RNA-Based Sensor Systems for Affordable Diagnostics in the Age of Pandemics.

In the era of the COVID-19 pandemic, the significance of point-of-care (POC) diagnostic tools has become increasingly vital, driven by the need for quick and precise virus identification. RNA-based sensors, particularly toehold sensors, have emerged as promising candidates for POC detection systems due to their selectivity and sensitivity. Toehold sensors operate by employing an RNA switch that changes the conformation when it binds to a target RNA molecule, resulting in a detectable signal. This review focuses on the development and deployment of RNA-based sensors for POC viral RNA detection with a particular emphasis on toehold sensors. The benefits and limits of toehold sensors are explored, and obstacles and future directions for improving their performance within POC detection systems are presented. The use of RNA-based sensors as a technology for rapid and sensitive detection of viral RNA holds great potential for effectively managing (dealing/coping) with present and future pandemics in resource-constrained settings.

Evaluating the validity and reliability of the Korean version of Scales for Outcomes in Parkinson's Disease-Cognition.

Objective: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to screen for cognition in PD. In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPA-cog. Methods: We recruited 129 PD patients from 31 clinics with movement disorders in South Korea. The original version of the SCOPA-cognition was translated into Korean using the translation-retranslation method. The test-rest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. The Spearman's Rank correlation analysis with Montreal Cognitive Assessment-Korean version (MOCA-K) and Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity. Results: The Cronbach's alpha coefficient was 0.797, and the ICC was 0.887. Spearman's rank correlation analysis showed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). Conclusions: Our results demonstrate that K-SCOPA-Cog exhibits good reliability and validity.

Proximal Row Carpectomy with and without Capitate Resurfacing: A Preliminary Systematic Review and Meta-Analysis.

BACKGROUND: In wrist salvage, proximal row carpectomy (PRC) has increasingly shown superior outcomes to four-corner fusion (4CF). Furthermore, PRC with resurfacing capitate pyrocarbon implants (PRC + RCPIs) provides a treatment option that may allow patients to avoid 4CF or wrist arthrodesis and help restore natural joint function and distribute loads evenly across the implant, though RCPI has yet to be evaluated on a large scale. We aimed to compare outcomes between PRC and PRC + RCPI for the treatment of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) wrists. METHODS: A systematic review and meta-analysis was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Embase, Web of Science, and Cochrane were queried for articles on PRC and PRC + RCPI performed for SLAC and SNAC wrist with minimum 12-month follow-up. Primary outcomes included wrist range of motion (ROM), grip strength, and outcome scores including Disabilities of Arm, Shoulder, and Hand (DASH) and QuickDASH scores, Patient-Rated Wrist and Hand Evaluation (PRWHE), and visual analog scale pain scores. RESULTS: Twenty-two studies reporting on 1,804 wrists were included (1,718 PRC alone, 86 PRC + RCPI). PRC + RCPI was associated with greater postoperative radial deviation, but poorer flexion. PRC + RCPI also had significantly lower postoperative QuickDASH (less disability and symptoms) and postoperative PRWHE (lower pain and disability) scores and an improvement in PRWHE compared with PRC. There was no significant difference in grip strength. CONCLUSION: PRC + RCPI demonstrated similar postoperative ROM to PRC alone. While PRC + RCPI was associated with more favorable outcome scores, further research is needed to confirm these findings and assess the incidence and profile of complications related to RCPIs. LEVEL OF EVIDENCE: Level IV. See Instructions for Authors for a complete description of levels of evidence.

Long-term efficacy of encapsulated xenogeneic islet transplantation: Impact of encapsulation techniques and donor genetic traits.

