Projected land ice contributions to twenty-first-century sea level rise.

The land ice contribution to global mean sea level rise has not yet been predicted1 using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models2-8, but primarily used previous-generation scenarios9 and climate models10, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios11,12 using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.

Thermal multiferroics in all-inorganic quasi-two-dimensional halide perovskites.

Multiferroic materials, particularly those possessing simultaneous electric and magnetic orders, offer a platform for design technologies and to study modern physics. Despite the substantial progress and evolution of multiferroics, one priority in the field remains to be the discovery of unexplored materials, especially those offering different mechanisms for controlling electric and magnetic orders1. Here we demonstrate the simultaneous thermal control of electric and magnetic polarizations in quasi-two-dimensional halides (K,Rb)3Mn2Cl7, arising from a polar-antipolar transition, as evidenced using both X-ray and neutron powder diffraction data. Our density functional theory calculations indicate a possible polarization-switching path including a strong coupling between the electric and magnetic orders in our halide materials, suggesting a magnetoelectric coupling and a situation not realized in oxide analogues. We expect our findings to stimulate the exploration of non-oxide multiferroics and magnetoelectrics to open access to alternative mechanisms, beyond conventional electric and magnetic control, for coupling ferroic orders.

Liver-specific DICER1 syndrome model mice develop cystic liver tumors with defective primary cilia.

DICER1 syndrome is a tumor predisposition syndrome caused by familial genetic mutations in DICER1. Pathogenic variants of DICER1 have been discovered in many rare cancers, including cystic liver tumors. However, the molecular mechanisms underlying liver lesions induced by these variants remain unclear. In the present study, we sought to gain a better understanding of the pathogenesis of these variants by generating a mouse model of liver-specific DICER1 syndrome. The mouse model developed bile duct hyperplasia with fibrosis, similar to congenital hepatic fibrosis, as well as cystic liver tumors resembling those in Caroli's syndrome, intrahepatic cholangiocarcinoma, and hepatocellular carcinoma. Interestingly, the mouse model of DICER1 syndrome showed abnormal formation of primary cilia in the bile duct epithelium, which is a known cause of bile duct hyperplasia and cyst formation. These results indicated that DICER1 mutations contribute to cystic liver tumors by inducing defective primary cilia. The mouse model generated in this study will be useful for elucidating the potential mechanisms of tumorigenesis induced by DICER1 variants and for obtaining a comprehensive understanding of DICER1 syndrome. © 2024 The Pathological Society of Great Britain and Ireland.

La2SrSc2O7: A-Site Cation Disorder Induces Ferroelectricity in Ruddlesden-Popper Layered Perovskite Oxide.

Rational design of ferroelectrics in layered perovskites, like n = 2 Ruddlesden-Popper (RP) phase A3B2O7, has been achieved by the hybrid-improper ferroelectric (HIF) mechanism, in which an electric polarization is induced via a trilinear coupling to nonpolar BO6 octahedral rotation and tilt distortions around crystallographic axes. In the present work, hybrid improper ferroelectricity in n = 2 RP-type La2SrSc2O7 induced by the disordering of Sr2+/La3+ cations on the A-sites in rocksalt ([Sr/La]Rs = 25/75) and perovskite ([Sr/La]Pv = 50/50) layers is demonstrated through experimental and theoretical investigations. The ferroelectric A21am structure (a-a-c+ in Glazer notation) at room temperature and the second-order phase transition to paraelectric Amam structure (a-a-c0) at TC ∼ 600 K are determined by a combination of X-ray and neutron diffraction and optical second harmonic generation. The ferroelectric hysteresis loop measurements prove the switchable electric polarization indicative of ferroelectricity. These results represent an unprecedented example of ferroelectricity in the n = 2 RP family of Ln2AB2O7 with inequivalent Ln3+ and A2+ cations. Combining the abovementioned experimental results with the first-principles calculations, we verify the role of Sr/La distributions in regulating the interlayer rumpling, which, in addition to the structural tolerance factor, is key to controlling the structural distortions of RP phases. The stabilization of the ferroelectric, a-a-c+ distorted structure is a consequence of the disordered Sr/La distribution on the A-sites, which suppresses the rumpling-induced octahedral deformations in competition with the octahedral rotations and thus enables the concurrence of a0a0c+ rotations and a-a-c0 tilts required for the HIF mechanism. This work demonstrates the possibility of altering the crystal symmetry of RP phases through the A-site cation disorder and provides a complementary approach to the rational design of new HIF materials.

