An interactive resource to identify cancer genetic and lineage dependencies targeted by small molecules.

The high rate of clinical response to protein-kinase-targeting drugs matched to cancer patients with specific genomic alterations has prompted efforts to use cancer cell line (CCL) profiling to identify additional biomarkers of small-molecule sensitivities. We have quantitatively measured the sensitivity of 242 genomically characterized CCLs to an Informer Set of 354 small molecules that target many nodes in cell circuitry, uncovering protein dependencies that: (1) associate with specific cancer-genomic alterations and (2) can be targeted by small molecules. We have created the Cancer Therapeutics Response Portal (http://www.broadinstitute.org/ctrp) to enable users to correlate genetic features to sensitivity in individual lineages and control for confounding factors of CCL profiling. We report a candidate dependency, associating activating mutations in the oncogene ß-catenin with sensitivity to the Bcl-2 family antagonist, navitoclax. The resource can be used to develop novel therapeutic hypotheses and to accelerate discovery of drugs matched to patients by their cancer genotype and lineage.

Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis.

Advanced pathological and genetic approaches have revealed that mutations in fused in sarcoma/translated in liposarcoma (FUS/TLS), which is pivotal for DNA repair, alternative splicing, translation and RNA transport, cause familial amyotrophic lateral sclerosis (ALS). The generation of suitable animal models for ALS is essential for understanding its pathogenesis and developing therapies. Therefore, we used CRISPR-Cas9 to generate FUS-ALS mutation in the non-classical nuclear localization signal (NLS), H517D (mouse position: H509D) and genome-edited mice. Fus WT/H509D mice showed progressive motor impairment (accelerating rotarod and DigiGait system) with age, which was associated with the loss of motor neurons and disruption of the nuclear lamina and nucleoporins and DNA damage in spinal cord motor neurons. We confirmed the validity of our model by showing that nuclear lamina and nucleoporin disruption were observed in lower motor neurons differentiated from patient-derived human induced pluripotent stem cells (hiPSC-LMNs) with FUS-H517D and in the post-mortem spinal cord of patients with ALS. RNA sequence analysis revealed that most nuclear lamina and nucleoporin-linking genes were significantly decreased in FUS-H517D hiPSC-LMNs. This evidence suggests that disruption of the nuclear lamina and nucleoporins is crucial for ALS pathomechanisms. Combined with patient-derived hiPSC-LMNs and autopsy samples, this mouse model might provide a more reliable understanding of ALS pathogenesis and might aid in the development of therapeutic strategies.

Comparing preprocessing strategies for 3D-Gene microarray data of extracellular vesicle-derived miRNAs.

BACKGROUND: Extracellular vesicle-derived (EV)-miRNAs have potential to serve as biomarkers for the diagnosis of various diseases. miRNA microarrays are widely used to quantify circulating EV-miRNA levels, and the preprocessing of miRNA microarray data is critical for analytical accuracy and reliability. Thus, although microarray data have been used in various studies, the effects of preprocessing have not been studied for Toray's 3D-Gene chip, a widely used measurement method. We aimed to evaluate batch effect, missing value imputation accuracy, and the influence of preprocessing on measured values in 18 different preprocessing pipelines for EV-miRNA microarray data from two cohorts with amyotrophic lateral sclerosis using 3D-Gene technology. RESULTS: Eighteen different pipelines with different types and orders of missing value completion and normalization were used to preprocess the 3D-Gene microarray EV-miRNA data. Notable results were suppressed in the batch effects in all pipelines using the batch effect correction method ComBat. Furthermore, pipelines utilizing missForest for missing value imputation showed high agreement with measured values. In contrast, imputation using constant values for missing data exhibited low agreement. CONCLUSIONS: This study highlights the importance of selecting the appropriate preprocessing strategy for EV-miRNA microarray data when using 3D-Gene technology. These findings emphasize the importance of validating preprocessing approaches, particularly in the context of batch effect correction and missing value imputation, for reliably analyzing data in biomarker discovery and disease research.

