FcRY is a key molecule controlling maternal blood IgY transfer to yolks during egg development in avian species.

Maternal immunoglobulin transfer plays a key role in conferring passive immunity to neonates. Maternal blood immunoglobulin Y (IgY) in avian species is transported to newly-hatched chicks in two steps: 1) IgY is transported from the maternal circulation to the yolk of maturing oocytes, 2) the IgY deposited in yolk is transported to the circulation of the embryo via the yolk sac membrane. An IgY-Fc receptor, FcRY, is involved in the second step, but the mechanism of the first step is still unclear. We determined whether FcRY was also the basis for maternal blood IgY transfer to the yolk in the first step during egg development. Immunohistochemistry revealed that FcRY was expressed in the capillary endothelial cells in the internal theca layer of the ovarian follicle. Substitution of the amino acid residue in Fc region of IgY substantially changed the transport efficiency of IgY into egg yolks when intravenously-injected into laying quail; the G365A mutant had a high transport efficiency, but the Y363A mutant lacked transport ability. Binding analyses of IgY mutants to FcRY indicated that the mutant with a high transport efficiency (G365A) had a strong binding activity to FcRY; the mutants with a low transport efficiency (G365D, N408A) had a weak binding activity to FcRY. One exception, the Y363A mutant had a remarkably strong binding affinity to FcRY, with a small dissociation rate. The injection of neutralizing FcRY antibodies in laying quail markedly reduced IgY uptake into egg yolks. The neutralization also showed that FcRY was engaged in prolongation of half-life of IgY in the blood; FcRY is therefore a multifunctional receptor that controls avian immunity. The pattern of the transport of the IgY mutants from the maternal blood to the egg yolk was found to be identical to that from the fertilized egg yolk to the newly-hatched chick blood circulation, via the yolk sac membrane. FcRY is therefore a critical IgY receptor that regulates the IgY uptake from the maternal blood circulation into the yolk of avian species, further indicating that the two steps of maternal-newly-hatched IgY transfer are controlled by a single receptor.

The tibial tubercle-to-trochlear groove distance changes in standing weight-bearing condition: An upright weight-bearing computed tomography analysis.

BACKGROUND: The tibial tubercle-to-trochlear groove (TT-TG) distance and Insall-Salvati (I/S) ratio are widely used to determine the need for distal realignment in conjunction with medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent patellar dislocation. A TT-TG distance >20 mm and an I/S ratio >1.3 are significant anatomical risk factors for patellar instability. However, these parameters have traditionally been measured using non-weight-bearing (NWB) imaging modalities. As patellar dislocation occurs during weight-bearing actions, these two parameters should be measured under weight-bearing conditions. Thus, this study aimed to measure the TT-TG distance and I/S ratio using upright full-weight-bearing (FWB) computed tomography (CT) scans and compare the data with NWB CT scans. METHODS: This study included 49 knee joints of 26 healthy volunteers. CT images were obtained under both FWB and NWB standing conditions using a 320-detector row upright CT scanner. TT-TGs in the axial plane and I/S ratios in the sagittal plane were measured and compared. RESULTS: The average FWB TT-TG distance was 20.3 ± 3.9 mm, whereas the average NWB TT-TG distance was 12.3 ± 4.7 mm. The TT-TG level was significantly higher in the FWB condition than that in the NWB condition (P < 0.001). The I/S ratios were comparable between the FWB and NWB conditions (P = 0.29). CONCLUSIONS: The TT-TG distance in the standing weight-bearing condition was larger than the conventional TT-TG distance and surpassed the historical cutoff value of TT-TG, which may affect the indication of additional distal realignment in MPFL reconstruction for patellar instability.

Smaller hypothalamic subregion with paraventricular nucleus in patients with panic disorder.

