Cancer history and physical function in patients with cardiovascular disease.

Both cancer and cardiovascular disease (CVD) cause skeletal muscle mass loss, thereby increasing the likelihood of a poor prognosis. We investigated the association between cancer history and physical function and their combined association with prognosis in patients with CVD. We retrospectively reviewed 3,796 patients with CVD (median age: 70 years; interquartile range [IQR]: 61-77 years) who had undergone physical function tests (gait speed and 6-minute walk distance [6MWD]) at discharge. We performed multiple linear regression analyses to assess potential associations between cancer history and physical function. Moreover, Kaplan-Meier curves and Cox regression analyses were used to evaluate prognostic associations in four groups of patients categorized by the absence or presence of cancer history and of high or low physical function. Multiple regression analyses showed that cancer history was significantly and independently associated with a lower gait speed and 6MWD performance. A total of 610 deaths occurred during the follow-up period (median: 3.1 years; IQR: 1.4-5.4 years). The coexistence of low physical function and cancer history in patients with CVD was associated with a significantly higher mortality risk, even after adjusting for covariates (cancer history/low gait speed, hazard ratio [HR]: 1.93, P < 0.001; and cancer history/low 6MWD, HR: 1.61, P = 0.002). Cancer history is associated with low physical function in patients with CVD, and the combination of both factors is associated with a poor prognosis.

Drug-drug conjugates of MEK and Akt inhibitors for RAS-mutant cancers.

Controlling RAS mutant cancer progression remains a significant challenge in developing anticancer drugs. Whereas Ras G12C-covalent binders have received clinical approval, the emergence of further mutations, along with the activation of Ras-related proteins and signals, has led to resistance to Ras binders. To discover novel compounds to overcome this bottleneck, we focused on the concurrent and sustained blocking of two major signaling pathways downstream of Ras. To this end, we synthesized 25 drug-drug conjugates (DDCs) by combining the MEK inhibitor trametinib with Akt inhibitors using seven types of linkers with structural diversity. The DDCs were evaluated for their cell permeability/accumulation and ability to inhibit proliferation in RAS-mutant cell lines. A representative DDC was further evaluated for its effects on signaling proteins, induction of apoptosis-related proteins, and the stability of hepatic metabolic enzymes. These in vitro studies identified a series of DDCs, especially those containing a furan-based linker, with promising properties as agents for treating RAS-mutant cancers. Additionally, in vivo experiments in mice using the two selected DDCs revealed prolonged half-lives and anticancer efficacies comparable to those of trametinib. The PK profiles of trametinib and the Akt inhibitor were unified through the DDC formation. The DDCs developed in this study have potential as drug candidates for the broad inhibition of RAS-mutant cancers.

The safety of exercise for older patients with severe aortic stenosis undergoing conservative management: A narrative review.

The incidence of aortic stenosis (AS) increases with age and is a serious problem in an aging society. In recent years, transcatheter aortic valve implantation (TAVI) has been performed widely; however, older patients may be ineligible for TAVI or surgical treatment because of medical ineligibility. Symptom-based rehabilitation is required for these patients to maintain and improve their physical function and ability to perform activities of daily living. No studies have examined exercise safety for older patients with severe AS who are ineligible for TAVI or surgery. We summarized the safety of exercise for older patients with severe AS, collecting 7 studies on maximal exercise stress tests and 16 studies on preoperative physical examinations. From this review, it may be unlikely that exercise under appropriate management can cause hemodynamic changes, leading to death. However, there were no studies on exercise intervention for older patients with AS who are chosen for conservative management. The optimal exercise intensity for symptomatic older patients with AS undergoing conservative management and the effects of continuous exercise intervention require future study.

Vogt-Koyanagi-Harada disease-like uveitis following nivolumab administration treated with steroid pulse therapy: a case report.

