Thyroid Dysfunction in Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (ICIs): Outcomes in a Multiethnic Urban Cohort.

We sought to characterize thyroid dysfunction and its association with baseline clinical and demographic characteristics, as well as progression-free survival (PFS), in a multiethnic cohort of lung cancer patients treated with ICIs. A retrospective chart review of lung cancer patients receiving an anti-PD1 or PD-L1 agent was performed. Multivariate Cox proportional hazards were fitted to compare time to thyroid dysfunction among race subgroups controlling for age, gender, treatment type, and duration. Thyroid dysfunction was based on laboratory testing; clinical symptoms were not required. PFS at a 24-week landmark analysis point among patients with and without thyroid dysfunction was compared using a log-rank test. We identified 205 subjects that received ICIs, including 76 (37.1%) who developed thyroid dysfunction. Rates of thyroid dysfunction by one year occurred at similar frequencies among all races (p = 0.92). Gender and concurrent chemotherapy showed no significant association with thyroid dysfunction (p = 0.81 and p = 0.67, respectively). Thyrotoxicosis occurred at higher rates in Black (25, 31.6%) subjects than in White (7, 16.7%) and Hispanic (8, 12.7%) subjects when employing the log-rank test (p = 0.016) and multivariate Cox regression (HR 0.48, p = 0.09 for White and HR 0.36, p = 0.01 for Hispanic compared to Black subjects). PFS was similar among subjects with and without thyroid dysfunction when applying the log-rank test (p = 0.353). Gender, concurrent treatment with chemotherapy, and PFS were not associated with thyroid dysfunction in patients receiving ICIs; however, Black race was a risk factor for thyrotoxicosis. The mechanisms underlying the role of race in the development of irAEs warrant further study.

Are we responding effectively to bone mineral density loss and fracture risks in people with epilepsy?

OBJECTIVE: A 2007 study performed at Montefiore Medical Center (Bronx, NY) identified high prevalence of reduced bone density in an urban population of patients with epilepsy and suggested that bone mineralization screenings should be regularly performed for these patients. We conducted a long-term follow-up study to determine whether bone mineral density (BMD) loss, osteoporosis, and fractures have been successfully treated or prevented. METHODS: In the current study, patients from the 2007 study who had two dual-energy absorptiometry (DXA) scans performed at least 5 years apart were analyzed. The World Health Organization (WHO) criteria to diagnose patients with osteopenia or osteoporosis were used, and each patient's probability of developing fractures was calculated with the Fracture Risk Assessment Tool (FRAX). RESULTS: The median time between the first and second DXA scans for the 81 patients analyzed was 9.4 years (range 5-14.7). The median age at the first DXA scan was 41 years (range 22-77). Based on WHO criteria, 79.0% of patients did not have worsening of bone density, while 21.0% had new osteopenia or osteoporosis; many patients were prescribed treatment for bone loss. Older age, increased duration of anti-epileptic drug (AED) usage, and low body mass index (BMI) were risk factors for abnormal BMDs. Based on the first DXA scan, the FRAX calculator estimated that none of the patients in this study had a 10-year risk of more than 20% for developing major osteoporotic fracture (hip, spine, wrist, or humeral fracture). However, in this population, 11 patients (13.6%) sustained a major osteoporotic fracture after their first DXA scan. SIGNIFICANCE: Despite being routinely screened and frequently treated for bone mineral density loss and fracture prevention, many patients with epilepsy suffered new major osteoporotic fractures. This observation is especially important as persons with epilepsy are at high risk for falls and traumas.

Changes in bone mineral density during 5 years of adjuvant treatment in premenopausal breast cancer patients.

