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 patho-physiology 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.

Immunogenicity, Safety and Efficacy Comparison of Wockhardt’s Biosimilar Insulin Glargine—Glaritus®with Reference Product— Lantus®: Study Protocol &Early Data Trends

Objective: Present Phase IV Trial is aimed at evaluating the immunogenicity, safety, and efficacy of Wockhardt’s insulin glargine, Glaritus®in comparison with reference insulin glargine, Lantus®in subjects with type 2 diabetes mellitus (T2DM), inadequately controlled on oral hypoglycaemics. Setting: A head-to-head, prospective, open-label, parallel group, randomized, Phase IV, non-inferiority study over 6 months treatment conducted in 10 centres in India. Participants: Considering 20% drop-out rate, 180 subjects of either sex, age 18 - 55 years, diagnosed with T2DM with body mass index (BMI) 18 - 38 kg/m2 and HbA1c levels 8.0% - 10.0% inadequately controlled by 1 or more oral hypoglycaemics and according to investigator needed glargine treatment were enrolled in the study. Interventions: Subjects self-administered insulin glargine (Glaritus®or Lantus®) subcutaneously once daily for 6 months. Treatment in Glaritus®arm was continued till 12 months. Percentage change in anti-insulin antibody (AIA) titre and HbA1C was ascertained at every 3 months interval. The tests were performed at accredited central laboratory. Treat-to-target dose titration: Starting doses of Glaritus®and Lantus®was 10 units (or 0.2 units/kg) once daily. The target fasting blood glucose was 70 to 130 mg/dL. Daily glargine dose was titrated by ±10% based on average of last 3 FBG values being out of target range and presence of nocturnal hypoglycemia. Early data trends: First interim analysis was planned once 100 subjects complete visit 8 (6 months treatment). By then, 119 subjects (78 males and 41 females) with mean age 46.3 years were enrolled, of which 90 (75.6%) subjects had evaluable data. The results of analysis indicated trend of comparability between Glaritus®and Lantus®at the end of 6 months in terms of immunogenicity (% change in AIA titre from baseline, −10.52 ± 23.06 vs. 0.48 ± 63.95), glycemic control (change in HbA1c from baseline, −1.09% ± 1.29% vs. 0.63% ± 1.19%) and hypoglycemic events (reported by 1 vs. 2 patients), respectively. Conclusion: The present study represents a robust design in line with international guidelines on biosimilar insulin development and the early data trends presents expected similarity of Glaritus®in immunogenicity, efficacy and safety to that of Lantus®in treatment of T2DM.

Indistinguishable cellular changes in gastric mucosa between Helicobacter pylori infected asymptomatic tribal and duodenal ulcer patients

AIM:To investigate the changing pattern of different histological parameters occurring in the stomach tissue of Helicobacter pylori (H pylori) infected tribal populations and duodenal ulcer patients among ethnic Bengalis and correlation of the genotypes of H pylori with different histological parameters.were enrolled into this study between 2002 and 2004. Among them,72 had clinical features of duodenal ulcer (DU) from ethnic Bengali population and 40 were asymptomatic ethnic tribals. Endoscopic gastric biopsy samples were processed for histology,genotyping and rapid urease test. Histologically,haematoxylin and eosin staining was applied to assess the pathomorphological changes and a modified Giemsa staining was used for better detection of H pylori. For intestinal metaplasia,special stainings,i.e. Alcian blue periodic acid-Schiff and high iron diamine-Alcian blue staining,were performed. PCR was performed on bacterial DNA to characterize the presence or absence of virulence-associated genes,like cagA,and distribution of different alleles of vacA and iceA. RESULTS:Intraglandular neutrophil infiltration,a hallmark of activity of gastritis,was present in 34 (94%) of tribals (TRs) and 42 (84%) of DU individuals infected with H pylori. Lymphoid follicles and aggregates,which are important landmarks in H pylori infection,were positive amongst 15 (41%) of TRs and 20 (40%) of DU subjects. Atrophic changes were observed in 60% and 27.7%,respectively,among DU cases and tribals (P > 0.003). Metaplastic changes were detected in low numbers in both groups. Moderate to severe density distribution of H pylori in the gastric mucosa was 63% among TRs,whereas it was 62% in DU subjects. There were no significant differences in the distribution of virulence-associated genes like cagA,vacA and iceA of H pylori strains carried by these two populations. CONCLUSION:Our study showed almost similar distribution of inflammatory cells among asymptomatic tribals and DU Bengali patients. Interestingly,the tribal population are free from any clinical symptoms despite evidence of active histologic gastritis and infection with H pylori strains carrying similar virulence markers as of strains isolated from patients with DU. There was an increased cellular response,especially in terms of neutrophil infiltration,but much lower risk of developing atrophy and metaplastic changes among the tribal population.