AIMS/INTRODUCTION: To investigate the long-term efficacy of various encapsulated xenogeneic islet transplantation, and to explore the impact of different donor porcine genetic traits on islet transplantation outcomes. MATERIALS AND METHODS: Donor porcine islets were obtained from wild-type, α1,3-galactosyltransferase knockout (GTKO) and GTKO with overexpression of membrane cofactor protein genotype. Naked, alginate, alginate-chitosan (AC), alginate-perfluorodecalin (A-PFD) and AC-perfluorodecalin (AC-PFD) encapsulated porcine islets were transplanted into diabetic mice. RESULTS: In vitro assessments showed no differences in the viability and function of islets across encapsulation types and donor porcine islet genotypes. Xenogeneic encapsulated islet transplantation with AC-PFD capsules showed the most favorable long-term outcomes, maintaining normal blood glucose levels for 180 days. A-PFD capsules showed comparable results to AC-PFD capsules, followed by AC capsules and alginate capsules. Conversely, blood glucose levels in naked islet transplantation increased to >300 mg/dL within a week after transplantation. Naked islet transplantation outcomes showed no improvement based on donor islet genotype. However, alginate or AC capsules showed delayed increases in blood glucose levels for GTKO and GTKO with overexpression of membrane cofactor protein porcine islets compared with wild-type porcine islets. CONCLUSION: The AC-PFD capsule, designed to ameliorate both hypoxia and inflammation, showed the highest long-term efficacy in xenogeneic islet transplantation. Genetic modifications of porcine islets with GTKO or GTKO with overexpression of membrane cofactor protein did not influence naked islet transplantation outcomes, but did delay graft failure when encapsulated.

Opicapone to Treat Early Wearing-off in Parkinson's Disease Patients: The Korean ADOPTION Trial.

BACKGROUND: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. OBJECTIVES: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. METHODS: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. RESULTS: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. CONCLUSIONS: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.

Intraoperative Brainstem Auditory Evoked Potentials and Postoperative Nausea and Vomiting After Microvascular Decompression.

BACKGROUND: We performed this study to investigate the effect of intraoperative brainstem auditory evoked potential (IBAEP) changes on the development of postoperative nausea and vomiting (PONV) after microvascular decompression (MVD) for neurovascular cross compression. METHODS: A total of 373 consecutive cases were treated with MVD. The use of rescue antiemetics after surgery was used as an objective indicator of PONV. IBAEP monitoring was routinely performed in all. RESULTS: The use of rescue antiemetics was significantly associated with female sex (OR = 3.427; 95% CI, 2.077-5.654; P < 0.001), PCA use (OR = 3.333; 95% CI, 1.861-5.104; P < 0.001), and operation time (OR = 1.017; 95% CI, 1.008-1.026; P < 0.001). A Wave V peak delay of more than 1.0 milliseconds showed a significant relation with the use of rescue antiemetics (OR = 1.787; 95% CI, 1.114-2.867; P = 0.016) and a strong significant relation with the use of rescue antiemetics more than 5 times (OR = 2.426; 95% CI, 1.372-4.290; P = 0.002). CONCLUSIONS: A wave V peak delay of more than 1.0 milliseconds might have value as a predictor of PONV after MVD. More detailed neurophysiological studies will identify the exact pathophysiology underlying PONV after MVD.

Long-term control of diabetes by tofacitinib-based immunosuppressive regimen after allo islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets.

Porcine islet xenotransplantation has been highlighted as an alternative to allo islet transplantation. Despite the remarkable progress that has been made in porcine-islet pre-clinical studies in nonhuman primates, immunological tolerance to porcine islets has not been achieved to date. Therefore, allo islet transplantation could be required after the failure of porcine islet xenotransplantation. Here, we report the long-term control of diabetes by allogeneic pancreatic islet transplantation in diabetic rhesus monkeys that rejected previously transplanted porcine islets. Four diabetic male rhesus monkeys received the porcine islets and then allo islets (5700-19 000 IEQ/kg) were re-transplanted for a short or long period after the first xeno islet rejection. The recipient monkeys were treated with an immunosuppressive regimen consisting of ATG, humira, and anakinra for induction, and sirolimus and tofacitinib for maintenance therapy. The graft survival days of allo islets in these monkeys were >440, 395, >273, and 127, respectively, similar to that in allo islet transplanted cynomolgus monkeys that received the same immunosuppressive regimen without xeno sensitization. Taken together, it is likely that prior islet xenotransplantation does not affect the survival of subsequent allo islets under clinically applicable immunosuppressants.

Variable Return to Play and Sport Performance After Elbow Ulnar Collateral Ligament Reconstruction in Baseball Players: A Systematic Review.

