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Immune checkpoint inhibitors (ICI), such as PD-1/PDL-1 and CTLA-4, have become widely used in the treatment of solid and hematological malignancies; their use and side effects are increasingly seen in the palliative care (PC) population. These drugs can result in immune-mediated endocrinopathies; the thyroid is the most common endocrine gland affected, but the pituitary, adrenals, and pancreas may be affected as well. Symptoms may be insidious and nonspecific. A high index of suspicion and routine laboratory monitoring allows for prompt diagnosis and treatment, which can significantly improve symptoms and increase quality of life. In this study, we present an approach to monitoring and initial management of ICI-induced endocrinopathies in the PC patient population.

Immune checkpoint inhibitors (ICIs) are a rapidly expanding class of targeted therapies effective in the treatment of various cancers. However, while efficacious, ICIs have been associated with treatment complications, namely immune-related adverse events (irAEs). IrAEs of the endocrine system are among the most commonly reported irAEs, but despite their high incidence, standardized disease definitions and endocrine IrAE-specific International Classification of Diseases (ICD) codes remain lacking. This dearth of standardized nomenclature and ICD codes has in many ways impeded both the clinical care of patients and the progress of endocrine irAE-related research. ICD codes are used internationally and are essential for medical claims reporting in the health care setting, and they provide a universal language system for recording, reporting, and monitoring diseases. These codes are also a well-accepted form of electronic health record data capture that facilitates the collection, storage, and sharing of data. Therefore, the lack of standardized disease definitions and ICD codes has been associated with misclassification and suboptimal management of individuals with endocrine irAEs and has also been associated with reduced data availability, comparability, and quality. Harmonized and clinically relevant disease definitions along with the subsequent development of endocrine-irAE-specific ICD codes will provide a systematic approach to understanding the spectrum and burden of endocrine irAE diseases, and will have a positive effect across clinical, public health, and research settings.

Agents with mechanisms novel to breast cancer care have been approved to treat breast cancer. These agents include drugs that target cyclin-dependent kinases, phosphoinositide 3-kinase PI3KCA gene mutations, PARP, checkpoint regulation, and novel antibody-drug conjugates. However, these novel approaches bring a risk of toxicities quite different from those of conventional cytotoxic chemotherapy. Here, we review these agents and discuss related adverse events, with particular attention to endocrine, pulmonary, and dermatologic toxicities. Endocrine toxicities associated with novel cancer therapies for breast cancer are distinct and often present with symptoms related to the specific hormonal deficiencies and rarely hormonal excess. Given the complex and sometimes irreversible nature of these toxicities, once recognized, transdisciplinary management with an endocrinologist experienced with managing drug-related toxicities is encouraged. Drug-related pneumonitis is a serious concern with new targeted therapies. Presentation may not be easily distinguished, and a multidisciplinary team approach can optimize patient care. Heightened awareness is crucial for early detection and treatment. Management should follow recommendations provided by the National Cancer Institute Common Terminology Criteria for Adverse Events and agent-specific guidelines. Cutaneous toxicities from anticancer therapies represent a common and often poorly characterized challenge for patients with breast cancer. Although our understanding of dermatologic effects from novel therapies continues to improve, the breadth of toxicities spans all dermatologic conditions. Targeted therapies offer effective and often novel therapeutic strategies for patients with breast cancer but also bring new adverse event profiles. In this era, it will be important both to closely follow monitoring recommendations and to remain vigilant for emerging toxicities.

Newly approved systemic treatment options for metastatic urothelial cancer (mUC) have diversified treatments and improved responses and survival for chemotherapy refractory disease. These systemic treatments have associated toxicities which need appropriate management for patients to stay on treatment and potentially have longer benefit from treatment. We review the expected toxicities of immune checkpoint inhibitors, FGFR inhibitors such as erdafitinib, and antibody drug conjugates such as enfortumab vedotin and sacituzumab govitecan.