Higher Indocyanine Green Retention Is Associated with Improved Prognosis in Patients with Hepatocellular Carcinoma Treated with Transcatheter Arterial Chemoembolization.

PURPOSE: To test indocyanine green retention rate at 15 minutes (ICG-R15) as a prognostic biomarker in patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) therapy. MATERIALS AND METHODS: This retrospective cohort study was performed on the data of 278 consecutive patients with HCC treated with TACE after ICG-R15 testing at a single university hospital. Cox proportional hazard model analysis was performed to identify independent prognostic factors. After adjusting for age, sex, stage of HCC, albumin-bilirubin score, etiologies, and baseline year by propensity score matching, the prognostic impact of higher ICG-R15 was evaluated using the Kaplan-Meier curve. RESULTS: Univariate and multivariate analyses identified higher ICG-R15 as a positive prognostic factor for overall survival. Propensity score matching generated two 77-patient cohorts: ICG-R15 <20% group and ICG-R15 >20% group. The overall survival of the ICG-R15 >20% group was significantly better than that of the ICG-R15 <20% group. CONCLUSIONS: Higher ICG-R15 acted as a positive long-term prognostic factor in patients with HCC treated with TACE.

Management of hepatocellular carcinoma, an important cause of death in Japanese autoimmune hepatitis patients.

BACKGROUND: Hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH) was considered rare but is increasing with prolonged prognosis. Its impact on the overall prognosis of AIH is unknown, and treatment has not been established. AIM: To investigate the risk factors and prognosis of HCC in patients with AIH and identify appropriate management strategies. METHODS: We studied patients with AIH including background liver disease, sex, age, complications, treatment, response to treatment, liver fibrosis, prognosis, and treatment. RESULTS: In 131 patients, deaths due to liver failure were more common early after the onset of AIH; however, deaths due to HCC increased gradually. HCC was observed in 12 patients (median age, 70 years; male/female, 4/8; cirrhosis at onset, 11; median time to carcinogenesis, 7 years). Cirrhosis at diagnosis was identified as a risk factor for carcinogenesis in the multivariate analysis (odds ratio, 41.36; p < 0.0001) and cumulative cancer rates were high. Multidisciplinary therapy other than immune checkpoint inhibitors was administered as treatment for HCC. Two of the three patients who used molecular-targeted drugs discontinued the treatment because of adverse events. CONCLUSION: HCC is an important cause of death in patients with AIH. Currently available drug therapies are limited and early detection is desirable. TRIAL REGISTRATION: This trial was retrospectively registered in the Ethics Committee of Kagawa University School of Medicine under the identifier 2019 - 238, registered on 4 Feb 2020.

Disordered network structure and function in dystonia: pathological connectivity vs. adaptive responses.

Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations. Both networks were characterized by contributions from the basal ganglia, cerebellum, thalamus, sensorimotor areas, as well as cortical association regions. Expression levels for the two networks were elevated in hereditary and sporadic dystonia, and in non-manifesting carriers of dystonia mutations. Nonetheless, the distribution of abnormal functional connections differed across groups, as did metrics of network organization and efficiency in key modules. Despite these differences, network expression correlated with dystonia motor ratings, significantly improving the accuracy of predictions based on thalamocortical tract integrity obtained with diffusion tensor MRI (DTI). Thus, in addition to providing unique information regarding the anatomy of abnormal brain circuits, rs-fMRI functional networks may provide a widely accessible method to help in the objective evaluation of new treatments for this disorder.

Estimation of the relationship between the thermal environment of a house in winter and its occupants' health.

This study aims to quantify the relationship between the arbitrary thermal environment of houses in winter and their occupants' health through a comprehensive questionnaire survey, involving approximately 24,000 individuals who moved into insulated dwellings in Japan. A relationship between the degree of the thermal insulation of these houses and corresponding rates of improvement in the following 10 diseases were formulated: heart disease, cerebrovascular disease, hypertension, diabetes mellitus, asthma, dermatitis and eczema, pneumonia, inflammatory polyarthropathies, allergic rhinitis, and conjunctivitis. Following the statistical analysis of these outcomes, significant differences in improvement rates were identified among the levels of the thermal insulation of houses for the following five diseases: cerebrovascular diseases, asthma, dermatitis and eczema, allergic rhinitis, and conjunctivitis. In addition, the thermal environments of houses corresponding to each thermal insulation level were estimated by numerical simulations. Using these results, we organized the relationships between the thermal environment conditions of houses and observed prevalence rate for the following four diseases for which the improvement rates increased with increasing insulation levels and significant differences were identified: asthma, dermatitis and eczema, allergic rhinitis, and conjunctivitis. Consequently, we formulated equations to predict the prevalence rates of these diseases using the "mean operative temperature of rooms occupied by each family member from January 1 to February 28."

