OBJECTIVE: The main aim of this study is to investigate whether acupuncture could be an effective complementary treatment for reducing the risk of macrovascular complications in diabetic patients currently taking antidiabetic medications using a nationwide population-based database. METHODS: We conducted a retrospective cohort study to assess the efficacy of acupuncture on cardiovascular complications in diabetic patients using data from patients between 40 and 79 years of age, newly diagnosed with diabetes between 2003 and 2006, found in the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in Korea. From the data, we identified 21,232 diabetic patients who were taking antidiabetic medication between 2003 and 2006. The selected patients were divided into two groups-those who received acupuncture at least three times and those who received no acupuncture (non-acupuncture) in the year following their diagnosis of diabetes. After 1:1 propensity score matching (PSM), each group had 3350 patients, and the observation ceased at the occurrence of a major adverse cardiovascular event (MACE), which was defined as either myocardial infarction, stroke, or death due to cardiovascular cause. RESULTS: After PSM, the acupuncture group had a lower incidence of MACE (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81-0.94; P = 0.0003) and all-cause mortality (HR: 0.77; 95% CI: 0.70-0.84; P < 0.0001) than the non-acupuncture group; the HRs for stroke-related mortality (HR: 0.75; 95% CI: 0.56-1.00; P = 0.0485), ischemic heart disease mortality (HR: 0.53; 95% CI: 0.34-0.84; P = 0.006) and circulatory system disease mortality (HR: 0.67; 95% CI: 0.55-0.82; P < 0.0001) were lower in the acupuncture group than in the non-acupuncture group in the secondary analysis. CONCLUSION Our results indicate that diabetic patients receiving acupuncture treatment might have a lower risk of MACE, all-cause mortality and cardiovascular mortality. This population-based retrospective study suggests beneficial effects of acupuncture in preventing macrovascular complications associated with diabetes. These findings call for further prospective cohort or experimental studies on acupuncture treatment for cardiovascular complications of diabetes. Please cite this article as: Jung H, Won T, Kim GY, Jang J, Yeo S, Lim S. Efficacy of acupuncture on cardiovascular complications in patients with diabetes mellitus in Korea: A nationwide retrospective cohort. J Integr Med. 2023; 21(2): 176-183.
Humans ; Retrospective Studies ; Cardiovascular Diseases/etiology* ; Diabetes Mellitus, Type 2/drug therapy* ; Hypoglycemic Agents/therapeutic use* ; Stroke/complications* ; Acupuncture Therapy ; Republic of Korea/epidemiology*

Purpose: To investigate the incidence and clinical course of acute endophthalmitis after idiopathic epiretinal membrane (iERM) surgery employing microincision vitrectomy (MIVS). Methods: We retrospectively reviewed the medical records of eyes with acute endophthalmitis developing after iERM surgery via 23- or 25-gauge MIVS from 2011 to 2021. The incidence, culture-positive rate (and responsible bacteria), final visual acuity (VA), and factors affecting poor visual outcomes were assessed. Results: Acute endophthalmitis developed in 20 of the 12,921 eyes (0.15%) after MIVS. Of these, 14 of 3,180 eyes treated via iERM (0.44%, one per 227 procedures) developed endophthalmitis; the incidence ratio (iERM versus non-iERM) was 7.1 (p < 0.001, 95% confidence interval [CI] = 2.6-22.7). At least one sclerotomy remained unsutured in all eyes after iERM surgery. Thirteen eyes (92.9%) were given intravitreal antibiotic injections after emergency vitrectomy, and one eye was treated with intravitreal antibiotic injection alone. Staphylococcus epidermidis was cultured from four eyes (28.6%); three strains were methicillin-resistant. All final VAs were not better than the initial VAs; the average VA decreased from 20/42 to 20/259 (p < 0.001). Six eyes (42.9%) attained legal blindness status (final VA < 20/200); Macular invasion was a unique risk factor for such blindness (p = 0.020, odds ratio = 35.0, 95% CI = 1.7-703.0). Conclusions Acute endophthalmitis developing after iERM surgery with MIVS was more common than such endophthalmitis after other retinal surgery. Approximately 40% of the former patients became legally blind, and the risk was higher in eyes with macular involvement of endophthalmitis.