Influence of Atmospheric Gas Species on an Argyrodite-Type Sulfide Solid Electrolyte During Moisture Exposure.

Sulfide solid electrolytes have potential in practical all-solid-state batteries owing to their high formability and ionic conductivity. However, sulfide solid electrolytes are limited by the generation of toxic hydrogen sulfide and conductivity deterioration upon moisture exposure. Although numerous studies have investigated the hydrolysis degradation induced by "moisture," the influence of "atmospheric gases" during moisture exposure has not been extensively investigated despite the importance for practical fabrication. Therefore, in this study, we investigated the impact of atmospheric gases during moisture exposure on an argyrodite-type Li6PS5Cl via electrochemical impedance spectroscopy, X-ray diffraction, X-ray absorption spectroscopy, and X-ray photoelectron spectroscopy. The electrolyte powder was exposed to various atmospheric gases, namely Ar, Ar + 500 ppm CO2, O2, and O2 + 500 ppm CO2, with moisture at a dew point of -20 °C, and H2S gas generation was monitored. As a result, the amount of H2S gas did not depend on the atmospheric gases. However, the atmospheric gases had a significant effect on the decrease in conductivity. Spectroscopic analyses revealed that CO2 facilitates the formation of carbonates and that O2 promotes the formation of phosphates and sulfonates. The formation of these compounds leads to surface degradation, which further decreases the conductivity.

Optimizing shoulder elevation assist rate in exoskeletal rehabilitation based on muscular activity indices: a clinical feasibility study.

BACKGROUND: Restoring shoulder function is critical for upper-extremity rehabilitation following a stroke. The complex musculoskeletal anatomy of the shoulder presents a challenge for safely assisting elevation movements through robotic interventions. The level of shoulder elevation assistance in rehabilitation is often based on clinical judgment. There is no standardized method for deriving an optimal level of assistance, underscoring the importance of addressing abnormal movements during shoulder elevation, such as abnormal synergies and compensatory actions. This study aimed to investigate the effectiveness and safety of a newly developed shoulder elevation exoskeleton robot by applying a novel optimization technique derived from the muscle synergy index. METHODS: Twelve chronic stroke participants underwent an intervention consisting of 100 robot-assisted shoulder elevation exercises (10 × 10 times, approximately 40 min) for 10 days (4-5 times/week). The optimal robot assist rate was derived by detecting the change points using the co-contraction index, calculated from electromyogram (EMG) data obtained from the anterior deltoid and biceps brachii muscles during shoulder elevation at the initial evaluation. The primary outcomes were the Fugl-Meyer assessment-upper extremity (FMA-UE) shoulder/elbow/forearm score, kinematic outcomes (maximum angle of voluntary shoulder flexion and elbow flexion ratio during shoulder elevation), and shoulder pain outcomes (pain-free passive shoulder flexion range of motion [ROM] and visual analogue scale for pain severity during shoulder flexion). The effectiveness and safety of robotic therapy were examined using the Wilcoxon signed-rank sum test. RESULTS: All 12 patients completed the procedure without any adverse events. Two participants were excluded from the analysis because the EMG of the biceps brachii was not obtained. Ten participants (five men and five women; mean age: 57.0 [5.5] years; mean FMA-UE total score: 18.7 [10.5] points) showed significant improvement in the FMA-UE shoulder/elbow/forearm score, kinematic outcomes, and pain-free passive shoulder flexion ROM (P < 0.05). The shoulder pain outcomes remained unchanged or improved in all patients. CONCLUSIONS: The study presents a method for deriving the optimal robotic assist rate. Rehabilitation using a shoulder robot based on this derived optimal assist rate showed the possibility of safely improving the upper-extremity function in patients with severe stroke in the chronic phase.

Maiden voyage: induced pluripotent stem cell-based drug screening for amyotrophic lateral sclerosis.