In panic disorder (PD), functional disturbance of the hypothalamus-pituitary-adrenal (HPA) axis has been considered. However, in neuroimaging studies of PD, the hypothalamus and pituitary gland are poorly studied.We investigated the volume of PD patients' hypothalamus and pituitary gland, enrolling 38 PD patients and 38 healthy controls. Severity of PD was mild to moderate according to the Panic Disorder Severity Scale, and the illness duration was relatively short (median = 2.8 years). The hypothalamus' gray matter was automatically extracted and segmented, whereas the pituitary gland was manually traced. Regarding the hypothalamus, the paraventricular nucleus (PVH), which produces the corticotropin-releasing hormone, was of interest.The volumes of the pituitary and the bilateral anterior-superior hypothalamic subunits, where the PVH would be located, were compared by the multiple regression analyses controlling for age and intracranial content volume. To compensate for limitation in the abovementioned segmentation and analyses, the voxel-based morphometry with small volume correction (VBM-SVC) targeting the whole hypothalamus was also performed.The multiple regression analyses did not find significant effect of PD diagnosis on the volumes. However, in the VBM-SVC analysis, volume reduction of the PVH was suggested in PD even when patients who experienced PD for ≥ 3 years were excluded [peak coordinate (x, y, z = -2, 3, -8), FWE-corrected P = .022 (cluster-level) and 0.003 (peak-level), voxel size = 63]. Our results suggested structural alteration of the PVH in PD patients for the first time, indicating importance of the HPA-axis in PD pathology.

New Implications of Metabolites and Free Fatty Acids in Quality Control of Crossbred Wagyu Beef during Wet Aging Cold Storage.

Efficient cold-chain delivery is essential for maintaining a sustainable global food supply. This study used metabolomic analysis to examine meat quality changes during the "wet aging" of crossbred Wagyu beef during cold storage. The longissimus thoracic (Loin) and adductor muscles (Round) of hybrid Wagyu beef, a cross between the Japanese Black and Holstein-Friesian breeds, were packaged in vacuum film and refrigerated for up to 40 days. Sensory evaluation indicated an increase in the umami and kokumi taste owing to wet aging. Comprehensive analysis using gas chromatography-mass spectrometry identified metabolite changes during wet aging. In the Loin, 94 metabolites increased, and 24 decreased; in the Round, 91 increased and 18 decreased. Metabolites contributing to the umami taste of the meat showed different profiles during wet aging. Glutamic acid increased in a cold storage-dependent manner, whereas creatinine and inosinic acid degraded rapidly even during cold storage. In terms of lipids, wet aging led to an increase in free fatty acids. In particular, linoleic acid, a polyunsaturated fatty acid, increased significantly among the free fatty acids. These results provide new insight into the effects of wet aging on Wagyu-type beef, emphasizing the role of free amino acids, organic acids, and free fatty acids generated during cold storage.

Unfractionated Heparin Safety in COVID-19: Incidence and Risks of Bleeding Complications in Japan.

AIM: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH. METHODS: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality. RESULTS: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P ＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test). CONCLUSIONS: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Low-intensity pulsed ultrasound phonophoresis with diclofenac alleviated inflammation and pain via downregulation of M1 macrophages in rats with carrageenan-induced knee joint arthritis.

Objective: This study aimed to investigate the effects of low-intensity pulsed ultrasound (LIPUS) phonophoresis with diclofenac on inflammation and pain in the acute phase of carrageenan-induced arthritis in rats. Design: 60 male Wistar rats were randomly divided into the arthritis, diclofenac, LIPUS, phonophoresis, and sham-arthritis control groups. LIPUS and transdermal diclofenac gel were applied to the lateral side of the inflamed knee for 7 days, initiated postinjection day 1. In the phonophoresis group, diclofenac gel was rubbed onto the skin, followed by LIPUS application over the medication. Knee joint transverse diameters, pressure pain thresholds (PPTs), and paw withdrawal thresholds (PWT) were evaluated. The number of CD68-, CD11c-, and CD206-positive cells, and IL-1ß and COX-2 mRNA expression were analyzed 8 days after injection. Results: In the phonophoresis group, the transverse diameter, PPT, PWT significantly recovered at the day 8 compared to those in the LIPUS and diclofenac groups. The number of CD68- and CD11c-positive cells in the phonophoresis group was significantly lower than that in the LIPUS and diclofenac groups, but no significant differences were observed among three groups in CD206-positive cells. IL-1ß and COX-2 mRNA levels were lower in the phonophoresis group than in the arthritis group, although there were no differences among the LIPUS, diclofenac, and phonophoresis groups. Conclusion: LIPUS phonophoresis with diclofenac is more effective to ameliorate inflammation and pain compared to diclofenac or LIPUS alone, and the mechanism involves the decrease of M1 macrophages.

Varying impact of lenvatinib or sorafenib therapy on skeletal muscle loss in patients with hepatocellular carcinoma.

