Driving adult tissue repair via re-engagement of a pathway required for fetal healing.

Fetal cutaneous wound closure and repair differ from that in adulthood. In this work, we identify an oxidant stress sensor protein, nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), that is abundantly expressed in normal fetal epidermis (and required for fetal wound closure), though not in adult epidermis, but is variably re-induced upon adult tissue wounding. NPGPx is a direct target of the miR-29 family. Following injury, abundance of miR-29 is lowered, permitting a prompt increase in NPGPx transcripts and protein expression in adult wound-edge tissue. NPGPx expression was required to mediate increased keratinocyte migration induced by miR-29 inhibition in vitro and in vivo. Increased NPGPx expression induced increased SOX2 expression and ß-catenin nuclear localization in keratinocytes. Augmenting physiologic NPGPx expression via experimentally induced miR-29 suppression, using cutaneous tissue nanotransfection or targeted lipid nanoparticle delivery of anti-sense oligonucleotides, proved to be sufficient to overcome the deleterious effects of diabetes on this specific pathway to enhance tissue repair.

Outcomes of Aural Rehabilitation Provided in Person or by Telehealth Among Deaf/Hard of Hearing Young Children with Cochlear Implants or Hearing Aids.

Background: Cochlear implants and hearing aids may facilitate the development of listening and spoken language (LSL) in deaf/hard of hearing young children, but they require aural rehabilitation therapy-often unavailable outside urban areas-for optimal outcomes. This trial assessed the relative effectiveness of LSL therapy delivered either in person or by interactive video. The hypothesis was that telehealth service delivery would be noninferior to in-person therapy. Methods: Most parents refused randomization of their children to telehealth or in-person conditions; therefore, randomization was impossible. In consultation with the funder (NIDCD), the study design was modified. Parents were allowed to select their preferred study condition, and the study team was blinded to group membership. Forty-two families were in the in-person group and 35 in telehealth (40 and 30, respectively, after attrition). Primary endpoints were total score, auditory comprehension, and expressive communication on the Preschool Language Scale, 5th edition. There were several secondary speech, hearing, and language outcome measures. Assessments occurred at baseline and at follow-up after 6 months of LSL therapy. Results: Propensity scores were used to create two matched groups. At baseline, groups did not differ on PLS-5 scores. Change from baseline to F/U on age-equivalents for all three scores was nearly identical for both groups, although the telehealth group was younger, on average, than the in-person group. Discussion: Telehealth was noninferior to in-person services for all primary endpoints. For secondary outcomes, neither group demonstrated a significant advantage. Magnitudes of estimated group differences were small, suggesting nonsignificant differences not predominantly because of sample size. The telehealth group showed greater improvement on 15/24 of secondary language outcome measures. The findings provide evidence that telehealth is equivalent to in-person care for providing LSL therapy to young children with cochlear implants and hearing aids.

CDMS Analysis of Intact 19S, 20S, 26S, and 30S Proteasomes: Evidence for Higher-Order 20S Assemblies at a Low pH†.

Charge detection mass spectrometry (CDMS) was examined as a means of studying proteasomes. To this end, the following masses of the 20S, 19S, 26S, and 30S proteasomes from Saccharomyces cerevisiae (budding yeast) were measured: m(20S) = 738.8 ± 2.9 kDa, m(19S) = 926.2 ± 4.8 kDa, m(26S) = 1,637.0 ± 7.6 kDa, and m(30S) = 2,534.2 ± 10.8 kDa. Under some conditions, larger (20S)x (where x = 1 to ∼13) assemblies are observed; the 19S regulatory particle also oligomerizes, but to a lesser extent, forming (19S)x complexes (where x = 1 to 4, favoring the x = 3 trimer). The (20S)x oligomers are favored in vitro, as the pH of the solution is lowered (from 7.0 to 5.4, in a 20 mM ammonium acetate solution) and may be related to in vivo proteasome storage granules that are observed under carbon starvation. From measurements of m(20S)x (x = 1 to ∼13) species, it appears that each multimer retains all 28 proteins of the 20S complex subunit. Several types of structures that might explain the formation of (20S)x assemblies are considered. We stress that each structural type [hypothetical planar, raft-like geometries (where individual proteasomes associate through side-by-side interactions); elongated, rodlike geometries (where subunits are bound end-to-end); and geometries that are roughly spherical (arising from aggregation through nonspecific subunit interactions)] is highly speculative but still interesting to consider, and a short discussion is provided. The utility of CDMS for characterizing proteasomes and related oligomers is discussed.