PURPOSE: To evaluate return to play (RTP) and return to same level of play (RTSP) rates as well as preoperative and postoperative in-game performance metrics in baseball pitchers who underwent ulnar collateral ligament reconstruction (UCLR). Secondarily, this review sought to assess outcomes based on primary versus revision UCLR as well as level of competition. METHODS: This review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Embase, Web of Science, and Cochrane Database of Systematic Reviews were queried to identify articles evaluating UCLR in baseball players between January 2002 and October 2022. Data included RTP, RTSP, and performance metrics including earned run average, innings pitched, walks and hits per inning pitched, batting average against, strikeouts per 9 innings, walks per 9 innings, percentage of fastballs thrown, and average fastball velocity. The Methodological Index for Non-randomized Studies criteria were used for quality assessment. RESULTS: Analysis included 25 articles reporting on 2,100 elbows. After primary UCLR, RTP ranged from 336 to 615 days (57% to 100% achieved) and RTSP ranged from 330 to 513 days (61% to 95%). After revision UCLR, RTP ranged from 381 to 631 days (67% to 98%) and RTSP ranged from 518 to 575 days (42% to 78%). When stratifying primary UCLR outcomes by competitive level, RTP and RTSP ranged respectively from 417 to 615 days (75% to 100%) and 513 days (73% to 87%) for Major League Baseball only, 409 to 615 days (57% to 100%) and 470 to 513 days (61% to 95%) for Major League Baseball plus Minor League Baseball, and 336 to 516 days (73% to 85%) and 330 days (55% to 74%) for college plus high school. Heterogeneity was seen in postoperative sports performance metrics. CONCLUSIONS: Although more than half of baseball players appear able to RTP after primary and revision UCLR, RTSP rates after revision UCLR were as low as 42% in the literature. Preoperative and postoperative performance metrics varied. LEVEL OF EVIDENCE: Level IV, systematic review.

Four-Corner Fusion Versus Proximal Row Carpectomy for Scapholunate Advanced Collapse and Scaphoid Nonunion Advanced Collapse Wrist: A Systematic Review and Meta-Analysis.

PURPOSE: Although proximal row carpectomy (PRC) has increasingly been shown to have superior features to four-corner fusion (4CF), individual surgeons may remain convinced of the superiority of one procedure based on personal experience and individual biases. Hence, we sought to perform an updated meta-analysis with some of the largest studies to date to compare outcomes and complications between these procedures in the treatment of scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists. METHODS: A systematic review and meta-analysis was performed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed/MEDLINE, Embase, Web of Science, and Cochrane were queried for articles on PRC and 4CF performed for scapholunate advanced collapse and scaphoid nonunion advanced collapse wrist. Primary outcomes included wrist range of motion; grip strength; outcome measures, including Disabilities of Arm, Shoulder, and Hand and Quick Disabilities of Arm, Shoulder, and Hand scores, Patient-Rated Wrist and Hand Evaluation, and visual analog scale pain scores; and surgical complications. RESULTS: Sixty-one studies reported on 3,174 wrists, of which 54% were treated with PRC and 46% were treated with 4CF. The weighted mean follow-up was 61 months (range, 12-216 months). Meta-analysis comparing PRC and 4CF demonstrated that PRC had significantly greater postoperative extension; ulnar deviation; postoperative improvement in extension, flexion, ulnar deviation; and visual analog scale score. No comparisons showed significant differences in grip strength. The percentage of wrists requiring arthrodesis was 5.2% for PRC and 11% for 4CF. There was an 8.9% (57/640 wrists) 4CF nonunion rate and 2.2% (17/789) hardware removal rate after 4CF. CONCLUSIONS: In the treatment of scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists, PRC results in better outcomes and a lower complication rate compared to 4CF. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Fully-automated multi-organ segmentation tool applicable to both non-contrast and post-contrast abdominal CT: deep learning algorithm developed using dual-energy CT images.

