An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma.

Adrenal incidentalomas (AIs) are common incidental findings in medical practice with clinical significance. Although most AIs are nonsecretory and nonmalignant, they require a short course of follow-up over one to two years to rule out malignancy or hormonal secretion according to clinical practice guidelines. However, this can result in some adrenocortical carcinomas (ACCs) being missed if they transform at a later stage or evolve slowly. Here, we report one such case of an AI, which although remained indolent, eventually transformed into an ACC many years after the initial detection.

Use and validation of text mining and cluster algorithms to derive insights from Corona Virus Disease-2019 (COVID-19) medical literature.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) late last year has not only led to the world-wide coronavirus disease 2019 (COVID-19) pandemic but also a deluge of biomedical literature. Following the release of the COVID-19 open research dataset (CORD-19) comprising over 200,000 scholarly articles, we a multi-disciplinary team of data scientists, clinicians, medical researchers and software engineers developed an innovative natural language processing (NLP) platform that combines an advanced search engine with a biomedical named entity recognition extraction package. In particular, the platform was developed to extract information relating to clinical risk factors for COVID-19 by presenting the results in a cluster format to support knowledge discovery. Here we describe the principles behind the development, the model and the results we obtained.

Multiple Endocrine Neoplasia Type 1 (MEN1) Presenting as an Invasive Macroprolactinoma Complicated by Acute Bacterial Meningitis.

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder characterized by tumors of parathyroid, anterior pituitary, and pancreatic islet cells. Pituitary adenomas in MEN1 can be aggressive and invade surrounding structures including the skull base. However, acute bacterial meningitis in patients with newly diagnosed macroprolactinomas is an exceptional finding. We present the case of a young man with suppurative meningitis complicating an invasive macroprolactinoma as the initial manifestation of MEN1. A 33-year-old male was admitted to the hospital with fever, headache, and nuchal rigidity and subsequently diagnosed with Haemophilus influenzae bacterial meningitis. Computed tomography (CT) and subsequent magnetic resonance imaging (MRI) of the sella turcica revealed a 5 x 3.5 cm pituitary mass invading both cavernous sinuses and the left sphenoid sinus. Laboratory evaluation was notable for significantly elevated serum prolactin level (2,484 ng/mL, 2.6-13.2) and evidence of hypopituitarism. Primary hyperparathyroidism was indicated by hypercalcemia (13.5 mg/dL, 8.5-10.5), low serum phosphorus (2.0 mg/dL, 2.5-4.9), and elevated intact parathyroid hormone (PTH) level (290 pg/mL, 15-60). No visual field deficits were identified. The patient was managed with hydrocortisone, levothyroxine, and cabergoline. However, cerebral spinal fluid (CSF) rhinorrhea compelled subtotal transsphenoidal resection of the tumor and repair of the CSF leak. Three-and-a-half gland parathyroid resection was performed after recovery from pituitary surgery and successfully treated hypercalcemia. Abdominal MRI revealed a 1.2 cm cystic mass in the neck of the pancreas, and pancreatic polypeptide was approximately fourfold elevated. A clinical diagnosis of MEN1 was made based on the occurrence of macroprolactinoma, multiple parathyroid adenomas, and pancreatic findings. This case appears to be the first in which bacterial meningitis was the initial presentation of an invasive macroprolactinoma in a patient with MEN1.

Novel Use of Calcimimetic Activity to Diagnose Primary Hyperparathyroidism in a Patient With Persistently Low-Normal Parathyroid Hormone Level.

Primary hyperparathyroidism (PHPT) is the most common etiology of hypercalcemia in the ambulatory setting and usually presents with an intact parathyroid hormone (PTH) level that is elevated or inappropriately near the upper limit of the laboratory reference range. However, PHPT with low-normal PTH level is reported in the peer-reviewed literature, and this atypical presentation may delay diagnosis of PHPT. We present a case of PHPT with persistently low-normal PTH level in which the PTH dependence of hypercalcemia was demonstrated by the response to treatment with the calcimimetic agent cinacalcet.