Best Practices: Indications and Procedural Controversies of Adrenal Vein Sampling for Primary Aldosteronism.

Primary hyperaldosteronism (PA) is the most common secondary form of hyper-tension in middle-aged adults. Its harmful effects exceed those of essential hyper-tension. Once PA is diagnosed, treatment hinges on whether aldosterone secretion is unilateral or bilateral, as the former can be effectively treated with adrenalectomy but the latter is treated medically with mineralocorticoid receptor antagonists such as spironolactone or eplerenone. Adrenal vein sampling (AVS) is critical in this determination. There is wide variation in how AVS is performed, including whether to use synthetic adrenocorticotropic hormone stimulation and where the catheter tip should be placed during left adrenal gland sampling. In addition, some institutions and guidelines omit AVS in young patients (i.e., those younger than an age threshold ranging from 35 to 40 years old) who have unilateral adrenal findings on cross-sectional imaging. In this article, we provide background on PA and performance of AVS and then summarize the evidence supporting best practices for these three areas of controversy regarding how and when to perform AVS.

Clinical letters to patients with intellectual disabilities after psychiatric review: A quality improvement project.

AIM: This Quality Improvement Project sought to improve communication between patients with intellectual disabilities and their psychiatrists by sharing medical information using an easy read letter format following psychiatric review. BACKGROUND: Writing directly to patients is in keeping with good medical practice. Previous studies have shown patients with intellectual disabilities prefer letters tailored to meet their needs. METHOD: An easy read letter was used by nine psychiatrists who handed them to 100 consecutive patients after review. Feedback of acceptability to patients was obtained using a three-item facial rating scale and the use of free text. Feedback of acceptability was obtained from participating psychiatrists. RESULTS: Patients found the easy read letter helpful and felt it should be used routinely. Psychiatrists felt this approach was beneficial as well as aiding patient understanding of review. CONCLUSIONS: The easy read letter was reported to improve communication following psychiatric review. Limitations are acknowledged but it is concluded that an easy read letter should be adopted as routine practice following psychiatric review, for people with intellectual disabilities.

Utility of mutational analysis for risk stratification of indeterminate thyroid nodules in a real-world setting.

OBJECTIVE: American Thyroid Association (ATAn) 2015 guidelines recommend repeat fine-needle aspiration with molecular marker profiling (MMP) or diagnostic lobectomy in thyroid nodules yielding atypia of unknown significance/follicular lesion of unknown significance (AUS/FLUS) or follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) cytology. Our objective is to describe the molecular profiles and histological correlates of these cytologically indeterminate nodules (CIN) to aid risk stratification. DESIGN: Retrospective chart review. PATIENTS: Adults with CIN that underwent MMP from 2017 to 2020. MEASUREMENTS: Pearsons' χ2 , Fisher's exact test, nonparametric testing and multiple regression analysis were performed. RESULTS: A total of 89 CIN underwent mutational analysis. Of 55% (n = 49) were Bethesda class III AUS/FLUS and 45% (n = 40) were Bethesda class IV FN/SFN. The US phenotype of a CIN was isoechoic (53%) or hypoechoic (32%) with well-defined margins (98%), absence of calcifications (75%) and mildly increased internal vascularity (70%). A total of 84% and 87% of nodules were classified as mild/moderate or low/intermediate risk per the Thyroid Imaging Reporting and Data System and ATA classifications, respectively. Based on the Thyroseq patient management resource, 6.7% (n = 6) of nodules had a high predicted probability of cancer (≥95%), 41.6% (n = 37) were intermediate probability (40%-94%) and 51.7% (n = 46) were low probability (<40%). MMP revealed positive mutations in 45% (n = 40) of nodules, with 71% demonstrating RAS mutations. Of the nodules that underwent resection (n = 38), 39% (n = 15) had malignant pathology. Increasing the threshold to recommend surgical resection to a Thyroseq predicted probability of cancer to ≥50%, had a 100% sensitivity and 65% specificity for detecting malignant nodules (area under the ROC curve: 0.86). The positive predictive value was 37% and the negative predictive value was 100%. CONCLUSION: US phenotypes of CIN nodules were variable and did not aid in differentiating malignant from benign nodules. Of the CIN nodules with a positive MMP, most were RAS and had a benign pathology. With the exception of high-risk genetic markers for malignancy, the threshold to recommend surgical resection should be raised for CIN. Further studies to improve risk stratification in these nodules are required.