Low-carbohydrate diets have been advocated as an effective method for promoting weight loss in overweight and obese individuals and preventing and treating type 2 diabetes. This article reviews the differences between various low-carbohydrate eating plans and discusses the benefits and drawbacks of such a diet based on available evidence. It also offers practical pointers for clinicians.

Immune checkpoint inhibitors (ICI) specifically target and dysregulate immune tolerance. As a result of this immune activation, immune related adverse events (irAEs) are common. These can include endocrinopathies like immune hypophysitis (IH), primary adrenal insufficiency (PAI), autoimmune thyroid disease, Graves disease and type 1 Diabetes Mellitus (T1DM)[1]. The aim of this retrospective review was to describe the prevalence, timing, and clinical characteristics of ICI-related endocrinopathies at our institution. Methods: A retrospective chart review was conducted for all patients between January 01, 2007 and February 01, 2017 who met predefined clinical, biochemical and imaging criteria for endocrinopathies including IH, T1DM, autoimmune thyroid disease, Graves disease and PAI. Results: Among 690 patients who received ICPI during the study period, 91 unique patients with complete data developed endocrinopathies, for an overall prevalence of 13%. The study included 50 (55%) men and 41 (45%) women with a median age of 64 years (range 20-96 years). Grade 2 endocrinopathies were reported more commonly (n=49, 54%); grade 3/4 events were rare (15%). Among the ICIs, Nivolumab was the most common ICI noted for study patients (n=51, 56%). Autoimmune thyroid disease was the most common irAE in our study (n= 63, 9.1% overall prevalence). We also report 25 cases of IH (3.6%), 2 cases of PAI (0.3%) and 1 case of Graves disease (0.1%). Most patients with autoimmune thyroid disease developed subclinical hypothyroidism (n=26, 3.8%) and overt hyperthyroidism (n=21, 3.0%). We note a high median TSH of 67.3 µIU/mL; range- 20.6-111.0 in overt hypothyroidism compared to subclinical hypothyroidism (14.0 µIU/mL; range- 5.6-100 µIU/mL). Overall, median time to developing any endocrinopathy after initiating ICI was 13.7 weeks; range- 0.7-351.5 weeks. Among the subjects who developed IH, the median TSH was 0.37 µIU/mL (0.01 - 62.39 µIU/mL) with a free T4 of 0.74 ng/dL (0.25-1.86 ng/dL) and the median cortisol was 0.80 µg/dL (0.25-24.5 µg/dL). Amongst the IH group, 17 patients developed isolated secondary adrenal insufficiency and 8 patients developed combination of other hormone deficiencies with secondary AI including 6 with secondary hypothyroidism, 1 patient with hypogonadotropic hypogonadism and 1 with hypothyroidism and hypogonadism in addition to secondary AI. Despite development of irAEs, ICI therapy was continued in 59 pts (65%) who developed an endocrine irAE. Conclusions: In summary, this is one of the largest single institution retrospective studies on ICI related endocrinopathies. The majority of endocrinopathies were low grade, and most patients continued ICI treatment. Reference: Barroso-Sousa, Romualdo. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA, Sept 2017

The purpose of this review is to summarize our current knowledge of factors that influence clinical decision making and management of type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) among South Asians (SA). ASCVD and T2DM in SAs have been examined in recent times. Pathophysiologic and genetic factors including the role of adiponectin, visceral adiposity, lower beta cell function, and psycho-social factors like sedentary lifestyle, poor adherence to medications, and carbohydrate dense meals play a role in early development and the high-risk presentation of both ASCVD and T2DM in SA. Recently, large population-based cohort studies have attempted to compare outcomes and interventions that can be translated to timely detection and targeted interventions in this high-risk group. SAs in the USA are more likely to be diagnosed with T2DM and ASCVD when compared to non-Hispanic whites, non-Hispanic Blacks, and Hispanic populations. The development of personalized ethnic risk assessment tools and better representation of SAs in prospective studies are essential to increasing our understanding and management of cardio-metabolic disease in SA living in the USA.

