Pioneering PGC-1αα–boosted secretome: a novel approach to combating liver fibrosis

Purpose@#Liver fibrosis is a critical health issue with limited treatment options. This study investigates the potential of PGC-Sec, a secretome derived from peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-overexpressing adipose-derived stem cells (ASCs), as a novel therapeutic strategy for liver fibrosis. @*Methods@#Upon achieving a cellular confluence of 70%–80%, ASCs were transfected with pcDNA-PGC-1α. PGC-Sec, obtained through concentration of conditioned media using ultrafiltration units with a 3-kDa cutoff, was assessed through in vitro assays and in vitro mouse models. @*Results@#In vitro, PGC-Sec significantly reduced LX2 human hepatic stellate cell proliferation and mitigated mitochondrial oxidative stress compared to the control-secretome. In an in vivo mouse model, PGC-Sec treatment led to notable reductions in hepatic enzyme activity, serum proinflammatory cytokine concentrations, and fibrosis-related marker expression. Histological analysis demonstrated improved liver histology and reduced fibrosis severity in PGC-Sec–treated mice. Immunohistochemical staining confirmed enhanced expression of PGC-1α, optic atrophy 1 (a mitochondrial function marker), and peroxisome proliferator-activated receptor alpha (an antifibrogenic marker) in the PGC-Sec–treated group, along with reduced collagen type 1A expression (a profibrogenic marker). @*Conclusion@#These findings highlight the therapeutic potential of PGC-Sec in combating liver fibrosis by enhancing mitochondrial biogenesis and function, and promoting antifibrotic processes. PGC-Sec holds promise as a novel treatment strategy for liver fibrosis.

Clinical Validation of the Unparalleled Sensitivity of the Novel Allele-Discriminating Priming System Technology–Based EGFR Mutation Assay in Patients with Operable Non–Small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. @*Materials and Methods@#In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee. @*Results@#The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. @*Conclusion@#The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

Differences in Nasal Shapes and the Degree of Changes Over a Decade or More: A Paired Analysis

Objectives@#. This study investigated age-related differences in nasal morphometry and the degree of changes within an individual over at least a 10-year period by pairing previous and recent three-dimensional reconstructed computed tomography (CT) images. @*Methods@#. Forty-eight adult Korean patients who underwent at least two CT scans of the nasal region with an interval of at least 10 years were selected. Patients were categorized into six subgroups according to sex and age (20–39 years, 40–49 years, and ≥50 years) at the time of initial imaging. Eight nasal parameters were measured on the initial and recent images, and paired comparisons between the two images were performed based on the data. The differences in the degree of change by age were also analyzed. @*Results@#. Over an average image interval of 12 years, men exhibited an increase in the nasofrontal angle (3.2°±5.4°, P=0.041), profile nasal length (1.7±1.7 mm, P=0.002), and nasal bridge height (1.2±1.6 mm, P=0.002). Conversely, they showed a decrease in the nasofacial angle (–2.3°±2.9°, P=0.010). Women also demonstrated an increase in the nasofrontal angle (2.5°±5.2°, P=0.010), profile nasal length (1.4±1.9 mm, P<0.001), and nasal bridge height (1.3±1.6 mm, P<0.001). However, they exhibited a decrease in the nasofacial angle (–2.0°±2.1°, P<0.001), glabella angle (–9.1°±9.8°, P<0.001), and pyriform angle (–8.5°±10.1°, P<0.001). With the exception of the nasal bridge height (P=0.036) and pyriform angle (P=0.022), the degree of changes in most parameters did not show significant differences across age groups. @*Conclusion@#. Our findings indicate that the aging nose exhibits a greater nasal length with inferior angulation of the nasal tip, with an increase in the nasofrontal angle, profile nasal length, and nasal bridge height, along with a decrease in the nasofacial angle. The degree of most nasal morphologic changes demonstrated no significant differences by specific age group.