Using patient-derived induced pluripotent stem cells, neurodegenerative disease phenotypes have been recapitulated and their pathogenesis analysed leading to significant progress in drug screening. In amyotrophic lateral sclerosis, high-throughput screening using induced pluripotent stem cells-derived motor neurons has identified candidate drugs. Owing to induced pluripotent stem cell-based drug evaluation/screening, three compounds, retigabine, ropinirole and bosutinib, have progressed to clinical trials. Retigabine blocks hyperexcitability and improves survival in amyotrophic lateral sclerosis patient-derived motor neurons. In a randomized clinical trial (n = 65), treatment with retigabine reduced neuronal excitability after 8 weeks. Ropinirole, identified in a high-throughput screening, attenuates pathological phenotypes in patient-derived motor neurons. In a trial limited by a small sample size (n = 20), ropinirole was tolerable and had clinical benefits on function and survival. A phase 1 study of bosutinib has reported safety and tolerability for 12 weeks. Thus, these clinical trials show safety and positive effects and confirm the reliability of stem cell-based drug discovery. This novel strategy leads to reduced costs and time when compared to animal testing and opens new avenues for therapy in intractable diseases.

Recent advances in basic research on prostate cancer: Where we are heading?

In the over 80 years since androgens were found to play a pivotal role in prostate cancer (PCa) progression, androgen deprivation therapy (ADT) has been a cornerstone in treating advanced PCa. Castration-resistant PCa persists, however, with some of these tumors evolving to androgen receptor (AR)-independent forms like neuroendocrine PCa. The development of novel diagnostic and therapeutic approaches to PCa is therefore crucial. This review provides an overview of recent basic research in PCa, focusing on two main areas: PCa cells and their tumor microenvironments. The first section describes current knowledge on the intricate mechanisms of AR signaling pathways, emphasizing the roles of coactivators and chromatin state alterations in gene regulation. Genomic analyses have revealed recurrent mutations and copy number alterations critical for precision medicine. Liquid biopsy has become a promising tool for real-time tumor monitoring, identifying genetic alterations in circulating-tumor DNA or extracellular vesicles. The second section describes the tumor microenvironment of PCa, highlighting its immunosuppressive landscape and the potential of combining ADT with immunotherapy. Advanced techniques, including single-cell RNA sequencing and spatial transcriptomics offer insights into cellular heterogeneity and interactions within the tumor microenvironment, paving the way for novel therapeutic strategies. Integration of these diverse research areas will provide a comprehensive understanding of the current state and future directions of PCa research, underscoring the importance of personalized medicine and the dynamic nature of cancer treatment strategies.

To What Age Do Japanese People Wish to Live?: The Impact of Age Stereotypes.

The images we have concerning aging and older people influence our health, well-being, and longevity; however, we do not know which of its aspects (e.g., health, appearance, and personality) positively or negatively affect us. Therefore, to clarify the impact of images of aging on our desire to live long, which impacts our healthy behavior, we conducted an internet survey targeting 1,000 people aged between 30 and 75 years old in Japan in 2018. We tested the following five hypotheses: 1) Respondents who are interested in interacting with older people wish to live longer than those who do not; 2) Respondents who have a positive stereotype about physiological traits of older people wish to live longer than those who do not; 3) Respondents who have a positive stereotype about social relations among older people wish to live longer than those who do not; 4) Respondents who have a positive stereotype about the functioning of older people wish to live longer than those who do not; 5) Respondents who have a positive stereotype about the functioning of older people are likely to engage in healthy behavior and perceive better subjective health than those who do not, which positively affects the age they wish to live to. As a result, we found that only 70-75-year-old participants who had positive images of social relations in old age tended to express a wish to live longer. However, other aspects of images of aging such as appearance, personality, and biological traits did not affect such desire. We conclude that the influence of aging images on the desire to live long may be less apparent among Japanese than other cultures. It is possible that Japanese people are less likely to internalize aging images regarding old age.

[Right Middle Lung Cancer with Double Aortic Arch:Report of a Case].