PURPOSE: Adjuvant treatment for breast cancer in postmenopausal women is a risk factor for bone loss. However, the association between bone mineral density (BMD) changes in premenopausal breast cancer patients and various adjuvant treatment regimens is not well characterized. In this study, we evaluated the changes in BMD according to adjuvant treatment in premenopausal women with breast cancer. METHODS: Between 2006 and 2010, BMD data of 910 premenopausal women with breast cancer before operation and 1, 2, 3.5, and 5 years post-operation were retrospectively analyzed. The patients were divided according to the type of treatment: observation (O), tamoxifen (T), chemotherapy (C), C followed by T (C → T), and gonadotropin-releasing hormone (GnRH) agonist with T (G + T). RESULTS: After 5 years of follow-up, BMD changes were similar between the T and O groups (all p > 0.05). Within 1 year of treatment, the C group showed the most significant BMD loss. The C → T and G + T groups showed more significant BMD loss in the lumbar spine and femur than the O and T groups (both p < 0.001, both). After 1 year of treatment, BMD loss in the lumbar spine was significantly greater in the C → T and G + T groups than in the T group; this tendency was maintained for 5 years of treatment (all p < 0.005). CONCLUSION: Premenopausal women who received adjuvant treatment which induced menopause showed significant bone loss which lasted for 5 years. Although no significant difference was observed between the O and T groups, tamoxifen treatment during chemotherapy or GnRH agonist treatment might prevent bone loss.

TREATMENT OF DIABETIC KETOACIDOSIS AND THE WEEKEND EFFECT AT AN URBAN TERTIARY-CARE CENTER.

Objective: Weekend admission has been associated with higher morbidity and mortality, but the relationship between diabetic ketoacidosis (DKA) outcomes and this weekend effect is unclear. To better characterize it, we examined the outcomes of patients admitted with DKA to an urban tertiary-care center. Methods: This retrospective study included pediatric and adult patients admitted to Montefiore Health System from January 1, 2008, through December 31, 2018, with a primary or secondary diagnosis of DKA as identified by International Classification of Diseases (ICD)-9 and -10 codes; all ICD diagnoses were present on admission. Only the first admission for each patient was analyzed, and patients were excluded if their initial anion gap was less than 13 mEq/L. A subcohort comprised of patients with documented biochemical evidence of DKA resolution was also analyzed. The Friday-Saturday weekend was defined as the period between midnight on Friday and midnight on Sunday; the Saturday-Sunday weekend was similarly defined. The following outcomes were compared between weekday and weekend groups: length of stay; time to initiation of subcutaneous insulin; and time to each of the following: venous pH >7.3, blood glucose <200 mg/dL, and anion gap ≤12 mEq/L. Odds of 30-day all-cause mortality and 30-day all-cause and DKA-specific readmission were also examined. Results: Over 11 years, 4,703 patients were included in the overall cohort, and 648 were included in the subcohort. For both weekend definitions, weekend admission did not produce differences in any outcome for either study cohort. Conclusion: No weekend effect on DKA outcomes was detected at an urban tertiary-care center. Abbreviations: AG = anion gap; CCI = Charlson Comorbidity Index; DKA = diabetic ketoacidosis; ICD = International Classification of Diseases; IVI = intravenous insulin; LOS = length of stay; SCI = subcutaneous insulin.

Thyroid Storm Presenting as Psychosis.

Thyroid storm is a life-threatening endocrine emergency with an incidence rate of 1% to 2%. It is a systemic condition of excessive thyroid hormone production and release leading to thermoregulatory, adrenergic, neuropsychiatric, cardiovascular, and abdominal manifestations. Although it is a rare condition, it carries a significant mortality rate. Hence, knowing the common and uncommon presentations of thyroid storm is important for its prompt diagnosis and treatment. In this article, we present an unusual case of a young woman who presented with psychosis as the manifesting symptom of thyroid storm. She did not respond adequately to conventional medical treatment, requiring plasmapheresis and a definitive thyroidectomy, which ultimately led to the return of patient's baseline mental status and a dramatic recovery.

Medical optimization of lumbar fusion in the osteoporotic patient.