Long-Term Outcomes of High-Flexion Design Total Knee Arthroplasty with a Short Posterior Flange

Background@#The purpose of this study was to evaluate the clinical and radiological outcomes of high-flexion total knee arthroplasty (TKA) using Vega Knee System (B. Braun, Aesculap) at a long-term follow-up and to analyze the implant survivorship. @*Methods@#We enrolled 165 patients (232 knees) with a minimum 7-year follow-up after TKA (VEGA Knee System). For clinical assessment, range of motion (ROM), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used. For radiologic assessment, hip-knee-ankle angle, component position, and the existence of radiolucent lines and loosening were used. Survival analysis was conducted using the Kaplan-Meier method. @*Results@#The mean follow-up period was 9.8 years. The mean ROM increased from 124.4° to 131.4° at the final follow-up. The WOMAC score decreased from 38.5 to 17.4 at the final follow-up (p < 0.001). All 5 subscales of the KOOS improved at the final follow-up (all subscales, p < 0.001). Revision TKA was performed in 10 cases (4.3%), which included 9 cases of aseptic loosing and 1 case of periprostatic joint infection. Of the 9 aseptic loosening cases (3.9%), 8 cases (3.4%) were loosening of the femoral component and 1 case (0.4%) was loosening of the tibial component. When revision for any reason was considered an endpoint, the 10-year survivorship was 96.2% (95% confidence interval [CI], 93.9%–98.5%). On the other hand, when revision for aseptic loosening was considered the endpoint, the 10-year survivorship was 96.6% (95% CI, 94.4%–98.8%). @*Conclusions@#The Vega Knee System provided good clinical results in the long-term follow-up period. Although the VEGA Knee System showed acceptable implant survivorship, loosening of the femoral component occurred in about 3.4% of the patients. For more accurate evaluation of the survivorship of high-flexion design TKA with a short posterior flange, it is necessary to conduct more long-term follow-up studies targeting diverse races, especially Asians who frequently perform high-flexion activities.

Optimization of Acetabular Cup Abduction by Adjusting Pelvic Pitch

Background@#The purposes of this study were to determine the accuracy of our cup positioning method and to evaluate the dislocation rate after total hip arthroplasty (THA). @*Methods@#After positioning the patient in the lateral decubitus position on the operation table, an anteroposterior view of the hip was taken. The pelvic pitch was measured on the X-ray. A positive pitch was defined as the caudal rotation of the upper hemipelvis. Our target abduction of the cup was 43°. We used the cup holder to guesstimate the cup abduction. In a preliminary study, we found that the weight of the cup holder increased the pelvic pitch by 5°. Thus, the target abduction of the cup holder was calculated by a formula: 43° – pelvic pitch – 5°. During the cup insertion, the cup holder was anteverted to the calculated target according to the concept of combined anteversion. We evaluated 478 THAs (429 patients), which were done with the use of the method. @*Results@#The mean cup abduction was 43.9° (range, 32.0°–53.0°) and the mean error of cup abduction was 2.4° (standard deviation [SD], 2.0°; range, 0.0°–11.0°). The mean cup anteversion was 28.5° (range, 10.0°–42.0°) and the mean error of cup anteversion was 6.7° (SD, 5.2°; range, 0.0°–27.6°). Of all, 82.4% of the cups (394 / 478) were within the safe zone: 30°–50° abduction and 10°–35° anteversion. During 2- to 5-year follow-up, no hip dislocated. @*Conclusions@#Our adjusting method according to the pelvic pitch can be a reliable option for optimizing the cup abduction in THA.

NKCC1 in Neonatal Cochlear Support Cells Reloads Ions Necessary for Cochlear Spontaneous Activity

