Sorbitol Intolerance in Adults

Sorbitol is a commonly used sugar substitute in "sugar-free" food products. Although sorbitol intolerance manifested by abdominal pain, bloating, and diarrhea has been observed in children, it has not been well documented in adults. Forty-two healthy adults (23 whites, 19 nonwhites) participated in this study. After ingestion of 10 g of sorbitol solution, end expiratory breath samples were collected at 15-min intervals for 4 h and analyzed for H2 concentration. Clinical sorbitol intolerance was detected in 43% of the whites and 55% of the nonwhites, the difference not being statistically significant. However, severe clinical sorbitol intolerance was significantly more prevalent in nonwhites (32%) as compared to whites (4%). There was a good correlation between the severity of symptoms and the amount of hydrogen exhaled. Dietetic foods, many of them containing sorbitol, are very popular with diabetics and "weight watchers." Based on our observations, we believe that a large number of adults could be suffering from sorbitol-induced nonspecific abdominal symptoms and diarrhea. These symptoms could lead to an extensive diagnostic work-up and lifelong diagnosis of irritable bowel syndrome.     

Transport of molecules across tumor vasculature

The vascular-extravascular exchange of fluid and solute molecules in a tissue is determined by three transport parameters (vascular permeability, P, hydraulic conductivity, L_p, and reflection coefficient, ); the surface area for exchange, A; and the transluminal concentration and pressure gradients. The transport parameters and the exchange area for a given molecule are governed by the structure of the vessel wall. In general, tumor vessels have wide interendothelial junctions; large number of fenestrae and transendothelial channels formed by vesicles; and discontinuous or absent basement membrane. While these factors favor movement of molecules across tumor vessels, high interstitial pressure and low microvascular pressure may retard extravasation of molecules and cells, especially in large tumors. These characteristics of the transvascular transport have significant implications in tumor growth, metastasis, detection and treatment.     

Macrocarposide, a new isoflavanone c-glucoside from Pterocarpus macrocarpus heart wood

Macrocarposide has been isolated for the first time as a natural product from the heartwood of PTEROCARPUS MACROCARPUS along with some known compounds. Based on its spectral and chemical evidence, it has been assigned the structure dalbergioidin-6- C-glucoside ( 1).     

Concurrent intrapericardial–pulmonary hydatidosis: an unusual multisystem echinococcosis

A 46-year-old male presented with breathlessness for a few months. He had been operated twice for liver hydatid cysts and once for right pulmonary hydatid cysts at other hospitals. Now he was found to have one hydatid cyst in the upper lobe of the left lung and multiple hydatid cysts adjoining left heart border. On computed tomography (CT) scan chest and echocardiography, it was difficult to ascertain whether these cysts were pulmonary or intrapericardial. Left ventricular ejection fraction (LVEF) was 25%. Enzyme-linked immunosorbent assay (ELISA) was positive for hydatid. Left posterolateral thoracotomy revealed dead hydatid cyst in upper lobe of the lung that was removed. Infected mother hydatid cyst was encountered inside pericardial sac. Scores of daughter hydatid cysts, varying in size from 1 to 30 mm, were scooped out intact from the pericardial cavity. There was significant improvement in cardiac activity, once the tamponade effect of hydatid cyst was removed. Pericardium was about 1 cm thick with lot of purulent and necrotic slough. To prevent future constrictive pericarditis, subtotal pericardiectomy was done. Intrapericardial hydatid cyst should be kept in mind whenever it obscures the heart border and patient has features of cardiac tamponade. Early surgical intervention may be required in these cases.     