Purpose: To investigate the changes in intraocular cytokines after ranibizumab treatment in patients with polypoidal choroidal vasculopathy (PCV). Methods: This multicenter, prospective study enrolled patients with PCV treated with three monthly ranibizumab followed by a pro re nata regimen for 24 weeks. Best corrected visual acuity, slit lamp examination, fundus photography, and optical coherence tomography were performed every 4 weeks. Aqueous humor was collected to measure intraocular cytokines at baseline, week 8, and the time of recurrence or week 20. The association of changes in intraocular cytokines with visual acuity, central macular thickness, central choroidal thickness, area of abnormal vessels, and polyp closure was assessed. Results: This study included 25 eyes. The mean patient age was 70.3 ± 6.1 years. The vascular endothelial growth factor (VEGF) concentration decreased at week 8, but only interferon (IFN)-γ, tissue inhibitors of matrix metalloproteinases (TIMP)-2, and monocyte chemoattractant protein (MCP)-2 decreased at the time of recurrence. The recurrence interval was positively associated with the baseline epithelial-neutrophil activating peptide (ENA)-78, interleukin (IL)-17, leptin, and transforming growth factor-β1, and baseline central macular thickness was positively correlated with the baseline fibroblast growth factor-4 and IL-10. Thick central choroidal thickness was associated with a low basic fibroblast growth factor and high IFN-γ at baseline. The MCP-3 and Tie-2 levels decreased in two eyes with polyp closure. Conclusions Ranibizumab significantly reduced intraocular VEGF concentrations and consequently improved PCV. However, the cytokines IFN-γ, TIMP-2, and MCP-2, rather than VEGF, were associated with PCV recurrence. Further studies of intraocular cytokines involved in neovascularization in PCV are needed.

Purpose: To report a case of poor visual prognosis complicated by residual subretinal fluid after use of the internal limiting membrane flap technique to treat macular hole retinal detachment in a patient with high myopia.Case summary: A 55-year-old male stated that he had experienced a transparent circle in the central visual field of the right eye for 1 month. His best-corrected visual acuity (BCVA) was 0.32 and the axial length of the right eye was 32.57 mm. Fundus examination revealed a macular hole with retinal detachment localized to the posterior pole. We performed vitrectomy, membrane peeling, internal limiting membrane peeling with inverted internal limiting membrane flap, and silicone oil injection. On day 1 after surgery, the macular hole was closed, but subretinal fluid was noticed in the macula. At 3 months after surgery, the BCVA was 0.16 and the silicone oil was removed. At 14 months after the first surgery, the subretinal fluid was completely absorbed, but leopard-pattern pigment degeneration became prominent and the macula exhibited ellipsoid zone disruption. The BCVA decreased to 0.1. Conclusions In patients exhibiting macular hole retinal detachment in the context of high myopia, an inverted internal limiting membrane flap may increase the macular hole closure rate but disturb subretinal fluid drainage. As persistent subretinal fluid may cause permanent retinal damage with a poor visual prognosis, the surgical method must be carefully chosen.

