A Fracture Liaison Service to Address Vitamin D Deficiency for Patients Hospitalized for Osteoporotic Fracture.

Context: Addressing vitamin D deficiency (VDD) is important for fracture secondary prevention. Objectives: To explore the function of a fracture liaison service (FLS) to address VDD. Design Setting and Patients: An observational study of patients admitted to the Massachusetts General Hospital with fractures between January 1, 2016, and October 31, 2023, cared for by the FLS. Intervention: Ergocalciferol 50 000 international units (50ku-D2) oral daily for 3 to 7 days. Main Outcomes Measures: VDD prevalence. Efficacy of inpatient daily 50ku-D2 in raising serum 25-hydroxyvitamin D (25OHD) levels. Results: Of the 2951 consecutive patients, 724 (24.53%) had VDD (defined by 25OHD ≤ 19 ng/mL). Men (252/897, or 28.09%) were more likely than women (472/2054, or 22.98%) to have VDD (P = .003). VDD was seen in 41.79% (117/280), 24.41% (332/1360), and 20.98% (275/1311) of patients of aged ≤59, 60 to 79, and ≥80 years, respectively (P < .00001). Of the 1303 patients with hip fractures, 327 (25.09%) had VDD, which was associated with a longer length of stay (8.37 ± 7.35 vs 7.23 ± 4.78 days, P = .009) and higher trend of 30-day-readmission rate (13.63% vs 18.35%, P = .037). In a cohort of 32 patients with complete data, each dose of 50ku-D2 increased serum 25OHD by 3.62 ± 2.35 ng/mL without affecting serum calcium or creatinine levels. Conclusion: VDD was seen in nearly 25% of Massachusetts General Hospital FLS patients and more prevalent in male and younger patients. VDD was associated with longer length of stay and higher 30-day-readmission risk in patients with hip fracture. Daily 50ku-D2 appeared to be a practical way to quickly replete vitamin D in the inpatient setting.

Safety of Inpatient Zoledronic Acid in the Immediate Postfracture Setting.

CONTEXT: Zoledronic acid (ZA) administered during the initial hospitalization for a fragility fracture improves the osteoporosis pharmacotherapy rate. Distinguishing the safety profile of inpatient ZA (IP-ZA) in this context is crucial if this approach is to be widely adopted. OBJECTIVE: To study the acute safety profile of IP-ZA. METHODS: An observational study of patients admitted to the Massachusetts General Hospital with fragility fractures who were eligible to receive IP-ZA. Patients were treated with or without IP-ZA. Acetaminophen, either as a single pre-ZA dose or standing multiple-doses-per-day regimen for 48 hours or longer after ZA infusion, was also administered along with protocolized vitamin D and calcium supplementation. Changes in body temperature, serum creatinine, and serum calcium were measured. RESULTS: A total of 285 consecutive patients, meeting inclusion and exclusion criteria, are included in this analysis; 204 patients received IP-ZA. IP-ZA treatment was associated with a transient mean rise of body temperature of 0.31 °C on the day following its administration. Temperatures above 38 °C were seen in 15% of patients in the IP-ZA group and 4% in the nontreated group. Standing multiple-doses-per-day but not a single pre-ZA dose of acetaminophen effectively prevented this temperature increase. IP-ZA did not affect serum creatinine levels. Mean levels of serum total calcium and albumin-corrected calcium decreased by 0.54 mg/dL and 0.40 mg/dL, respectively, at their nadirs (Day 5). No patient experienced symptomatic hypocalcemia. CONCLUSION: IP-ZA along with standing multiple-doses-per-day acetaminophen, administered to patients in the immediate postfracture period, is not associated with significant acute adverse effects.

Inpatient Zoledronic Acid and Integrated Orthopedic and Fracture Liaison Services Improve Osteoporosis Treatment Rates.

