Using Bedside Spectral Doppler Ultrasound for the Assessment of Patients With Thyrotoxicosis.

OBJECTIVE: To assess the bedside utility of Spectral Doppler Ultrasound (SDUS) in the initial evaluation of patients presenting with thyrotoxicosis. METHODS: This is a retrospective cross-sectional study of patients diagnosed with thyrotoxicosis at an academic outpatient endocrinology clinic from August 2019 to November 2022. The thyroid arteries' peak systolic velocities (PSV) were measured bilaterally using SDUS. PSV ≥40 cm/s in at least a single thyroid artery was considered a reasonable cut-off for Graves' disease and PSV of perinodular artery ≥ 25 cm/s for toxic adenoma. RESULTS: We identified 73 patients. Mean age ± standard deviation 45.2 ± 16.4 years, 54 (74.0%) were female, 49 (67.1%) were Caucasian, 23 (31.5%) were African American, and 1 (1.4%) was Asian. The confirmed diagnoses were 48 (65.8%) Graves' disease, 13 (17.8%) thyroiditis, four (5.5%) toxic adenoma, four (5.5%) amiodarone-induced thyroiditis type 2, 1 (1.4%) toxic multinodular goiter, 1 (1.4%) had an unremarkable repeat thyroid function testing, and two (2.7%) were unconfirmed. Diagnosis based on the SDUS initial assessment was accurate in 65 (89.0%) of the patients, and it was conclusive and confirmatory during the initial encounter in 55 (75.3%) of the patients before additional testing. A thyroid scan was obtained in nine (12.3%) patients. Incorrectly diagnosed patients were observed in two patients of each of the following categories: Graves' disease, thyroiditis, toxic adenoma, and unconfirmed diagnoses. CONCLUSIONS: SDUS can be a valuable, efficient, and cost-effective bedside tool in the initial assessment of patients presenting with thyrotoxicosis.

Fracture Risk Assessment and Drug Holiday in a Real-Life Setting.

PURPOSE: Describe fracture risk assessment practices among physicians treating osteoporosis in a real-life setting. METHODS: This is a retrospective cohort study in a tertiary academic center. Inclusion criteria involved adults (aged ≥18 years) who received minimum adequate therapy (bisphosphates, raloxifene, or denosumab ≥ 3 years or teriparatide ≥ 18 months). Of 1,814 charts randomly selected and reviewed, 274 patients met the inclusion criteria. Risk stratification tools included fragility fractures, Dual-energy X-ray Absorptiometry (DXA), and fracture risk assessment using the FRAX tool. Fracture risk assessment was performed before therapy initiation (N= 274) and at the time of institution of the drug holiday (N=119). High-risk patients were defined as the presence of a fragility fracture, T-score ≤-2.5, or a high-risk score by FRAX calculation. FRAX scores were independently calculated by the research team for comparison and assessment purposes. RESULTS: Before initiation of therapy (N=274) versus upon starting a drug holiday (DH; N=119), 29.9% versus 3.4% had a history of fragility fractures (P<0.001), 58.8% versus 67.2% had a DXA scan performed (P>0.05), 10.5% versus 10.9% of physicians calculated a FRAX score (P>0.05), and 71.5% versus 66.4% were considered at high risk and eligible for therapy. A DXA scan was performed after DH in 40.2% of these patients and at least once in 95.3% of the entire cohort. CONCLUSION: The reporting of FRAX score in DXA scan reports may significantly increase its utilization in fracture risk assessment. We recommend comprehensive fracture risk assessment utilizing history of prevalent osteoporosis fractures, DXA assessment, and FRAX scoring.

Unusual local epidemic of paediatric respiratory syncytial virus during a time of global pandemic.