BACKGROUND: Immune checkpoint inhibitors can cause various adverse effects. Recently it has been shown that Vogt-Koyanagi-Harada (VKH) disease-like uveitis can occur in patients treated with nivolumab. CASE PRESENTATION: A 69-year-old man developed bilateral panuveitis after nivolumab treatment for recurrent hypopharyngeal cancer. Slit lamp examination revealed bilateral granulomatous keratic precipitates, anterior chamber cells and partial synechiae. Fundus examination revealed bilateral optic disc edema and diffuse serous retinal detachment. His human leukocyte antigen (HLA) typing showed HLA-DRB1*04:05 allele. A lumbar puncture did not demonstrate pleocytosis. Bilateral sub-tenon injections of triamcinolone acetonide were initiated. As his panuveitis did not regress completely, steroid pulse therapy was administered. That therapy led to the resolution of his serous retinal detachment and to rapid improvement in his vision. Following this, we treated him with 50 mg/day of prednisolone for 1 week and then reduced it by 5 mg every week. No bilateral uveitis relapse had occurred by his 3-month follow-up; however, he subsequently died because of his cancer. CONCLUSION: To our knowledge, this is the first report of a patient with NVKH who underwent a lumbar puncture. Unlike VKH, our case did not show meningismus or pleocytosis. NVKH may, therefore, have a different etiology from VKH. In cases of NVKH with posterior uveitis, steroid pulse therapy may be considered as a treatment option, as it is in VKH.

The benefit of exercise in patients who undergo allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is increasingly used in the treatment of hematologic cancers such as leukemias, lymphomas, and myeloma, and for other hematologic disorders such as primary immunodeficiency, aplastic anemia, and myelodysplasia. Allo-HSCT entails a conditioning regimen of frequent high-dose chemotherapy in combination with total body irradiation, followed by infusion of donor-harvested bone marrow or peripheral blood stem cells. As an aggressive and demanding medical therapy that profoundly impacts patient quality of life (QOL), allo-HSCT is associated with numerous treatment-related physical, psychological, and psychosocial side effects. The procedure can result in decreased respiratory and balance function, skeletal muscle strength, and exercise capacity. Thus, as physical exercise has been shown to positively effect physical and psychosocial function and QOL in allo-HSCT patients, it is a recommended intervention for improving essential functions and offsetting lost exercise capacity after the procedure. Furthermore, recent evidence has shown that physical exercise can influence survival rate and mortality in allo-HSCT patients. This review provides an overview of the current research on the effectiveness of physical exercise for allo-HSCT patients.

Imaging characteristics of the postoperative globe: a pictorial essay.

Recognizing imaging characteristics after ophthalmic surgery is necessary for radiologists to prevent misdiagnosis. We review typical appearances of intraorbital implanted devices and materials on CT and MRI with demonstration of the common surgical procedures. EX-PRESS glaucoma filtration devices appear as punctate areas of metal attenuation on CT and are typically placed at the corneoscleral junction. The imaging manifestations after cataract extraction are absence of the native lens of ovoid mass and the intraocular lens with high attenuation on CT and low signal intensity on MRI. The treatment of retinal detachment is achieved with intraocular tamponade or scleral buckling. In intraocular tamponade, the eye is filled with a bubble of gas or silicone oil. Gas results in air attenuation on CT and low signal intensity on MRI in the vitreous cavity. Silicone oil is hyperattenuating on CT and has variable intensity on MRI. In scleral buckling, the eye wall is indented with silicone buckling elements that show high or low attenuation on CT and low T1- and T2-weighted intensity on MRI. Degraded hydrogel buckling elements appear as swollen masses showing low attenuation on CT and high T2-weighted intensity on MRI.

Low-intensity resistance training with blood flow restriction improves vascular endothelial function and peripheral blood circulation in healthy elderly people.

PURPOSE: The present study aimed to investigate the effects of low-intensity resistance training with blood flow restriction (BFR resistance training) on vascular endothelial function and peripheral blood circulation. METHODS: Forty healthy elderly volunteers aged 71 ± 4 years were divided into two training groups. Twenty subjects performed BFR resistance training (BFR group), and the remaining 20 performed ordinary resistance training without BFR. Resistance training was performed at 20 % of each estimated one-repetition maximum for 4 weeks. We measured lactate (Lac), norepinephrine (NE), vascular endothelial growth factor (VEGF) and growth hormone (GH) before and after the initial resistance training. The reactive hyperemia index (RHI), von Willebrand factor (vWF) and transcutaneous oxygen pressure in the foot (Foot-tcPO2) were assessed before and after the 4-week resistance training period. RESULTS: Lac, NE, VEGF and GH increased significantly from 8.2 ± 3.6 mg/dL, 619.5 ± 243.7 pg/mL, 43.3 ± 15.9 pg/mL and 0.9 ± 0.7 ng/mL to 49.2 ± 16.1 mg/dL, 960.2 ± 373.7 pg/mL, 61.6 ± 19.5 pg/mL and 3.1 ± 1.3 ng/mL, respectively, in the BFR group (each P < 0.01). RHI and Foot-tcPO2 increased significantly from 1.8 ± 0.2 and 62.4 ± 5.3 mmHg to 2.1 ± 0.3 and 68.9 ± 5.8 mmHg, respectively, in the BFR group (each P < 0.01). VWF decreased significantly from 175.7 ± 20.3 to 156.3 ± 38.1 % in the BFR group (P < 0.05). CONCLUSIONS: BFR resistance training improved vascular endothelial function and peripheral blood circulation in healthy elderly people.

