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Chronic rhinosinusitis (CRS) is further classified as CRS with nasal polyp and CRS without nasal polyp. It is also divided into type 2 and none-type 2 by immunological endotype. Nowadays, novel biological products targeting type 2 inflammation are developed and used for the treatment of CRS with nasal polyp.Current Concepts: Dupilumab, which inhibits interleukin-4 and interleukin-13, and omalizumab, which targets immunoglobulin E, were recently approved and are currently being used as the treatment regimen for patients with recurrent CRS with nasal polyp in Korea. Many studies demonstrated enough effects of both biological products on nasal symptoms, including smell, quality of life, and polyp size. The indication of biological products is refractory CRS with nasal polyp with severe symptoms even after endoscopic sinus surgery. However, the main drawback of these biological products is a high cost since they are non-reimbursement regimens as defined by Korean national health insurance.Discussion and Conclusion: Further research on the use of dupilumab and omalizumab in Korean patients will be needed because the Korean CRS endotype, which is characterized by less-type-2 CRS, is different from Western CRS endotypes. Additionally, investigations on the comparison of efficacy among various biological products are essential to prescribe the most appropriate biological products depending on the patients’ endotypes.
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Background and Objectives@#Endoscopic sinus surgery is commonly performed for maxillary sinus (MS) disease, and the surgical extent of the MS medial wall or ostium varies. We examined the effect of MS surgery on nasal airflow and air-conditioning using computational fluid dynamics in five nasal cavity numerical models. @*Methods@#Four types of unilateral virtual MS surgery were conducted on the right MS based on computed tomography images of a 49-year-old man with normal anatomy. The five models were as follows: baseline (normal), middle meatal antrostomy (MMA), MMA with inferior meatal antrostomy (MMA+IMA), mega-antrostomy (MEGA), and endoscopic medial maxillectomy (EMM). Virtual simulator software and a stereoscopic display with haptic device were used for virtual surgery. Meshing software and computer fluid dynamics software were used to generate meshes and analyze airflow. @*Results@#The MMA and MMA+IMA results were similar to the baseline model. However, EMM and MEGA exhibited some physiological changes. The amount of airflow moving into the MS was largest in the EMM model, followed by the MEGA model. The distributions of wall shear stress and surface water-vapor increased near the enlarged MS ostium in EMM and MEGA. Skewed airflow partition and different airflow rates between the operated and unoperated sites of the nose also changed the air-conditioning characteristics. EMM substantially reduced the relative humidity in the nasopharynx, and MEGA showed a smaller reduction. @*Conclusion@#Among four surgery techniques, EMM produced the largest increase in wall shear stress and surface water vapor flux on the posterior surface of the MS and the greatest deterioration in the nasal cavity’s air-conditioning capacity. MEGA reduced the local airflow disturbance inside the MS and prevented excessive degeneration of the cavity’s overall air-conditioning capacity. In conclusion, MEGA and modified EMM approaches have physiological advantages over EMM, while securing a sufficient spatial extent of resection for surgery.
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Multiple cerebral infarctions coexisting with peripheral artery occlusion have been rarely reported and occur only in specific conditions. Also, the characteristics of thrombosis related to the outbreak of the coronavirus disease 2019 (COVID-19) have been observed and studied recently. We report a case of concurrent multiple cerebral infarctions and peripheral embolism in a patient with a recent history of COVID-19 infection. A 62-year-old male patient who had recently been infected with COVID-19 presented to our emergency department with left hemiparesis. Supportive treatments were given post the diagnosis of multiple cerebral infarctions in the right cerebral hemisphere. During the supportive treatments, motor weakness was seen in the right upper extremity. Computed tomography revealed thrombi in the right axillary, brachiocephalic, and brachial arteries. The patient was already taking antiplatelet and anticoagulant agents and had no other underlying disease to develop such occlusions except his recent history of COVID-19 infection. We checked his laboratory tests for coagulation profiles throughout the hospitalization to verify a possible cause. We believe that large thrombi formation due to COVID-19 can simultaneously cause embolism in the cerebrum and peripheral regions. This pathology can result in symptoms that could make diagnosis difficult, delaying treatment decisions. This report, therefore, suggests that it is necessary to take into account a patient’s history of COVID-19 infection in such situations, especially when the patient presents with symptoms of a stroke.