A novel 3D nnU-Net-based of algorithm was developed for fully-automated multi-organ segmentation in abdominal CT, applicable to both non-contrast and post-contrast images. The algorithm was trained using dual-energy CT (DECT)-obtained portal venous phase (PVP) and spatiotemporally-matched virtual non-contrast images, and tested using a single-energy (SE) CT dataset comprising PVP and true non-contrast (TNC) images. The algorithm showed robust accuracy in segmenting the liver, spleen, right kidney (RK), and left kidney (LK), with mean dice similarity coefficients (DSCs) exceeding 0.94 for each organ, regardless of contrast enhancement. However, pancreas segmentation demonstrated slightly lower performance with mean DSCs of around 0.8. In organ volume estimation, the algorithm demonstrated excellent agreement with ground-truth measurements for the liver, spleen, RK, and LK (intraclass correlation coefficients [ICCs] > 0.95); while the pancreas showed good agreements (ICC = 0.792 in SE-PVP, 0.840 in TNC). Accurate volume estimation within a 10% deviation from ground-truth was achieved in over 90% of cases involving the liver, spleen, RK, and LK. These findings indicate the efficacy of our 3D nnU-Net-based algorithm, developed using DECT images, which provides precise segmentation of the liver, spleen, and RK and LK in both non-contrast and post-contrast CT images, enabling reliable organ volumetry, albeit with relatively reduced performance for the pancreas.

The relevance of structural variability in the time-domain for computational reflection anisotropy spectroscopy at solid-liquid interfaces.

In electrochemistry, reactions and charge-transfer are to a large extent determined by the atomistic structure of the solid-liquid interface. Yet due to the presence of the liquid electrolyte, many surface-science methods cannot be applied here. Hence, the exact microscopic structure that is present under operating conditions often remains unknown. Reflection anisotropy spectroscopy (RAS) is one of the few techniques that allow for anin operandoinvestigation of the structure of solid-liquid interfaces. However, an interpretation of RAS data on the atomistic scale can only be obtained by comparison to computational spectroscopy. While the number of computational RAS studies related to electrochemical systems is currently still limited, those studies so far have not taken into account the dynamic nature of the solid-liquid interface. In this work, we investigate the temporal evolution of the spectroscopic response of the Au(110) missing row reconstruction in contact with water by combiningab initiomolecular dynamics with computational spectroscopy. Our results show significant changes in the time evolution of the RA spectra, in particular providing an explanation for the typically observed differences in intensity when comparing theory and experiment. Moreover, these findings point to the importance of structural surface/interface variability while at the same time emphasising the potential of RAS for probing these dynamic interfaces.

Endothelial periostin regulates vascular remodeling by promoting endothelial dysfunction in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling associated with extracellular matrix (ECM) deposition, vascular cell hyperproliferation, and neointima formation in the small pulmonary artery. Endothelial dysfunction is considered a key feature in the initiation of vascular remodeling. Although vasodilators have been used for the treatment of PAH, it remains a life-threatening disease. Therefore, it is necessary to identify novel therapeutic targets for PAH treatment. Periostin (POSTN) is a secretory ECM protein involved in physiological and pathological processes, such as tissue remodeling, cell adhesion, migration, and proliferation. Although POSTN has been proposed as a potential target for PAH treatment, its role in endothelial cells has not been fully elucidated. Here, we demonstrated that POSTN upregulation correlates with PAH by analyzing a public microarray conducted on the lung tissues of patients with PAH and biological experimental results from in vivo and in vitro models. Moreover, POSTN overexpression leads to ECM deposition and endothelial abnormalities such as migration. We found that PAH-associated endothelial dysfunction is mediated at least in part by the interaction between POSTN and integrin-linked protein kinase (ILK), followed by activation of nuclear factor-κB signaling. Silencing POSTN or ILK decreases PAH-related stimuli-induced ECM accumulation and attenuates endothelial abnormalities. In conclusion, our study suggests that POSTN serves as a critical regulator of PAH by regulating vascular remodeling, and targeting its role as a potential therapeutic strategy for PAH.

Midterm Clinical and Radiological Outcomes of Revision Lateral Meniscal Allograft Transplantation.