In the auditory system, the spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from inner supporting cells (ISCs). This ATP release sets off a cascade, activating purinergic autoreceptors, opening of Ca 2+ -activated Cl- channel TMEM16A, Cl- efflux and osmotic cell shrinkage. Then, the shrunken ISCs efficiently regain their original volume, suggesting the existence of mechanisms for refilling Cl- and K + , priming them for subsequent activity. This study explores the potential involvement of NKCCs (Na+ -K+ -Cl- cotransporters) and KCCs (K+ -Cl- cotransporters) in ISC spontaneous activity, considering their capability to transport both Cl- and K+ ions across the cell membrane. Employing a combination of immunohistochemistry, pharmacological interventions, and shRNA experiment, we unveiled the pivotal role of NKCC1 in cochlear spontaneous activity. Immunohistochemistry revealed robust NKCC1 expression in ISCs, persisting until the 2nd postnatal week. Intriguingly, we observed a developmental shift in NKCC1 expression from ISCs to synaptophysin-positive efferent terminals at postnatal day 18, hinting at its potential involvement in modulating synaptic transmission during the post-hearing period. Experiments using bumetanide, a well-known NKCC inhibitor, supported the functional significance of NKCC1 in ISC spontaneous activity. Bumetanide significantly reduced the frequency of spontaneous extracellular potentials (sEP) and spontaneous optical changes (sOCs) in ISCs. NKCC1-shRNA experiments conducted in cultured cochlear tissues further supported these findings, demonstrating a substantial decrease in event frequency and area. Taken together, we revealed the role of NKCC1 in shaping the ISC spontaneous activity that govern auditory pathway development.

Long-term Outcomes of Ampullary Adenoma According to Resected Margin Status after Endoscopic Papillectomy

Background/Aims@#Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the longterm outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. @*Methods@#This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean followup duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. @*Results@#Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). @*Conclusions@#Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Harnessing the Power of IL-7 to BoostT Cell Immunity in Experimental and Clinical Immunotherapies

The cytokine IL-7 plays critical and nonredundant roles in T cell immunity so that the abundance and availability of IL-7 act as key regulatory mechanisms in T cell immunity.Importantly, IL-7 is not produced by T cells themselves but primarily by non-lymphoid lineage stromal cells and epithelial cells that are limited in their numbers. Thus, T cells depend on cell extrinsic IL-7, and the amount of in vivo IL-7 is considered a major factor in maximizing and maintaining the number of T cells in peripheral tissues. Moreover, IL-7 provides metabolic cues and promotes the survival of both naïve and memory T cells. Thus, IL-7 is also essential for the functional fitness of T cells. In this regard, there has been an extensive effort trying to increase the protein abundance of IL-7 in vivo, with the aim to augment T cell immunity and harness T cell functions in anti-tumor responses. Such approaches started under experimental animal models, but they recently culminated into clinical studies, with striking effects in reestablishing T cell immunity in immunocompromised patients, as well as boosting anti-tumor effects. Depending on the design, glycosylation, and the structure of recombinantly engineered IL-7 proteins and their mimetics, recombinant IL-7 molecules have shown dramatic differences in their stability, efficacy, cellular effects, and overall immune functions. The current review is aimed to summarize the past and present efforts in the field that led to clinical trials, and to highlight the therapeutical significance of IL-7 biology as a master regulator of T cell immunity.

Navigation guided small craniectomy and direct cannulation of pure isolated sigmoid sinus for treatment of dural arteriovenous fistula

Dural arteriovenous fistula (DAVF) is a rare condition affecting approximately 1.5% of 1,000,000 individuals annually. It frequently occurs in the transsigmoid and cavernous sinuses. An isolated sigmoid sinus is extremely rare and is treated by performing transfemoral transvenous embolization along the opposite transverse sinus.A 69-year-old woman presented with asymptomatic Borden type III/Cognard type III DAVF involving an isolated sigmoid sinus. She underwent a staged operation in which a navigation system was used to expose the sigmoid sinus in the operating room before transferring the patient to the angio suite for transvenous embolization.Various modalities have been used to treat DAVF, including surgical disconnection, transarterial embolization, transvenous embolization, and stereotactic radiosurgery. However, treating DAVF cases where the affected sinus is isolated can be challenging because an easily accessible surgical route may not be available. In this case, direct sinus cannulation and transvenous embolization were the most effective treatments.