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An increased pericoronary fat attenuation index (FAI) on computed tomography angiography (CTA) is associated with increased all-cause and cardiac mortality in the general population. However, the ability of pericoronary FAI to predict long-term outcomes in chronic kidney disease (CKD) patients is unknown. Methods: In this single-center retrospective longitudinal cohort study, we assessed the utility of CTA-based pericoronary FAI measurement to predict mortality of CKD patients, including those with end-stage renal disease (ESRD). Mapping and analysis of pericoronary FAI involved three major proximal coronary arteries. The prognostic value of pericoronary FAI for long-term mortality was assessed with multivariable Cox regression models. Results: Among 268 CKD participants who underwent coronary CTA, 209 participants with left anterior descending artery (LAD) FAI measurements were included. The pericoronary FAI measured at the LAD was not significantly associated with adjusted risk of allcause mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 0.94–3.51) in any CKD group. However, ESRD patients with elevated pericoronary FAI values had a greater adjusted risk of all-cause mortality compared with the low-FAI group (HR, 2.26; 95% CI, 1.11–4.61). Conclusion: The pericoronary FAI measured at the LAD predicted long-term mortality in patients with ESRD, which could provide an opportunity for early primary intervention in ESRD patients.
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Although hypertension is a well-known risk factor for chronic kidney disease (CKD), the blood pressure (BP) at which antihypertensive interventions should be initiated remains to be determined. Therefore, we investigated the association between BP and CKD in treatment-naïve individuals. Methods: This prospective cohort study considered 7,343 individuals in the Korean Genome and Epidemiology Study who were not taking antihypertensive medications. Subjects were categorized into six groups according to their systolic BP (SBP) and five groups according to their diastolic BP (DBP). The primary outcome was incident CKD, which was defined as an estimated glomerular filtration rate of <60 mL/min/1.73 m2 or the development of proteinuria. The secondary outcome was incident cardiovascular disease (CVD). Results: In the time-varying Cox models, the hazard ratios (95% confidence interval [CI]) for CKD were 1.39 (1.10–1.77) with SBP 130–139 mmHg, 1.79 (1.40–2.28) with SBP 140–159 mmHg, and 3.22 (2.35–4.40) with SBP ≥ 160 mmHg, compared with SBP 100–119 mmHg. In addition, the hazard ratios (95% CI) for CKD were 1.88 (1.48–2.37) with DBP 90–99 mmHg and 4.30 (3.20– 5.76) with DBP ≥ 100 mmHg, compared with DBP 70–79 mmHg. A significantly increased CVD risk was also observed in subjects with SBP ≥ 130 mmHg or DBP ≥ 90 mmHg. Conclusion: Our findings indicate that SBP ≥ 130 mmHg and DBP ≥ 90 mmHg are associated with an increased risk of CKD. Therefore, BP-lowering strategies should be considered starting at those thresholds to prevent CKD development.
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The claustrum, a brain nucleus located between the cortex and the striatum, has recently been highlighted in drug-related reward processing. Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that represses or activates the expression of the target gene and has been known to have an important role in the regulation of drug addiction in the dopaminergic reward system. The claustrum is an important region for regulating reward processing where most neurons receive dopamine input; additionally, in this region, MeCP2 is also abundantly expressed. Therefore, here, we hypothesized that MeCP2 would be involved in drug addiction control in the Claustrum as well and investigated how claustral MeCP2 regulates drug addiction. To better understand the function of human claustral MeCP2, we established a non-human primate model of methamphetamine (METH) - induced conditioned place preference (CPP). After a habituation of two days and conditioning of ten days, the CPP test was conducted for three days. Interestingly, we confirmed that virus-mediated overexpression of MECP2 in the claustrum showed a significant reduction of METH-induced CPP in the three consecutive days during the testing period. Moreover, they showed a decrease in visit scores (frequency for visit) for the METH-paired room compared to the control group although the scores were statistically marginal. Taken together, we suggest that the claustrum is an important brain region associated with drug addiction, in which MeCP2 may function as a mediator in regulating the response to addictive drugs.