PURPOSE: In patients undergoing lumbar fusion, osteoporosis has been shown to lead to poorer outcomes and greater incidence of fusion-related complications. Given the undesirable effect of osteoporosis on lumbar fusion surgery, a number of medications have been proposed for use in the peri- and postoperative period to mitigate risks and enhance outcomes. The purpose of this review was to summarize and synthesize the current literature regarding medical management of osteoporosis in the context of lumbar fusion surgery. METHODS: A literature search of PubMed, Embase, and Web of Science was conducted in October 2016, using permutations of various search terms related to osteoporosis, medications, and lumbar fusion. RESULTS: Teriparatide injections may lead to faster, more successful fusion, and may reduce fusion-related complications. Bisphosphonate therapy likely does not hinder fusion outcomes and may be useful in reducing certain complications of fusion in osteoporotic patients. Calcitonin and selective estrogen receptor modulator therapy show mixed results, but more research is necessary to make a recommendation. Vitamin D deficiency is associated with poor fusion outcomes, but evidence for supplementation in patients with normal serum levels is weak. CONCLUSIONS: Overall, the current body of research appears to support the use of teriparatide therapy to enhance lumbar fusion outcomes in the osteoporotic patient, although the extent of research on this topic is limited. Additionally, very little evidence exists to cease any of the mentioned osteoporosis treatments prior to lumbar fusion.

Testosterone Treatment and Sexual Function in Older Men With Low Testosterone Levels.

CONTEXT: The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men ≥65 years old with unequivocally low T levels. Initial results of the Sexual Function Trial showed that T improved sexual activity, sexual desire, and erectile function. OBJECTIVE: To assess the responsiveness of specific sexual activities to T treatment; to relate hormone changes to changes in sexual function; and to determine predictive baseline characteristics and T threshold for sexual outcomes. DESIGN: A placebo-controlled trial. SETTING: Twelve academic medical centers in the United States. PARTICIPANTS: A total of 470 men ≥65 years of age with low libido, average T <275 ng/dL, and a partner willing to have sexual intercourse at least twice a month. METHODS: Men were assigned to take T gel or placebo for 1 year. Sexual function was assessed by three questionnaires every 3 months: the Psychosexual Daily Questionnaire, the Derogatis Interview for Sexual Function, and the International Index of Erectile Function. RESULTS: Compared with placebo, T administration significantly improved 10 of 12 measures of sexual activity. Incremental increases in total and free T and estradiol levels were associated with improvements in sexual activity and desire, but not erectile function. No threshold T level was observed for any outcome, and none of the 27 baseline characteristics predicted responsiveness to T. CONCLUSIONS: In older men with low libido and low T levels, improvements in sexual desire and activity in response to T treatment were related to the magnitude of increases in T and estradiol levels, but there was no clear evidence of a threshold effect.

Recruitment and Screening for the Testosterone Trials.

BACKGROUND: We describe the recruitment of men for The Testosterone (T) Trials, which were designed to determine the efficacy of T treatment. METHODS: Men were eligible if they were ≥65 years, had an average of two morning total T values <275 ng/dL with neither value >300 ng/mL, and had symptoms and objective evidence of mobility limitation, sexual dysfunction, and/or low vitality. Men had to be eligible for and enroll in at least one of these three main trials (physical function, sexual function, vitality). RESULTS: Men were recruited primarily through mass mailings in 12 U.S. communities: 82% of men who contacted the sites did so in response to mailings. Men who responded were screened by telephone to ascertain eligibility. Of 51,085 telephone screens, 53.5% were eligible for further screening. Of 23,889 initial screening visits (SV1), 2,781 (11.6%) men were eligible for the second screening visit (SV2), which 2,261 (81.3%) completed. At SV2, 931 (41.2%) men met the criteria for one or more trials, the T level criterion and had no other exclusions. Of these, 790 (84.6%) were randomized; 99 (12.5%) in all three trials and 348 (44%) in two trials. Their mean age was 72 years and mean body mass index (BMI) was 31.0 kg/m(2). Mean (standard deviation) total T (ng/dL) was 212.0 (40.0). CONCLUSION: Despite the telephone screening to enrollment ratio of 65 to 1, we met the recruitment goals for each trial. Recruitment of symptomatic older men with low testosterone levels is difficult but feasible.

Association of sex hormones with sexual function, vitality, and physical function of symptomatic older men with low testosterone levels at baseline in the testosterone trials.