Quadriceps isometric strength as a predictor of exercise capacity in coronary artery disease patients.

BACKGROUND: Quadriceps strength is related to exercise capacity in normal subjects and different patient populations, but the relationship between maximal quadriceps isometric strength (QIS) and different exercise capacity levels in coronary artery disease (CAD) patients has not been systematically evaluated yet. METHOD: We studied 621 patients (60.6 ± 9.9 years, 538 males) with recent coronary artery bypass grafting or myocardial infarction, who underwent treadmill exercise testing, maximal QIS measurement (hand-held dynamometry), and coronary arteriography. Maximal QIS was expressed as absolute value (kg), %bodyweight, and %predicted maximum. Logistic regression was used to assess the relationship of maximal QIS, age, sex, number of diseased coronary vessels, peak systolic blood pressure, peak heart rate, brain natriuretic peptide, and left ventricular ejection fraction with 5, 7, and 10 estimated metabolic equivalents (eMETs) exercise capacity levels. RESULTS: Maximal QIS %bodyweight was the strongest predictor of exercise capacity in each eMETs category. Receiver-operating characteristics curves identified maximal QIS of 46, 51, and 59 % bodyweight as the best predictive cut offs for 5, 7 and 10 eMETs, respectively, with positive predictive values of 0.72, 0.66, and 0.67, respectively. CONCLUSIONS: Maximal QIS is related with eMETs levels reached at exercise testing in CAD patients, and identified maximal QIS cut-off values for eMETs prediction may be used to set strength training goals according to patients' needs with regard to habitual physical activity level. Hand-held dynamometry may meet the need of easiness of use and low cost required for strength evaluation in large-scale clinical trials.

Usefulness of pet ownership as a modulator of cardiac autonomic imbalance in patients with diabetes mellitus, hypertension, and/or hyperlipidemia.

Among patients with coronary artery disease, pet owners exhibit a greater 1-year survival rate than nonowners. Lifestyle-related diseases are well-known risk factors for coronary artery disease and induce imbalances in autonomic nervous activity. The purpose of the present study was to determine whether pet ownership modulates cardiac autonomic nervous activity imbalance in patients with lifestyle-related diseases such as diabetes mellitus, hypertension, and hyperlipidemia. A total of 191 patients (mean age 69 ± 8 years) were interviewed about their pet ownership status and were classified into pet owner and nonowner groups. After recording a 24-hour Holter electrocardiogram for heart rate variability analysis, frequency-domain and nonlinear-domain analyses were performed to determine the high-frequency (HF) and low-frequency (LF) components, LF/HF ratio, and entropy. The heart rate variability parameters were assessed for 24 hours, during the day (8.00 A.M. to 5.00 P.M.), and during the night (0:00 A.M. to 6.00 A.M.), and compared between the 2 groups. To evaluate the potential predictive factors for cardiac autonomic imbalance, univariate and multivariate analyses of HF and LF/HF were conducted for potential confounding variables. The pet owner group exhibited significantly greater HF(24h), HF(day), HF(night), entropy(24h), entropy(day), and entropy(night) and significantly lower LF/HF(24h) and LF/HF(night) compared to the nonowner group. On multivariate analysis, pet ownership was independently and positively associated with HF(24h,) HF(day), and HF(night) and inversely associated with LF/HF(24h) and LF/HF(night). In conclusion, these results suggest that pet ownership is an independent modulator of cardiac autonomic imbalance in patients with lifestyle-related diseases.

Surgically induced necrotizing scleritis after primary pterygium surgery with conjunctival autograft.