Background: It is unknown whether the outcomes achieved in the early period after revision lateral meniscal allograft transplantation (RLMAT) are maintained through the midterm period. Purpose: To evaluate the midterm clinical and radiological results of patients who underwent RLMAT. Study Design: Case series; Level of evidence, 4. Methods: We reviewed the outcomes of 19 RLMATs in 18 patients with at least 5 years of follow-up data. The mean follow-up period was 6 ± 1.1 years (range, 5-8.5 years). Clinical outcomes were assessed using the modified Lysholm score, the International Knee Documentation Committee (IKDC) subjective score, and the Tegner activity level. Radiographic progression of arthritis was measured by the absolute and relative joint space widths on 45° of knee flexion posteroanterior radiographs preoperatively, 1 year postoperatively, and at the latest follow-up.Failure was defined as meniscocapsular separation, removal, or tear of more than half of the meniscal allograft on postoperative magnetic resonance imaging (MRI) or conversion to total knee arthroplasty. Of the 18 patients, 3 underwent ≥2 RLMATs. The survival rate was evaluated according to the number of revision surgeries. Results: For knees with an intact meniscus transplant at the final follow-up, the modified Lysholm and IKDC scores were significantly improved compared with preoperatively, but the Tegner activity level was unchanged. No significant differences were found in the absolute and relative joint space widths postoperatively. There were 6 failures within 3 years after RLMAT; the overall 5-year survival rate was 68.4% (13/19 knees). All failed knees showed bucket-handle tear patterns on MRI due to meniscocapsular healing failure. The survival rate decreased as the number of RLMATs increased-73.3% for a first RLMAT (n = 15 knees), 66.7% for a second RLMAT (n = 3 knees), and 0% for a third RLMAT (n = 1 knee). Midterm MRIs of 8 well-healed RLMATs showed evidence of meniscal degeneration; nonetheless, this did not affect clinical outcomes. Conclusion: The midterm results of RLMATs demonstrated a 5-year survival rate of 68.4% and positive clinical and radiological outcomes for failed MATs despite unimproved activity levels. Inadequate meniscocapsular healing was the leading cause of failure, and it needs to be carefully considered when performing RLMATs.

Risk Factor for Clinical Failure of Medial Meniscal Allograft Transplant: Early vs Late Graft Tear.

BACKGROUND: Graft tears are common postoperative findings in meniscal allograft transplant (MAT). Graft tear in medial MAT may be different from that of lateral MAT, considering the difference between medial meniscal tears and lateral meniscal tears. Moreover, medial MAT is frequently accompanied by ligament reconstruction, which is associated with graft tear. The effect of graft tear on the long-term survivorship of medial MAT has not been investigated. HYPOTHESIS: Graft tear would adversely affect the survivorship of medial MAT and the effect would be different according to the timing of graft tear. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 55 patients undergoing medial MAT between June 2019 and March 2000 were retrospectively reviewed. Postoperative magnetic resonance imaging (MRI) scans were reviewed to identify graft tears, and the timing of their occurrence was investigated. Postoperative MRI was performed routinely during the first postoperative year and every 2 years thereafter. The patients were classified into a no graft tear (NT) group, early graft tear (occurring within 1 year; ET) group, and late graft tear (occurring 1 year after surgery; LT) group. The survival rate of medial MAT was estimated according to graft tear, with a failure being defined as (1) reoperations including arthroplasty, realignment osteotomy, revision MAT, and meniscectomy (>50% of the graft or to the zone of the meniscocapsular junction) or (2) Lysholm score <65. Clinical scores were compared between the groups. RESULTS: The mean follow-up duration was 8.6 ± 5.3 years. During that period, clinical failures occurred in 6 (10.9%) patients. The overall survival rate at 5 years was 94.0% (95% CI, 90.6%-97.4%). Graft tears were seen in 18 patients: 6 patients in the ET group and 12 patients in the LT group. The median time when the graft tear was noted on MRI scans was 5.5 months (range, 1-11 months) postoperatively in the ET group and 99.5 months (range, 19-264 months) postoperatively in the LT group. Five patients in the ET group had root tears, whereas 9 patients in the LT group had complex or horizontal tears. The 5-year survival rate of the ET group was 62.5% (95% CI, 41.2%-83.8%), which was significantly lower than that of the NT group (96.8%; 95% CI, 93.6%-99.9%) and the LT group (85.7%; 95% CI, 72.5%-98.9%; P = .002). The mean postoperative Lysholm scores were 85.6 ± 17.9 in the NT group, 93.0 ± 2.8 in the ET group, and 79.3 ± 11.6 in the LT group, showing no significant difference between the groups (Kruskal-Wallis test, P = .058). CONCLUSION: Clinical relevance of graft tear that occurred after medial MAT was dependent upon its timing. ET was a risk factor for clinical failure, whereas LT did not adversely affect graft survivorship. Lysholm scores did not differ according to graft tear.