BACKGROUND: Lenvatinib and sorafenib are key therapeutic agents for hepatocellular carcinoma. However, there are no useful biomarkers for selecting molecular-targeted agents (MTAs). Skeletal muscle volume is associated with the clinical outcomes in these patients. We investigated the effects of lenvatinib and sorafenib on the skeletal muscles of patients with HCC. METHODS: We evaluated the impact of skeletal muscle changes over a 3-month period for each MTA (n = 117; lenvatinib/sorafenib, 45/72). The skeletal muscle mass index (SMI) was measured at the third lumbar vertebra. Furthermore, we evaluated the direct effect of each MTA on primary human skeletal muscle cells by estimating muscle protein synthesis using western blot analysis. RESULTS: The median change in SMI was -0.7% (p = 0.959) and -5.9% (p <0.001) for the lenvatinib and sorafenib groups, respectively. Sorafenib had a greater effect on skeletal muscle loss than lenvatinib (p < 0.001). Additionally, SMI significantly decreased in the sorafenib group regardless of initial skeletal muscle volume (p < 0.001), whereas no significant differences were observed in the lenvatinib group. Sorafenib therapy (odds ratio [OR], 2.98; p = 0.023) and non-muscle depletion (OR, 3.31; p = 0.009) were associated with a decreased SMI. In vitro analysis showed that sorafenib negatively affected muscle synthesis compared to lenvatinib. CONCLUSIONS: Sorafenib may have a more negative effect on skeletal muscle than lenvatinib.

Balancing risk-return decisions by manipulating the mesofrontal circuits in primates.

Decision-making is always coupled with some level of risk, with more pathological forms of risk-taking decisions manifesting as gambling disorders. In macaque monkeys trained in a high risk-high return (HH) versus low risk-low return (LL) choice task, we found that the reversible pharmacological inactivation of ventral Brodmann area 6 (area 6V) impaired the risk dependency of decision-making. Selective optogenetic activation of the mesofrontal pathway from the ventral tegmental area (VTA) to the ventral aspect of 6V resulted in stronger preference for HH, whereas activation of the pathway from the VTA to the dorsal aspect of 6V led to LL preference. Finally, computational decoding captured the modulations of behavioral preference. Our results suggest that VTA inputs to area 6V determine the decision balance between HH and LL.

Reverse Shock Index multiplied by Glasgow Coma Scale score as a point-of-care severity assessment for initial trauma management: A nationwide cohort study.

BACKGROUND: Severe trauma patients often require emergent interventions, such as massive transfusion, resuscitative procedures, and surgical procedures, and consume considerable human and medical resources. However, few practical indices can be easily used for emergent interventions. In recent years, it has become clear that rSIG (Reverse Shock Index multiplied by Glasgow Coma Scale [GCS] score), which can be easily calculated from vital signs, is a promising predictor of mortality. However, it is unclear whether rSIG is useful for emergent interventions. METHODS: Data collected by the Japan Trauma Data Bank for adult patients admitted directly from the scene of trauma between April 2019 and December 2020 were analysed. The outcomes were massive transfusion, resuscitative procedures, surgical procedures and emergent interventions. Emergent interventions were defined as the composite outcome of massive transfusion, resuscitative procedures, and surgical procedures. The ability of rSIG to predict massive transfusion was compared with that of the ABC score and FASILA score by receiver-operating characteristic curve analysis. The ability of rSIG to predict resuscitative and surgical procedures was compared with that of the Shock Index (SI), GCS, Triage Revised Trauma score (T-RTS), and Previous Simple Prediction (PSP) score. The ability of rSIG to predict emergent interventions was compared with that of T-RTS, PSP, ABC, and FASILA. In addition to rSIG, rSIM (Reverse Shock Index multiplied by best motor response score) was also analysed as a supplement. RESULTS: The study included 32,201 patients, 6,371 of whom required emergent interventions. The area under the receiver-operating characteristic curve (AUROC) for massive transfusion was highest for rSIG (0.846 [95 % confidence interval 0.832-0.859]) and significantly higher for rSIG than for rSIM, ABC and FASILA (all p < 0.0001). AUROCs for resuscitative and surgical procedures were highest for rSIG (0.777 [0.769-0.785] and 0.731 [0.720-0.741], respectively) and significantly higher than those for rSIM, SI, GCS, T-RTS, and PSP (all p < 0.0001). The AUROC for emergent interventions was highest for rSIG (0.760 [0.753-0.768]) and significantly higher for rSIG than for rSIM, T-RTS, PSP, ABC, or FASILA (all p < 0.0001). CONCLUSIONS: rSIG is a simple and effective point-of-care predictor of emergent interventions during initial management of trauma.

Novel dry EEG electrode with composite filler of PEDOT:PSS and carbon particles.

