A Case of Vogt-Koyanagi-Harada Disease-Like Uveitis Induced by Nivolumab and Ipilimumab Combination Therapy.

Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.

Prognostic value of exercise left ventricular end-systolic volume index in patients with asymptomatic aortic regurgitation: an exercise echocardiography study.

BACKGROUND: Surgical timing of chronic aortic regurgitation (AR) remains a matter of debate because of limited data. This study assessed the prognostic value of exercise echocardiography in asymptomatic AR. METHODS: This prospective study included 60 consecutive asymptomatic patients with isolated moderate or severe AR (mean regurgitant volume 56.7 ± 11.8 ml) and preserved ejection fraction who underwent exercise echocardiography. The clinical outcomes were defined by the presence of major adverse cardiovascular events (MACE) and the indication for aortic valve replacement (AVR) with class I or IIa classification in the current guidelines. RESULTS: During the average follow-up of 731 days, 12 patients suffered from the clinical events, including two patients developing MACE (3%) and ten patients indicating for AVR (17%). No difference in left ventricular (LV) ejection fraction at rest was found between the patients with and without the clinical events. The indexed LV diameters and LV volumes were significantly dilated in the patients with the clinical events. The Cox proportional hazards regression analysis resulted that the exercise LV end-systolic volume index (LVESVi) was significantly associated with the clinical outcomes [hazard ratio, 1.116; 95% CI (1.032-1.205); p = 0.006]. The Kaplan-Meier analysis showed that exercise LVESVi was clearly stratified the event-free survival. CONCLUSIONS: Exercise LVESVi might be an independent predictor of prognosis in patients with asymptomatic moderate or severe AR.

Influence of aortic valve leaflet calcification on dynamic aortic valve motion assessed by cardiac computed tomography.

BACKGROUND: Computed tomography is the best noninvasive imaging modality for evaluating valve leaflet calcification. OBJECTIVE: To evaluate the association of aortic valve leaflet calcification with instantaneous valve opening and closing using dynamic multidetector computed tomography (MDCT). METHODS: We retrospectively evaluated 58 consecutive patients who underwent dynamic MDCT imaging. Aortic valve calcification (AVC) was quantified using the Agatston method. The aortic valve area (AVA) tracking curves were derived by planimetry during the cardiac cycle using all 20 phases (5% reconstruction). da/dt in cm2/s was calculated as the rate of change of AVA during opening (positive) or closing (negative). Patients were divided into 3 three groups according to Agatston score quartile: no AVC (Q2, Score 0, n = 18), mild AVC (Q3, Score 1-2254, n = 24), and severe AVC (Q4 Score >2254, n = 14). RESULTS: In multivariable linear regression, compared to the non AVC group, the mild and severe AVC groups had lower maximum AVA (by -1.71 cm2 and -2.25 cm2, respectively), lower peak positive da/dt (by -21.88 cm2/s and -26.65 cm2/s, respectively), and higher peak negative da/dt (by 13.78 cm2/s and 18.11 cm2/s, respectively) (p < 0.05 for all comparisons). CONCLUSIONS: AVA and its opening and closing were influenced by leaflet calcification. The present study demonstrates the ability of dynamic MDCT imaging to assess quantitative aortic valve motion in a clinical setting.

Impaired ß-cell function attenuates training effects by reducing the increase in heart rate reserve in patients with myocardial infarction.

BACKGROUND: Insulin resistance (IR) is characterized as a metabolic disorder syndrome that is upstream of hypertension, dyslipidemia, and diabetes mellitus (DM). This study investigated exercise training effects on the exercise tolerance and heart rate dynamics in patients with IR or pancreatic ß-cell dysfunction. METHODS: Seventy patients (mean age, 60.1 years) with myocardial infarction (MI) participating in a phase II cardiac rehabilitation program were studied. Patients diagnosed with DM were excluded. Homeostasis model-assessment indices were used to divide patients into three groups - A: IR; B: normal; and C: ß-cell dysfunction. A cardiopulmonary exercise test (CPX) was performed and peak oxygen uptake (V˙O2) was measured. After baseline testing, subjects participated in a supervised, combined aerobic and resistance exercise program. RESULTS: Peak V˙O2 at baseline was comparable among the three groups, and it improved after training in all groups (p<0.05). However, both the increase and percentage increase in peak V˙O2 were smaller in Group C than in Group A (p<0.05). Heart rate (HR) reserve (peak HR-rest HR), and HR recovery immediately 1min after exercise during CPX were calculated in 45 patients who were not taking negative chronotropic agents. Group C alone did not show any significant increase in HR reserve. HR reserve at both baseline and after training had significant positive correlations with peak V˙O2. HR recovery was 1.9 beats/min lower in group C than group A, but this was not significant. HR recovery in group C did not increase after cardiac rehabilitation. CONCLUSION: Impaired HR reserve increase after training in patients with pancreatic ß-cell dysfunction attenuates exercise training effects on functional capacity. Comprehensive treatment including vigorous exercise training will be needed in such prediabetic patients.

A case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma.

We report on a case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. A 70-year-old man was admitted to our hospital with fatigue, myalgia and an elevated creatine phosphokinase level. He was diagnosed as rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. After discontinuation of sorafenib, his fatigue and myalgia resolved and his creatine phosphokinase level returned to normal. Rhabdomyolysis related to sorafenib treatment is rare adverse effect. This is the first detailed case report of rhabdomyolysis related to sorafenib treatment.