BACKGROUND: Western Australia (WA) public health measures to eradicate SARS-CoV-2 resulted in a secondary reduction in paediatric respiratory syncytial virus (RSV) admissions. Following an absent expected 2020 winter peak, RSV-positive admissions surged during the summer of 2020. AIM: This report examines the number of RSV-positive admissions and severities across 36 months to better understand this out-of-season epidemic. METHODS: A retrospective observational study was performed assessing the number and severity of RSV-related respiratory hospitalisations at a peripheral paediatric centre from March 2018 to February 2021. Data were extracted from the hospital clinical database. RESULTS: The total number of included participants was n = 294. The total number of RSV hospitalisations in SY (study year) 2018 (March 2018 to February 2019), SY 2019 (March 2019 to February 2020) and SY 2020 (March 2020 to February 2021) was 67, 98 and 129, respectively. Prior to SARS-CoV-2, RSV hospitalisations were highest during the winter months. In SY 2020, there were 0 RSV hospitalisations during winter, while 101 admissions in the following summer season. The proportion of admissions requiring respiratory support was significantly reduced in SY 2020 (34.1%) compared to SY 2018 (46.9%, P = 0.050) and SY 2019 (55.2%, P = 0.004). The median length of stay (LOS) in 2020 was 2.0 which was significantly reduced from 2018 and 2019 which was 3.0, P = 0.001; and 3.0, P < 0.001, respectively. CONCLUSION: Following a period of RSV absence, there was an unprecedented surge in admission, however, with lower severity and shorter LOS.

The Use of Unilateral Erector Spinae Plane Block in Minimally Invasive Cardiac Surgery.

OBJECTIVES: To examine the efficacy of continuous unilateral erector spinae plane (ESP) blocks in minimally invasive cardiac surgery patients. DESIGN: A retrospective nonrandomized study. SETTING: At a single-center, tertiary academic institution. PARTICIPANTS: The study comprised 129 adult patients undergoing minimally invasive cardiac surgery with cardiopulmonary bypass or extracorporeal membrane oxygenation. INTERVENTIONS: Patient data were retrospectively collected and compared. Group 1 patients received ultrasound-guided ESP blocks, and group 2 patients underwent conventional intraoperative management without ESP blocks. After intubation in the group 1 cohort, 20-to- 25 mL of 0.25% ropivacaine were deposited beneath the erector spinae plane, along with catheter placement for continuous postoperative infusion. MEASUREMENTS AND MAIN RESULTS: Patient characteristics (ie, age, sex, and comorbidities) were well-matched between both cohorts. The total 48-hour opioid consumption, as measured in morphine equivalents (mg), was significantly decreased in patients receiving erector spinae plane blocks compared to patients receiving conventional therapy (30.24 mg ± 23.8 v 47.82 mg ± 53.6, p = 0.04). The length of stay in the intensive care unit (ICU) also was reduced in the treatment group in comparison to the control group (1.99 days ± 1.7 v 2.65 days ± 2.4, p = 0.03). Lastly, patients receiving the blocks benefitted from a decrease in overall hospital length of stay when compared to the control group (5.93 days ± 2.4 v 7.35 days ± 5.8, p = 0.04). CONCLUSION: Erector spinae plane catheter use may safely improve postoperative measures, including decreased opioid consumption and improved pain relief, as well as reductions in ICU and hospital lengths of stay in patients undergoing minimally invasive cardiac surgery.

Calcium Challenge to Confirm Secondary Hyperparathyroidism Caused by Decreased Calcium Intake.