CONTEXT: Fragility fractures increase risks for future fractures, morbidity, and mortality. Available pharmacotherapy for underlying osteoporosis is safe and effective but underused. OBJECTIVE: To improve pharmacotherapy rate representing secondary prevention of osteoporotic fractures. METHODS: This single-center, observational, follow-up study included patients with fragility fractures admitted to the Massachusetts General Hospital between February 2016 and December 2019. For patients admitted to the orthopedics service with fragility fracture, the Massachusetts General Hospital Fracture Liaison Service (FLS) was systematically consulted. Initial outpatient follow-up with FLS was established in conjunction with the orthopedic postoperative follow-up visit. Patients at risk for failing timely outpatient follow-up were administered zoledronic acid (ZA) during the index fracture hospitalization. The main outcome measures were percentage of patients with fragility fracture(s) started on pharmacotherapy for osteoporosis and average length of stay and 30-day readmission rate of patients treated with ZA. RESULTS: Compared with baseline (8-11%) and reference (5-20%) rates, integration of FLS to the orthopedics service, along with appropriate inpatient administration of ZA, increased the pharmacotherapy rate to 70% (412/589) among eligible patients with verified treatment status. Inpatient ZA administration neither affected the average length of stay nor 30-day readmission rate. Treatment status of 37.9% (471/1240) of the study patients remained unknown due to lack of or unknown follow-up. CONCLUSION: Integration of a FLS and orthopedics services along with inpatient ZA administration improved the osteoporosis pharmacotherapy rate among patients with fragility fracture(s) who often had obstacles for outpatient follow-up.

Exenatide, Metformin, or Both for Prediabetes in PCOS: A Randomized, Open-label, Parallel-group Controlled Study.

CONTEXT: Up to 40% of patients with polycystic ovary syndrome (PCOS) have prediabetes; an optimal pharmacotherapy regimen for diabetes prevention in PCOS is yet to be established. OBJECTIVE: To evaluate clinical efficacy of exenatide (EX), metformin (MET), or combination (COM) for prediabetes in PCOS. DESIGN: Randomized, open-label, parallel-group controlled trial. SETTING: Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine. PATIENTS: PCOS with prediabetes (fasting plasma glucose 5.6-6.9 mmol/L and/or 2 hour post glucose 7.8-11.0 mmol/L on oral glucose tolerance test [OGTT]). A total of 150 out of 183 eligible enrollees completed the study. INTERVENTION: EX (10-20µg daily), MET (1500-2000 mg daily), or COM (EX plus MET) for 12 weeks. MAIN OUTCOME MEASURES: Sustained remission rate of prediabetes (primary endpoint, a normal OGTT after 12 weeks of treatment followed by 12 weeks of washout on no drug treatment) along with anthropometric, hormonal, metabolic, and pancreatic ß-cell function parameters (secondary endpoints) and potential mechanisms were assessed. RESULTS: Impaired glucose tolerance was found the dominant prediabetes phenotype. Overall sustained prediabetes remission rate was 50.7%. Remission rate of COM group (64%, 32/50) or EX group (56%, 28/50) was significantly higher than that of the MET group (32%, 16/50) (P = .003 and .027, respectively). EX was associated with superior suppression of 2-hour glucose increment in OGTT. A 2-step hyperglycemic clamp study revealed that EX had led to higher postprandial insulin secretion than MET, potentially explaining the higher remission rate. CONCLUSIONS: Compared with MET monotherapy, EX or COM achieved higher rate of remission of prediabetes among PCOS patients by improving postprandial insulin secretion.

Complete Resolution of Sellar Metastasis in a Patient With NSCLC Treated With Osimertinib.