Use of artificial intelligence and machine learning for estimating malignancy risk of thyroid nodules.

PURPOSE OF REVIEW: Current methods for thyroid nodule risk stratification are subjective, and artificial intelligence algorithms have been used to overcome this shortcoming. In this review, we summarize recent developments in the application of artificial intelligence algorithms for estimating the risks of malignancy in a thyroid nodule. RECENT FINDINGS: Artificial intelligence have been used to predict malignancy in thyroid nodules using ultrasound images, cytopathology images, and molecular markers. Recent clinical trials have shown that artificial intelligence model's performance matched that of experienced radiologists and pathologists. Explainable artificial intelligence models are being developed to avoid the black box problem. Risk stratification algorithms using artificial intelligence for thyroid nodules are now commercially available in many countries. SUMMARY: Artificial intelligence models could become a useful tool in a thyroidolgist's armamentarium as a decision support tool. Increased adoption of this emerging technology will depend upon increased awareness of the potential benefits and pitfalls in using artificial intelligence.

Implementation and challenges unique to teleretinal diabetic retinal screening (TDRS) in a private practice setting in the United States.

PURPOSE: Adherence rates to published guidelines for diabetic retinopathy (DR) screening is between 35 and 60%. We evaluate a teleretinal DR screening (TDRS) program in a private practice vertically integrated system to increase compliance with retinal screening. METHODS: A retrospective pre-post intervention longitudinal study was conducted in a private endocrinology practice using TDRS as the primary intervention. Compliance rates for diabetic retinal screening were compared between December 31, 2016 and December 31, 2018. RESULTS: A total population of 3479 patients were evaluated. Retinal screening compliance improved from 56.5% of patients (1964) pre-intervention to 59.3% of patients (2064) post intervention. The McNemar test was used for statistical analysis and found the change significant (p = 0.004). CONCLUSIONS: TDRS as an adjunct tool in a private practice endocrinology office significantly improved screening rates and can increase access to recommended diabetic eye care. However, the improvement in screening rates was smaller than other types of practice settings. We explore some of the unique challenges to implementation of TDRS in private practice settings.

Targeting Inflammatory Processes Mediated by TRPVI and TNF-α for Treating Noise-Induced Hearing Loss.

Noise trauma is the most common cause of hearing loss in adults. There are no known FDA approved drugs for prevention or rescue of noise-induced hearing loss (NIHL). In this study, we provide evidence that implicates stress signaling molecules (TRPV1, NOX3, and TNF-α) in NIHL. Furthermore, we provide evidence that inhibiting any one of these moieties can prevent and treat NIHL when administered within a window period. Hearing loss induced by loud noise is associated with the generation of reactive oxygen species (ROS), increased calcium (Ca2+) in the endolymph and hair cells, and increased inflammation in the cochlea. Increased (Ca2+) and ROS activity persists for several days after traumatic noise exposure (NE). Chronic increases in (Ca2+) and ROS have been shown to increase inflammation and apoptosis in various tissue. However, the precise role of Ca2+ up-regulation and the resulting inflammation causing a positive feedback loop in the noise-exposed cochlea to generate sustained toxic amounts of Ca2+ are unknown. Here we show cochlear TRPV1 dysregulation is a key step in NIHL, and that inflammatory TNF-α cytokine-mediated potentiation of TRPV1 induced Ca2+ entry is an essential mechanism of NIHL. In the Wistar rat model, noise produces an acute (within 48 h) and a chronic (within 21 days) increase in cochlear gene expression of TRPV1, NADPH oxidase 3 (NOX3) and pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX2). Additionally, we also show that H2O2 (100 µM) produces a robust increase in Ca2+ entry in cell cultures which is enhanced by TNF-α via the TRPV1 channel and which involves ERK1/2 phosphorylation. Mitigation of NIHL could be achieved by using capsaicin (TRPV1 agonist that rapidly desensitizes TRPV1. This mechanism is used in the treatment of pain in diabetic peripheral neuropathy) pretreatment or by inhibition of TNF-α with Etanercept (ETA), administered up to 7 days prior to NE or within 24 h of noise. Our results demonstrate the importance of the synergistic interaction between TNF-α and TRPV1 in the cochlea and suggest that these are important therapeutic targets for treating NIHL.