Objective: To describe a rare case of primary adrenal insufficiency (PAI) from immune checkpoint inhibitors (ICPIs).Methods: We describe the clinical presentation, supportive laboratory findings, long-term outcomes, and a review of the current available literature on PAI following administration of ipilimumab and nivolumab.Results: A 49-year-old Caucasian male with stage IIIB metastatic melanoma and failed standard chemotherapy and monotherapy with ipilimumab was started on nivolumab in addition to ipilimumab. Two months after starting the combination therapy, he presented with weakness, lethargy, nausea, and diarrhea for 1 to 2 weeks. Since there was a concern for treatment-associated endocrinopathy, an 8 am cortisol and adrenocorticotrophic hormone (ACTH) were measured and noted to be 5.4 μg/dL (normal, 5 to 25 μg/dL) and 224 pg/mL (normal, 15 to 66 pg/mL), respectively. The cortisol was interpreted as normal, and follow-up was arranged in the endocrinology clinic. ACTH was drawn at the same time but reported after discharge. He presented again in 2 weeks with progressive symptoms, and a prestimulus cortisol was 1.6 μg/dL and 60 minutes after cosyntropin administration did not change, at 1.7 μg/dL. The patient was diagnosed with PAI based on additional data that included a plasma ACTH concentration of 827 pg/mL, elevated renin, and undetectable aldosterone with concurrent hyponatremia and hyperkalemia. He was treated with glucocorticoid and mineralocorticoid replacement and has since been in cancer remission.Conclusion: This case exemplifies how the diagnosis of a classic disease can be confounded in a complex patient and adds to the list of endocrinopathies from ICPI, where a high clinical suspicion should be maintained.Abbreviations: ACTH adrenocorticotrophic hormone anti-CTLA-4 Ab anti–cytotoxic T-cell antigen 4 antibody ICPI immune checkpoint inhibitor PAI primary adrenal insufficiency PD-1 programmed death 1 PDL-1 programmed death ligand 1

Objective: To describe a rare case of Wernicke encephalopathy (WE) as a result of hyperemesis gravidarum due to primary hyperparathyroidism (PHPT) in pregnancy.Methods: We present the clinical presentation, supportive laboratory values, diagnostic dilemmas, treatment, clinical outcome, and supportive literature review of a patient with WE as a result of hyperemesis gravidarum due to PHPT in pregnancy.Results: A 27-year-old previously healthy G1P0 female presented with initial symptoms of right upper-quadrant pain, nausea, vomiting, and paresthesias at 17.3 weeks of gestation. The patient later developed neurologic symptoms including acute encephalopathy, ataxia, and intranuclear ophthalmoplegia. The suspicion for WE was confirmed with characteristic findings on brain magnetic resonance imaging. WE was attributed to severe malnutrition from hyperemesis gravidarum and poor prenatal care. Hypercalcemia with an elevated parathyroid hormone level was identified following an unfortunate intrauterine fetal demise, raising suspicion for PHPT. PHPT was confirmed, and after undergoing successful parathyroidectomy, the patient regained normal neurologic function, with the exception of mild lower-extremity paresthesias.Conclusion: This case is an example where early recognition and treatment of hyperparathyroidism can be masked by severe malnutrition and present in an unusual way with neurologic symptoms of WE. Early recognition and suspicion are critical in preventing poor fetal outcomes and long-term consequences.Abbreviations: IV = intravenous; MRI = magnetic resonance imaging; PTH = parathyroid hormone; PHPT = primary hyperparathyroidism; WE = Wernicke encephalopathy