Non-small cell lung cancer with pituitary metastasis (NSCLC-PM) is a devastating disease; however, treatment is being revolutionized by a novel therapy targeting highly specific tumor signals, such as the mutation of epidermal growth factor receptors (EGFRs). Long-term management of hormonal defects in this population has become a unique neuroendocrine clinical challenge. We report the case of a 73-year-old female nonsmoker who was diagnosed with stage IV non-small cell lung cancer. The initial staging evaluation revealed a 7 × 11 × 21-mm sellar lesion abutting the optic chiasm and causing clinical hypopituitarism. The patient received three cycles of chemotherapy with carboplatin and pemetrexed, which was discontinued because of major cumulative side effects of myelosuppression and kidney disease. Eight months later, scans demonstrated evidence of disease progression. A repeated lung nodule biopsy revealed an EGFR exon 19 deletion mutation. EGFR-targeted therapy with osimertinib 80 mg daily was initiated. A complete resolution of the pituitary lesion was evident on a follow-up pituitary MRI 5 weeks later and was sustained 1 year after. However, the panhypopituitarism persisted. This is an illustrative case of NSCLC-PM with EGFR exon 19 deletion mutation, wherein osimertinib, a third-generation EGFR‒tyrosine kinase inhibitor, eradicated the sellar metastasis and prevented the need for radiotherapy. However, the neuroendocrine deficits persisted despite anatomic improvement.

Low Plasma Oxytocin Levels and Increased Psychopathology in Hypopituitary Men With Diabetes Insipidus.

CONTEXT: Oxytocin (OT) and vasopressin share anatomical pathways of synthesis and secretion, and patients with central diabetes insipidus (CDI) presumably are at risk for OT deficiency. However, an OT-deficient state in hypopituitary patients has not been established. OBJECTIVES: We hypothesized that men with CDI compared to patients with similar anterior pituitary deficiencies (APD) but no CDI and healthy controls (HC) of similar age and body mass index, would have lower plasma OT levels, associated with increased psychopathology. DESIGN: Cross-sectional. SETTING: Clinical research center. PARTICIPANTS: Sixty-two men (20 CDI, 20 APD, 22 HC), age 18 to 60 years. INTERVENTIONS: Frequent sampling of blood every 5 minutes for OT over 1 hour and validated questionnaires to assess psychopathology. MAIN OUTCOMES: Pooled plasma OT levels; depressive, anxiety, and alexithymia symptoms; and quality of life. RESULTS: The mean 1-hour pool of fasting OT levels was lower in CDI compared with APD and HC (P = 0.02 and P = 0.009, respectively), with no differences between APD and HC (P = 0.78). Symptoms of depression, anxiety, and alexithymia were more pronounced in CDI than in HC (P = 0.001, P = 0.004, and P = 0.02, respectively). Although CDI and APD reported worse physical health compared with HC (P = 0.001 and P = 0.005) with no differences between APD and CDI, only CDI reported worse mental health compared with HC (P = 0.009). CONCLUSIONS: We have demonstrated low plasma OT levels and increased psychopathology in hypopituitary men with CDI, suggestive of a possible OT-deficient state. Larger studies of both sexes are required to confirm these findings and clinically characterize hypopituitary patients with OT deficiency.

Estimating HbA1c from timed Self-Monitored Blood Glucose values.

AIMS: To analyze mathematical relationships between timed Self-Monitored Blood Glucose (SMBG) and HbA1c, and to identify the SMBG values that correlate most strongly with HbA1c. METHODS: We utilized the average premeal (Pre) and 90-min postmeal (Post) SMBG results from 547 A1c-Derived Average Glucose (ADAG) study participants (285 type 1, 178 type 2 and 84 non-diabetic) to analyze the mathematical relationships with HbA1c levels. Specific times of daily SMBG that best correlate with HbA1c were identified. RESULTS: Linear regression analyses showed the following correlations for Pre and Post, Pre only and Post only, respectively: HbA1c = 2.488 + 0.018 × Premg/dl + 0.012 × Postmg/dl, R2 = 0.741, P < 0.0001; HbA1c = 2.887 + 0.029 × Premg/dl, R2 = 0.695, P < 0.0001; and HbA1c = 2.815 + 0.025 × Postmg/dl, R2 = 0.657, P < 0.0001. Among patients with type 2 diabetes mellitus (DM), of the 6 individual timepoints, pre-dinner SMBG had the strongest correlation with HbA1c (R2 = 0.577). This was followed by pre-breakfast (R2 = 0.562). Examining combinations of timepoints revealed that pre-breakfast + pre-dinner (R2 = 0.666) performed similarly to the full 6-timepoints (pre-meals + post-meals, R2 = 0.712). CONCLUSIONS: We have established mathematical relationships between HbA1c and timed SMBG values and identified pre-dinner and pre-breakfast as the two SMBG timepoints that best correlate with HbA1c in patients with type 2 DM.