A Deep Clustering-based Novel Approach for Binning of Metagenomics Data.

Background: One major challenge in binning Metagenomics data is the limited availability of reference datasets, as only 1% of the total microbial population is yet cultured. This has given rise to the efficacy of unsupervised methods for binning in the absence of any reference datasets. Objective: To develop a deep clustering-based binning approach for Metagenomics data and to evaluate results with suitable measures. Methods: In this study, a deep learning-based approach has been taken for binning the Metagenomics data. The results are validated on different datasets by considering features such as Tetra-nucleotide frequency (TNF), Hexa-nucleotide frequency (HNF) and GC-Content. Convolutional Autoencoder is used for feature extraction and for binning; the K-means clustering method is used. Results: In most cases, it has been found that evaluation parameters such as the Silhouette index and Rand index are more than 0.5 and 0.8, respectively, which indicates that the proposed approach is giving satisfactory results. The performance of the developed approach is compared with current methods and tools using benchmarked low complexity simulated and real metagenomic datasets. It is found better for unsupervised and at par with semi-supervised methods. Conclusion: An unsupervised advanced learning-based approach for binning has been proposed, and the developed method shows promising results for various datasets. This is a novel approach for solving the lack of reference data problem of binning in metagenomics.

MetaConClust - Unsupervised Binning of Metagenomics Data using Consensus Clustering.

Background: Binning of metagenomic reads is an active area of research, and many unsupervised machine learning-based techniques have been used for taxonomic independent binning of metagenomic reads. Objective: It is important to find the optimum number of the cluster as well as develop an efficient pipeline for deciphering the complexity of the microbial genome. Methods: Applying unsupervised clustering techniques for binning requires finding the optimal number of clusters beforehand and is observed to be a difficult task. This paper describes a novel method, MetaConClust, using coverage information for grouping of contigs and automatically finding the optimal number of clusters for binning of metagenomics data using a consensus-based clustering approach. The coverage of contigs in a metagenomics sample has been observed to be directly proportional to the abundance of species in the sample and is used for grouping of data in the first phase by MetaConClust. The Partitioning Around Medoid (PAM) method is used for clustering in the second phase for generating bins with the initial number of clusters determined automatically through a consensus-based method. Results: Finally, the quality of the obtained bins is tested using silhouette index, rand Index, recall, precision, and accuracy. Performance of MetaConClust is compared with recent methods and tools using benchmarked low complexity simulated and real metagenomic datasets and is found better for unsupervised and comparable for hybrid methods. Conclusion: This is suggestive of the proposition that the consensus-based clustering approach is a promising method for automatically finding the number of bins for metagenomics data.

Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer.