Over the last decade, there has been a shift in the focus of cancer therapy from conventional cytotoxic drugs to therapies more specifically directed to cancer cells. These novel therapies include immunotherapy, targeted therapy and precision medicine, each developed in great part with a goal of limiting collateral destruction of normal tissues, while enhancing tumor destruction. Although this approach is sound in theory, even new, specific therapies have some undesirable, ‘off target effects’, in great part due to molecular pathways shared by neoplastic and normal cells. One such undesirable effect is hyperglycemia, which results from either the loss of immune tolerance and autoimmune destruction of pancreatic β-cells or dysregulation of the insulin signaling pathway resulting in insulin resistance. These distinct pathogenic mechanisms lead to clinical presentations similar to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Both types of diabetes have been reported in patients across clinical trials, and data on the mechanism(s) for developing hyperglycemia, prevalence, prognosis and effect on cancer mortality is still emerging. With the rapidly expanding list of clinical indications for new cancer therapies, it is essential to understand the impact of their adverse effects. In this review, we focus on hyperglycemia and diabetes related to cancer therapies, describe what is known about mechanism(s) leading to dysregulated glucose metabolism and provide a guide to management of complex oncology patients with a new diagnosis of diabetes.

e21683 Background: Combination chemo-immunotherapy is a well-established frontline therapeutic option for treatment naïve NSCLC. Dual immune checkpoint blockade (ICB) with nivolumab (nivo) and ipilimumab (ipi) has demonstrated improved clinical outcomes compared with chemotherapy alone in this setting. Combination dual ICB with low-dose chemotherapy may have advantages of preventing early disease progression and potentiating immunogenic response to treatment. Methods: We are conducting a single arm phase II clinical trial of nivo 360 mg IV Q3 weeks, ipi 1 mg/kg IV Q6 weeks, and weekly paclitaxel 80 mg/m2 IV on d1 and d8 of a 21 day cycle in ECOG 0-1 patients (pts) with treatment naïve NSCLC. Paclitaxel is stopped after a total of 4-6 cycles. The primary endpoint of the trial is progression free survival (PFS) with secondary endpoints of safety and objective response rate (ORR) by independent radiologic review. Interim results are presented from the first 23 evaluable pts, of a planned sample size of 49. Results: 23 pts were enrolled and evaluable with a mean age 63.8 years, 56.5% ECOG 0, 87% current/previous smoking history, and 70% adenocarcinoma. PDL1 score for < 1%, 1-49%, ³ 50% was seen in 9 (39.1%), 4 (17.4%), and 10 (43.5%) pts, respectively. Median time of follow up was 6.5 months (range 1.4–15.0). Partial response was observed in 14 pts, stable disease was seen in 8 pts, and 1 pt progressed during cycle 1, resulting in an ORR of 61%. Grade 3 or higher toxicity at least possibly attributed to study treatment was seen in 47.8% of 23 AE evaluable patients, of which included 4 cases of secondary adrenal insufficiency. Other toxicity rates were as expected for the respective agents. Conclusions: This is the first trial to evaluate weekly paclitaxel with nivo plus ipi in pts with untreated NSCLC. This regimen has demonstrated highly encouraging clinical activity with a manageable toxicity profile. The study is ongoing and updated results will be presented at the annual meeting. Clinical trial information: NCT03573947.

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have recently been associated with diabetic ketoacidosis (DKA). Initial case reports were largely among patients using SGLT2i off label in the setting of type 1 diabetes and were unusual because of limited associated hyperglycemia (1). More recently, the problem has been specifically noted in patients with type 2 diabetes (2). Meta-analysis of data from initial randomized controlled trials of SGLT2i suggests little risk of DKA (

Twitter is the fastest growing social media network. It offers participants the ability to network with other individuals. Medical societies are interested in helping individuals network to boost recruitment, encourage collaboration, and assist in job placement. We hypothesized that the American Society of Nephrology (ASN) successfully used Twitter to create a network between participants and itself to stay connected with its members. Tweets from 3 Twitter networking sessions during Kidney Week 2011 were analyzed for content. These messages were used to create a network between all participants of the networking sessions. The network was analyzed for strength and influence by calculating clustering coefficients (CC) and eigenvector centrality (EC) scores, respectively. Eight moderators and 9 trainees authored 376 Twitter messages. Most tweets by trainees (64%) and moderators (61%) discussed 1 of 3 themes: networking, education, or navigating Kidney Week 2011. A total of 25 online network connections were established during the 3 sessions; 20% were bidirectional. The CC for the network was 0.300. All moderators formed at least 1 connection, but 7 of the 9 trainees failed to make any connections. ASN made 5 unidirectional and 0 bidirectional connections with a low EC of 0.108. ASN was unable to form powerful connections with trainees through Twitter, but medical societies should not be discouraged by the results reported in this investigation. As societies become more familiar with Twitter and understand the mechanisms to develop connections, these societies will have a greater influence within increasingly stronger networks.