Oral Administration of Caffeine Exacerbates Cisplatin-Induced Hearing Loss.

Adenosine A1 receptors (A1AR) are well characterized for their role in cytoprotection. Previous studies have demonstrated the presence of these receptors in the cochlea where their activation were shown to suppress cisplatin-induced inflammatory response and the resulting ototoxicity. Inhibition of A1AR by caffeine, a widely consumed psychoactive substance, could antagonize the endogenous protective role of these receptors in cochlea and potentiate cisplatin-induced hearing loss. This hypothesis was tested in a rat model of cisplatin ototoxicity following oral administration of caffeine. We report here that single-dose administration of caffeine exacerbates cisplatin-induced hearing loss without increasing the damage to outer hair cells (OHCs), but increased synaptopathy and inflammation in the cochlea. These effects of caffeine were mediated by its blockade of A1AR, as co-administration of R-PIA, an A1AR agonist, reversed the detrimental actions of caffeine and cisplatin on hearing loss. Multiple doses of caffeine exacerbated cisplatin ototoxicity which was associated with damage to OHCs and cochlear synaptopathy. These findings highlight a possible drug-drug interaction between caffeine and cisplatin for ototoxicity and suggest that caffeine consumption should be cautioned in cancer patients treated with a chemotherapeutic regimen containing cisplatin.

Capsaicin Protects Against Cisplatin Ototoxicity by Changing the STAT3/STAT1 Ratio and Activating Cannabinoid (CB2) Receptors in the Cochlea.

Capsaicin, the spicy component of hot chili peppers activates the TRPV1 pain receptors, and causes rapid desensitization. Capsaicin also ameliorates cisplatin-induced nephrotoxicity. Cisplatin, a commonly used anti-neoplastic agent for solid tumors causes significant hearing loss, nephrotoxicity and peripheral neuropathy. Upregulation of cochlear TRPV1 expression is related to cisplatin-mediated ototoxicity. Here we report that direct TRPV1 activation by localized trans-tympanic (TT) or oral administration of capsaicin (TRPV1 agonist) prevents cisplatin ototoxicity by sustained increased activation of pro-survival transcription factor signal transducer and activator of transcription (STAT3) in the Wistar rat. Cisplatin treatment produced prolonged activation of pro-apoptotic Ser727 p-STAT1 and suppressed Tyr705-p-STAT3 for up to 72 h in the rat cochlea. Our data indicate that capsaicin causes a transient STAT1 activation via TRPV1 activation, responsible for the previously reported temporary threshold shift. Additionally, we found that capsaicin increased cannabinoid receptor (CB2) in the cochlea, which leads to pro-survival Tyr705-p-STAT3 activation. This tilts the delicate balance of p-STAT3/p-STAT1 towards survival. Furthermore, capsaicin mediated protection is lost when CB2 antagonist AM630 is administered prior to capsaicin treatment. In conclusion, capsaicin otoprotection appears to be mediated by activation of CB2 receptors in the cochlea which are coupled to both STAT1 and STAT3 activation.

Hepatic Involvement in Systemic Sarcoidosis.

BACKGROUND Sarcoidosis is a systemic disease that can affect any organ, including the liver. It is manifested by the presence of non-caseating granulomas within involved organs, most commonly the pulmonary, lymphatic, and hepatic system. Unlike pulmonary or lymphatic involvement, hepatic involvement is usually asymptomatic and it is underdiagnosed. Here, we report a case of a patient with a history of pulmonary sarcoidosis who developed hepatic sarcoidosis. CASE REPORT 68-year-old female with pulmonary sarcoidosis with a 2-week history of severe abdominal pain and epigastric tenderness presented to our center. Abdominal magnetic resonance imaging (MRI) demonstrated mild hepatic fibrosis and cirrhosis. A thorough workup was performed including a liver biopsy which showed chronic non-necrotizing granulomas consistent with sarcoidosis. She was started on prednisone and subsequently improved. The patient was symptom-free on follow-up 1 month later. CONCLUSIONS The majority of patients with hepatic sarcoidosis are usually asymptomatic, with only 5-30% presenting with abdominal pain, jaundice, nausea, vomiting, and hepatosplenomegaly. In rare cases, hepatic sarcoidosis can lead to cholestasis, portal hypertension, cirrhosis, or Budd-Chiari syndrome. Treatment with steroids is the mainstay of therapy; however, in severe cases, patients may require liver transplantation. This case report demonstrates that hepatic sarcoidosis is a serious condition, and if not treated, can lead to portal hypertension and cirrhosis. In patients with sarcoidosis, early detection and longitudinal follow-up is important in preventing overt liver failure.