Opposite impact of Methylene tetrahydrofolate reductase C677T and Methylene tetrahydrofolate reductase A1298C gene polymorphisms on systemic inflammation.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been found to be related with many diseases. Systemic inflammation is now considered as a major predisposition factor for diseases including diabetes mellitus (DM), coronary arterial disease (CAD), stroke, and cancer. This study aimed to investigate whether systemic inflammation is a possible underlying pathogenesis for MTHFR gene polymorphism-related disease. METHODS: A total of 292 patients were enrolled, and single nucleotide polymorphisms for MTHFR C667T and A1298C were genotyped. Systemic inflammation markers, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were collected. RESULTS: In our study population, MTHFR 677 variants had significant higher NLR level than MTHFR 677 wild type (3.77 ± 0.26 vs 3.06 ± 0.18, P = .028). Logistic regression analysis showed that MTHFR 677 variants were significantly associated with increased NLR level. MTHFR 1298 variants showed the opposite effects which tended to have lower level of NLR (3.21 ± 0.16 vs 3.79 ± 0.34, P = .087) and PLR (137.0 ± 4.8 vs 157.7 ± 9.4, P = .052) than MTHFR 1298 wild type. General linear model showed that there was no statistically significant interaction between MTHFR C667T and A1298C gene polymorphism on NLR or PLR. CONCLUSIONS: This study indicates that MTHFR C677T and MTHFR A1298C gene polymorphisms have opposite effect on systemic inflammation, and systemic inflammation may contribute to the pathogenesis for diseases associated with MTHFR C667T gene polymorphism.

CYP2C19 genetic variation and individualized clopidogrel prescription in a cardiology clinic.

Background: Clopidogrel (Plavix) is an antiplatelet medication that is routinely used in patients with cardiovascular disease. Cytochrome P2C19 enzymes play a major role in its metabolism, which determines its varied therapeutic level and its effectiveness. Objectives: To customize clopidogrel therapy and evaluate its efficacy by using CYP2C19 genotypic and phenotypic information to improve clinical outcomes in patients. Methods: A total of 465 patients with underlying cardiovascular disease were selected from our out-patient cardiology clinic. DNA sequences of CYP2C19 were analyzed in 465 patients. Results: Of 465 patients, 183 were wild-type homozygous (*1/*1) and 18.8% gain-of function and 19.8% loss-of-function alleles in our patient population The following changes were made: 1) Switching to prasugrel in patients whose genotype noted them to be "Slow metabolizers. This medication adjustment improved clinical outcomes in this patient group. 2) Discontinuing or lowering clopidogrel doses in patients whose genotypes noted them to be "Fast or ultra-fast metabolizes" to decrease bleeding risk. For those who were not on clopidogrel but carried abnormal allele(s), "clopidogrel caution" was documented. These individuals were followed up for 3 years and there has not been any cardiac clinical symptoms, cardiac death or excessive bleeding reported. Conclusions: Given the varied effectiveness of clopidogrel due to its metabolism by CYP2C19 enzyme, and the relatively high frequency of both gain-of-function (18.8%) and loss-of-function (19.8%) alleles in our patient population, we believe that genotyping CYP2C19 is clinically important in order to improve patient outcomes and minimize patient risk.

Linkage disequilibrium between the CYP2C19*2,*17 and CYP2C9*1 alleles and impact of VKORC1, CYP2C9, CYP2C19 gene polymorphisms and gene-gene interactions on warfarin therapy.