Periosteum-attached Autogenous Block Bone Graft with Simultaneous Implant Placement on the Anterior Maxilla: A Case Report

This case report presents the long-term radiographic outcomes of a novel approach for simultaneous lateral augmentation and implant surgery. A 60-year-old male patient who required tooth extraction of the maxillary central and lateral incisors due to trauma visited the clinic. After tooth extraction, severe horizontal and vertical deficiencies occurred owing to atrophy of the alveolar ridge, and a simultaneous guided bone regeneration (GBR) procedure was planned along with the installation of two implants. In the present case, a modification of the conventional ‘sandwich technique’ was used by placing the mixture of autogenous bone chips and xenografts at the outermost layer to maximize the osteogenic potential at the coronal part of augmentation while applying solely xenografts at the inner layer. To enhance volumetric stability, an autogenous block of periosteum harvested from the maxillary tuberosity was incorporated between the two layers. Cone-beam computed tomography was performed at baseline and 3 years after the surgery to compare radiographic outcomes. Dehiscence after fixture installation was successfully observed at the re-entry of the surgery site. Three years after the surgery, average horizontal bone gains of 6.11 mm and 4.12 mm were observed in the maxillary central and lateral incisor areas, respectively. Healthy peri-implant mucosa and well maintained marginal bone levels were observed 8 years after the surgery, meeting the criteria for implant success. The findings of this case suggest that a substantial amount of horizontal bone gain can be obtained with a layered approach using autogenous bone materials and xenografts, highlighting the advantages of incorporating autogenous blocks into the simultaneous GBR procedure.

Various Pathologic Conditions of Sinus Tarsi Syndrome Assessed by Imaging and Arthroscopic Findings / 대한족부족관절학회지

Purpose@#Sinus tarsi syndrome (STS) is caused by various pathologies. However, the exact etiology of STS remains controversial. This study evaluated the imaging and arthroscopic findings of patients who underwent surgical treatment after conservative treatment for STS failed. @*Materials and Methods@#Between December 2014 and August 2018, 20 patients (21 cases) who underwent surgical treatment for STS were included in the study. The clinical results were analyzed using the visual analog scale (VAS) and the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot functional scale. The radiographic results were analyzed using Meary’s angle, calcaneal pitch angle, and hindfoot alignment angle. The pathologic conditions of sinus tarsi were confirmed by magnetic resonance imaging (MRI) and subtalar arthroscopy. Synovitis, bone edema, and accessory anterolateral talar facet (AALTF) were evaluated on MRI. Synovial thickening, cartilage damage, interosseous talocalcaneal ligament (ITCL) and cervical ligament rupture, soft tissue impingement, AALTF, and accessory talar facet impingement (ATFI) were evaluated by subtalar arthroscopy. @*Results@#The mean duration of symptoms was 28.7 months (4~120). All patients showed significant improvement in the VAS and AOFAS ankle-hindfoot scale. Significant improvements in hindfoot alignment angle and Meary’s angle postoperatively were noted in patients who underwent medial displacement calcaneal osteotomy. MRI confirmed synovitis in all patients, AALTF in 19 cases (90.5%), and ATFI with bone edema in seven cases (33.3%). In subtalar arthroscopy, pathologic conditions were observed in the following order:synovitis in 21 cases (100%), AALTF in 20 cases (95.2%), ITCL partial rupture in nine cases (42.9%), and soft tissue impingement in seven cases (33.3%). All cases had two or more pathological conditions, and 15 (71.4%) had three or more. @*Conclusion@#In cases of STS that do not respond to conservative treatment, a comprehensive examination of the lesions of the tarsal sinus and lesions around the subtalar joint is essential.

Effectiveness of Live-Streaming Tele-Exercise Intervention in Patients With Parkinson’s Disease: A Pilot Study