Immune checkpoint therapy (ICT) has transformed cancer treatment in recent years; however, treatment response is not uniform across tumor types. The tumor immune microenvironment plays a critical role in determining response to ICT; therefore, understanding the differential immune infiltration between ICT-sensitive and ICT-resistant tumor types will help to develop effective treatment strategies. We performed a comprehensive analysis of the immune tumor microenvironment of an ICT-sensitive tumor (melanoma, n = 44) and an ICT-resistant tumor (pancreatic cancer, n = 67). We found that a pancreatic tumor has minimal to moderate infiltration of CD3, CD4, and CD8 T cells; however, the immune infiltrates are predominantly present in the stromal area of the tumor and are excluded from tumoral area compared with melanoma, where the immune infiltrates are primarily present in the tumoral area. Metastatic pancreatic ductal adenocarcinomas (PDACs) had a lower infiltration of total T cells compared with resectable primary PDACs, suggesting that metastatic PDACs have poor immunogenicity. Further, a significantly higher number of CD68+ macrophages and VISTA+ cells (also known as V-domain immunoglobulin suppressor of T cell activation) were found in the pancreatic stromal area compared with melanoma. We identified VISTA as a potent inhibitory checkpoint that is predominantly expressed on CD68+ macrophages on PDACs. These data suggest that VISTA may be a relevant immunotherapy target for effective treatment of patients with pancreatic cancer.

Standardized statement for the ethical use of human cadaveric tissues in anatomy research papers: Recommendations from Anatomical Journal Editors-in-Chief.

Human cadaveric donors are essential for research in the anatomical sciences. However, many research papers in the anatomical sciences often omit a statement regarding the ethical use of the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To rectify this issue, 22 editors-in-chief of anatomical journals, representing 17 different countries, developed standardized and simplified language that can be used by authors of studies that use human cadaveric tissues. The goal of these editor recommendations is to standardize the writing approach by which the ethical use of cadaveric donors is acknowledged in anatomical studies that use donor human cadavers. Such sections in anatomical papers will help elevate our discipline and promote standardized language use in others non anatomy journals and also other media outlets that use cadaveric tissues.

Copper@ZIF-8 Core-Shell Nanowires for Reusable Antimicrobial Face Masks.

SARS-CoV-2 and other respiratory viruses spread via aerosols generated by infected people. Face masks can limit transmission. However, widespread use of disposable masks consumes tremendous resources and generates waste. Here, a novel material for treating blown polypropylene filtration media used in medical-grade masks to impart antimicrobial activity is reported. To produce thin copper@ZIF-8 core-shell nanowires (Cu@ZIF-8 NWs), Cu NWs are stabilized using a pluronic F-127 block copolymer, followed by growth of ZIF-8 to obtain uniform core-shell structures. The Cu@ZIF-8 NWs are applied to filtration media by dip coating. Aerosol filtration efficiency decreases upon exposure to ethanol (solvent for dip-coating), but increases with addition of Cu@ZIF-8 NWs. Cu@ZIF-8 NWs shows enhanced antibacterial activity, compared to Cu NWs or ZIF-8 alone, against Streptococcus mutans and Escherichia coli. Antiviral activity against SARS-CoV-2 is assayed using virus-infected Vero E6 cells, demonstrating 55% inhibition of virus replication after 48 h by 1 µg of Cu@ZIF-8 NWs per well. Cu@ZIF-8 NWs' cytotoxicity is tested against four cell lines, and their effect on inflammatory response in A549 cells is examined, demonstrating good biocompatibility. This low-cost, scalable synthesis and straightforward deposition of Cu@ZIF-8 NWs onto filter media has great potential to reduce disease transmission, resource consumption, and environmental impact of waste.

The "Quiet TED"-A Special Subgroup of Thyroid Eye Disease.

PURPOSE: Thyroid eye disease (TED) or Graves' orbitopathy starts with an active inflammatory stage (active disease) followed by resolution of inflammation and progression to a fibrotic, inactive stage. In our practice, we have encountered cases that have not had active disease despite presence of fibrotic sequelae and disease progression. We aim to delineate the clinical characteristic of this unique group of patients. METHODS: We conducted a single-center (Mayo Clinic Rochester) retrospective chart review of TED patients who throughout the course of their disease had only evidence for inactive TED, defined as clinical activity score <3. RESULTS: Median age in the cohort (n = 19) was 54 years (IQR 47-61). 58% had a prior diagnosis of Graves' disease (GD) before referral. 80% (n = 15) were euthyroid at the time of TED onset (median thyroid-stimulating hormone 1.7 mIU/L). The most common finding was diplopia (100%, n = 19) followed by proptosis (63%, n = 12). Interestingly the disease was asymmetric in 42% of cases. Overall median clinical activity score on presentation was 1 (IQR 0-1). Severity wise, 85% (n = 16) of patients were classified as moderate-to-severe during follow up. Orbital decompression was performed in only 1 case, while extraocular muscle surgery was performed in 13 cases. CONCLUSIONS: Quiet TED is a subgroup of TED patients that defies the classic disease paradigm. It presents primarily with diplopia and proptosis. Further evaluation of this group might identify useful insights in TED pathophysiology and help optimize therapeutic choices.