Double aortic arch is an embryological abnormality of the aortic arch forming a vascular ring. It has been noted that the right recurrent nerve travels differently in patients with a duplicated aortic arch and may be in close proximity to the area of superior mediastinal lymph node dissection in lung cancer. We report a surgical case of a patient with right middle lung cancer associated with a duplicated aortic arch. A 64-year-old man was referred to our hospital because of a nodular shadow in the right lung field noted on chest X-ray during a medical checkup. A transbronchial needle biopsy revealed a diagnosis of adenocarcinoma, and right middle lobe resection and lymph node dissection were performed. When dissecting the superior mediastinal lymph nodes in a patient with an overlapping aortic arch, it was necessary to carefully perform the operation, paying attention to the running of the right recurrent nerve.

[Primary Pulmonary Diffuse Large B-cell Lymphoma Mimics Advanced Lung Cancer:Report of a Case].

Primary pulmonary diffuse large B-cell lymphoma( DLBCL) is rare, accounting for 0.4% to 1.0% of all malignant lymphomas and 0.45% of all lung malignancies. We report a case of primary pulmonary DLBCL caused by methotrexate-associated lymphoproliferative disorder (MTX-LPD). A 73-year-old man was referred to our hospital due to a growing lung nodule. Transbronchoscopic biopsy did not confirm the diagnosis, but positron emission tomography-computed tomography (PET-CT) showed an accumulation of SUVmax 28.7 in the same area and SUVmax 40.5 in the contralateral mediastinum, suggesting an advanced primary lung cancer. A partial thoracoscopic left lower lobe resection was performed in our department. Histopathological examination revealed AE1/AE3 negative, CD20 and 79a positive, bcl-2 positive, and a diagnosis of primary lung DLBCL. MTX-LPD was suspected, and discontinuation of the drug resulted in subsequent shrinkage of the residual tumor. If the diagnosis cannot be made by transbronchoscopic biopsy of an expanding nodule shadow, aggressive surgical diagnosis should be considered.

Prediction of voluntary movements of the upper extremities by resting state-brain regional glucose metabolism in patients with chronic severe brain injury: A pilot study.

Confirmation of the exact voluntary movements of patients with disorder of consciousness following severe traumatic brain injury (TBI) is difficult because of the associated communication disturbances. In this pilot study, we investigated whether regional brain glucose metabolism assessed by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) at rest could predict voluntary movement in severe TBI patients, particularly those with sufficient upper limb capacity to use communication devices. We visually and verbally instructed patients to clasp or open their hands. After video capture, three independent rehabilitation therapists determined whether the patients' movements were voluntary or involuntary. The results were compared with the standardized uptake value in the primary motor cortex, referring to the Penfield's homunculus, by resting state by FDG-PET imaged 1 year prior. Results showed that glucose uptake in the left (p = 0.0015) and right (p = 0.0121) proximal limb of the primary motor cortex, based on Penfield's homunculus on cerebral cartography, may reflect contralateral voluntary movement. Receiver operating characteristic curve analysis showed that a mean cutoff standardized uptake value of 5.47 ± 0.08 provided the best sensitivity and specificity for differentiating between voluntary and involuntary movements in each area. FDG-PET may be a useful and robust biomarker for predicting long-term recovery of motor function in severe TBI patients with disorders of consciousness.

Administration of spermidine attenuates concanavalin A-induced liver injury.