Objective@#Exercise can improve both motor and nonmotor symptoms in people with Parkinson’s disease (PwP), but there is an unmet need for accessible and sustainable exercise options. This study aimed to evaluate the effect, feasibility, and safety of a regularly performed live-streaming tele-exercise intervention for PwP. @*Methods@#A live-streaming exercise intervention for PwP was implemented twice a week for 12 weeks. We measured the motor and nonmotor symptom scores of the included patients before and after the intervention. Changes in clinical scores from baseline to postintervention were analyzed using paired t-tests. Factors associated with improvements in clinical scores and compliance were analyzed using Pearson’s correlation analysis. @*Results@#Fifty-six participants were enrolled in the study. There were significant improvements in Hospital Anxiety and Depression Scale (HADS)-anxiety (p = 0.007), HADS-depression (p < 0.001), Unified Parkinson’s Disease Rating Scale (UPDRS) part III (p < 0.001), UPDRS total (p = 0.015), Hoehn and Yahr stage (p = 0.027), and Parkinson’s Disease Fatigue Scale-16 (p = 0.026) scores after the intervention. Improvements in motor symptoms were associated with improvements in mood symptoms and fatigue. Higher motor impairment at baseline was associated with a greater compliance rate and better postintervention composite motor and nonmotor outcomes (ΔUPDRS total score). Overall, the 12-week tele-exercise program was feasible and safe for PwP. No adverse events were reported. The overall adherence rate was 60.0% in our cohort, and 83.4% of the participants were able to participate in more than half of the exercise routines. @*Conclusion@#The live-streaming tele-exercise intervention is a safe, feasible, and effective nonpharmacological treatment option that can alleviate fatigue and improve mood and motor symptoms in PwP.

Adjunctive recombinant human parathyroid hormone agents for the treatment of medication-related osteonecrosis of the jaw: a report of three cases

Teriparatide has been effective in treating people diagnosed with medication-related osteonecrosis of the jaw (MRONJ). However, its efficacy is not well established to be accepted as a standard of care. The objective of this paper was to investigate the efficacy of recombinant human parathyroid hormone for the treatment of MRONJ. We report three cases of MRONJ patients with osteoporosis as the primary disease who were treated with a teriparatide agent along with other adjunctive measures. Each patient was administered a teriparatide injection subcutaneously for 16 weeks, 36 weeks, or 60 weeks. Surgical intervention including partial resection, sequestrectomy, decortication, and saucerization took place during the teriparatide administration. Complete lesion resolution was identified clinically and radiographically in all three patients. In patients diagnosed with MRONJ, teriparatide therapy is an efficacious and safe therapeutic option to improve healing of bone lesions. These findings demonstrate that teriparatide in combination with another therapy, especially bone morphogenetic protein, platelet-rich fibrin, or antibiotic therapy, can be an effective protocol for MRONJ.

Current Status of Public Long-term Care Insurance Services and Future Perspective: A Questionnaire Survey and National Health Insurance Service Data of South Korea

The continuing growth of population aged 65 years and above, the socioeconomic burden of long-term care insurance has consistently increased. This study aimed to review the current system and efficiently develop long-term care insurance services according to changes in socioeconomic situations. First, a 21 items questionnaire survey was conducted from August 16 to August 31, 2022, for all members of the Korean Neurological Association. The survey was divided into seven areas, and individualized results were analyzed. Second, cumulative data on long-term care insurance services were collected and analyzed from July 1, 2008 to December 31, 2021, for the National Health Insurance system, and the results were summarized. In the survey, approximately 21% of the neurologists answered a web-based questionnaire survey on current doctors’ referral slips for long-term insurance services. Most (94%) had doctor referral slips for long-term insurance services. However, the authors estimated that doctors’ referral slips did not sufficiently affect the grading of longterm insurance services. The long-term care insurance services data according to several categories were classified and then, we statistically analyzed the socioeconomic burden of long-term insurance. Those cumulative data showed a gradual increase in the recipient number, diversity of geriatric diseases, and socioeconomic burden. We suggested that it is necessary for the government and academic society to continue to cooperate to develop the long-term care insurance systems for elderly.