Predictors of severe dengue amongst children as per the revised WHO classification.

BACKGROUND & OBJECTIVES: World Health Organization (WHO) revised its guidelines for classification and management of dengue in 2009. This revised system was found out to have good sensitivity and negative predictive value but poor specificity as well as positive predictive value. METHODS: This retrospective study was carried out in a tertiary care hospital of Delhi, India to assess factors predicting the occurrence of severe dengue in children as per the revised classification. A total of 647 suspected dengue cases were admitted in the hospital in the year 2015. Detailed clinical and epidemiological data of 170 patients who were confirmed as dengue either by NS1 antigen test or by serology (Ig M positive) were recorded and statistically analyzed. RESULTS: The number of laboratory-confirmed cases was 170 and included thirty (17.65%) dengue fever (DF), 106 (62.35%) dengue with warning signs (DWS) and 34 (20.0%) severe dengue (SD) patients. Regression analysis revealed that presence of vomiting, altered sensorium, shock, peri-orbital edema, hepatomegaly, splenomegaly, severe anemia, thrombocytopenia, elevated urea and creatinine, decreased total protein and globulin were significantly associated with occurrence of severe disease. INTERPRETATION & CONCLUSION: The addition of clinical features (peri-orbital edema and splenomegaly); and laboratory findings (elevated urea and creatinine, decreased serum protein and globulin) might help improve the sensitivity and specificity of the revised WHO dengue classification in predicting severe dengue.

VASCULARITY-TARGETED PERCUTANEOUS ETHANOL INJECTION OF TOXIC THYROID ADENOMAS: OUTCOMES OF A FEASIBILITY STUDY PERFORMED IN THE USA.

Objective: The recommended treatment options for toxic adenoma (TA) in the USA are radioactive iodine ablation and surgical resection, with continued observation for pre-toxic adenoma (PTA). Percutaneous ethanol ablation (PEI) has proven efficacy in the treatment of TA and is widely available in Europe but not in the USA. Methods: Retrospective analysis was performed of all patients who underwent PEI for TA/PTA at the University of Utah, from January 2010 to 2018. Ultrasound-guided PEI, with injections targeting power Doppler-mapped blood vessels within the adenomas, was conducted. Functionality was confirmed using thyroid scintigraphy prior to PEI. Results: Eighteen adults (15 female) underwent PEI. Mean age was 41 ± 13.7 years. Baseline thyroid-stimulating hormone (TSH) was suppressed (0.06 ± 0.09 mU/L), with normal free thyroxine (FT4) 1.43 ± 0.39 ng/dL. Median nodule volume was 5.7 cm3 (interquartile range [IQR], 4.8 to 7.7 cm3). Seventy-eight percent (n = 14) underwent two or less PEI sessions. Median volume of ethanol used was 0.46 mL/mL nodule volume (IQR, 0.3 to 0.6 mL). There was a significant increase in TSH concentrations within the first 3 months after PEI (0.06 ± 0.09 mU/L vs. 1.22 ± 1.88 mU/L; P = .02), with a concomitant significant decrease in FT4 concentrations (1.43 ± 0.39 ng/day vs. 1.13 ± 0.25 ng/day; P<.01). Significant nodular volume reduction was observed following PEI (median 5.7 cm3 [IQR 4.8-7.7 cm3] vs. 2.5 cm3 [IQR 2.0-7.8 cm3]; P<.01). Conclusion: Vascularity-targeted PEI is safe and effective for treating PTA and TA. This unique approach required lower injected alcohol volume and fewer injections for therapeutic success. Abbreviations: ATA = American Thyroid Association; FT4 = free thyroxine; IQR = interquartile range; PD = power Doppler; PEI = percutaneous ethanol injection; PTA = pre-toxic adenoma; RAI = radioactive iodine ablation; RFA = radiofrequency ablation; TA = toxic adenoma; TT3 = total triiodothyronine; US = ultrasound.

