interquartile range of 3 - 5.5 days. Subgroup analysis of subjects with AAD showed that the incidence of severe diarrhoea (watery stools) was 96% in the placebo group (25 out of 26) compared to 31.6% (6 out of 19) in the probiotic group and this difference was significant statistically (p < 0.001). Four mild, non-serious, adverse events were detected (2.0%) in the probiotic group but there were none in the placebo group. CONCLUSION: This randomised controlled trial shows that prophylactic administration of the probiotic formulation containing Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12, did not effectively lower the incidence of AAD in adults. However, compared to placebo the duration of diarrhoea in the probiotic group was significantly reduced. Its tolerability and safety profile were good.

Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Critical review of bone health, fracture risk and management of bone fragility in diabetes mellitus.

The risk of fracture is increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the pathophysiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Heterogeneity of non-alcoholic fatty liver disease: Implications for clinical practice and research activity.

Non-alcoholic fatty liver disease (NAFLD) is a heterogeneous condition with a wide spectrum of clinical presentations and natural history and disease severity. There is also substantial inter-individual variation and variable response to a different therapy. This heterogeneity of NAFLD is in turn influenced by various factors primarily demographic/dietary factors, metabolic status, gut microbiome, genetic predisposition together with epigenetic factors. The differential impact of these factors over a variable period of time influences the clinical phenotype and natural history. Failure to address heterogeneity partly explains the sub-optimal response to current and emerging therapies for fatty liver disease. Consequently, leading experts across the globe have recently suggested a change in nomenclature of NAFLD to metabolic-associated fatty liver disease (MAFLD) which can better reflect current knowledge of heterogeneity and does not exclude concomitant factors for fatty liver disease (e.g. alcohol, viral hepatitis, etc.). Precise identification of disease phenotypes is likely to facilitate clinical trial recruitment and expedite translational research for the development of novel and effective therapies for NAFLD/MAFLD.

Prevalence of End-Organ Damage, Beta Cell Reserve, and Exocrine Pancreas Defect in Fibrocalculous Pancreatic Diabetes: An Eastern India Perspective.

BACKGROUND: Data on prevalence and burden of end-organ damage in fibrocalculous pancreatic diabetes (FCPD) from eastern India is scant. This study investigated the burden of end-organ damage and exocrine pancreatic defect in FCPD patients in Eastern India. MATERIALS AND METHODS: Consecutive FCPD patients underwent evaluation of glycemic control, C-peptide, fecal elastase, body fat percent, tests for cardiac autonomic neuropathy (CAN), neuropathy, nephropathy, and retinopathy which were compared with data from type-1 diabetes (T1DM) and type-2 diabetes (T2DM). RESULTS: Data from 101 FCPD, 41 T1DM, 40 T2DM, and 40 controls were analyzed. Body fat percent was lowest in FCPD and T1DM. Similarly, fasting and stimulated C-peptide was significantly lowest in T1DM, followed by FCPD. Significant elevations in stimulated C-peptide were observed in FCPD. Fecal elastase was lowest in FCPD. Exocrine pancreas defect in FCPD, T1DM, and T2DM was 100%, 53.66%, 27.5%, respectively. HbA1c was worst in FCPD. About 40% of FCPD patients had CAN while 13.33% had borderline CAN. Isolated parasympathetic dysfunction was the commonest (66.67%) among them. FCPD patients with CAN had lower fecal elastase, higher HbA1c, microalbuminuria, steatorrhea, neuropathy, retinopathy, and nephropathy, compared to those without CAN. On binary logistic regression, diabetes duration was a significant predictor of end-organ damage in FCPD. Fecal elastase and body fat percent were independent predictors for insulin therapy in FCPD. CONCLUSION: CAN is common in FCPD while exocrine pancreas defect is most severe in FCPD followed by T1DM and T2DM. Fecal elastase has an important prognostic role for insulinization in FCPD. Role of pancreatic enzyme replacement on glycemic control in diabetes with exocrine pancreas defect needs investigation.

Parathyroid Carcinoma and Persistent Hypercalcemia: A Case Report and Review of Therapeutic Options.

Parathyroid carcinomas are very uncommon, accounting for 0.1% to 5% of all causes of primary hyperparathyroidism. Parathyroid-jaw tumor syndrome, with a mutation in HRPT2 that encodes parafibromin, is the most common genetic association. Unique features include aggressive clinical course and a lack of preoperative definitive diagnostic criteria. The authors report a case of a 33-year-old male with bilateral nephrocalcinosis, a left-sided neck mass, high calcium, very high parathormone level and a history of parathyroid adenectomy. Computed tomography and 99m-technetium methoxyisobutylisonitrile scan revealed a localized tumor in the left inferior parathyroid region. The patient underwent radical surgery, and histopathology revealed characteristic features of parathyroid carcinoma. Preoperative identification with clinical clues is very important to plan a more radical surgical approach, as both radiotherapy and chemotherapy are ineffective. Recurrence is common and mostly occurs within 2-3 years after surgery. Patient's age, histology and tumor DNA aneuploidy are predictors of survival. Hypercalcemia is controlled with calcimimetics, bisphosphonates and denosumab in inoperable cases. Furthermore, biologic therapy with parafibromin and telomerase inhibitors is under development.