We have developed a novel composite filler with Poly(3,4-ethylenedioxythiophene) : poly(styrenesulfonic acid) (PEDOT:PSS), a biocompatible organic conductive polymer, adsorbed on carbon particles for biological electrodes. This composite filler enables to fabricate high-performance biological electrodes simply by adding it to resin in the same way as conventional conductive fillers. The fabricated electrodes achieve ion exchange properties similar to those of PEDOT:PSS polymers and therefore low skin and electrode contact impedance. Electroencephalogram (EEG) measurements show that these electrodes capture various brain activities and exhibit high correlation (≥ 0.9) to commercially available wet and AgCl electrodes. Additionally, each electrode can be molded into various shapes and structures while retaining its electrode characteristics. Therefore, the proposed electrode is promising for EEG measurement, which requires high comfort and signal quality.

Safety and Clinical Effects of a Muse Cell-Based Product in Patients With Amyotrophic Lateral Sclerosis: Results of a Phase 2 Clinical Trial.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of motor neurons. Multilineage-differentiating stress-enduring (Muse) cells are unique endogenous stem cells that show therapeutic effects on motor function in ALS mouse models. We conducted a single-center open phase II clinical trial to evaluate the safety and clinical effects of repeated intravenous injections of an allogenic Muse cell-based product, CL2020, in patients with ALS. Five patients with ALS received CL2020 intravenously once a month for a total of six doses. The primary endpoints were safety and tolerability, and the secondary endpoint was the rate of change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score. In addition, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), sphingosine-1-phosphate (S1P), cerebrospinal fluid chitotriosidase-1 (CHIT-1), and neurofilament light chain (NfL) levels were evaluated. The CL2020 treatment was highly tolerated without serious side effects. The ALSFRS-R score change trended upward at 12 months post-CL2020 treatment compared with that at 3 months pre-administration, but the difference was not statistically significant. Among five patients diagnosed with ALS, three exhibited a decrease in the rate of ALSFRS-R score change, one demonstrated an increase, and another showed no change. In addition, the patients' serum IL-6 and TNF-α levels and cerebrospinal fluid CHIT-1 and NfL levels increased for up to 6 months post-treatment; however, their serum S1P levels continuously decreased over 12 months. These findings indicate a favorable safety profile of CL2020 therapy. In the near future, a double-blind study of a larger number of ALS patients should be conducted to confirm the efficacy of ALS treatment with CL2020.

Accessory fragment migration in a professional baseball player with bipartite patella: A case report.

INTRODUCTION: Bipartite patella (BP) is usually recognized as an incidental radiographic finding. Therefore, no reports have observed the process of accessory fragment migration. We present the case of a professional baseball pitcher with significant migration of the fragment during follow-up. PRESENTATION OF CASE: A 26-year-old man was diagnosed with symptomatic BP and underwent conservative therapy. Eleven months later, he was unable to play baseball because of gradually worsening knee pain without obvious trauma. On radiographs, the accessory fragment which had located at the superolateral pole 11 months earlier migrated posterolaterally. The diagnosis of Saupe's type III BP was established, and open excision of the accessory fragment was performed. Postoperatively, full-weight-bearing walking and range-of-motion exercises were started the day after surgery. Three months after surgery, he could pitch with all his power without pain. DISCUSSION: Since our patient was a professional baseball right-handed pitcher who needed to step strongly on his left knee during pitching, strong traction force from the vastus lateralis was likely to have been repeatedly applied to the accessory fragment. It might lead to migration of the accessory fragment. The open excision of the accessory fragment was performed because the accessory fragment had migrated away from the patella body. CONCLUSION: We report a case of professional baseball player with symptomatic BP, in which case the chronological migration of the accessory fragment was observed without obvious trauma. When the accessory fragment is identified without obvious trauma, one of the differential diseases could be a BP.

The use of tourniquet is useful in terms of blood loss and soft tissue damage in arthroscopic anterior cruciate ligament reconstruction: a retrospective study.