Warfarin therapy is complicated by its large inter-individual and intra-individual variability. Both genetic and non-genetic factors can affect warfarin therapy. This study aims to investigate the allele distribution of VKORC1, CYP2C9 and CYP2C19, contribution of different allele variants and possible gene-gene interaction on warfarin therapy. Four hundreds and ninety-two patients were enrolled and single nucleotide polymorphisms for vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 CYP2C9 and cytochrome P450 CYP2C19 were genotyped. CYP2C9*1 allele is in complete linkage disequilibrium with CYP2C19*2 and CYP2C19*17 (D' = 1) in our study population. Patient with VKORC1-1639 G > A, CYP2C9*2 and CYP2C9*3 genetic variants need significant lower warfarin dose than patient with wild type allele of VKORC1 1639 G or CYP2C9*1. There is no significant differences between CYP2C19 allele variants for warfarin stable dose and INR > 5 event. Because of the complete linkage disequilibrium between CYP2C19*2,*17 and CYP2C9*1, patient with CYP2C19 *2/*2, *2/*17 and *17/*17 genotypes tend to have higher warfarin dose than patient with CYP2C19*1/*1 genotype. Stepwise regression analysis showed that VKORC1, CYP2C9, body mass index (BMI), age and gender were included as a factor significantly contributing to warfarin dose, whereas CYP2C19 did not contribute to warfarin dose. No statistically significant interaction between CYP2C9 and VKORC1 on warfarin dose and INR > 5 event was detected in univariate general linear model analysis. Our study suggests that polymorphic variants of VKORC1 and CYP2C9 affect warfarin dose independently, whereas CYP2C19 did not contribute to warfarin therapy.

Thyroid storm presenting as psychosis: masked by diabetic ketoacidosis.

INTRODUCTION: While extremely uncommon, diabetic ketoacidosis (DKA) and thyroid storm (TS) are endocrine emergencies that can coexist. We describe a case with a confounding clinical presentation that identifies these two emergencies within the setting of sepsis and influenza. CASE: A 69-year-old diabetic female was found by the paramedic staff to be disoriented. She demonstrated tachycardia and had a foul-smelling abdominal wound. Laboratory evaluation revealed DKA, leukocytosis, influenza B, and urinary tract infection. After appropriate management in the intensive care unit, the DKA resolved the following morning. However, the patient developed a fever, and her psychosis became more pronounced. Extensive analysis was performed but did not explain her mental status. The patient was found to have thyroid stimulating hormone of 0.06 mIU/mL, free T4 (thyroxine) of 2.38 ng/dL, and total T3 (triiodothyronine) of 72 ng/dL. Based on the Burch and Wartofsky criteria (score of 65), TS was diagnosed. Based on more recent diagnostic criteria suggested by Akamizu et al., the patient met criteria for TS grade 1. Within several hours of initiating treatment, the patient's mental state and tachycardia improved, and her psychosis resolved by the third day. CONCLUSION: This case highlights the importance of recognizing the clinical diagnosis of TS, as the magnitude of thyroid hormone derangements may not correlate with clinical severity. While rare, DKA and TS can simultaneously occur and are associated with increased morbidity and mortality if not promptly recognized and treated.

Left ventricular outflow track obstruction and mitral valve regurgitation in a patient with takotsubo cardiomyopathy.