Impact of Titer of Toxoplasma Immunoglobulin G on the Diagnosis of Ocular Toxoplasmosis

Purpose@#To assess the impact of toxoplasma immunoglobulin G (IgG) titers on the diagnosis of active ocular toxoplasmosis. @*Methods@#We retrospectively analyzed the medical records of patients tested for toxoplasma IgG at our uveitis clinic. Active ocular toxoplasmosis was clinically diagnosed based on wide-angle fundus photography and disease progression. Patients with IgG titers ≥ 30 IU/mL were classified as seropositive-high titer, those with IgG titers of 1.6-30 IU/mL as seropositive-low titer, and the remaining patients as seronegative. We compared the proportion of active ocular toxoplasmosis among these groups. Additionally, we evaluated the sensitivity and specificity of each titer and attempted to determine an ideal reference titer for toxoplasma IgG in diagnosing active ocular toxoplasmosis. @*Results@#Out of 824 patients, 86 (10.4%), 88 (10.7%), and 650 (78.9%) were categorized as seropositive-high titer, seropositivelow titer, and seronegative, respectively. Among these patients, 34 in the seropositive-high titer group and 2 in the seropositive- low titer group were clinically diagnosed with active ocular toxoplasmosis. The false-positive rate was significantly different between the groups, being 60.5% in the seropositive-high titer group and 97.7% in the seropositive-low titer group (p < 0.001). The receiver operating characteristic curve indicated that 37.70 IU/mL could be an ideal reference titer for diagnosing ocular toxoplasmosis. @*Conclusions@#The false-positive rate was notably lower (60.5%) in patients with IgG titers ≥ 30 IU/mL compared to those with titers of 1.6-30 IU/mL (97.7%). Therefore, not only the presence of IgG but also the level of titer appears to be important in diagnosing ocular toxoplasmosis.

One-year Outcomes of Ultrathin Descemet Stripping Automated Endothelial Keratoplasty Combined with Cataract Surgery in the Korean Population

Purpose@#To evaluate the refractive outcomes after ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) combined with phacoemulsification and intraocular lens implantation (triple procedure) in the South Korean population. @*Methods@#This retrospective observational study included 37 eyes of 36 patients who underwent the UT-DSAEK triple procedure between 2012 and 2021 in a single tertiary hospital. Preoperative and postoperative refractive outcomes and endothelial parameters at 1, 3, 6, and 12 months were observed. @*Results@#At the final postoperative 12-month period, the average best-corrected visual acuity was 0.4 ± 0.5 in logarithm of the minimum angle of resolution. The mean endothelial cell density at 12 months was 1,841.92 ± 731.24 cells/mm2, indicating no significant endothelial cell loss compared to the baseline (p = 0.128). The mean postoperative central corneal thickness at 12 months was 597.41 ± 86.26 μm. The postoperative mean absolute error at 12 months was 0.96 ± 0.89 diopters (D) and mean error was 0.89 ± 0.97 D. @*Conclusions@#The results of our South Korean cohort study on UT-DSAEK triple surgery showed favorable and safe outcomes. Regardless of graft thickness, it should be noted that a hyperopic shift of 1.00 to 2.00 D needs to be considered in the case of UT-DSAEK triple surgery.

Medial Arterial Calcification and the Risk of Amputation of Diabetic Foot Ulcer in Patients With Diabetic Kidney Disease

We assessed the risk factors for major amputation of diabetic foot ulcers (DFUs) in patients with diabetic kidney disease (DKD) stages 3b–5. For DFU assessment, in addition to DFU location and presence of infection, ischemia, and neuropathy, vascular calcification was assessed using the medial arterial calcification (MAC) score. Of 210 patients, 26 (12.4%) underwent major amputations. Only the location and extension of DFU, represented by Texas grade differed between the minor and major amputation groups. However, after adjusting for covariates, ulcer location of mid- or hindfoot (vs. forefoot, odds ratio [OR] = 3.27), Texas grades 2 or 3 (vs. grade 0, OR = 5.78), and severe MAC (vs. no MAC, OR = 4.46) was an independent risk factor for major amputation (all P < 0.05). The current use of antiplatelets was a possible protective factor for major amputations (OR = 0.37, P = 0.055). In conclusion, DFU with severe MAC is associated with major amputation in patients with DKD.