CONTEXT: The prevalence of sexual dysfunction, low vitality, and poor physical function increases with aging, as does the prevalence of low total and free testosterone (TT and FT) levels. However, the relationship between sex hormones and age-related alterations in older men is not clear. OBJECTIVE: To test the hypotheses that baseline serum TT, FT, estradiol (E2), and sex hormone-binding globulin (SHBG) levels are independently associated with sexual function, vitality, and physical function in older symptomatic men with low testosterone levels participating in the Testosterone Trials (TTrials). DESIGN: Cross-sectional study of baseline measures in the TTrials. SETTING: The study was conducted at 12 sites in the United States. PARTICIPANTS: The 788 TTrials participants were ≥ 65 years and had evidence of sexual dysfunction, diminished vitality, and/or mobility disability, and an average of two TT < 275 ng/dL. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Question 4 of Psychosocial Daily Questionnaire (PDQ-Q4), the FACIT-Fatigue Scale, and the 6-minute walk test. RESULTS: Baseline serum TT and FT, but not E2 or SHBG levels had small, but statistically significant associations with validated measures of sexual desire, erectile function, and sexual activity. None of these hormones was significantly associated within or across trials with FACIT-Fatigue, PHQ-9 Depression or Physical Function-10 scores, or gait speed. CONCLUSIONS: FT and TT levels were consistently, independently, and positively associated, albeit to a small degree, with measures of sexual desire, erectile function, and sexual activity, but not with measures of vitality or physical function in symptomatic older men with low T who qualified for the TTrials.

The aging thyroid.

PURPOSE OF REVIEW: As life expectancy increases and population age advances, diagnosis and treatment of diseases common in the geriatric population assume an increasingly important role in modern medicine. In the last few years, the emergence of age-specific reference ranges for thyroid-stimulating hormone (TSH) has added to the complexity of diagnosis of thyroid dysfunction in this age group, especially in the 'subclinical' category. RECENT FINDINGS: The recent studies confirm an increase in population TSH distribution with age, both in cross-sectional and longitudinal studies. Conclusive evidence about adverse cardiovascular, metabolic, and cognitive consequences of subclinical hypothyroidism in the elderly remains elusive. The transient nature of subtle degrees of thyroid dysfunction in a significant proportion of elderly patients has also been reproduced in the recent publications. SUMMARY: A growing body of literature in the last few years, reviewed here, highlights the importance of employing additional caution before assigning diagnoses of hypothyroidism or hyperthyroidism to elderly patients and initiation of treatment modalities that can have long-lasting effects.

Exceptional longevity is associated with decreased reproduction.

A number of leading theories of aging, namely The Antagonistic Pleiotropy Theory (Williams, 1957), The Disposable Soma Theory (Kirkwood, 1977) and most recently The Reproductive-Cell Cycle Theory (Bowen and Atwood, 2004, 2010) suggest a tradeoff between longevity and reproduction. While there has been an abundance of data linking longevity with reduced fertility in lower life forms, human data have been conflicting. We assessed this tradeoff in a cohort of genetically and socially homogenous Ashkenazi Jewish centenarians (average age ~100 years). As compared with an Ashkenazi cohort without exceptional longevity, our centenarians had fewer children (2.01 vs 2.53, p<0.0001), were older at first childbirth (28.0 vs 25.6, p<0.0001), and at last childbirth (32.4 vs 30.3, p<0.0001). The smaller number of children was observed for male and female centenarians alike. The lower number of children in both genders together with the pattern of delayed reproductive maturity is suggestive of constitutional factors that might enhance human life span at the expense of reduced reproductive ability.

Influence of age and primary tumor size on the risk for residual/recurrent well-differentiated thyroid carcinoma.

BACKGROUND: Though age and primary tumor size predict cancer-specific survival in well-differentiated thyroid carcinoma (WDTC), their influence on residual/recurrent disease has not been elucidated. METHODS: In a retrospective study, residual/recurrent disease was defined by the surrogate outcome of positive (>or=2 microg/L) follow-up stimulated thyroglobulin after surgery and radioactive remnant ablation. Age, primary tumor size, and clinical staging systems were examined in the context of stimulated thyroglobulin outcome. RESULTS: A total of 246 patients were followed up for a mean of 5.8 years. No significant difference in age (t(239) = 0.61, p > .05) or tumor size (t(237) = 0.16, p > .05) was found among patients with positive follow-up stimulated thyroglobulin compared with those with negative results. pTNM staging failed to demonstrate significant, stage-dependent increase in the percentage of patients with positive stimulated thyroglobulin, chi(2)(2, N = 229) = 0.17, p > .05, unlike staging based solely on surgical pathology, chi(2)(2, N = 241) = 34.97, p < .001. CONCLUSION: Age, primary tumor size, and pTNM staging do not predict risk for residual/recurrent WDTC, whereas extrathyroidal extension at initial surgery is predictive.