Zinc deficiency is a potential risk factor for COVID-19 progression to pneumonia requiring oxygen therapy.

INTRODUCTION: Various risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19. METHODS: The study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 µg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders. RESULTS: Patients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70-31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors. CONCLUSIONS: Zinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies.

The membrane-linked adaptor FRS2ß fashions a cytokine-rich inflammatory microenvironment that promotes breast cancer carcinogenesis.

Although it is held that proinflammatory changes precede the onset of breast cancer, the underlying mechanisms remain obscure. Here, we demonstrate that FRS2ß, an adaptor protein expressed in a small subset of epithelial cells, triggers the proinflammatory changes that induce stroma in premalignant mammary tissues and is responsible for the disease onset. FRS2ß deficiency in mouse mammary tumor virus (MMTV)-ErbB2 mice markedly attenuated tumorigenesis. Importantly, tumor cells derived from MMTV-ErbB2 mice failed to generate tumors when grafted in the FRS2ß-deficient premalignant tissues. We found that colocalization of FRS2ß and the NEMO subunit of the IκB kinase complex in early endosomes led to activation of nuclear factor-κB (NF-κB), a master regulator of inflammation. Moreover, inhibition of the activities of the NF-κB-induced cytokines, CXC chemokine ligand 12 and insulin-like growth factor 1, abrogated tumorigenesis. Human breast cancer tissues that express higher levels of FRS2ß contain more stroma. The elucidation of the FRS2ß-NF-κB axis uncovers a molecular link between the proinflammatory changes and the disease onset.

Radiographic and clinical comparisons between loose-fit and press-fit stems in monopolar radial head arthroplasty for comminuted radial head fractures.

PURPOSE: Few clinical studies have compared the operative outcomes between loose- and press-fit stems in radial head arthroplasty (RHA). We aimed to evaluate the radiographic and clinical results of the two radial head implant concepts. METHODS: In this retrospective multicenter study, 32 patients (24 women and 8 men) with a mean age of 63.1 years who underwent RHA for comminuted radial head fractures were reviewed between 2005 and 2021. Seventeen patients underwent RHA with a loose-fit stem (L-group), whereas the remaining fifteen patients underwent RHA with a press-fit stem (P-group). The mean follow-up period was 40.1 ± 9.9 months, with the minimum follow-up duration of 12 months. The radiographic findings were evaluated for periprosthetic osteolysis; furthermore, clinical outcomes were analyzed to measure the range of motion of the elbow. The rate of reoperations and prosthesis removal were also reviewed. RESULTS: The general characteristics of the patients were similar in the two groups. The rate of periprosthetic osteolysis was 17.6% in the L-group, whereas it was 53.3% in the P-group. The mean elbow flexions were 128° and 133° in the L- and P-groups, respectively. The mean elbow extensions were -12° and -9° in the L- and P-groups, respectively. The rate of reoperation was 23.5% in the L-group and 15.2% in the P-group. One patient in the L-group had the prosthesis removed because of surgical site infection, whereas one patient in the P-group had the prosthesis removed owing to painful loosening. CONCLUSIONS: No significant differences in the clinical outcomes and reoperation rate were observed between the two radial head implant concepts in this study. However, osteolysis occurred more frequently in the P-group. Although patients with periprosthetic osteolysis are currently asymptomatic, they should be carefully followed up for the symptoms in the long term.

Anionic Sublattices in Halide Solid Electrolytes: A Case Study with the High-Pressure Phase of Li3ScCl6.

The Li3MX6 compounds (M=Sc, Y, In; X=Cl, Br) are known as promising ionic conductors due to their compatibility with typical metal oxide cathode materials. In this study, we have successfully synthesized γ-Li3ScCl6 using high pressure for the first time in this family. Structural analysis revealed that the high-pressure polymorph crystallizes in the polar and chiral space group P63mc with hexagonal close-packing (hcp) of anions, unlike the ambient-pressure α-Li3ScCl6 and its spinel analog with cubic closed packing (ccp) of anions. Investigation of the known Li3MX6 family further revealed that the cation/anion radius ratio, rM/rX, is the factor that determines which anion sublattice is formed and that in γ-Li3ScCl6, the difference in compressibility between Sc and Cl exceeds the ccp rM/rX threshold under pressure, enabling the ccp-to-hcp conversion. Electrochemical tests of γ-Li3ScCl6 demonstrate improved electrochemical reduction stability. These findings open up new avenues and design principles for lithium solid electrolytes, enabling routes for materials exploration and tuning electrochemical stability without compositional changes or the use of coatings.