INTRODUCTION: Takotsubo cardiomyopathy (TCM) can be complicated by left ventricular outflow tract (LVOT) obstruction and severe acute mitral regurgitation (MR), leading to hemodynamic instability in an otherwise benign disorder. Despite the severity of these complications, there is a paucity of literature on the matter. Because up to 20-25% of TCM patients develop LVOT obstruction and/or MR, it is important to recognize the clinical manifestations of these complications and to adhere to specific management in order to reduce patient morbidity and mortality. We report the clinical history, imaging, treatment strategy, and clinical outcome of a patient with TCM that was complicated with severe MR and LVOT obstruction. We then discuss the pathophysiology, characteristic imaging, key clinical features, and current treatment strategy for this unique patient population. CASE REPORT: A postmenopausal woman with no clear risk factor for coronary artery disease (CAD) presented to the emergency department with chest pain after an episode of mental/physical stress. Physical examination revealed MR, mild hypotension, and pulmonary vascular congestion. Her troponins were mildly elevated. Cardiac catheterization excluded obstructive CAD, but revealed severe apical hypokinesia and ballooning. Notably, multiple diagnostic tests revealed the presence of severe acute MR and LVOT obstruction. The patient was diagnosed with TCM complicated by underlying MR and LVOT obstruction, and mild hemodynamic instability. The mechanism of her LVOT and MR was attributed to systolic anterior motion of the mitral valve (SAM), which the transesophageal echocardiogram clearly showed during workup. She was treated with beta-blocker, aspirin, and ACE-I with good outcome. Nitroglycerin and inotropes were discontinued and further avoided. CONCLUSIONS: Our case illustrated LVOT obstruction and MR associated with underlying SAM in a patient with TCM. LVOT obstruction and MR are severe complications of TCM and may result in heart failure and/or pulmonary edema. Timely and accurate identification of these complications is critical to achieve optimal clinical outcomes in patients with TCM.

The power of anecdotes on resident HVCCC curriculum.

A formal high value, cost-conscious care (HVCCC) curriculum was implemented at a community hospital-based university-affiliated residency program starting January 1, 2014, based on the recommendations of the American Board of Internal Medicine's (ABIM) Choosing Wisely campaign. The program included a competition requiring each resident to write a HVCCC case based on an actual patient experience. Residents completed a questionnaire assessing their understanding of HVCCC near the end of the program. Residents subsequently reviewed two actual cases that had vividly described unexpected adverse outcomes ('anecdotal' cases). Postexposure data were collected and the results were analyzed.

Key clinical features a general internist needs to know about Brugada syndrome: a case-based discussion.

INTRODUCTION: Brugada syndrome (BrS) is an autosomal dominant genetic disorder involving the abnormal function of cardiac voltage-gated sodium ion channels. Sodium channel loss of function can lead to early repolarization and loss of the Phase 2 action potential dome in cardiomyocytes. In BrS, this sodium channelopathy occurs in some, but not all, epicardial cells thus creating 1) juxtaposition of depolarized and repolarized cells in the epicardium and 2) a transmural voltage gradient. Together, these conditions can set up a Phase 2 reentry and resultant malignant cardiac arrhythmia. Of the three types of electrocardiogram (EKG) changes seen in BrS, only the Type 1 EKG is considered diagnostic. In a controlled setting, sodium channel blockers and Brugada EKG leads may be used to unmask this diagnostic EKG finding. Fever and certain medications that interfere with the sodium channel can also trigger these changes, which can be catastrophic. CASE REPORT: A 26-year-old white male presented with febrile upper respiratory infection symptoms and had an EKG change, which was initially misinterpreted as an ST elevated myocardial infarction due to ST-T segment elevation in leads V1 and V2. The patient reported past recurrent syncopal episodes leading to a recent suspected diagnosis of BrS. A later episode of febrile illness, triggering a Type 1 EKG pattern, led to a subsequent hospital admission for continuous cardiac monitoring. On that occasion, he was placed on a wearable external defibrillator pending placement of implantable cardioverter defibrillator (ICD) device. CONCLUSION: Due to the gravity of symptoms that can manifest in the BrS patient, it is important to recognize and treat this condition promptly and effectively. BrS patients require admission for continuous cardiac monitoring when febrile and certain medications interfering with the sodium channel should be avoided in this population. Although medications may be used as one treatment modality, definitive therapy is placement of an ICD device.

Modified Early Warning System improves patient safety and clinical outcomes in an academic community hospital.