Clinical outcome of orbital apex syndrome in COVID associated mucormycosis patients in a tertiary care hospital

AIM: To share clinical pattern of presentation, the modalities of surgical intervention and the one month postsurgical outcome of rhino-orbito-mucormycosis(ROCM) cases.METHODS: All COVID associated mucormycosis(CAM) patients underwent comprehensive multidisciplinar y examination by ophthalmologist, otorhinolaryngologist and physician. Patients with clinical and radiological evidence of orbital apex involvement were included in the study. Appropriate medical and surgical intervention were done to each patient. Patients were followed up one-month post intervention. RESULTS: Out of 89 CAM patients, 31(34.8%) had orbital apex syndrome. Sixty-six(74.2%) of such patients had pre-existing diabetes mellitus, 18(58%) patients had prior documented use of steroid use, and 55(61.8%) had no light perception(LP) presenting vision. Blepharoptosis, proptosis, complete ophthalmoplegia were common clinical findings. Seventeen(19.1%) of such patients had variable amount of cavernous sinus involvement. Endoscopic debridement of paranasal sinuses and orbit with or without eyelid sparing limited orbital exenteration was done in most cases, 34(38.2%) patients could retain vision in the affected eye. CONCLUSION: Orbital apex involvement in CAM patients occur very fast. It not only leads to loss of vision but also sacrifice of the eyeball, orbital contents and eyelids. Early diagnosis and prompt intervention can preserve life, vision and spare mutilating surgeries.

Novel variants in the hepatocyte nuclear factor-1-alpha gene in MODY and early onset NIDDM: Evidence for a mutational hotspot in exon 5

The disorder, Maturity Onset of Diabetes of the young (MODY) is a monogenic form of Non-Insulin dependent Diabetes Mellitus (NIDDM), characterized by autosomal dominant mode of inheritance and onset is usually before 25 years of age. Clinical studies of subjects with the different forms of MODY indicate that each is associated with a different defect in the normal pattern of glucose stimulated insulin secretion. MODY can result from mutations in any one of the six different genes, one of which encodes the glycolytic enzyme Glucokinase, associated with MO-DY2 and the other five encode transcription factors HNF4-alpha associated with MODY 1, HNF1-alpha associated with MODY 3, IPF with MODY 4, HNF1-Beta with MODY 5 and NeuroD1 with MO-DY6. Studies related to mutations in the MODY genes have led to a better understanding of the genetic causes of the Beta cell dysfunction as genetic factors plays a great role in this disorder. Objective: To investigate the mutation pattern in the different transcription factor genes with special reference to HNF1-alpha which are highly penetrant with 63% mutation carriers manifesting clinical diabetes by the age of 25 years. Hence study of mutation pattern in this gene is essential in our population i.e. Eastern Indian population. Our study is focused on HNF1-alpha related to MODY 3, which is the most common one. Methods: In our study enzyme amplification (PCR) of the 10 target exons of the said gene with simultaneous mutation detection in them by PCR-SSCP (Polymerase chain reaction-single strand conformational polymorphism) reaction analysis method was attempted by screening of exon 1 - 10 with respect to normal healthy controls without Diabetes Mellitus. The nature of the specific mutations was also determined by sequencing. Result: It was observed that maximum number of variations exist in exon 5 of HNF1-alpha gene which may be referred to as “Mutational Hotspot” in our Eastern Indian population. Conclusions: Since maximum number of variations exists in exon 5 of the said gene, hence one can initially go for exon5 followed by other exons, while screening for pathogenic MODY 3 mutations in the responsible gene by PCR-SSCP method.