Cytokine storm syndrome after anti-thymoglobulin infusion in a cynomolgus monkey with systemic lymphadenopathy caused by follicular hyperplasia: A case report.

Nonhuman primates are widely used in transplantation research as preclinical xeno- or allo-transplantation models. Rabbit anti-thymoglobulin (ATG) is often used for T-cell depletion as an immunosuppressant. T-cell depletion can cause a secondary cytokine storm syndrome that can be minimized/prevented by a prophylactic administration of systemic corticosteroids and antihistamines. We report a case of death due to CSS in a cynomolgus monkey with follicular hyperplasia-induced systemic lymphadenopathy after ATG administration. A 6-year-old female cynomolgus monkey was rendered diabetic and then transplanted with a genetically modified porcine pancreatic islets (PPI) (50 000 IEQ/kg) through the portal vein 22 days later without immunosuppressant. Because graft function was not comparable, we planned re-transplantation of PPI. For re-transplantation of the PPI, we performed an intravenous (IV) ATG infusion for inductive immunosuppression. The monkey died 3 h and 30 min after ATG administration despite cardiopulmonary resuscitation. Systemic lymphadenopathy was observed on submandibular, axillary, inguinal, foregut, colic, and hilar lymph nodes, and splenomegaly was also observed on necropsy. Histopathologic examination of the lymph node revealed follicular hyperplasia. The IL-6 level was higher after ATG infusion compared to before ATG infusion (before vs. after ATG infusion; 14.9 vs. >5000 pg/mL). The death of the cynomolgus monkey was caused by severe CSS because of apoptosis of B cells in the systemic lymph nodes caused by the ATG administration. A thorough physical examination of palpable lymph nodes and pre-ATG sonographic or computed tomographic screening could have identified lymphadenopathy, potentially preventing its infusion and reducing mortality risk.

Lateral Distance From the Osteotomy Hinge Point to the Tibial Cortex Is Associated With Lateral Hinge Fracture Type and Fracture Occurrence Time After Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To verify whether the distance from the hinge point to the tibial cortex affects the occurrence time and characteristics of the lateral hinge fracture (LHF) in medial open-wedge high tibial osteotomy. METHODS: We retrospectively reviewed 171 knees in 171 patients (121 women, 50 men; mean age, 53.9 years; range, 36-67 years) who had undergone medial open-wedge high tibial osteotomy with locking plate fixation between January 2011 and December 2020. Osteotomy hinge point and LHFs were identified on intraoperative fluoroscopy and immediate postoperative radiographs. LHF type was classified as suggested by Takeuchi et al. Acute fracture was defined as a fracture that occurred during surgery, and delayed fracture was defined as a fracture observed after 1 month postoperatively. The nearest distances from osteotomy hinge point to lateral, distal, and proximal cortex were measured on postoperative radiographs. We compared the distance between the different types and between acute and delayed LHFs. RESULTS: There were 55 LHFs (32%) (type I, 40 knees; type II, 14 knees; type III, 1 knee) that occurred acutely in 41 knees and were found as delayed fractures in 14 knees. The patient demographics were not significantly different between non-LHFs and each type of LHFs. Proximal and distal distances were not statistically different among fracture types and between occurrence times. However, lateral distances were significantly shorter in type I LHFs (6.2 ± 1.8 mm) and longer in type II LHFs (9.3 ± 2.3 mm) than in non-LHFs (7.1 ± 2.7 mm) (P = .020 and .004, respectively). The lateral cortical distances were also different between acute LHFs (6.4 ± 1.9 mm) and delayed LHF (9.0 ± 2.7 mm) (P < .001). In the case of fracture type, the frequency of type I decreases with increase in the lateral distance, whereas that of type II increases with increase in the lateral cortical distance. In acute fracture, type I was dominant (85.4%), whereas in delayed fracture, type II was dominant (57.2%). CONCLUSIONS: The lateral cortical distance from the hinge point was significantly associated with LHF occurrence. Shorter distance increased the risk for acute type I LHF, whereas longer distance increased the risk for delayed type II LHFs. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

The novel HLA-A*30:01:25 allele found in a Korean hematopoietic stem cell recipient.