BACKGROUND: Although pterygium excision with conjunctival autograft is a widely performed surgical procedure, surgically induced necrotizing scleritis (SINS) following such surgery is extremely rare. METHODS: A 68-year-old man underwent nasal pterygium excision with conjunctival autograft uneventfully. On postoperative day 17, the conjunctival graft was avascular, with epithelial defect. Although topical steroid and antibacterial treatments were continued, the graft and sclera melted, with the ischemic sclera showing gradual thinning. The thinning area spread to the adjoining cornea, and active inflammation with epithelial defect was observed adjacent to the site of thinning. RESULTS: Systemic and microbiological examination was noncontributory. The patient was suspected of having SINS, and administration of oral prednisolone was started. Although the necrotic area was reduced temporarily, medication was discontinued due to nausea, and the area of thinning increased. Conjunctival flap surgery was later performed, and the graft was well accepted. CONCLUSIONS: SINS must be considered in the differential diagnosis of patients with scleritis following pterygium surgery, especially if radiation or mitomycin C has not been used.

Outcomes of cataract surgery in eyes with a low corneal endothelial cell density.

PURPOSE: To evaluate the surgical outcomes of cataract surgery in eyes with a low preoperative corneal endothelial cell density (ECD) and analyze factors affecting the prognosis. SETTING: Tokyo Dental College, Ichikawa General Hospital, Chiba, Japan. DESIGN: Noncomparative case series. METHODS: Eyes with a preoperative ECD of less than 1000 cells/mm(2) that had cataract surgery between 2006 and 2010 were identified. Standard phacoemulsification with intraocular lenses was performed using the soft-shell technique. The rate of endothelial cell loss, incidence of bullous keratopathy, and risk factors were retrospectively assessed. RESULTS: Sixty-one eyes (53 patients) with a low preoperative ECD were identified. Preoperative diagnoses or factors regarded as causing endothelial cell loss included Fuchs dystrophy (20 eyes), laser iridotomy (16 eyes), keratoplasty (10 eyes), traumatic injury (3 eyes), trabeculectomy (3 eyes), corneal endotheliitis (2 eyes), and other (7 eyes). The corrected distance visual acuity improved from 0.59 ± 0.49 logMAR preoperatively to 0.32 ± 0.48 logMAR postoperatively (P<.001). The mean ECD was 693 ± 172 cells/mm(2) and 611 ± 203 cells/mm(2), respectively (P=.001). The mean rate of endothelial cell loss was 11.5% ± 23.4%. Greater ECD loss was associated with a shorter axial length (AL) (<23.0 mm) and diabetes mellitus. Bullous keratopathy developed in 9 eyes (14.8%) and was associated with posterior capsule rupture. CONCLUSIONS: The results suggest that modern techniques for cataract surgery provide excellent visual rehabilitation in many patients with a low preoperative ECD. Shorter AL, diabetes mellitus, and posterior capsule rupture were risk factors for greater ECD loss and bullous keratopathy.

Postoperative refractive error of secondary intraocular lens implantation after simultaneous vitrectomy and lensectomy.

To determine postoperative refractive errors of secondary intraocular lens (IOL) implantation, this study was performed in 42 eyes of 42 patients following secondary IOL implantation fixed in the sulcus after simultaneous vitrectomy and phacoemulsification and aspiration. Controls were 138 eyes of 124 patients with cataract who underwent phacoemulsification and aspiration and IOL implantation. The spread between expected and actual refraction (actual - expected) was -0.81 +/- 0.86 diopters (average +/- standard deviation) in the study group and 0.01 +/- 0.91 diopters in the control group (statistically significant, P < .001, Student's t test). The actual refractive errors in the study subjects were shifted toward myopia compared with the controls.

Case of recurrent macular haemorrhage after removal of a sub-internal limiting membrane haematoma secondary to retinal artery macroaneurysm.

The authors report the case of an 80-year-old man with sub-internal limiting membrane haematoma secondary to retinal artery macroaneurysm in the right eye. Corrected visual acuity was 6/60 in the right eye. Vitreous surgery was performed. The internal limiting membrane over the haematoma was removed by pulling with a soft-tipped extrusion cannula, and then the haematoma was removed with a vitreous cutter. One month post surgery vision had improved to 6/9. Two months post surgery, however, the same macroaneurysm ruptured again, and vision decreased to 6/60. Clinicians should be aware that recurrent macular haemorrhage may occur after removal of sub-internal limiting membrane haematoma secondary to macroaneurysm.

Early postoperative macular features determined by optical coherence tomography after idiopathic macular hole surgery with silicone oil tamponade.