Introduction Twitter channels are increasingly popular at medical conferences. Many groups, including healthcare providers and third party entities (e.g., pharmaceutical or medical device companies) use these channels to communicate with one another. These channels are unregulated and can allow third party commercial entities to exert an equal or greater amount of Twitter influence than healthcare providers. Third parties can use this influence to promote their products or services instead of sharing unbiased, evidence-based information. In this investigation we quantified the Twitter influence that third party commercial entities had in 13 major medical conferences. Methods We analyzed tweets contained in the official Twitter hashtags of thirteen medical conferences from 2011 to 2013. We placed tweet authors into one of four categories based on their account profile: healthcare provider, third party commercial entity, none of the above and unknown. We measured Twitter activity by the number of tweet authors per category and the tweet-to-author ratio by category. We measured Twitter influence by the PageRank of tweet authors by category. Results We analyzed 51159 tweets authored by 8778 Twitter account holders in 13 conferences that were sponsored by 5 medical societies. A quarter of all authors identified themselves as healthcare providers, while only 18% could be identified as third party commercial entities. Healthcare providers had a greater tweet-to-author ratio than their third party commercial entity counterparts (8.98 versus 6.93 tweets). Despite having less authors and composing less tweets, third party commercial entities had a statistically similar PageRank as healthcare providers (0.761 versus 0.797). Conclusion The Twitter influence of third party commercial entities (PageRank) is similar to that of healthcare providers. This finding is interesting because the number of tweets and third party commercial entity authors required to achieve this PageRank is far fewer than that needed by healthcare providers. Without safety mechanisms in place, the Twitter channels of medical conferences can devolve into a venue for the spread of biased information rather than evidence-based medical knowledge that is expected at live conferences. Continuing to measure the Twitter influence that third parties exert can help conference organizers develop reasonable guidelines for Twitter channel activity.

Medical educators and patients are turning to YouTube to teach and learn about medical conditions. These videos are from authors whose credibility cannot be verified & are not peer reviewed. As a result, studies that have analyzed the educational content of YouTube have reported dismal results. These studies have been unable to exclude videos created by questionable sources and for non-educational purposes. We hypothesize that medical education YouTube videos, authored by credible sources, are of high educational value and appropriately suited to educate the public. Credible videos about cardiovascular diseases were identified using the Mayo Clinic's Center for Social Media Health network. Content in each video was assessed by the presence/absence of 7 factors. Each video was also evaluated for understandability using the Suitability Assessment of Materials (SAM). User engagement measurements were obtained for each video. A total of 607 videos (35 hours) were analyzed. Half of all videos contained 3 educational factors: treatment, screening, or prevention. There was no difference between the number of educational factors present & any user engagement measurement (p NS). SAM scores were higher in videos whose content discussed more educational factors (p

In recent years, the American Society of Nephrology (ASN) has increased its efforts to use its annual conference to inform and educate the public about kidney disease. Social media, including Twitter, has been one method used by the Society to accomplish this goal. Twitter is a popular microblogging service that serves as a potent tool for disseminating information. It allows for short messages (140 characters) to be composed by any author and distributes those messages globally and quickly. The dissemination of information is necessary if Twitter is to be considered a tool that can increase public awareness of kidney disease. We hypothesized that content, citation, and sentiment analyses of tweets generated from Kidney Week 2011 would reveal a large number of educational tweets that were disseminated to the public. An ideal tweet for accomplishing this goal would include three key features: 1) informative content, 2) internal citations, and 3) positive sentiment score. Informative content was found in 29% of messages, greater than that found in a similarly sized medical conference (2011 ADA Conference, 16%). Informative tweets were more likely to be internally, rather than externally, cited (38% versus 22%, p