OBJECTIVE: Secondary hyperparathyroidism commonly occurs in the setting of mid-to low-normal serum calcium levels, often in the setting of chronic kidney disease, phosphate loading, vitamin D deficiency, or insufficient calcium intake or absorption. In this article, we report 9 patients who had adequate kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m2) and normal 25-hydroxy vitamin D level (≥30 ng/dL) and whose secondary hyperparathyroidism resolved after starting adequate oral calcium intake. METHODS: Our retrospective case series included 8 women and 1 man; the mean age was 69.0 ± 12.2 years (mean ± standard deviation). The initial intact parathyroid hormone (iPTH) level was 80.6 ± 13.4 pg/mL (reference range [ref], 10-65 pg/mL), corrected serum calcium level was 9.2 ± 0.2 mg/dL (ref, 8.5-10.5 mg/dL), serum phosphate level was 3.6 ± 0.4 mg/dL (ref, 2.5-4.9 mg/dL), 25-hydroxy vitamin D level was 42.2 ± 10.5 mg/dL (ref, 20-50 ng/mL), and estimated glomerular filtration rate was 72.6 ± 14.4 mL/min/1.73 m2. Patients were treated clinically with oral calcium 600 mg twice a day. RESULTS: iPTH was retested after a mean duration of 17.6 ± 12.7 days of calcium supplementation; the iPTH level decreased to 51.0 ± 10.6 pg/mL, with all patients achieving iPTH in the normal range with normocalcemia, consistent with hyperparathyroidism being because of insufficient calcium intake or absorption. All patients were normocalcemic after supplementation. CONCLUSION: Secondary hyperparathyroidism can result from insufficient oral calcium intake. Calcium challenge is an efficacious and cost-effective tool for confirming and treating secondary hyperparathyroidism in the setting of normal vitamin D levels and kidney function.

Patterns of Osteoporosis Medications Selection After Drug Holiday or Continued Therapy: A Real-World Experience.

OBJECTIVE: Published literature on physicians' preferences and sequential treatment patterns of osteoporosis therapy is scarce. METHODS: A retrospective cohort study of patients who received bisphosphonates, denosumab, and/or raloxifene for at least 3 consecutive years or teriparatide for at least 18 months for osteoporosis. Data collection spanned 10 years, from October 2007 to September 2016, at a tertiary care center in the United States. RESULTS: In total, 12 885 patients were identified on the basis of receiving at least 1 treatment at any point in time; 1814 patients were randomly reviewed, and 274 patients met the inclusion criteria. The mean age was 68.8 ± 10.7 years, and women represented 90.9% of all the cases. Primary care physicians and rheumatologists constituted 65.7% and 22.6% of the prescribers, respectively. Before instituting a drug holiday, alendronate was the most common initial treatment (percentage, mean duration ± standard deviation in years: 69%, 5.4 ± 2.4 years) followed by ibandronate (9.5%, 4.9 ± 2.1 years) and raloxifene (9.1%, 5.2 ± 1.6 years). Denosumab was the most common second course of treatment, accounting for 29.3% of 82 patients who were subsequently prescribed another therapy, followed by alendronate (24.4%) and zoledronate (20.7%). Among patients who were placed on a drug holiday and eventually restarted on osteoporosis therapy, denosumab was the most common treatment instituted (n = 21), accounting for 40% of the total patients, followed by alendronate (32%) and zoledronate (16%). There was a progressive decline in osteoporosis therapy over the duration of the study. CONCLUSION: Alendronate was the most common initial therapy. Denosumab was the most common second course of treatment prescribed.

EXTERNAL VALIDATION OF A PREDICTIVE MODEL FOR ACUTE PANCREATITIS RISK IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA.

Objective: We previously developed a predictive model to assess the risk of developing acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG). In this study, we aimed to externally validate this model. Methods: The validation cohort included cross-sectional data between 2013 and 2017. Adult patients (≥18 years old) with triglyceride levels ≥1,000 mg/dL were identified. Based on our previous 4-factor predictive model (age, triglyceride [TG], excessive alcohol use, and gallstone disease), we estimated the probability of developing AP. Model performance was assessed using area under receiver operating characteristic curve (AUROC). Results: In comparison to the original cohort, patients in the validation cohort had more prevalent acute pancreatitis (16.2% versus 9.2%; P<.001) and gallstone disease (7.5% versus 2.1%; P<.001). Other characteristics were comparable and not statistically significant. The AUROCs were almost identical: 0.8337 versus 0.8336 in the validation and the original cohorts, respectively. In univariable analyses, the highest increase in odds of AP was associated with HTG, followed by gallstones, excessive alcohol use, and younger age. Conclusion: This study externally validates the 4-factor predictive model to estimate the risk of AP in adult patients with severe HTG (TG ≥1,000 mg/dL). Younger age was confirmed to place patients at high risk of AP. The clinical risk categories suggested in this study may be useful to guide treatment options. Abbreviations: AP = acute pancreatitis; ASCVD = atherosclerotic cardiovascular disease; AUROC = area under the receiver operating characteristic curve; FRAX = fracture risk assessment tool; HTG = hypertriglyceridemia; OR = odds ratio; TG = triglyceride level.