The configuration of idiopathic macular holes in the early postoperative period after pars plana vitrectomy using optical coherence tomography through silicone oil was evaluated. Pars plana vitrectomy with internal limiting membrane peeling and silicone oil instillation was performed on 20 eyes. Optical coherence tomography images were obtained preoperatively and postoperatively. Nineteen eyes (95%) achieved a closed fovea. None of them had a transit foveal contour with flat retina without closure. In the early phase of postoperative idiopathic macular hole repair, inner retinal tissue closure rather than flattening of the fovea is essential for those undergoing pars plana vitrectomy with internal limiting membrane peeling and silicone oil instillation.

Primary squamous cell carcinoma of the lacrimal gland.

A 55-year-old Japanese woman presented with proptosis of the left eye that showed rapid progression with profound lid oedema and chemosis with pain. Magnetic resonance imaging and helical computed tomography demonstrated a large mass of the upper temporal orbit and extended bony destruction of the frontal and zygomatic bones. She was successfully treated with orbital exenteration. A diagnosis of primary squamous cell carcinoma of the lacrimal gland was made, which was confirmed by characteristic findings seen on histopathological examination.

Refractive changes in silicone oil-filled pseudophakic eyes.

PURPOSE: We examined the refractive changes in pseudophakic eyes of patients with idiopathic macular hole treated with silicone oil injection. METHODS: Twenty consecutive eyes of 19 patients with idiopathic macular hole who had undergone successful pars plana vitrectomy using silicone oil tamponade were studied retrospectively. Lensectomy with intraocular lens (IOL) implantation was performed on each patient before vitreous surgery. Five biconvex type IOL models were used. After pars plana vitrectomy and fluid-air exchange, silicone oil was injected to replace the air completely. Macular hole closure was confirmed by optical coherence tomography, and silicone oil removal was performed. Manifest refractions before silicone oil filling, with silicone oil filling, and after silicone oil removal were determined. RESULTS: A mean hyperopic shift +/- SD in spherical equivalents of +5.69 +/- 1.71 diopters (P < 0.0001) was observed with silicone oil instillation. In contrast, a mean myopic shift +/- SD of -5.63 +/- 1.33 diopters was observed after silicone oil removal (P < 0.0001). The absolute value of the refractive shift showed a strong correlation with the posterior radius of the IOL (r = 0.699, P < 0.0001). CONCLUSION: IOL models with steeper posterior convex curvature result in larger refractive deviations in patients scheduled for silicone oil instillation.

Unsuccessful vitrectomy without gas tamponade for macular retinal detachment and retinoschisis without optic disc pit.

The mechanism of subretinal fluid accumulation in optic disc pit maculopathy is unknown. A 67-year-old Japanese woman complaining of blurred vision in her right eye presented with a best-corrected visual acuity of 20/200. Slit-lamp biomicroscopy and optical coherence tomography examination showed maculopathy typically associated with optic disc pits, except that the patient had no optic disc pit. Long-acting gas tamponade was required to achieve reattachment of the retina and retinoschisis after initial failure of surgery using surgically induced vitreous detachment without either fluid-air exchange or gas injection. Vitreous traction may not have played a major role in introducing fluid into the submacular space in this case. Gas tamponade may be indispensable to achieve surgical success. This may also pertain to some cases of optic nerve pits.

Pars plana vitrectomy without long-acting gas tamponade for primary rhegmatogenous retinal detachment.

PURPOSE: To report the anatomical and visual results of primary pars plana vitrectomy (PPV) without long-acting gas tamponade to repair primary rhegmatogenous retinal detachments (RRDs). METHODS: Twenty-seven consecutive patients (27 eyes) with peripheral retinal tears and new RRDs were treated according to the surgical protocol. Patients underwent PPV with fluid-air exchange and endolaser treatment to repair the RRD. Neither long-acting gas nor silicone oil tamponade was combined with PPV. All patients were followed from 6 to 26 months with an average follow-up of 11 months. Reattachment of the retina and visual outcome were compared to the results of previously published studies. RESULTS: Reattachment was achieved in 24 of 27 eyes (89%) with a single operation, and in all 27 (100%) eyes, the retina was ultimately reattached with subsequent operations. The median initial visual acuity was 0.4, and the median final visual acuity was 1.0. CONCLUSIONS: Primary PPV with fluid-air exchange alone and laser treatment is a safe, effective method for the repair of primary retinal detachments. The anatomical reattachment rate and the visual acuity obtained with this technique appear to be at least as good as those reported in the literature for primary PPV combined with long-acting gas tamponade.