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Purpose@#The purpose of this study was to compare the efficacy of low-dose steroid, highdose steroid, and low-dose steroid combined with hyaluronidase with respect to intra-articular injection therapy for adhesive capsulitis (AC) of the shoulder. @*Methods@#Thirty patients with primary AC in the initial stage were randomly assigned into three groups to receive ultrasound-guided intra-articular injections with 20 mg of triamcinolone acetonide (group A, n=10), 40 mg of triamcinolone acetonide (group B, n=10) and 20 mg of triamcinolone acetonide combined with hyaluronidase (group C, n=10). The outcome measures included a visual analogue scale (VAS), the Shoulder Disability Questionnaire (SDQ), abduction and external rotation range of motion, and intra-sheath fluid (ISF) before treatment and at 2, 4, 8, and 16 weeks after treatment. @*Results@#Among the 30 patients, one participant in group B dropped out; therefore, a total of 29 patients completed this study and were successfully injected. After the injection, the VAS, SDQ, range of flexion and external rotation, and ISF improved in all groups compared with the preinjection status, regardless of treatment or time point. In the comparison between groups, the SDQ and ISF showed significantly greater improvements in groups B and C than in group A. @*Conclusion@#The therapeutic efficacy of combined low-dose corticosteroid and hyaluronidase is superior to that of low-dose corticosteroid and equivalent to that of high-dose corticosteroid in early AC.
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Background@#Telemetry is a wireless implanted device that measures biological signals in conscious animals and usually requires surgery for its removal when the study is finished. After removing the device, the animals are either used for other studies or euthanatized.Case presentation: Herein, we report the case of a living cynomolgus monkey (Macaca fascicularis) that was used for the entire experimental period, instead of euthanasia, after surgical removal of an implanted telemetry system.Radiography was used to determine the status of the implanted telemetry, following which, a repair surgery was performed for removing the system; clinical signs were used to preserve the life of the cynomolgus monkey. Postoperative clinical signs, food consumption, hematology, and serum biochemistry were examined during the 12-month observational period. No abnormal readings or conditions were observed in the subject after implant removal. @*Conclusions@#This study may be a useful case report for living cynomolgus monkeys in telemetry implantations used throughout the study period. We suggest minimizing the suffering and improving the welfare of these animals.
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Background@#Olfactory and gustatory dysfunction are frequently reported in patients with coronavirus disease 2019 (COVID-19). However, the reported prevalence of olfactory and/or gustatory dysfunction varies widely, and the reason for the inter-study differences is unclear.Hence, in this meta-analysis, we performed subgroup analyses to investigate the factors that contribute to the inter-study variability in the prevalence of olfactory and gustatory dysfunction. @*Methods@#Out of 943 citations, we included 55 eligible studies with 13,527 patients with COVID-19 for a meta-analysis. Calculating the data extracted from each study, the weighted summary prevalence of olfactory and gustatory dysfunction was estimated using a FreemanTukey transformation with models based on random-effects assumptions. A meta-analysis of variance compared the prevalence of olfactory and gustatory dysfunction according to regional, chronological, demographic, and methodologic factors, respectively. @*Results@#The overall pooled prevalence rates of olfactory and gustatory dysfunction were 51.4% and 47.5%, respectively, in the random-effect model. In subgroup analyses, the prevalence rates of olfactory and gustatory dysfunction were significantly different among four geographical regions (both P < 0.001, respectively). Although the prevalence rates of olfactory and gustatory dysfunction did not significantly differ according to the time of enrollment, the subgroup analyses including only studies from the same geographical region (Europe) revealed a significant difference in olfactory dysfunction according to the time of enrollment. @*Conclusion@#The regional and chronological differences in the prevalence rates of olfactory and gustatory dysfunctions partly explain the wide inter-study variability.
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Particle therapy is a promising and evolving modality of radiotherapy that can be used to treat tumors that are radioresistant to conventional photon beam radiotherapy. It has unique biological and physical advantages compared with conventional radiotherapy. The characteristic feature of particle therapy is the “Bragg peak,” a steep and localized peak of dose, that enables precise delivery of the radiation dose to the tumor while effectively sparing normal organs. Especially, the charged particles (e.g., proton, helium, carbon) cause a high rate of energy loss along the track, thereby leading to high biological effectiveness, which makes particle therapy attractive. Using this property, the particle beam induces more severe DNA double-strand breaks than the photon beam, which is less influenced by the oxygen level. This review describes the general biological and physical aspects of particle therapy for oncologists, including non-radiation oncologists and beginners in the field.