Novel targeted therapies and immunotherapy for advanced thyroid cancers.

Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC. These advanced therapies exert their effects by blocking the MAPK pathway, which has been widely correlated to different types of thyroid cancers. While these drugs remain reserved for thyroid cancer patients who failed all treatment options, their ability to improve patients' overall survival remain hindered by their low efficacy and other molecular factors. Among these factors is the tumor's ability to activate parallel proliferative signaling pathways other than the cascades blocked by these drugs, along with overexpression of some tyrosine kinase receptors (TKR). These facts urge the search for novel different treatment strategies for advanced thyroid cases beyond these drugs. Furthermore, the growing knowledge of the dynamic immune system interaction with tumor microenvironment has revolutionized the cancer immune therapy field. In this review, we aim to discuss the molecular escape mechanisms of thyroid tumors from these drugs. We also highlight novel therapeutic options targeting other pathways than MAPK, including PI3K pathway, ALK translocations and HER2/3 receptors and their clinical impact. We also aim to discuss the usage of targeted therapy in restoring thyroid tumor sensitivity to RAI, and finally turn to extensively discuss the role of immunotherapy as a potential alternative treatment option for advanced thyroid diseases.

Factors Associated with Diabetes Control in Predominately African American and Hispanic Population with Newly Diagnosed Type 2 Diabetes.

BACKGROUND: This study characterizes factors affecting glycemic control in a predominately African American and Hispanic population with newly diagnosed type 2 diabetes (T2DM). METHODS: Retrospective longitudinal cohort study of 1638 patients with newly diagnosed T2DM to determine factors associated with improved HbA1c (ΔHbA1c ≤ - 0.5%) and achieving target HbA1c < 7%. RESULTS: At baseline, mean age 51.7 ± 11.5 years, males 52.9%, mean BMI 33.9 ± 7.8 kg/m2, median HbA1c 9.9 (7.6-12.1)%. At study end, median follow-up duration 27 (13-54) months, median HbA1c 7.0 (6.2-8.7)%, 69.6% with improved HbA1c, 48.3% achieved target HbA1c < 7%, 88.4% monitored blood glucose, 40.1% used insulin, and 72.4% reported not missing medications. In multivariate analysis, improved HbA1c significantly correlated with glucose monitoring (OR = 2.65), higher initial HbA1c (OR = 1.85), and medication adherence (OR = 1.66) and inversely correlated with insulin use (OR = 0.38) and follow-up duration (OR = 0.99). Achieving HbA1c < 7% significantly correlated with glucose monitoring (OR = 2.14), medication adherence (OR = 1.88), more provider visits (OR = 1.04), and older age (OR = 1.03). It inversely correlated with insulin use (OR = 0.47), initial HbA1c (OR = 0.93), and follow-up duration (OR = 0.98). CONCLUSIONS: In those with newly diagnosed T2DM, achieving better glycemic control was mainly related to patient self-management behaviors and inversely related to insulin use. Emphasis on patients' diabetes education and empowerment are critical to improved glycemic control.

Insulin management in hospitalized patients with diabetes mellitus on high-dose glucocorticoids: Management of steroid-exacerbated hyperglycemia.