Large Perpendicular Magnetic Anisotropy Induced by an Intersite Charge Transfer in Strained EuVO2H Films.

Perovskite oxides ABO3 continue to be a major focus in materials science. Of particular interest is the interplay between A and B cations as exemplified by intersite charge transfer (ICT), which causes novel phenomena including negative thermal expansion and metal-insulator transition. However, the ICT properties were achieved and optimized by cationic substitution or ordering. Here we demonstrate an anionic approach to induce ICT using an oxyhydride perovskite, EuVO2H, which has alternating layers of EuH and VO2. A bulk EuVO2H behaves as a ferromagnetic insulator with a relatively high transition temperature (TC) of 10 K. However, the application of external pressure to the EuIIVIIIO2H bulk or compressive strain from the substrate in the thin films induces ICT from the EuIIH layer to the VIIIO2 layer due to the extended empty V dxy orbital. The ICT phenomenon causes the VO2 layer to become conductive, leading to an increase in TC that is dependent on the number of carriers in the dxy orbitals (up to a factor of 4 for 10 nm thin films). In addition, a large perpendicular magnetic anisotropy appears with the ICT for the films of <100 nm, which is unprecedented in materials with orbital-free Eu2+, opening new perspectives for applications. The present results provide opportunities for the acquisition of novel functions by alternating transition metal/rare earth layers with heteroanions.

Influence of diabetes mellitus and effectiveness of metformin on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers, and it is important to elucidate the carcinogenic factors and improve the recurrence and prognosis of HCC patients. Diabetes mellitus (DM) has been reported to be a risk factor for the carcinogenesis of many cancers including HCC, and the mechanism of DM for carcinogenesis is gradually being elucidated. Metformin, a drug for DM, has been reported to have anticancer effects on many cancers, including HCC. Metformin not only suppresses carcinogenesis but also improves the prognosis of recurrence after treatment, and there are many reports on the mechanism of these effects. In this review, we describe the mechanism of action of hyperglycemia and hyperinsulinemia on carcinogenesis by DM against HCC. The carcinogenic effects of DM on hepatitis B, hepatitis C, and nonalcoholic fatty liver disease by etiology are also described. In addition, the carcinogenic effect of metformin on HCC and its mechanism of action are reviewed. We also discuss the effects of metformin on recurrence after hepatectomy and radiofrequency therapy and the effects of metformin in combination with anticancer medicine, focusing on the inhibition of HCC development.

Olfactory identification ability among schizophrenia patients, their first-degree relatives and healthy subjects.

OBJECTIVE: Olfactory impairments, including identification, have been reported in patients with schizophrenia, while few studies have examined the olfactory function of unaffected first-degree relatives of patients with schizophrenia, and the sample sizes of first-degree relatives were relatively small. Here, we investigated olfactory identification ability among patients with schizophrenia, first-degree relatives and healthy controls (HCs) using relatively large sample sizes at a single institute. METHODS: To assess olfactory identification ability, the open essence odorant identification test was administered to 172 schizophrenia patients, 75 first-degree relatives and 158 healthy controls. Differences in olfactory identification and correlations between olfactory ability and clinical variables were examined among these participants. RESULTS: We found a significant difference in olfactory identification ability among the diagnostic groups (p = 7.65 × 10-16). Schizophrenia patients displayed lower olfactory identification ability than first-degree relatives (Cohen's d = -0.57, p = 3.13 × 10-6) and healthy controls (d = -1.00, p = 2.19 × 10-16). Furthermore, first-degree relatives had lower olfactory identification ability than healthy controls (d = -0.29, p = 0.039). Olfactory identification ability moderately and negatively correlated with the duration of illness (r = -0.41, p = 1.88 × 10-8) and negative symptoms (r = -0.28, p = 1.99 × 10-4) in schizophrenia patients, although the correlation with the duration of illness was affected by aging (r = -0.24). CONCLUSIONS: Our results demonstrated that schizophrenia patients have impaired olfactory identification ability compared with first-degree relatives and healthy controls, and the impaired olfactory identification ability of first-degree relatives was intermediate between those in schizophrenia patients and healthy controls. Olfactory identification ability was relatively independent of clinical variables. Therefore, olfactory identification ability might be an intermediate phenotype for schizophrenia.