Sutureless Repair of Left Primary Pulmonary Vein Stenosis—A Case Report

Primary left pulmonary vein stenosis is a very rare condition. It is associated with variable form of Pulmonary artery hypertension. Catheter based intervention is used to treat the disease like balloon dilation and stenting but this has high recurrence rate. Here is a case in which we did a sutureless repair of left pulmonary vein thus decreasing the possibility of recurrence. Sutureless surgical management is technically superior and less challenging than direct left atrial wall anastomosis and it provides better results than catheter based intervention in terms of recurrence of stenosis.

Unruptured Right Sinus of Valsalva Aneurysm Dissecting into Interventricular Septum Causing Complete Heart Block: Can Early Surgical Correction Revert Rhythm Disturbances?

A sinus of Valsalva aneurysm (SOVA) is abnormal dilatation of the either aortic sinuses, area of the aortic root between the aortic valve annulus and the sinotubular junction. Their clinical presentation may range from being asymptomatic as an incidental finding on cardiac imaging to symptomatic presentations related to the compression of adjoining structures or intracardiac shunting caused by rupture of the SOVA mostly into the right side of the heart. The compression leads to findings of tricuspid valve regurgitation, right ventricular outflow tract (RVOT) obstruction and rarely complete heart block (CHB). Dissection or erosion into interventricular septum is one of the rarest complications of SOVA. The symptomatic presentation is almost always a surgical emergency. Here we present a case report of a patient with unruptured sinus of valsalva originating from right sinus dissecting into interventricular septum causing complete heart bock. In this case after surgical correction the complete heart block reverted to sinus rhythm.

Surgical Retrieval of Atrial Septal Occluder Device after Late Embolization in Right Ventricle

Atrial septal defect (ASD) is the fourth most common congenital heart disease in the world. It was treated with surgical closure with the help of CPB in the earlier days. Now there are two approaches available, open surgery under CPB and transcatheter closure. Here we are going to present late complication of transcatheter closure of ASD.

Unusual Presentation of a Mediastinal Tumour: A Case Report

Neurofibroma arising from intrathoracic vagus nerve is a rare entity. We present a 6-year-old child with stigmata of neurofibromatosis along with a lump in the back. She also had history of on and off cough. On investigation there was a large mediastinal mass abutting the trachea. She underwent a posterolateral thoracotomy with partial resection of the lump. Intraoperatively the mass appeared to arise from the vagus nerve. Post operative stay was uneventful. Biopsy of the mass revealed a benign neurofibroma with no evidence of invasion. She is presently asymptomatic after 1 year of follow-up.

Late Presentation of Bronchial Foreign Body in Young Adult: A Case Report

Foreign body aspiration is common in young children or in adults with advanced age and altered mentation. Usually symptoms present acutely, leading to early intervention. We present a rare case of a healthy young female who aspirated her nasal ring but remained asymptomatic for almost eight years. The patient ultimately required a right upper lobe lobectomy for bronchiectasis.

Gut dysfunction in Parkinson's disease

Early involvement of gut is observed in Parkinson's disease(PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and nonpharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required.