Impact of Pocket Insulin Dosing Guide on Utilization of Basal/Bolus Insulin by Internal Medicine Resident Physicians.

Introduction Basal/bolus insulin (BBI) is superior to sliding scale insulin (SSI) for diabetic patients admitted to hospital general medicine and surgery services, but little has been published on strategies to promote the utilization of BBI by resident physicians. New approaches that promote the effective management of hyperglycemia in hospitals need to be developed. Materials and methods  A prospective study with historical controls was conducted to evaluate the impact of a pocket insulin dosing guide on the diabetes management practices of internal medicine resident physicians at the Southern Illinois University (SIU) School of Medicine, rotating on general medicine. The primary endpoint was the proportion of patients with preexisting diabetes mellitus managed with BBI. Pocket insulin dosing guides with instructions for initiating BBI and daily insulin adjustments were provided to all internal medicine residents in November 2010. BBI utilization rates were monitored over the period November 2010-February 2011 and were compared to the corresponding four-month period over the previous academic year (November 2009-February 2010), which was before the pocket insulin dosing guides were introduced (pilot study). Internal medicine house staff insulin ordering practices were subsequently evaluated for a 12-month period between October 2010-November 2011, with November 2009-October 2010 used as a historical control (study extension). New interns that were starting their residency training from July 2011 were provided with the pocket insulin dosing guides and given the same instructions as the previous academic year's resident physicians. Results  Historical controls (N = 579) and study patients (N = 584) were well matched, with the exception of the male gender (49% vs. 41%, P = 0.01) and diet-managed diabetes (10.5% vs. 6.4%, P = 0.01). During the pilot study, BBI increased from 12.8% of all resident insulin orders in November 2010 to 58.1% of all orders in February 2011 (P < 0.01 for trend). Overall, BBI as a proportion of all resident insulin orders was 35.7% during the pilot phase, which is a six-fold increase over the previous academic year (6%), and was also statistically significant (P<0.01). For the 12-month period of evaluation between November 2010 and October 2011, internal medicine residents ordered BBI for 41.9% of diabetes patients, compared to 16.7% of patients in the 12 months before the pocket insulin dosing guide was introduced (P < 0.01). Patients managed with BBI had higher blood glucose values at admission than patients managed with SSI (195 ± 95 mg/dL vs. 178 ± 83 mg/dL, P < 0.01) and experienced a 41 mg/dL improvement in mean daily capillary blood glucose (CBG) as compared to no change for patients managed with SSI (P = 0.01 for trend). The rate of hypoglycemia, defined as CBG < 70 mg/dL, was 2.4% for both BBI and SSI managed patients (P = 0.93). Conclusion The SIU pocket insulin dosing guide significantly increased the utilization of BBI, decreased SSI orders, and improved hospital glycemic control for patients with diabetes mellitus. However, over half of the general medicine patients were still managed with SSI despite the pocket insulin dosing guides. Conversion of the insulin dosing guide to a smartphone app might improve utilization of the protocol and further increase the use of BBI for inpatient diabetes management by internal medicine house staff.

Rhabdomyolysis Associated with Influenza A Virus Infection.