Foot characteristics of the daily-life gait in postmenopausal females with distal radius fractures: a cross-sectional study.

BACKGROUND: Gait decline in older adults is related to falling risk, some of which contribute to injurious falls requiring medical attention or restriction of activity of daily living. Among injurious falls, distal radius fracture (DRF) is a common initial fragility fracture associated with the subsequent fracture risk in postmenopausal females. The recent invention of an inertial measurement unit (IMU) facilitates the assessment of free-living gait; however, little is known about the daily gait characteristics related to the risk of subsequent fractures. We hypothesized that females with DRF might have early changes in foot kinematics in daily gait. The aim of this study was to evaluate the daily-life gait characteristics related to the risk of falls and fracture. METHODS: In this cross-sectional study, we recruited 27 postmenopausal females with DRF as their first fragility fracture and 28 age-matched females without a history of fragility fractures. The participants underwent daily gait assessments for several weeks using in-shoe IMU sensors. Eight gait parameters and each coefficient of variance were calculated. Some physical tests, such as hand grip strength and Timed Up and Go tests, were performed to check the baseline functional ability. RESULTS: The fracture group showed lower foot angles of dorsiflexion and plantarflexion in the swing phase. The receiver operating characteristic curve analyses revealed that a total foot movement angle (TFMA) < 99.0 degrees was the risk of subsequent fracture. CONCLUSIONS: We extracted the daily-life gait characteristics of patients with DRF using in-shoe IMU sensors. A lower foot angle in the swing phase, TFMA, may be associated with the risk of subsequent fractures, which may be effective in evaluating future fracture risk. Further studies to predict and prevent subsequent fractures from daily-life gait are warranted.

The Potential of ChatGPT as a Self-Diagnostic Tool in Common Orthopedic Diseases: Exploratory Study.

BACKGROUND: Artificial intelligence (AI) has gained tremendous popularity recently, especially the use of natural language processing (NLP). ChatGPT is a state-of-the-art chatbot capable of creating natural conversations using NLP. The use of AI in medicine can have a tremendous impact on health care delivery. Although some studies have evaluated ChatGPT's accuracy in self-diagnosis, there is no research regarding its precision and the degree to which it recommends medical consultations. OBJECTIVE: The aim of this study was to evaluate ChatGPT's ability to accurately and precisely self-diagnose common orthopedic diseases, as well as the degree of recommendation it provides for medical consultations. METHODS: Over a 5-day course, each of the study authors submitted the same questions to ChatGPT. The conditions evaluated were carpal tunnel syndrome (CTS), cervical myelopathy (CM), lumbar spinal stenosis (LSS), knee osteoarthritis (KOA), and hip osteoarthritis (HOA). Answers were categorized as either correct, partially correct, incorrect, or a differential diagnosis. The percentage of correct answers and reproducibility were calculated. The reproducibility between days and raters were calculated using the Fleiss κ coefficient. Answers that recommended that the patient seek medical attention were recategorized according to the strength of the recommendation as defined by the study. RESULTS: The ratios of correct answers were 25/25, 1/25, 24/25, 16/25, and 17/25 for CTS, CM, LSS, KOA, and HOA, respectively. The ratios of incorrect answers were 23/25 for CM and 0/25 for all other conditions. The reproducibility between days was 1.0, 0.15, 0.7, 0.6, and 0.6 for CTS, CM, LSS, KOA, and HOA, respectively. The reproducibility between raters was 1.0, 0.1, 0.64, -0.12, and 0.04 for CTS, CM, LSS, KOA, and HOA, respectively. Among the answers recommending medical attention, the phrases "essential," "recommended," "best," and "important" were used. Specifically, "essential" occurred in 4 out of 125, "recommended" in 12 out of 125, "best" in 6 out of 125, and "important" in 94 out of 125 answers. Additionally, 7 out of the 125 answers did not include a recommendation to seek medical attention. CONCLUSIONS: The accuracy and reproducibility of ChatGPT to self-diagnose five common orthopedic conditions were inconsistent. The accuracy could potentially be improved by adding symptoms that could easily identify a specific location. Only a few answers were accompanied by a strong recommendation to seek medical attention according to our study standards. Although ChatGPT could serve as a potential first step in accessing care, we found variability in accurate self-diagnosis. Given the risk of harm with self-diagnosis without medical follow-up, it would be prudent for an NLP to include clear language alerting patients to seek expert medical opinions. We hope to shed further light on the use of AI in a future clinical study.