Development of bicalutamide-loaded PLGA nanoparticles: preparation, characterization and in-vitro evaluation for the treatment of prostate cancer.

In this study we report the development and optimization of poly (D, L-lactide-co-glycolide) (PLGA) polymer encapsulated poorly aqueous soluble nonsteroidal antiandrogen drug bicalutamide, to develop a sustained release formulation for the treatment of prostate cancer. The bicalutamide-loaded PLGA nanoparticles were prepared by single emulsion (O/W) solvent evaporation method, and different process parameters like polymer concentration in the organic phase, surfactant concentration in aqueous phase and centrifugation speed for separation of nanoparticles were evaluated to optimize the drug-loaded nanoparticles. The optimum formulation of bicalutamide-loaded PLGA nanoparticles characterized extensively by different analytical techniques like laser light scattering to determine average particle size and size distribution, scanning electron microscopy (SEM) for surface morphology, powder X-ray diffraction (PXRD) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. Significant decrease of crystallinity of bicalutamide confirms entrapment of the drug within the PLGA polymer matrix. Further, the drug encapsulation efficiency (EE) and in vitro drug release profile were measured by high-performance liquid chromatography and UV-spectrophotometry. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release up to 5 days. Optimum formulation of bicalutamide-loaded PLGA nanoparticles shows significant anti-tumor activity over prostate cancer cell lines (DU 145). The newly developed optimum formulation nanoparticles could be useful for sustained release delivery of bicalutamide.

In vivo pharmacological evaluation and efficacy study of methotrexate-encapsulated polymer-coated layered double hydroxide nanoparticles for possible application in the treatment of osteosarcoma.

Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD50) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.

siRNA-nanoparticle conjugate in gene silencing: A future cure to deadly diseases?

Alzheimers, cancer, acquired immune deficiency syndrome (AIDS) are considered to be some of the most deadly diseases of the 21st century on account of their severity and rapid increase in the number of affected population and with scarce cases of recovery, they still remain a troubling paradox. Specifically, with millions of cancer patients worldwide and lack of proper cure for the same, understanding the deadly disease at the molecular level and planning a therapeutic strategy in the same line is the need of the hour. Further, the potential threat of prevalence and escalation of Alzheimer's and HIV (human immunodeficiency virus) infection by more than three times as of recent past, needs a medical breakthrough to arrive at a meaningful solution to tackle the present day scenario. It is evident that these diseases initiate and propagate based on certain genes and their expression which needs to be silenced by the help of small interfering RNA (siRNA) by at least 70%. For short term silencing of the protein coding genes, siRNA is the most appropriate tool. Hence, the present communication explores the possibility for treatment and cure of a plethora of deadly diseases, e.g., cancer, including Alzheimer's and AIDS to some extent, emphatically at the molecular level, using the current trend of RNAi (RNA interference) delivery via a wide variety of nanoparticles.

Mucopolysaccharidosis type I disguised as rickets.

A 16-year-old boy with widening of the large joints of the extremities and bilateral genu valgum had been extensively treated with oral vitamin D, with little clinical benefit. A diagnosis of vitamin D-resistant rickets was considered initially but a thorough clinical examination and skeletal survey was suggestive of mucopolysaccharidosis. The diagnosis was confirmed biochemically and subtype classification pointed toward the type I variety of the storage disorder. Absence of mental retardation is very unusual in mucopolysaccharidosis type I, which itself is an uncommon clinical entity. This particular disease can be misdiagnosed as vitamin D-resistant rickets in the absence of thorough systemic examination and an attentive look at the skeletal surveys. Spondyloepiphyseal dysplasia is another close differential of mucopolysaccharidosis and it should be ruled out in all cases of suspected spondyloepiphyseal dysplasia.

"Petrified Ears" in Secondary Adrenal Insufficiency.

Petrification of the auricle, a rarely encountered clinical entity usually results from ectopic calcification of the auricular cartilages and manifests as rigid ear. The underlying pathogenesis remains ambiguous with several proposed hypotheses till date. Auricular calcification may be the sole cutaneous marker of underlying endocrinopathy at times. Adrenal insufficiency is the most common endocrinological disorder to be associated with such stiff ears and it has been described in both primary as well as secondary forms of the disease. We present here a 30-year-old man whose clinical condition deteriorated following levothyroxine supplementation and the presence of "petrified ears" ultimately provided a clue to the diagnosis of associated secondary adrenal insufficiency.