A reliable assay for ensuring the biological activity of anti T lymphocyte immunoglobulin as an alternate to compendial flow cytometry method.

The assay of Anti T lymphocyte immunoglobulin for final drug product testing is carried out using flow cytometry on Peripheral Blood Mononuclear Cells (PBMCs) as specified in European and British Pharmacopeia. An alternate assay was developed wherein the potency based quality control evaluation of Anti T lymphocyte immunoglobulin is carried out by measuring complement dependent cytotoxicity (CDC) using fluorescent resazurin dye. The reported bioassay was specific, linear (R2 = 0.98), precise (%GCV for repeatability was 3.54% and intermediate precision was 4.27%) and accurate with relative bias of -5.54%. On the basis of results obtained from the repeated performances on single available product, system suitability criteria and sample acceptance criteria were proposed wherein Slope from 4 PL curve fit results for Reference Standard (RS) should be > 0.9, EC50 for RS should lie between 0.264 and 1.131 µg/ml and fold response should be > 2. Confidence interval range and estimated relative potency range obtained from the method validation were narrower than those mentioned for compendial method.

Mesenchymal stem cells from orthodontic premolar teeth.

BACKGROUND: Considering the limitations in isolating Bone Marrow Mesenchymal Stem Cells (BMSCs), alternate sources of Mesenchymal Stem Cells (MSCs) are being intensely investigated. This study evaluated dental pulp MSCs (DP-MSCs) isolated from orthodontically extracted premolar teeth from a bone tissue engineering perspective. METHODS: MSCs isolated from premolar teeth pulp were cultured and studied using BMSCs as the control. Flow cytometry analysis was performed for the positive and negative MSC markers. Multilineage differentiation focusing on bone regeneration was evaluated by specific growth induction culturing media and by alkaline phosphatase (ALP) activity. Data were compared by repeated measurement analysis of variance and Student's t-test at a p value <0.05. RESULTS: Proliferation rate, population doubling time, and colony formation of DP-MSCs were significantly higher (p < 0.001) than BMSCs. More than 85% of DP-MSCs expressed CD44, CD73, CD90, CD105, and CD166. Negative reaction was found for CD11b CD33, CD34, and CD45. Positive reaction was displayed by 7.2% of cells for early MSC marker, Stro-1. Both the cell populations differentiated into adipogenic, osteogenic, and chondrogenic lineages, with adequate ALP expression. CONCLUSION: Because DP-MSCs from orthodontic premolars hold a neural crest/ectomesenchymal ancestry, its prudent growth characteristics and multilineage differentiation open up exciting options in craniofacial tissue engineering.

Assessment of pulsatile insulin secretion derived from peripheral plasma C-peptide concentrations by nonparametric stochastic deconvolution.

The characteristics of pulsatile insulin secretion are important determinants of type 2 diabetes pathophysiology, but they are understudied due to the difficulties in measuring pulsatile insulin secretion noninvasively. Deconvolution of either peripheral C-peptide or insulin concentrations offers an appealing alternative to hepatic vein catheterization. However, to do so, there are a series of methodological challenges to overcome. C-peptide has a relatively long half-life and accumulates in the circulation. On the other hand, peripheral insulin concentrations reflect relatively fast clearance and hepatic extraction as it leaves the portal circulation to enter the systemic circulation. We propose a method based on nonparametric stochastic deconvolution of C-peptide concentrations, using individually determined C-peptide kinetics, to overcome these limitations. The use of C-peptide (instead of insulin) concentrations allows estimation of portal (and not post-hepatic) insulin pulses, whereas nonparametric stochastic deconvolution allows evaluation of pulsatile signals without any a priori assumptions of pulse shape and occurrence. The only assumption required is the degree of smoothness of the (unknown) secretion rate. We tested this method first on simulated data and then on 29 nondiabetic subjects studied during euglycemia and hyperglycemia and compared our estimates with the profiles obtained from hepatic vein insulin concentrations. This method produced satisfactory results both in the ability to fit the data and in providing reliable estimates of pulsatile secretion, in agreement with hepatic vein measurements. In conclusion, the proposed method enables reliable and noninvasive measurement of pulsatile insulin secretion. Future studies will be needed to validate this method in people with type 2 diabetes.