The novel HLA-A*30:01:25 allele differs from HLA-A*30:01:01:01 by a single nucleotide substitution located within exon 2, codon 1.

Three-dimensional body composition parameters using automatic volumetric segmentation allow accurate prediction of colorectal cancer outcomes.

BACKGROUND: Parameters obtained from two-dimensional (2D) cross-sectional images have been used to determine body composition. However, data from three-dimensional (3D) volumetric body images reflect real body composition more accurately and may be better predictors of patient outcomes in cancer. This study aimed to assess the 3D parameters and determine the best predictive factors for patient prognosis. METHODS: Patients who underwent surgery for colorectal cancer (CRC) between 2010 and 2016 were included in this study. Preoperative computed tomography images were analysed using an automatic segmentation program. Body composition parameters for muscle, muscle adiposity, subcutaneous fat (SF) and abdominal visceral fat (AVF) were assessed using 2D images at the third lumbar (L3) level and 3D images of the abdominal waist (L1-L5). The cut-off points for each parameter were determined using X-tile software. A Cox proportional hazards regression model was used to identify the association between the parameters and the treatment outcomes, and the relative influence of each parameter was compared using a gradient boosting model. RESULTS: Overall, 499 patients were included in the study. At a median follow-up of 59 months, higher 3D parameters of the abdominal muscles and SF from the abdominal waist were found to be associated with longer overall survival (OS) and disease-free survival (all P < 0.001). Although the 3D parameters of AVF were not related to survival outcomes, patients with a high AVF volume and mass experienced higher rate of postoperative complications than those with low AVF volume (27.4% vs. 18.7%, P = 0.021, for mass; 27.1% vs. 19.0%, P = 0.028, for volume). Low muscle mass and volume (hazard ratio [HR] 1.959, P = 0.016; HR 2.093, P = 0.036, respectively) and low SF mass and volume (HR 1.968, P = 0.008; HR 2.561, P = 0.003, respectively), both in the abdominal waist, were identified as independent prognostic factors for worse OS. Along with muscle mass and volume, SF mass and volume in the abdominal waist were negatively correlated with mortality (all P < 0.001). Both AVF mass and volume in the abdominal waist were positively correlated with postoperative complications (P < 0.05); 3D muscle volume and SF at the abdominal waist were the most influential factors for OS. CONCLUSIONS: 3D volumetric parameters generated using an automatic segmentation program showed higher correlations with the short- and long-term outcomes of patients with CRC than conventional 2D parameters.

Is Autophagy a Prerequisite for Steroidogenesis in Leydig Cells?

We investigated the involvement of autophagy with steroidogenesis in testicular Leydig cells. Human chorionic gonadotropin (hCG)-stimulated T production in Leydig cells was not remarkably altered in the presence of an autophagy inhibitor 3-methyladenine (3-MA). Although pretreatment with 3-MA demonstrated a tendency to decrease hCG-induced T production, the differences were significant only at a higher time point of 24 h following hCG. Microtubule associated protein light chain 3 (LC3)-II was detectable in the control cells in all the experiments. The hCG-induced increase in steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleave (P450scc) protein levels were not significantly altered by 3-MA. Leydig cells isolated from immature rat testes 12 h following hCG treatment showed relatively increased levels of LC3-II protein compared to the control group. Furthermore, LC3-II levels shown in these cells reached almost the identical to those from normal adult testes. However, LC3-II protein levels were almost comparable or even slightly lower than the controls at 48 h following hCG. Expression of StAR and P450scc was upregulated at both 12 and 48 h after hCG. We also used MA-10 cells, the mouse Leydig cell line, in this experiment. When dibutyryl cyclic-AMP was treated with MA-10 cells, P4 levels were significantly increased in the cell culture medium. However, P4 levels tended to decrease in the presence of 3-MA, but the difference was not statistically significant. This was consistent with the results of the rat Leydig cell experiments. Together, we believe that although autophagy participates in steroidogenesis and enhances steroidogenic efficacy of Leydig cells, it may not be a decisive cellular process for steroidogenesis, specifically in the mature Leydig cells.