Covid-19 Pandemic: Resumption of Orthopedic Care and Medical Education

Covid-19 is a respiratory disease caused by coronavirus 2 (SARS-CoV-2) first identified in Wuhan, China (December 2019). The disease rapidly crossed the barrier of countries, continents and spread globally. Non-pharmaceutical measures such as social distancing, face mask, frequent hand washing and use of sanitizer remained the best available option to prevent the spread of disease. OPD, IPD admissions, elective O. Ts were curtailed. Orthopedic care was only limited to emergency and semi-urgent procedures like necrotizing fasciitis, open fracture, and compartment syndrome. These measures were taken to preserve infrastructure and manpower to manage covid-19 pandemic. The children were thought to have a low susceptibility to covid-19 as compared to an adult. Deferring the patient during pandemic has led to high orthopedic disease burden, morbidity and disease-related sequelae, hence elective care must be resumed with modified hospital infrastructure. Resumption of elective/emergent orthopedic care should be slow, phasic and strategic, much similar to unlocking. Cases must be stratified depending on covid status and severity. Dedicated O.Ts with neutral/negative pressure and HEPA filter for covid positive and suspected patients are to be used. All symptomatic and suspected patients should be investigated for covid-19 by RT-PCR, blood counts and CT scan. Regional anaesthesia should be preferred to General anaesthesia. Power drill/saw/burr/pulse lavage should be minimized to avoid aerosol generation. Postoperatively continuous surveillance and monitoring to be done for covid related symptoms. Medical institutes rapidly shifted to the online mode of education. Blended learning (virtual & physical) and imparting skills have to be continued in post covid phase with equitable distribution of teaching hours to students of different years.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Maternal and fetal outcomes following elexacaftor-tezacaftor-ivacaftor use during pregnancy and lactation

BackgroundWith the improved health afforded by cystic fibrosis transmembrane conductance regulator (CFTR) modulators, pregnancy rates are increasing in women with CF. In animal reproductive models, the three components of elexacaftor-tezacaftor-ivacaftor (ETI) did not cause teratogenicity at normal human doses. Although the limited human data available in the literature for previously approved modulators did not suggest cause for concern, there is currently no data in the literature regarding use of ETI in pregnant women. Thus, the decision to continue therapy during pregnancy (with the associated unknown fetal impact) versus discontinuing therapy (with the known risk of maternal health decline) is challenging.MethodsCF Center staff completed an anonymous questionnaire regarding pregnancy and infant outcomes for women who used ETI during pregnancy and/or lactation.ResultsOf 45 ETI-exposed pregnancies reported to date, complications in 2 mothers and in 3 infants (2 born to mothers with poorly controlled diabetes) were rated by clinicians as unknown (possible) or suspected relatedness to ETI use. Two women terminated unplanned pregnancies. Miscarriage rates were consistent with that known in the general U.S. population. Five of the six women who discontinued ETI out of concern for unknown fetal risk restarted because of clinical deterioration. No infant cataracts were reported though only two infants were formally evaluated.ConclusionsIn the context of the known increased rate of complications in women with CF and their infants, data from this retrospective survey is reassuring for women who choose to continue ETI during pregnancy. However, a large, multi-center prospective study is needed to assess impact of use of ETI in pregnancy.     

Multi-dimensional clinical phenotyping of a national cohort of adult cystic fibrosis patients

BackgroundCystic Fibrosis (CF) is a multi-systemic disorder resulting from genetic variation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene which can result in bronchiectasis, chronic sinusitis, pancreatic malabsorption, cholestatic liver disease and distal intestinal obstructive syndrome. This study generates multi-dimensional clinical phenotypes that capture the complexity and spectrum of the disease manifestations seen in adult CF patients using statistically robust techniques.MethodsPre-transplant clinical data from adult (age ≥18 years) CF patients (n = 992) seen in six regionally distinct US CF centers between 1/1/2014 and 6/30/2015 were included. Demographic, spirometry, nutritional, microbiological and therapy data were used to generate clusters using the Random Forests statistical-learning and Partitioning around Medoids (PAM) clustering algorithms. Five commonly measured demographic, physiological and nutritional parameters were needed to create the final phenotypes that are highly similar to a regionally matched group of patients from the CF Foundation Patient RegistryResultsThis approach identified high-risk phenotypes with expected characteristics including high rates of pancreatic insufficiency, diabetes and Pseudomonas aeruginosa colonization. It also identified unexpected populations including a) a male-dominated, well-nourished group with good lung function with a high prevalence of severe genotypes (i.e. 60% subjects had two minimal function CFTR variations), b) and an older, “survivor” phenotype that had high rates of chronic P. aeruginosa infection.ConclusionsThis study identified recognizable phenotypes that capture the clinical complexity in a statistically robust manner and which may aide in the identification of specific genetic and environmental factors responsible for these disease manifestation patterns.