Objective: : Through our previous clinical trials, the demonstrated therapeutic effects of MSC in chronic spinal cord injury (SCI) were found to be not sufficient. Therefore, the need to develop stem cell agent with enhanced efficacy is increased. We transplanted enhanced Wnt3asecreting human mesenchymal stem cells (hMSC) into injured spines at 6 weeks after SCI to improve axonal regeneration in a rat model of chronic SCI. We hypothesized that enhanced Wnt3a protein expression could augment neuro-regeneration after SCI. Methods: : Thirty-six Sprague-Dawley rats were injured using an Infinite Horizon (IH) impactor at the T9–10 vertebrae and separated into five groups : 1) phosphate-buffered saline injection (injury only group, n=7); 2) hMSC transplantation (MSC, n=7); 3) hMSC transfected with pLenti vector (without Wnt3a gene) transplantation (pLenti-MSC, n=7); 4) hMSC transfected with Wnt3a gene transplantation (Wnt3a-MSC, n=7); and 5) hMSC transfected with enhanced Wnt3a gene (1.7 fold Wnt3a mRNA expression) transplantation (1.7 Wnt3a-MSC, n=8). Six weeks after SCI, each 5×105 cells/15 µL at 2 points were injected using stereotactic and microsyringe pump. To evaluate functional recovery from SCI, rats underwent Basso-Beattie-Bresnahan (BBB) locomotor test on the first, second, and third days post-injury and then weekly for 14 weeks. Axonal regeneration was assessed using growth-associated protein 43 (GAP43), microtubule-associated protein 2 (MAP2), and neurofilament (NF) immunostaining. Results: : Fourteen weeks after injury (8 weeks after transplantation), BBB score of the 1.7 Wnt3a-MSC group (15.0±0.28) was significantly higher than that of the injury only (10.0±0.48), MSC (12.57±0.48), pLenti-MSC (12.42±0.48), and Wnt3a-MSC (13.71±0.61) groups (p<0.05). Immunostaining revealed increased expression of axonal regeneration markers GAP43, MAP2, and NF in the Wnt3a-MSC and 1.7 Wnt3a-MSC groups. Conclusion : Our results showed that enhanced gene expression of Wnt3a in hMSC can potentiate axonal regeneration and improve functional recovery in a rat model of chronic SCI.

Purpose: To report a case of unilateral progressive atypical acute zonal outer retinitis in a healthy young female.Case summary: A 32-year-old healthy woman presented with visual disturbance in the left eye for 1 week. Best corrected visual acuity was 0.4 in the left eye. No abnormal findings were detected on brain magnetic resonance imaging and a laboratory work-up. Zonal retinal opacity around the optic nerve disc was noticed in a fundus photo which was consistent with the outer retinal signal defect on optical coherence tomography and a defect in the central visual field from perimetry. Multiple evanescent white dot syndrome was suspected based on fluorescein angiography and indocyanine green angiography. Prednisolone was prescribed. Visual acuity was reduced to hand-motion after 10 days with extended zonal retinal opacity. No virus was detected by multiplex polymerase chain reaction of the aqueous humor. The lesion did not improve despite high-dose intravenous steroid and antiviral treatment. Conclusions Visual function was lost with the progression of outer retinitis. This case differed from previous cases as the outer retinitis progressed rapidly from the posterior pole to the peripheral retina. It was named fulminant progressive atypical acute zonal outer retinitis.

Purpose: To report the effect of an intravitreal dexamethasone implant on refractory posterior scleritis. Methods: The medical records of patients treated with an intravitreal dexamethasone implant for non-infectious refractory posterior scleritis were retrospectively reviewed, including age, sex, duration of follow-up, and presence of associated systemic diseases. The duration until relapse, changes in visual acuity, number of implants, and side effects associated with the implant were also analyzed. Results: Seven eyes from five patients were included. The mean age was 73.2 ± 12.5 years (59-92 years). Although all patients had been treated with high-dose systemic steroid, and immunosuppressants were added, the posterior scleritis was poorly controlled. The duration from the diagnosis to the first dexamethasone implant was a mean of 8.2 months (3-27 months). The scleritis was well controlled in all eyes until at least 2 months (2-5 months) after inserting the implant. An average of 2.1 (total of 15 times in the seven eyes) implants were inserted. No complications related to the implant were observed other than a temporary increase in intraocular pressure in one eye. Conclusions Intravitreal dexamethasone implants were an effective treatment option for refractory posterior scleritis.