BACKGROUND: Glucocorticoid (GC)-exacerbated hyperglycemia is prevalent in hospitalized patients with diabetes mellitus (DM) but evidence-based insulin guidelines in inpatient settings are lacking. METHODS AND FINDINGS: Retrospective cohort study with capillary blood glucose (CBG) readings and insulin use, dosed with 50% basal (glargine)-50% bolus (lispro) insulin, analyzed in hospitalized patients with insulin-treated DM given GC and matched controls without GC (n = 131 pairs). GC group (median daily prednisone-equivalent dose: 53.36 mg (IQR 30.00, 80.04)) had greatest CBG differences compared to controls at dinner (254±69 vs. 184±63 mg/dL, P<0.001) and bedtime (260±72 vs. 182±55 mg/dL, P<0.001). In GC group, dinner CBG was 30% higher than lunch (254±69 vs. 199±77 mg/dL, P<0.001) when similar lispro to controls given at lunch. Bedtime CBG not different from dinner when 20% more lispro given at dinner (0.12 units/kg (IQR 0.08, 0.17) vs. 0.10 units/kg (0.06, 0.14), P<0.01). Despite receiving more lispro, bedtime hypoglycemic events were lower in GC group (0.0% vs. 5.9%, P = 0.03). CONCLUSIONS: Since equal bolus doses inadequately treat large dinner and bedtime GC-exacerbated glycemic excursions, initiating higher bolus insulin at lunch and dinner with additional enhanced GC-specific insulin supplemental scale may be needed as initial insulin doses in setting of high-dose GC.

Micafungin-Induced Hypoglycemia in a Patient With Type 1 Diabetes: A Case Report and Review of Literature.

Objective: Patients with type 1 diabetes mellitus (T1DM) are insulin dependent. Infection increases insulin resistance and subsequently increases insulin needs. We are reporting a case of a patient with T1DM and severe infection who has reduced insulin needs after starting micafungin therapy. Participant: A 29-year-old Hispanic woman with known history of long-standing, uncontrolled T1DM presented for evaluation of worsening dysphagia and dyspnea. She was found to have cervical necrotizing fasciitis extending into the mediastinum and required several debridement surgeries along with broad-spectrum antibiotics and antifungal therapy. She had uncontrolled diabetes with a glycosylated hemoglobin of 13.4% (18.8 mM) on admission. Her insulin requirements progressively increased as a result of worsening infection, continuous tube feeds, and multiple debridement surgeries. She was started on micafungin, a potent 1,3-ß-D glucan synthase inhibitor, to broaden antimicrobial coverage when her insulin requirement decreased to zero for >48 hours. Right after discontinuation of micafungin and her switch to a different antifungal, insulin requirements increased back to her baseline needs. Results: This is a report of decreased insulin requirements in a patient with T1DM correlating with micafungin administration. The mechanism of micafungin-induced hypoglycemia is not yet established. Oral administration of linear 1,3-ß-D glucan has been documented to decrease blood glucose levels significantly by inhibition of expression of sodium-glucose transporter 1 (SGLT1) in intestinal mucosa. Conclusion: We hypothesize that micafungin may inhibit SGLT-1 function and decrease insulin requirements in patient with T1DM.

PROTRACTED ACUTE HYPERVOLEMIC HYPERNATREMIA UNMASKED AFTER VASOPRESSIN THERAPY: CASE REPORT, LITERATURE REVIEW, AND PROPOSED ALGORITHMIC APPROACH.