Filarial tropical pulmonary eosinophilia: a condition masquerading asthma, a series of 12 cases.

INTRODUCTION: Tropical pulmonary eosinophilia (TPE) is a form of occult filariasis, clinically characterized by paroxysmal cough, wheezing and dyspnea which is often misdiagnosed and treated as asthma. These manifestations result from a host immune response to trapped antigens of the microfilarial parasites Wuchereria bancrofti or Brugia malayi in the pulmonary microcirculation. CASE STUDY: We describe three rare presentations of TPE (cor pumonale, cystic lung disease and respiratory distress mimicking acute severe asthma) in our series of 12 cases. All cases were from filaria endemic areas and presented with cough, wheezing and dyspnea, either alone or in combination. Subsequent work-up revealed peripheral eosinophilia, raised serum IgE levels and positive serum filarial antibody and/or antigen in all the cases. RESULTS: All patients were treated with diethylcarbamazine (DEC), while few required inhaled/systemic corticosteroid. Prompt improvement in clinical symptoms with a decrease in eosinophil count was seen in all. Two cases relapsed requiring a second course of DEC. Long-term outcome was good, however, there was a persistence of restrictive lung function and echocardiographic feature of pulmonary hypertension in the patients with cystic lung disease and cor pulmonale, respectively. CONCLUSION: TPE should always be considered in patients from filaria endemic areas presenting with cough, dyspnea or wheezing. High eosinophil count (>3 × 109 cells) with raised IgE level (>1000 IU/mL) in such cases should alert the physician to look for TPE. Early diagnosis and treatment can prevent disease progression and complications.

IMPAIRED AWARENESS OF HYPOGLYCEMIA CONTINUES TO BE A RISK FACTOR FOR SEVERE HYPOGLYCEMIA DESPITE THE USE OF CONTINUOUS GLUCOSE MONITORING SYSTEM IN TYPE 1 DIABETES.

Objective: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in patients with type 1 diabetes (T1D) not using a continuous glucose monitoring (CGM) system. The current study investigated the prevalence of IAH and its relationship with severe hypoglycemia in T1D patients using CGM systems. Methods: This cross-sectional observational study enrolled 135 patients with T1D and ongoing real-time CGM use. A survey was conducted to assess hypoglycemia awareness with the Gold, Clarke, and Pedersen-Bjergaard questionnaires and the 6-month history of severe hypoglycemia. Other diabetes histories and the CGM glucose data were collected. Results: The Gold, Clarke, and Pedersen-Bjergaard questionnaires demonstrated the overall prevalence of IAH/abnormal awareness to be 33.3%, 43.7%, and 77.0%, respectively. Participant age and duration of T1D were consistently related to IAH or hypoglycemia unawareness with all three questionnaires (P<.05). Amongst the patients using CGM for >6 months, 24.5% were found to have at least one episode of severe hypoglycemia in the preceding 6 months. IAH identified by the Gold and Clarke questionnaires and hypoglycemia unawareness identified by the Pedersen-Bjergaard questionnaire were related to 6-, 4.63-, and 5.83-fold increased risk of severe hypoglycemia (P = .001, .004, and .013), respectively. IAH identified by the Gold/Clarke questionnaires was associated with a longer duration of CGM glucose <54 mg/dL and higher glucose coefficients of variation (P<.05). Conclusion: IAH is highly prevalent and related to a higher risk for severe hypoglycemia in T1D patients using CGM. Abbreviations: CGM = continuous glucose monitoring; CI = confidence interval; HAAF = hypoglycemia-associated autonomic failure; HbA1c = hemoglobin A1C; IAH = impaired awareness of hypoglycemia; T1D = type 1 diabetes.