Whether a tourniquet should be used for anterior cruciate ligament reconstruction (ACLR) when the operative field is secured remains controversial. Little is known about the influence of not using a tourniquet on total perioperative blood loss and soft tissue damage. The aim of this study was to compare total perioperative blood loss and soft tissue damage with and without tourniquet use during ACLR. Seventy-seven consecutive ACLRs in 76 patients were performed without tourniquet use at our hospital and enrolled in this study (T- group) between November 2018 and September 2021. The control group (T + group) comprised 55 historical ACLRs in 55 patients performed with tourniquet use at our hospital between April 2017 and September 2018. Total perioperative blood loss, calculated from the change in hemoglobin between that preoperatively and on postoperative day (POD) 1, and indicators of soft tissue damage including serum white blood cell (WBC) counts, creatine phosphokinase (CPK), and C-reactive protein (CRP) values measured on POD 1 and POD 7 were compared between groups. Total blood loss was significantly higher in the T- group (339 ± 216 mL) than in the T + group (258 ± 199 mL; P = 0.030). On POD 1, WBC counts were significantly higher in the T- group (9.7 ± 2.4 × 103 cells/µL) than in the T + group (9.1 ± 2.5 × 103 cells/µL; P = 0.043), CPK levels were significantly higher in the T- group (294 ± 417 U/L) than in the T + group (255 ± 88 U/L; P = 0.046), and CRP levels were also significantly higher in the T- group (1.40 ± 1.12 mg/dL) than in the T + group (0.91 ± 0.76 mg/dL; P = 0.016). No significant differences in WBC counts or CPK or CRP levels were seen between groups on POD 7. Total blood loss and soft tissue damage were significantly increased without tourniquet use during ACLR. No advantage was found for not using a tourniquet in terms of blood loss or soft tissue damage.

Human Cord Blood-Endothelial Progenitor Cells Alleviate Intimal Hyperplasia of Arterial Damage in a Rat Stroke Model.

Human cord blood-endothelial progenitor cells (hCB-EPCs) isolated from the human umbilical cord can be used to repair damaged arteries. In this study, we used an animal model with pathological changes that mimics artery wall damage caused by stent retrievers in humans. We injected hCB-EPCs to investigate their effect on endothelial hyperplasia and dysfunction during intimal repair. Four groups were established based on the length of reperfusion (3 and 28 days), as well as the presence or absence of hCB-EPC therapy. Damage to the internal carotid artery was evaluated by hematoxylin-eosin and immunohistochemical staining. Stroke volume was not significantly different between non-EPC and EPC groups although EPC treatment alleviated intimal hyperplasia 28 days after intimal damage. Vascular endothelial growth factor (VEGF) and eNOS expression were significantly higher in the EPC-treated group than in the non-EPC group 3 days after intimal damage. In addition, MMP9 and 4HNE expression in the EPC-treated group was significantly lower than in the non-EPC group. Ultimately, this study found that venous transplantation of hCB-EPCs could inhibit neointimal hyperplasia, alleviate endothelial dysfunction, suppress intimal inflammation, and reduce oxidative stress during healing of intimal damage.

Regular walking exercise prior to knee osteoarthritis reduces joint pain in an animal model.

We investigated the effect of regular walking exercise prior to knee osteoarthritis (OA) on pain and synovitis in a rat monoiodoacetic acid (MIA)-induced knee OA model. Seventy-one male Wistar rats were divided into three groups: (i) Sedentary + OA, (ii) Exercise + OA, and (iii) Sedentary + Sham groups. The Exercise + OA group underwent a regular treadmill walking exercise at 10 m/min (60 min/day, 5 days/week) for 6 weeks, followed by a 2-mg MIA injection in the right knee. The right knee joint was removed from rats in this group at the end of the 6-week exercise period and at 1 and 6 weeks after the MIA injection. After the 6 weeks of treadmill exercise but before MIA injection, there were no significant differences among the three groups in the pressure pain threshold, whereas at 1 week post-injection, the Exercise + OA group's pressure pain threshold was significantly higher than that in the Sedentary + OA group, and this difference persisted until the end of the experimental period. The histological changes in articular cartilage and subchondral bone revealed by toluidine blue staining showed no difference between the Sedentary + OA and EX + OA groups. The expression levels of interleukin (IL)-4 and IL-10 mRNA in the infrapatellar fat pad and synovium were significantly increased by the treadmill exercise. Significant reductions in the number of CD68-, CD11c-positive cells and IL-1ß mRNA expression and an increase in the number of CD206-positive cells were observed at 1 week after the MIA injection in the Exercise + OA group compared to the Sedentary + OA group. These results suggest that regular walking exercise prior to the development of OA could alleviate joint pain through increases in the expressions of anti-inflammatory cytokines in the rat infrapatellar fat pad and synovium.

Extra-articular location of the three-dimensional mechanical axis in advanced knee osteoarthritis: an upright computed tomography study.