BACKGROUND AND OBJECTIVE: Severe adverse events such as cardiac arrest and death are often heralded by abnormal vital signs hours before the event. This necessitates an organized track and trigger approach of early recognition and response to subtle changes in a patient's condition. The Modified Early Warning System (MEWS) is one of such systems that use temperature, blood pressure, pulse, respiratory rate, and level of consciousness with each progressive higher score triggering an action. Root cause analysis for mortalities in our institute has led to the implementation of MEWS in an effort to improve patient outcomes. Here we discuss our experience and the impact of MEWS implementation on patient care at our community academic hospital. METHODS: MEWS was implemented in a protocolized manner in June 2013. The following data were collected from non-ICU wards on a monthly basis from January 2010 to June 2014: 1) number of rapid response teams (RRTs) per 100 patient-days (100PD); 2) number of cardiopulmonary arrests 'Code Blue' per 100PD; and 3) result of each RRT and Code Blue (RRT progressed to Code Blue, higher level of care, ICU transfer, etc.). Overall inpatient mortality data were also analyzed. RESULTS: Since the implementation of MEWS, the number of RRT has increased from 0.24 per 100PD in 2011 to 0.38 per 100PD in 2013, and 0.48 per 100PD in 2014. The percentage of RRTs that progressed to Code Blue, an indicator of poor outcome of RRT, has been decreasing. In contrast, the numbers of Code Blue in non-ICU floors has been progressively decreasing from 0.05 per 100PD in 2011 to 0.02 per 100PD in 2013 and 2014. These improved clinical outcomes are associated with a decline of overall inpatient mortality rate from 2.3% in 2011 to 1.5% in 2013 and 1.2% in 2014. CONCLUSIONS: Implementation of MEWS in our institute has led to higher rapid response system utilization but lower cardiopulmonary arrest events; this is associated with a lower mortality rate, and improved patient safety and clinical outcomes. We recommend the widespread use of MEWS to improve patient outcomes.

Oscillating hypothyroidism and hyperthyroidism - a case-based review.

OBJECTIVE/BACKGROUND: To discuss a unique clinical entity where inappropriate activity of inhibitory and stimulatory thyroid antibodies resulted in alternating hypothyroidism and hyperthyroidism. METHODS: We report the clinical history, laboratory data, and results of imaging studies, along with the pathophysiological mechanism and the subsequent treatment in a patient with fluctuating thyroid functional status. RESULTS: A 52-year-old female was treated for hypothyroidism for more than two decades. She started having symptoms of hyperthyroidism along with a suppressed thyroid-stimulating hormone (TSH). She continued to have persistent symptoms despite stopping her levothyroxine. Her free T3 and T4 were elevated along with an increased radioactive uptake scan. She was diagnosed with Graves' disease and started on methimazole, which relieved her symptoms for a few months. Subsequently, her TSH began to rise beyond expected level, her hypothyroid symptoms reappeared, and methimazole was discontinued. Following this, she again developed symptoms of hyperthyroidism and thyroid values revealed an undetectable TSH. She had at least two such documented cycles of hyperthyroidism alternating with hypothyroidism. She was eventually treated with radioactive iodine ablation followed by levothyroxine replacement. Swinging dominance of TSH-blocking autoantibodies (TBAb) and thyroid-stimulating autoantibodies (TSAb) triggered by methimazole and levothyroxine, respectively, is likely the underlying mechanism. CONCLUSIONS: Physicians should be vigilant to the phenomenon of spontaneous conversion of hypothyroidism to hyperthyroidism, or vice versa, in a subset of patients with autoimmune thyroid disease. Repeated assessment of thyroid function along with measurement of TBAb and TSAb are invaluable in identifying this rare clinical entity.