Radiation educational program significantly reduces intraoperative fluoroscopy time during locking plate fixation for distal radius fractures.

BACKGROUND: The use of C-arm fluoroscopy poses a risk of radiation exposure to the surgeons. This study aimed to examine the intraoperative fluoroscopy time of the distal radius plating before and after radiation educational program. METHODS: A total of 68 cases (48 women and 20 men; average age, 61.8 years) were reviewed between July 2017 and October 2019. All patients were treated with volar locking plate fixation for distal radius fractures. On October 2018, we had a 1-h radiation educational program for orthopedic surgeons. Intraoperative fluoroscopy time was compared between 34 cases in the preintervention group (group A) and 34 cases in the postintervention group (group B). Radiographic correction loss of the fracture was assessed by ulnar variance (UV), radial inclination (RI), and volar tilt (VT) between immediately after surgery and at the time of bone union. RESULTS: A significant difference was found in intraoperative fluoroscopy time between 329 s in group A and 123 s in group B. ΔUV between immediately after surgery and at the time of bone union was 0.6 mm in group A and 0.3 mm in group B; ΔRI was -0.3° in group A, -0.1° in group B, ΔVT is -0.4° in group A, and -0.1° in group B. No significant difference was found among them. CONCLUSIONS: After an educational program on radiation exposure, the intraoperative fluoroscopy time was significantly saved in the plating surgery for the distal radius fractures. The shortening of the intraoperative fluoroscopy time did not affect the loss of radiographic correction of the fractures.

Comparison of ceftriaxone and cefazolin as prophylactic antibiotics for surgical site infection in orthopedic upper extremity surgery: The nationwide shortage of cefazolin in March 2019.

BACKGROUND: Due to the nationwide supply shortage of cefazolin in March 2019 in Japan, ceftriaxone was used as an alternative prophylaxis antibiotic agent. This retrospective study was designed to investigate the impact of cefazolin and ceftriaxone as a prophylactic antibiotic agent for surgical site infection (SSI) in orthopedic upper extremity surgery. METHODS: We used cefazolin for antibiotic prophylaxis to prevent SSI before March 2019. Because of cefazolin shortage, ceftriaxone was used as an alternative agent in our hospital. From April 2014 to May 2021, 2493 upper extremity surgeries were reviewed. The exclusion criteria in this study were as follows: patients aged under 16 years, those with an open wound, those with infectious diseases, those who underwent trigger finger surgery, and those who underwent percutaneous pinning surgery. The incidence of deep SSI was evaluated according to the Centers for Disease Control and Prevention guidelines. RESULTS: Among the 2493 eligible cases, 1674 were included in this study. In the cefazolin group, 1140 cases were included, whereas, in the ceftriaxone group, 534 cases were included. No significant differences in the demographic data of the patients were observed between the two groups. The incidence of deep SSI was 0.08% (1/1140 cases) in the cefazolin group and 1.1% (6/534 cases) in the ceftriaxone group, with a significant difference between the two groups (odds ratio, 12.9; p = 0.005). CONCLUSIONS: This study indicated that the use of ceftriaxone instead of cefazolin after upper extremity surgery increases the risk of deep SSI.

The Roles of Epigenetic Regulation and the Tumor Microenvironment in the Mechanism of Resistance to Systemic Therapy in Hepatocellular Carcinoma.

Primary liver cancer is the sixth most common cancer and the third most common cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is a major histologic type with a poor prognosis owing to the difficulty in early detection, the chemotherapy resistance, and the high recurrence rate of the disease. Despite recent advancements in HCC prevention and diagnosis, over 50% of patients are diagnosed at Barcelona Clinic Liver Cancer Stage B or C. Systemic therapies are recommended for unresectable HCC (uHCC) with major vascular invasion, extrahepatic metastases, or intrahepatic lesions that have a limited response to transcatheter arterial chemoembolization, but the treatment outcome tends to be unsatisfactory due to acquired drug resistance. Elucidation of the mechanisms underlying the resistance to systemic therapies and the appropriate response strategies to solve this issue will contribute to improved outcomes in the multidisciplinary treatment of uHCC. In this review, we summarize recent findings on the mechanisms of resistance to drugs such as sorafenib, regorafenib, and lenvatinib in molecularly targeted therapy, with a focus on epigenetic regulation and the tumor microenvironment and outline the approaches to improve the therapeutic outcome for patients with advanced HCC.