OBJECTIVE: Acute hypervolemic hypernatremia (HHN) is the most common form of hypernatremia in critical care settings. Previous reports implicated acute kidney injury and vasopressin withdrawal-induced central diabetes insipidus. METHODS: We present the case of a 52-year-old woman who developed HHN after treatment of septic shock due to complicated bowel perforation. RESULTS: After discontinuation of a 30-hour infusion of vasopressin analog, the patient manifested hypernatremia (150 to 156 mEq/L, equivalent to mmol/L) with hyponatriuria (49 mEq/L), hypoosmotic urine (163 mOsm/L), and polyuria (6.9 L/day) in a setting of cumulative positive fluid balance of 20.1 L. A trial of desmopressin yielded incomplete urinary concentration suggestive of renal resistance to desmopressin likely due to fluid overload. Despite positive water balance, her urine sodium was low at 36 to 49 mEq/L compared to serum sodium of 152 to 156 mEq/L. The hypernatremia with polyuria persisted for 16 days and resolved after treatment of the positive cumulative water balance (with controlled diuresis prioritizing natriuresis). CONCLUSION: HHN may result in insufficient urine sodium clearance. We propose modifying the diagnostic/treatment algorithm by including HHN in a critical care setting, and recommending judicious administration of a loop diuretic to prioritize natriuria in hypernatremia with extreme cumulative fluid overload.

Virtual Reality Improves the Patient Experience during Wide-Awake Local Anesthesia No Tourniquet Hand Surgery: A Single-Blind, Randomized, Prospective Study.

Wide-awake local anesthesia no tourniquet surgery has been shown to decrease cost and hospital length of stay. The authors studied the use of virtual reality during wide-awake local anesthesia no tourniquet outpatient upper extremity surgery to assess its effect on patient pain, anxiety and fun. Patients undergoing wide-awake local anesthesia no tourniquet surgery were randomized to use (virtual reality) or not use (non-virtual reality) virtual reality during their procedures. Pain, fun, and anxiety were measured with a Likert scale at several time points, as were blood pressure and heart rate. A postoperative questionnaire was used to assess overall satisfaction. Virtual reality patients exhibited lower anxiety scores during injection, during the procedure, and at the end of the procedure. There were no differences in blood pressure, heart rate, or pain scores. Compared with non-virtual reality patients, virtual reality patients' fun scores were higher. Virtual reality patients felt the experience helped them to relax, and they would recommend virtual reality-assisted wide-awake local anesthesia no tourniquet surgery. Among patients with self-reported preexisting anxiety, virtual reality patients had lower pain and anxiety scores during injection of local anesthesia compared with non-virtual reality patients. This study demonstrates that readily available virtual reality hardware and software can provide a virtual reality experience that reduces patient anxiety both during the injection of local anesthesia and during the surgical procedure. (Plast. Reconstr. Surg. 144: 408, 2019.) CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, II.

Newly diagnosed type 2 diabetes in an ethnic minority population: clinical presentation and comparison to other populations.

OBJECTIVE: To characterize the clinical presentation of newly diagnosed type 2 diabetes of ethnic minority adults in Chicago and compare with other populations. RESEARCH DESIGN AND METHODS: Cross-sectional study examining the data of 2280 patients newly diagnosed with type 2 diabetes treated between 2003 and 2013 in a large Chicago public healthcare system. RESULTS: Mean age of the patients was 49±11.3 years, men 54.4%, African-Americans 48.1%, Hispanics 32.5%, unemployed 69.9%, uninsured 82.2%, English-speaking 75.1%, and body mass index was 32.8±7.4 kg/m2. Microvascular complications were present in 50.1% and macrovascular complications in 13.4%. There was a presence of either macrovascular or microvascular complications correlated with older age, hypertension, dyslipidemia, inactivity, speaking English, and being insured (p<0.01). Glycosylated hemoglobin A1c (HbA1c) at presentation did not correlate with diabetes complications. In our cohort, when compared with a diverse population in the UK and insured population in the USA, HbA1c at presentation was 10.0% (86 mmol/mol), 6.6% (49 mmol/mol), and 8.2% (66 mmol/mol); nephropathy was 22.2%, 16.7%, and 5.7%; retinopathy was 10.7%, 7.9%, and 1.4%; and neuropathy was 27.7%, and 6.7% in the UK (p<0.001). There were no significant differences between groups in the prevalence of macrovascular complications. CONCLUSION: These results show the vulnerability of underserved and underinsured patients for developing diabetes complications possibly related to a delayed diagnosis.