Application of ICD guidelines and indications in a community-based academic hospital: a case series-based discussion.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are indeed beneficial in selected patients as evidenced by multiple large randomized controlled trials (RCTs) since 1980. A systematic method for stratification of patients and hospital-wide criteria/guidelines to ascertain appropriate device implantation became necessary. METHODS: Major ICD/CRT (cardiac resynchronization therapy) clinical studies and relevant guidelines were reviewed, and an institution-wide inclusion and exclusion criteria for ICD/CRT was formulated. A retrospective analysis of selected cases was performed to discuss the criteria and special clinical situations. RESULTS: We have translated the evolving ICD/CRT studies into a standard of care at our hospital by formulating a standard, practical, and update-to-date ICD inclusion and exclusion criteria. Thirteen cases were selected to represent major indications and contraindications of ICDs in our practice. These cases cover indications of ICD for secondary prevention of sudden cardiac death (SCD), primary prevention of SCD in patients with CHF resulted from either ischemic or non-ischemic cardiomyopathy, as well as for infiltrative cardiomyopathy and inherited conditions. We discussed the application of CRT in patients with CHF associated with prolonged QRS duration. We then covered the potential benefits of ICD with/without CRT in certain special populations of patients that have not been adequately evaluated by currently available RCTs; these include alcoholic, elderly, female, and ESRD/HD patients. Finally, we addressed risks, complications and contraindications of ICD, as well as application of an external wearable defibrillator in AMI, or status post-CABG patient during the mandatory waiting period for an ICD. CONCLUSIONS: Establishment of the ICD/CRT criteria represents a practical translation of emerging CRTs and helps to standardize patient care in our hospital. It also improves cost-effectiveness as well as appropriate utilization of institute and device resources.

Recurrent syncope, orthostatic hypotension and volatile hypertension: think outside the box.

The baroreceptors in the neck and aortic arch are important regulators of sudden blood pressure changes. They are innervated by CN IX and X and synapse in the brainstem. Baroreceptor failure is an under-recognized cause of recurrent syncope, orthostatic hypotension, and volatile hypertension, which is refractory to and may in fact worsen with conventional treatments. Baroreflex failure can be the result of neck and chest radiation, head and neck surgery, and cerebrovascular accidents involving the brainstem nuclei. The management of baroreflex failure is a challenge since patient education, lifestyle changes, and family support are extremely important in managing blood pressure. Leg exercises and Thrombo-Embolic Deterrent Stockings (TED) stockings are important in treating orthostatic hypotension. Clonidine is the antihypertensive of choice for supine hypertension. Low-dose benzodiazepines are helpful in suppressing sympathetic surges. We have encountered two patients with baroreflex failure after chemotherapy and radiation to the neck or upper chest. Temporal relationship between symptoms onset and the history of head, neck, and upper chest radiation or trauma is important in reaching a diagnosis.

Free fatty acids induce Lhb mRNA but suppress Fshb mRNA in pituitary LßT2 gonadotropes and diet-induced obesity reduces FSH levels in male mice and disrupts the proestrous LH/FSH surge in female mice.

Female obesity is associated with insulin resistance, hyperandrogenemia, and reproductive dysfunction. We hypothesized that elevated free fatty acids (FFAs) might directly modulate pituitary gonadotropin production. FFAs caused a time- and dose-dependent increase in phosphorylation of the MAPKs p38MAPK, c-Jun N-terminal kinase (JNK)-1/2, and ERK1/2 in LßT2 gonadotrope cells. Furthermore, FFAs up-regulated Lhb mRNA expression acutely, an effect that was blocked by JNK inhibition, but suppressed Fshb mRNA expression, an effect that was independent of MAPK signaling. FFAs enhanced the activation of the MAPKs in the presence of GnRH, although the cotreatment did not alter Lhb induction but did eliminate the GnRH induction of Fshb. FFAs also suppressed activin-induced Fshb expression. Knockdown experiments showed that the FFA effect on the inflammatory kinases p38MAPK and JNK and on Lhb, but not Fshb, mRNA expression is mediated via toll-like receptor-2 and toll-like receptor-4 and was mimicked by lipopolysaccharide stimulation. In vivo, male C57BL/6 mice on a high-fat diet showed reduced FSH levels consistent with the suppression of Fshb seen in vitro. Histological analysis of the testes showed an increased number of abnormal seminiferous tubules. Female mice on a high-fat diet lacked the expected proestrus LH and FSH surge and exhibited an increase in the number of days at estrus and a reduced number of days at proestrus, and ovaries had significantly fewer corpora lutea. Taken together, our findings suggest that lipid excess can lead to reproductive defects in both male and female mice.