Management of adverse effects in hyperosmolar therapy of brain edema

Mannitol and hypertonic saline are the most frequently used hyperosmolar agents to treat cerebral edema resulting from acute brain injury. However, there are several issues with using hyperosmolar therapies. Here, we focus on the potential adverse effects of hyperosmolar therapies and practical tips to overcome these issues in the neurointensive care unit.Current Concepts: Among the hyperosmolar agents used, mannitol may decrease intravascular volume and pose a potential risk of acute kidney injury for patients. Complications associated with using hypertonic saline include the risk of central pontine myelinolysis, coagulopathy, electrolyte imbalances, metabolic acidosis, and pulmonary edema. In addition, prolonged use of hypertonic saline increases the risk of hyperchloremic metabolic acidosis, which may be overcome with the concomitant use of sodium acetate.Discussion and Conclusion: Several laboratory variables were monitored in the neurointensive care unit to limit and possibly detect early complications related to hyperosmolar therapies. When using hyperosmolar agents, including mannitol and hypertonic saline, for therapeutic purposes in patients with cerebral edema, determining whether to use peripheral or central lines and determining the appropriate rate and infusion dose can minimize their adverse effects. Clinicians need to be aware of the potential adverse events of administering hyperosmolar agents.

Perfluoro-n-octane-assisted Superior Inverted ILM Flap without Using the Peeling-off Technique for Large Macular Holes

Purpose@#To evaluate the surgical outcomes of a perfluoro-n-octane (PFO)-assisted superior inverted internal limiting membrane (ILM) flap without the peeling-off technique for the treatment of a large macular hole (MH). @*Methods@#This retrospective interventional case series examined 13 eyes with a MH ≥ 400 μm. All eyes underwent 25-gauge pars plana vitrectomy. An ILM flap stained with 0.025% brilliant blue G was made in the superior area of the hole. The ILM in the temporal, nasal, and inferior areas around the hole was not peeled off. The hole was gently covered using the inverted ILM flap, which was stabilized using a small amount of PFO. Fluidair exchange was performed slowly. The small amount of residual PFO was removed by evaporation. The patients were instructed to maintain a facedown position for 1 day postoperatively. Anatomical closure of the hole and visual acuity were assessed postoperatively. @*Results@#The average hole size was 605.08 ± 102.41 μm. Nine eyes had an idiopathic MH, two exhibited age-related macular degeneration, and one each had high myopia and a traumatic MH. All eyes achieved type I closure. The foveal contour improved gradually during follow-up: 92.3% of eyes had a U-shaped fovea, and 61.5% exhibited complete recovery of the ellipsoid zone. The visual acuity improved from 0.91 to 0.55 logarithm of the minimum angle of resolution (p = 0.003). @*Conclusions@#The PFO-assisted superior inverted ILM flap without peeling-off was effective for stabilizing the flap over the hole and consequently achieving good anatomical and visual outcomes in large MHs.

The Clinical Outcomes of Marginal Donor Hearts: A Single Center Experience

Background and Objectives@#Although the shortage of donor is a common problem worldwide, a significant portion of unutilized hearts are classified as marginal donor (MD) hearts. However, research on the correlation between the MD and the prognosis of heart transplantation (HTx) is lacking. This study was conducted to investigate the clinical impact of MD in HTx. @*Methods@#Consecutive 73 HTxs during 2014 and 2021 in a tertiary hospital were analyzed.MD was defined as follows; a donor age >55 years, left ventricular ejection fraction 240 minutes, or significant cardiac structural problems. Preoperative characteristics and postoperative hemodynamic data, primary graft dysfunction (PGD), and the survival rate were analyzed. Risk stratification by Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was performed to examine the outcomes according to the recipient state. Each group was sub-divided into 2 risk groups according to the IMPACT score (low <10 vs. high ≥10). @*Results@#A total of 32 (43.8%) patients received an organ from MDs. Extracorporeal membrane oxygenation was more frequent in the non-MD group (34.4% vs. 70.7, p=0.007) There was no significant difference in PGD, 30-day mortality and long-term survival between groups. In the subgroup analysis, early outcomes did not differ between low- and high-risk groups. However, the long-term survival was better in the low-risk group (p=0.01). @*Conclusions@#The outcomes of MD group were not significantly different from non-MD group. Particularly, in low-risk recipient, the MD group showed excellent early and longterm outcomes. These results suggest the usability of selected MD hearts without increasing adverse events.