Purpose: To report complications requiring surgical management related to intravitreal dexamethasone implant. Methods: The medical records of patients who received intravitreal dexamethasone implant injection from June 2013 to March 2020 were reviewed retrospectively. Patients who had undergone intraocular surgical management within 6 months after implant injection, with the exception of cataract surgery, were included. Of them, only the cases in which the surgery was definitely related to complications with the Ozurdex implant were included. In these patients, underlying disease, intraocular pressure change, and the number of injections were analyzed. Results: A total of 1,168 injections of 473 eyes (439 patients) were enrolled in the study. The mean number of injections was 2.5 per eye. The mean age was 61.4 ± 11.3 years. The complications requiring an additional surgical procedure occurred in six (0.5%) injections. Of them, four, one, and one eyes showed uveitis, diabetic macular edema, and branch retinal vein occlusion, respectively. Surgical management was performed to control the increased intraocular pressure in two eyes, inappropriate implant location in two eyes, scleral wound leakage in one eye, and retinal detachment in one eye. The incidence of severe complications requiring surgical management was high in cases with a history of previous vitrectomy (p = 0.007, Fisher’s exact test) and uveitis (p = 0.007, Fisher’s exact test). Conclusions Severe complications requiring surgical management occurred in 0.5% of cases (six cases) after intravitreal dexamethasone implant injections. These complications were related to a history of previous vitrectomy and uveitis. Five eyes recovered to favorable visual function after surgery, with the exception of one eye with retinal detachment.

Objective: : Through our previous clinical trials, the demonstrated therapeutic effects of MSC in chronic spinal cord injury (SCI) were found to be not sufficient. Therefore, the need to develop stem cell agent with enhanced efficacy is increased. We transplanted enhanced Wnt3asecreting human mesenchymal stem cells (hMSC) into injured spines at 6 weeks after SCI to improve axonal regeneration in a rat model of chronic SCI. We hypothesized that enhanced Wnt3a protein expression could augment neuro-regeneration after SCI. Methods: : Thirty-six Sprague-Dawley rats were injured using an Infinite Horizon (IH) impactor at the T9–10 vertebrae and separated into five groups : 1) phosphate-buffered saline injection (injury only group, n=7); 2) hMSC transplantation (MSC, n=7); 3) hMSC transfected with pLenti vector (without Wnt3a gene) transplantation (pLenti-MSC, n=7); 4) hMSC transfected with Wnt3a gene transplantation (Wnt3a-MSC, n=7); and 5) hMSC transfected with enhanced Wnt3a gene (1.7 fold Wnt3a mRNA expression) transplantation (1.7 Wnt3a-MSC, n=8). Six weeks after SCI, each 5×105 cells/15 µL at 2 points were injected using stereotactic and microsyringe pump. To evaluate functional recovery from SCI, rats underwent Basso-Beattie-Bresnahan (BBB) locomotor test on the first, second, and third days post-injury and then weekly for 14 weeks. Axonal regeneration was assessed using growth-associated protein 43 (GAP43), microtubule-associated protein 2 (MAP2), and neurofilament (NF) immunostaining. Results: : Fourteen weeks after injury (8 weeks after transplantation), BBB score of the 1.7 Wnt3a-MSC group (15.0±0.28) was significantly higher than that of the injury only (10.0±0.48), MSC (12.57±0.48), pLenti-MSC (12.42±0.48), and Wnt3a-MSC (13.71±0.61) groups (p<0.05). Immunostaining revealed increased expression of axonal regeneration markers GAP43, MAP2, and NF in the Wnt3a-MSC and 1.7 Wnt3a-MSC groups. Conclusion : Our results showed that enhanced gene expression of Wnt3a in hMSC can potentiate axonal regeneration and improve functional recovery in a rat model of chronic SCI.

Purpose: To report a case of unilateral progressive atypical acute zonal outer retinitis in a healthy young female.Case summary: A 32-year-old healthy woman presented with visual disturbance in the left eye for 1 week. Best corrected visual acuity was 0.4 in the left eye. No abnormal findings were detected on brain magnetic resonance imaging and a laboratory work-up. Zonal retinal opacity around the optic nerve disc was noticed in a fundus photo which was consistent with the outer retinal signal defect on optical coherence tomography and a defect in the central visual field from perimetry. Multiple evanescent white dot syndrome was suspected based on fluorescein angiography and indocyanine green angiography. Prednisolone was prescribed. Visual acuity was reduced to hand-motion after 10 days with extended zonal retinal opacity. No virus was detected by multiplex polymerase chain reaction of the aqueous humor. The lesion did not improve despite high-dose intravenous steroid and antiviral treatment. Conclusions Visual function was lost with the progression of outer retinitis. This case differed from previous cases as the outer retinitis progressed rapidly from the posterior pole to the peripheral retina. It was named fulminant progressive atypical acute zonal outer retinitis.