Influenza A associated with rhabdomyolysis has become more commonly recognized in recent years. It requires prompt recognition and treatment in order to prevent heme pigment-induced acute kidney injury. Here we report a 50-year-old female without a significant past medical history who presented with a one-week history of fevers, chills, fatigue, and generalized body aches. She was on no prior medication. Laboratory studies were significant for leukocytosis and elevated creatinine kinase up to a peak of 28,216 IU/L. Rapid influenza antigen testing was positive for influenza A virus. The patient was diagnosed with influenza A-induced rhabdomyolysis. According to our literature review, we are the first to report a case of influenza A-induced rhabdomyolysis in the 2017-2018 flu season. This case highlights the importance of considering rhabdomyolysis as a manifestation of an influenza infection.

Acute Pericarditis as a Presentation of Adrenal Insufficiency.

Acute pericarditis as a presenting sign of adrenal insufficiency is rarely reported. We present a rare case that highlights pericarditis as a clinical presentation of secondary adrenal insufficiency later complicated by cardiac tamponade. A 44-year-old lady who presented to the hospital with a one-day history of pleuritic chest pain and shortness of breath. In the emergency room, she had a blood pressure of 70/35 mmHg. Laboratory evaluation revealed white blood cell count of 16.08 k/cumm with neutrophilia, normal renal function and elevated troponin (0.321 ng/mL, normal 0.000-0.028). An electrocardiogram (EKG) showed sinus tachycardia, low voltage, PR suppression and ST changes consistent with acute pericarditis. Echocardiogram showed small pericardial effusion without tamponade physiology. Infectious workup was negative; she was thought to have acute adrenal insufficiency likely secondary to viral pericarditis. We treated the patient with high dose nonsteroidal anti-inflammatory drugs (NSAIDS) and hydrocortisone. Three weeks later, she presented to emergency room with complaints of persistent nausea, vomiting, chills, weakness. Her blood pressure was 49/23 mmHg. Random serum cortisol level was <1.2 mcg/dl (normal A.M. specimens 3.7-19.4 mcg/dl). Echocardiogram showed loculated pericardial fluid adjacent to the right ventricle with echocardiographic evidence of tamponade. Emergent pericardiocentesis yielded 250 ml of straw color fluid. Blood pressure improved after the procedure. The patient was initially started on IV stress dose steroids, but following clinical stabilization, hydrocortisone was switched to a physiological dose of 15 mg in am and 10 mg in pm. Although the mechanism of pericarditis in adrenal failure is unknown, this clinical presentation may help early diagnosis of adrenal failure and pericarditis. Early recognition and prompt treatment of this rare presentation are critical to prevent morbidity and mortality.

Achalasia in a Patient with Polyglandular Autoimmune Syndrome Type II.

Achalasia is a rare disease characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter to relax. The etiology of this disease remains unknown. Polyglandular autoimmune syndrome type II is a well-identified disease characterized by the occurrence of autoimmune Addison's disease in combination with autoimmune thyroid disease and/or type 1 diabetes mellitus. We report a case that suggests autoimmunity and immunogenicity as a probable contributing factor for association of these two rare disorders.

Association between blood glucose level and outcomes in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Increased blood glucose is associated with adverse clinical outcomes among patients with major illnesses. This study examined the association between blood glucose and adverse outcomes among hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease, for which limited prior data were available. METHODS: We studied a cohort of 209 hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease. Univariate analyses and multivariate logistic regression analyses with backward elimination method were performed to evaluate factors associated with in-hospital complications, length of hospitalization, 30-day hospital readmission, and 90-day all-cause mortality. RESULTS: Multivariate logistic regression analysis with backward elimination method revealed that lower blood glucose and age at hospital admission were the most significant risk factors for in-hospital complication. Received respiratory support and in-hospital complications were the most significant risk factors for the length of hospitalization. There were no significant risk factors associated with 30-day hospital readmission and 90-day all-cause mortality. CONCLUSION: The analyses failed to reveal significant associations between higher blood glucose levels and adverse outcomes. We showed that lower glucose levels (hypoglycemia) results in higher risk for in-hospital complications. In-hospital complications results in longer length of hospitalization, which implies that lower glucose levels (hypoglycemia) indirectly may result in longer length of hospitalization. More studies are needed to better clarify the cause for these associations.