PURPOSE: One of the most widely used benchmarks of lower-limb alignment is the mechanical axis (MA), which passes through the centers of the femoral head and the ankle in the weight-bearing position. However, where the MA passes through three-dimensionally (3D) is unclear. We investigated the MA in 3D (3D-MA) in knee osteoarthritis (OA) using upright computed tomography (CT). MATERIALS AND METHODS: This study included 66 varus OA knees from 38 patients [age 70.0 (64.8-77.0) years; median (interquartile range)]. The 3D-MA was determined using upright CT data and compared among Kellgren-Lawrence (KL) grades. Further, correlations between the 3D-MA and other parameters were evaluated. RESULTS: The 3D-MA was located at 5.3 (1.3-14.4)% medially and 7.1 (0.7-15.3)% posteriorly on the tibial plateau in KL-1, and was translated medioposteriorly with increased KL grade. The 3D-MA in KL-3 [30.6 (22.6-42.6)% medially and 50.9 (45.8-80.2)% posteriorly] and KL-4 [56.7 (48.5-62.9)% medially and 92.3 (50.2-127.1)% posteriorly] was located extra-articularly. The mediolateral position of the 3D-MA correlated with the femorotibial angle [correlation coefficient (CC) = - 0.85, p < 0.001], and the anteroposterior position of the 3D-MA correlated with the knee flexion angle (CC = - 0.93, p < 0.001). CONCLUSION: Our analysis demonstrated that the 3D-MA in low-grade OA knees passes slightly medial and posterior to the knee center, and the 3D-MA is translated medioposteriorly with the progression of knee OA. Further, the 3D-MA is translated medially with varus progression and posteriorly with the progression of knee flexion contracture.

Early Prediction of Response Focused on Tumor Markers in Atezolizumab plus Bevacizumab Therapy for Hepatocellular Carcinoma.

Despite the promising efficacy of atezolizumab plus bevacizumab (atezo/bev), some patients with unresectable hepatocellular carcinoma (HCC) experience disease progression. This retrospective study, which included 154 patients, aimed to evaluate predictors of treatment efficacy of atezo/bev for unresectable HCC. Factors associated with treatment response were examined, focusing on tumor markers. In the high-alpha-fetoprotein (AFP) group (baseline AFP ≥ 20 ng/mL), a decrease in AFP level > 30% was an independent predictor of objective response (odds ratio, 5.517; p = 0.0032). In the low-AFP group (baseline AFP < 20 ng/mL), baseline des-gamma-carboxy prothrombin (DCP) level < 40 mAU/mL was an independent predictor of objective response (odds ratio, 3.978; p = 0.0206). The independent predictors of early progressive disease were an increase in AFP level ≥ 30% at 3 weeks (odds ratio, 4.077; p = 0.0264) and the presence of extrahepatic spread (odds ratio, 3.682; p = 0.0337) in the high-AFP group and up-to-seven criteria, OUT (odds ratio, 15.756; p = 0.0257) in the low-AFP group. In atezo/bev therapy, focusing on early AFP changes, baseline DCP, and tumor burden of up-to-seven criteria are useful in predicting response to treatment.

Innsbruck-style Retromandibular Anterior Trans-parotid Approach for Condylar Fractures: A Retrospective Review of 39 Fractures.

The retromandibular anterior trans-parotid (RAT) approach and a triangular-positioned double mini-plate osteosynthesis (TDO) technique have been reported from Innsbruck Medical University. This minimally invasive technique involves direct visualization of the condyle and is associated with lower incidence of facial palsy. Methods: A retrospective review was performed on the RAT approach and TDO technique conducted by a surgeon and team at two hospitals in Tokyo during a period of 3 years and 10 months. Results: This technique was performed on 35 patients with 39 condylar fractures. Sixty-nine percent of cases were due to accidental fall, 17% to traffic accidents, and 9% to sports. Furthermore, 92% cases were condylar base fractures. Nighty-seven percent of cases achieved good occlusion. The mean maximum mouth opening was 49 ± 1.3 mm. Postoperatively, facial palsy developed in three patients (7.7%), and two of them developed Frey syndrome at approximately 2.5 years postoperatively (5.1%). All patients completely recovered within 3 months postoperatively. One case each of salivary fistula, visible scar, and condylar resorption was found (2.6%). No case of massive bleeding during surgery, hematoma, or TMJ pain after surgery was found. Conclusion: This technique could achieve good occlusion with low incidence of complications and could contribute to early social reintegration among patients.