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BACKGROUND@#Since primates have more biological similarities to humans than do other animals, they are a valuable resource in various field of research, including biomedicine, regenerative medicine, and drug discovery. However, there remain limitations to maintenance and expansion of primary hepatocytes derived from nonhuman primates. To overcome these limitations, we developed a novel culture system for primate cells. @*METHODS@#Primary hepatocytes from Macaca fascicularis (mf-PHs) were isolated from hepatectomized liver. To generate chemically derived hepatic progenitor cells (mf-CdHs), mf-PHs were cultured with reprogramming medium containing A83-01, CHIR99021, and hepatocyte growth factor (HGF). The bi-potent differentiation capacity of mf-CdHs into hepatocytes and biliary epithelial cells was confirmed by treatment with hepatic differentiation medium (HDM) and cholangiocytic differentiation medium (CDM), respectively. @*RESULTS@#mf-PHs cultured with reprogramming medium showed rapid proliferation capacity in vitro and expressed progenitor-specific markers. Moreover, when cultured in HDM, these progenitor cells stably differentiated into hepatocytelike cells expressing the mature hepatic markers. On the other hand, when cultured in CDM, the differentiated biliary epithelial cells expressed mature cholangiocyte characteristics. @*CONCLUSION@#The results of the present study demonstrate that we successfully induced the formation of hepatic progenitor cells from mf-PHs by culturing them with a combination of small molecules, including growth factors. These results offer a means of expanding nonhuman primate hepatocytes without genetic manipulation for cellular resource, preclinical applications and regenerative medicine for the liver.
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Background@#Metformin has recently been shown not to increase the risk of lactic acidosis in patients with chronic kidney disease (CKD). Thus, the criteria for metformin use in this population has expanded. However, the relationship between metformin use and clinical outcomes in CKD remains controversial. @*Methods@#This study considered data from 97,713 diabetes patients with an estimated glomerular filtration rate of <60 mL/min/1.73 m2. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), and the secondary outcomes were all-cause mortality and incident end-stage renal disease (ESRD). @*Results@#Metformin users had a significantly higher risk of MACCE than non-users (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.14–1.26; p < 0.001). However, metformin users had a lower risk of all-cause mortality (HR, 0.78; 95% CI, 0.74–0.81; p < 0.001) and ESRD (HR, 0.44; 95% CI, 0.42–0.47; p < 0.001) during follow-up than non-users did. The relationships between metformin use and clinical outcomes remained consistent in propensity score matching analyses and subgroup analyses of patients with adequate adherence to anti-diabetes medication. @*Conclusion@#Treatment with metformin was associated with an increased risk of MACCE in patients with diabetes and CKD. However, metformin users had a lower risk of all-cause mortality and ESRD during follow-up than non-users did. Therefore, metformin needs to be carefully used in patients with CKD.
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Nora et al. first reported a bizarre parostealosteochondromatous proliferation (BPOP) as a small size bone malformation mainly in the foot and hand in April 1983 that was called Nora’s lesion or Nora’s disease. Nora’s disease is known for its low incidence and is characterized as a benign lesion, without a malignancy or metastasis with different histological, radiological, and clinical features from other common lesions. Several cases of Nora’s disease on the hand, foot, and long bone have been reported in Korea. This paper reports a case of BPOP of the proximal phalanx of the great toe.
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Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from graymatter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.
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BACKGROUND@#Since primates have more biological similarities to humans than do other animals, they are a valuable resource in various field of research, including biomedicine, regenerative medicine, and drug discovery. However, there remain limitations to maintenance and expansion of primary hepatocytes derived from nonhuman primates. To overcome these limitations, we developed a novel culture system for primate cells. @*METHODS@#Primary hepatocytes from Macaca fascicularis (mf-PHs) were isolated from hepatectomized liver. To generate chemically derived hepatic progenitor cells (mf-CdHs), mf-PHs were cultured with reprogramming medium containing A83-01, CHIR99021, and hepatocyte growth factor (HGF). The bi-potent differentiation capacity of mf-CdHs into hepatocytes and biliary epithelial cells was confirmed by treatment with hepatic differentiation medium (HDM) and cholangiocytic differentiation medium (CDM), respectively. @*RESULTS@#mf-PHs cultured with reprogramming medium showed rapid proliferation capacity in vitro and expressed progenitor-specific markers. Moreover, when cultured in HDM, these progenitor cells stably differentiated into hepatocytelike cells expressing the mature hepatic markers. On the other hand, when cultured in CDM, the differentiated biliary epithelial cells expressed mature cholangiocyte characteristics. @*CONCLUSION@#The results of the present study demonstrate that we successfully induced the formation of hepatic progenitor cells from mf-PHs by culturing them with a combination of small molecules, including growth factors. These results offer a means of expanding nonhuman primate hepatocytes without genetic manipulation for cellular resource, preclinical applications and regenerative medicine for the liver.
