Refractory hypotension due to Nivolumab-induced adrenal insufficiency.

Nivolumab, a new immune checkpoint inhibitor that has been found to improve outcomes for patients with some advanced cancers, is being increasingly used. Immune checkpoint inhibitors can cause immune-related adverse events, including dermatitis, enterocolitis, hepatitis and hypophysitis, but adrenal insufficiency rarely occurs. We present a case of Nivolumab-induced adrenal insufficiency in a man who complained of refractory hypotension. A 52-year-old man with non-small cell lung cancer visited our emergency department complaining of fatigue and diarrhea. He had received Nivolumab every 2 weeks as third-line therapy for a total of 10 times. On arrival, his vital signs revealed shock: blood pressure, 68/48 mmHg; heart rate, 141 beats per minutes. Laboratory examination showed severe hemoconcentration with a hemoglobin level of 19.9 g/dL, normal electrolyte levels and hyperglycemia. We started intravenous infusion of 4.5 L of extracellular fluid, but his vital signs remained unstable. After admission, endocrine examination revealed abnormally low values of serum cortisol (4.86 µg/dL) and ACTH (<1.0 pg/mL), which had been normal at 2 months before admission (21.14 µg/dL and 20.1 pg/mL, respectively). We therefore made a diagnosis of adrenal insufficiency induced by Nivolumab and administered 100 mg hydrocortisone succinate sodium intravenously. He recovered soon after hydrocortisone replacement therapy. Nivolumab is a new immune checkpoint inhibitor and general physicians are not familiar with it. However, adverse events caused by Nivolumab, especially adrenal insufficiency, can lead to serious adverse outcomes if overlooked. We should recognize Nivolumab-induced adrenal insufficiency and administer a glucocorticoid immediately in cancer patients treated with immune checkpoint inhibitors.

Diagnostic accuracy of pelvic imaging for acute pelvic inflammatory disease in an emergency care setting: a systematic review and meta-analysis.

The aim of this review is to investigate the diagnostic accuracy or performance of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) for acute pelvic inflammatory disease (PID) in an emergency care setting. We searched for studies on the diagnostic test accuracy of contrast-enhanced CT or MRI for women of reproductive age with acute abdominal pain using MEDLINE, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov. The reference standard was gynecological examinations by gynecologists using standard diagnostic criteria with or without laparoscopy or transcervical endometrial biopsy. Two reviewers undertook screening of records, data extraction, and assessment of the risk of bias in each included study using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate model was used for the meta-analysis. Of 2,619 screened studies, three studies investigating contrast-enhanced CT and one study investigating MRI were eligible, including a total 635 patients and with a median prevalence of acute PID of 29%. All of the included studies had a high risk of bias for a reference standard and had some applicability concerns. Contrast-enhanced CT had a pooled sensitivity of 0.79 (95% confidence interval [CI], 0.52-0.93) and specificity of 0.99 (95% CI, 0.94-1.00). Magnetic resonance imaging had a sensitivity of 0.95 (95% CI, 0.76-1.00) and specificity of 0.89 (95% CI, 0.52-1.00). Contrast-enhanced CT might serve as a practical alternative to gynecological examination in the diagnosis of acute PID in an emergency care setting, however, the evidence was uncertain. The evidence on MRI was also very uncertain.

Author Correction: The choroid plexus is an important circadian clock component.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The choroid plexus is an important circadian clock component.

Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN. Our computational analysis and modeling show that the CP achieves these properties by synchronization of "twist" circadian oscillators via gap-junctional connections. Using an in vitro tissue coculture model and in vivo targeted deletion of the Bmal1 gene to silence the CP circadian clock, we demonstrate that the CP clock adjusts the SCN clock likely via circulation of cerebrospinal fluid, thus finely tuning behavioral circadian rhythms.