Post-challenge hyperglycemia in older adults is associated with increased cardiovascular risk profile.

CONTEXT: Post-challenge hyperglycemia (PCH) is common in older adults and is associated with increased cardiovascular disease (CVD) risk and total mortality. However, PCH is rarely recognized in clinical settings, and the glycemic exposure and CVD risk profile of elderly individuals with PCH has not been defined. OBJECTIVE: The aim of the study was to characterize metabolic and CVD risk profile of elderly subjects with PCH and to determine the effect of acute postprandial metabolic changes on vascular biomarkers. DESIGN: We conducted a cross-sectional study with a standard meal challenge protocol. PARTICIPANTS: Older adults with normal glucose tolerance (n = 30) or PCH (fasting glucose <126 mg/dl and 2-h glucose >or=170 mg/dl; n = 28) participated in the study. MAIN OUTCOME MEASURES: We assessed fasting and postprandial levels of glucose, insulin, lipids, high sensitivity C-reactive protein, plasminogen activator inhibitor-1, and adiponectin and endothelial function using reactive hyperemia peripheral arterial tonometry. RESULTS: Normal glucose tolerance and PCH subjects were matched for age, sex, body mass index, and ethnicity. Fasting glucose (102 +/- 3 vs. 93 +/- 2 mg/dl; P < 0.001) and glycosylated hemoglobin (5.7 vs. 5.4%; P = 0.01) were modestly higher in the PCH group, which was also more insulin resistant (homeostasis model assessment for insulin resistance, 7.0 +/- 1.3 vs. 4.1 +/- 0.6; P = 0.03). Fasting high sensitivity C-reactive protein was higher (2.6 +/- 0.5 vs. 1.3 +/- 0.2 mg/dl; P = 0.05), and adiponectin was lower (11.6 +/- 1.6 vs. 14.0 +/- 1.3 microg/ml; P = 0.03) in subjects with PCH. Peak and 6-h postprandial area under the curve glucose, insulin, and lipids were higher in PCH subjects, who also had higher fasting and postprandial levels of plasminogen activator inhibitor-1. Reactive hyperemia peripheral arterial tonometry declined postprandially only in PCH. CONCLUSIONS: Older adults with PCH experience significant fasting and postprandial metabolic dysregulation, which is accompanied by a proatherosclerotic and prothrombotic vascular profile.

Prognostic value of postsurgical stimulated thyroglobulin levels after initial radioactive iodine therapy in well-differentiated thyroid carcinoma.

BACKGROUND: In well-differentiated thyroid carcinoma, predictors of future positivity of stimulated thyroglobulin (>2 microg/L) after initial radioactive iodine treatment are not known. METHODS: In a retrospective study, we used logistic regression analysis to determine whether postoperative stimulated thyroglobulin measurements and pathologic stage independently predict future stimulated thyroglobulin positivity. RESULTS: We followed 141 patients with well-differentiated thyroid carcinoma for a median of 35 months; follow-up stimulated thyroglobulin measurements were positive in 20.6% (29/141). The natural logarithm of the postsurgical stimulated thyrogolobulin was independently associated with a positive stimulated thyroglobulin at long-term follow-up (odds ratio [OR], 4.44; 95% confidence interval [CI], 2.33-8.45; p < .001); there was a trend for a positive association of TNM stage with positive follow-up stimulated thyroglobulin (p = .054). Lymph node positivity predicted a positive stimulated thyroglobulin in papillary cancer. CONCLUSIONS: Stimulated thyroglobulin measurements prior to initial radioactive iodine treatment independently predict future stimulated thyroglobulin positivity in well-differentiated thyroid carcinoma.