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Fibrous dysplasia (FD) is a non-malignant progressive condition, which replaces normal bone and marrow with fibrous tissue and woven bone. Sinus mucocele is a cystic, expansile, and destructive lesion that occurs as a result of obstruction of the sinus ostium secondary to inflammation, trauma, anatomical variation, previous sinus surgery, tumor or FD. Among them, FD combined with mucocele has been rarely reported. Here we report the first case of FD combined with ethmoid mucocele. The patient underwent endoscopic debulking of FD and marsupialization of mucocele. The mucocele was successfully marsupialized, and the patient’s symptoms were completely resolved. We propose a new hypothesis that nasal mucosa invaginates into FD and forms a mucocele. For the treatment of ethmoid FD combined with mucocele, we recommend an endoscopic transnasal approach for debulking and marsupialization.
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Particle therapy is a promising and evolving modality of radiotherapy that can be used to treat tumors that are radioresistant to conventional photon beam radiotherapy. It has unique biological and physical advantages compared with conventional radiotherapy. The characteristic feature of particle therapy is the “Bragg peak,” a steep and localized peak of dose, that enables precise delivery of the radiation dose to the tumor while effectively sparing normal organs. Especially, the charged particles (e.g., proton, helium, carbon) cause a high rate of energy loss along the track, thereby leading to high biological effectiveness, which makes particle therapy attractive. Using this property, the particle beam induces more severe DNA double-strand breaks than the photon beam, which is less influenced by the oxygen level. This review describes the general biological and physical aspects of particle therapy for oncologists, including non-radiation oncologists and beginners in the field.
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The incidence of heterotopic ossification (HO) was reported to be higher in combat-injured patients than in civilian trauma patients. HO is often considered a possible cause of residual limbs pain in amputee. Here, we report the case of a 21-year-old male, who underwent a traumatic right transfemoral and left transtibial amputation with two segments of painful HO around his left amputation site. We report the effect of extracorporeal shock wave therapy (ESWT) on size and pain associated with HO. After ESWT, the visual analog scale score decreased from 5∼6 to 0∼1 and the size of two masses decreased from 13.1 × 6.7 mm and 12.5 mm to 11.9 × 4.7 mm and 12.2 mm, respectively. To the best of our knowledge, this is the first case that has reported on the treatment of HO using ESWT for a traumatic transtibial amputation patient. The case suggests that ESWT could serve as a complementary treatment for HO in traumatic amputation patient.
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Congenital aural atresia is an ear malformation evident at birth, involving various degrees of failed external ear canal development. A true external ear canal is desirable, as devices that replace the canal are inconvenient and expensive. Therefore, an optimal surgical technique is required. Here, we review useful preoperative and operative techniques. Surgical correction is often not the preferred treatment; the hearing outcome is no better than the outcomes afforded by bone-conduction devices, and surgery may be associated with recurrence or complications such as meatal stenosis. Preoperative evaluation and appropriate management are important. Several means of preventing meatal stenosis are discussed in this review.
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A 39-year-old man visited the department of otolaryngology due to an ongoing hearing disturbance that had lasted for 1 year. Temporal bone computed tomography revealed soft tissue density nearly obliterating the left external auditory canal (EAC). The mass was composed of sheets of round tumor cells containing moderate amounts of fine granular cytoplasm and salt and pepper chromatin. Neither mitosis nor necrosis was found. The Ki-67 proliferation index was less than 2%. Cells were positive for CD56 and synaptophysin but negative for chromogranin, cytokeratin (CK) 20, and CK7. Based on these findings, the tumor was diagnosed as a carcinoid tumor, well differentiated neuroendocrine carcinoma, grade 1 (G1) according to current World Health Organization (WHO) classification of head and neck tumors; and a neuroendocrine tumor, G1 according to neuroendocrine neoplasm (NEN)-2018 WHO standard classification. He remained free of local recurrence and metastasis after 20 months of follow up. To date, only six cases of primary NENs in the EAC have been reported. Metastatic tumor should be included in the differential diagnoses. Because of its rarity, the prognosis and treatment have not yet been clarified.