Cholera:a great global concern

Cholera,caused by the infection of toxigenic Vibrio cholerae(V.cholerae) to humans,is a life threatening diarrheal disease with epidemic and pandemic potential.The V.cholerae,both 01 and 0139 serogroups,produce a potent enterotoxin(cholera toxin) responsible for the lethal symptoms of the disease.The O1 serogroup has two biotypes(phenotypes),classical and El Tor;each of which has two major serotypes(based on antigenic responses),Ogawa and Inaba and the extremely rare Hikojima.V.cholerae O1 strains interconvert and switch between the Ogawa and Inaba serotypes.Fluid and electrolyte replacement is the mainstay of treatment of cholera patients;the severe cases require antibiotic treatment to reduce the duration of illness and replacement of fluid intake.The antibiotic therapy cunenlly has faced difficulties due to the rapid emergence and spread o(multidrug resistant V.cholerae causing several outbreaks in the globe.Currently,cholera has been becoming endemic in an increasing number of geographical areas,reflecting a failure in implementation of control measures.However,the current safe oral vaccines lower the number of resistant infections and could thus represent an effective intervention measure to control antibiotic resistance in cholera.Overall,the priorities for cholera control remain public health interventions through improved drinking water,sanitation, surveillance and access to health care facilities,and lurther development of safe,effective and appropriate vaccines.Thus,this review describes the facts and phenomena related to the disease cholera,which is still a great threat mainly to the developing countries,and hence a grave global concern too.

Gastroenteropancreatic neuroendocrine neoplasms:A clinical snapshot

Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past decade.Gastroenteropancreatic(GEP)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors.Most NENs are welldifferentiated,and slow growing.Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA levels.Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs.Emerging novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and prognosis.In terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as options.Surgery is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Medical management is helpful to alleviate the symptoms,manage inoperable lesions,suppress postoperative tumour growth,and manage recurrences.Several molecular-targeted therapies are considered second line to somatostatin analogues.This review is a clinical update on the pathophysiological aspects,diagnostic algorithm,and management of GEP NENs.

Clinical and laboratory profile in confirmed vs. suspected septic arthritis patients and its relevance in decision making: A comparative cross-sectional study

Purpose:There were 10%e30%of patients with adult-onset septic arthritis(SA)exhibiting sterile synovial fluid(SF),and the uncertainty in the determining diagnosis of these patients posed a challenge in management.The purpose of this study was to investigate the differences between confirmed(Newman A)and suspected(Newman B&C)SA in adults.Methods:This was a descriptive study with a cross-sectional study design conducted at a tertiary referral centre from July 2016 to February 2019.Patients aged over 18 years presented to the emergency department with clinical features suggestive of SA and were scheduled to undergo arthrotomy and joint lavage by the treating surgeon were included in the study.Patients with prosthetic joint infections and open joint injuries were excluded.Patients’demographic data,clinical features and laboratory parameters were collected.The clinical and laboratory profile(blood and SF)of the adult patients presenting with features suggestive of SA based on Newman criteria was statistically analyzed by SPSS version 20 software and Microsoft Excel.The categorical variables were expressed as proportions while the continuous variables were expressed as mean(SD)or median(IQR)depending upon the normality of distribution.The difference between the two groups for categorical variables was assessed using the Chisquare test and the difference for continuous variables was assessed using the unpaired t-test and the Mann-Whitney test depending upon normality.A p value<0.05 was considered significant.Results:Thirty-six patients were divided into confirmed(n¼19)or suspected(n¼17)SA for assessment based on SF culture.The median(IQR)age of the patients was 50 years(37e60 years).There was no significant difference in demographic,clinical and laboratory parameters between the concerned groups.Eight patients presented with fever.Among the confirmed SA cases,8 were negative for C-reactive protein and 6 had synovial white blood cell count<50,000.Staphylococcus species were isolated in 8 cases.The most common risk factors for SA were chronic kidney disease(25.0%),diabetes mellitus(25.0%),pharmacologic immunosuppression(16.7%),recent joint surgery(11.1%)and distant site infection(11.1%).Conclusion:SA is an orthopaedic emergency that needs prompt and aggressive treatment to prevent catastrophic complications.Confirmed and suspected cases of SA exhibit similar demography,clinical features and laboratory parameters at presentation which may mislead the treating surgeon.Management should be based on sound clinical judgment in the event of failure to culture microorganisms.