A previous study revealed that treatment with the anticoagulant heparin attenuated concanavalin A (ConA)-induced liver injury. The administration of spermidine (SPD) increased urokinase-type plasminogen activator (uPA) levels in the serum. uPA is clinically used for the treatment of some thrombotic diseases such as cerebral infarction. Therefore, SPD may attenuate ConA-induced liver injury that is exacerbated by blood coagulation. The present study investigated the effect of SPD on liver injury in mice with autoimmune hepatopathy induced by ConA. A model of liver injury was created by intravenous injection of ConA into mice. SPD was administered in free drinking water and was biochemically and pathologically examined over time. The administration of SPD to ConA-treated mice significantly reduced liver injury. However, SPD treatment upregulated the mRNA expression of TNF-α and IFN-ϒ in the livers of ConA-treated mice. In contrast, the mRNA expression of tissue factor in the livers of SPD-treated mice was decreased after ConA injection. The frequency of lymphocytes and lymphocyte activation were not affected by SPD administration in ConA-treated mice. SPD treatment increased uPA levels in the serum and decreased the level of D-dimer in ConA-treated mice. Moreover, SPD decreased fibrin in the livers of ConA-treated mice. These results indicated that SPD treatment increased anticoagulant ability by increasing of uPA and attenuated ConA-induced liver injury.

Promise of Nucleic Acid Therapeutics for Amyotrophic Lateral Sclerosis.

Nucleic acid therapeutics have been attracting attention as novel drug discovery modalities for intractable diseases, including amyotrophic lateral sclerosis. This review provides an overview of the current status and prospects of antisense oligonucleotide treatment for amyotrophic lateral sclerosis. Recently, the results of a phase I/II study using the antisense oligonucleotides Tofersen to treat familial amyotrophic lateral sclerosis with superoxide dismutase 1 mutation have been reported. Intrathecal Tofersen administration resulted in a 36% reduction in superoxide dismutase 1 level in the cerebrospinal fluid. Another report described 2 patients with mutant superoxide dismutase 1 treated with an adeno-associated virus encoding a microRNA targeting superoxide dismutase 1. The first patient, who possessed the fast progressive mutant A5V, received a single intrathecal infusion. Although the patient died of respiratory arrest 16 months after treatment, autopsy findings showed a reduction of >90% in superoxide dismutase 1 level in the spinal cord. Clinical trials on antisense oligonucleotide therapies targeting other major amyotrophic lateral sclerosis-causative genes, fused in sarcoma and chromosome 9 open reading frame 72, are ongoing. To attenuate the pathology of TDP-43, strategies targeting regulators of TDP-43 (ataxin 2) and proteins downstream of TDP-43 (stathmin 2) by antisense oligonucleotides are being developed. The advent of nucleic acid therapeutics has enabled to specifically attack the molecules in the amyotrophic lateral sclerosis pathological cascade, expanding the options for therapeutic targets. ANN NEUROL 2022;91:13-20.

Genetic factors affecting survival in Japanese patients with sporadic amyotrophic lateral sclerosis: a genome-wide association study and verification in iPSC-derived motor neurons from patients.

BACKGROUND: Several genetic factors are associated with the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) and its phenotypes, such as disease progression. Here, in this study, we aimed to identify the genes that affect the survival of patients with sporadic ALS. METHODS: We enrolled 1076 Japanese patients with sporadic ALS with imputed genotype data of 7 908 526 variants. We used Cox proportional hazards regression analysis with an additive model adjusted for sex, age at onset and the first two principal components calculated from genotyped data to conduct a genome-wide association study. We further analysed messenger RNA (mRNA) and phenotype expression in motor neurons derived from induced pluripotent stem cells (iPSC-MNs) of patients with ALS. RESULTS: Three novel loci were significantly associated with the survival of patients with sporadic ALS-FGF1 at 5q31.3 (rs11738209, HR=2.36 (95% CI, 1.77 to 3.15), p=4.85×10-9), THSD7A at 7p21.3 (rs2354952, 1.38 (95% CI, 1.24 to 1.55), p=1.61×10-8) and LRP1 at 12q13.3 (rs60565245, 2.18 (95% CI, 1.66 to 2.86), p=2.35×10-8). FGF1 and THSD7A variants were associated with decreased mRNA expression of each gene in iPSC-MNs and reduced in vitro survival of iPSC-MNs obtained from patients with ALS. The iPSC-MN in vitro survival was reduced when the expression of FGF1 and THSD7A was partially disrupted. The rs60565245 was not associated with LRP1 mRNA expression. CONCLUSIONS: We identified three loci associated with the survival of patients with sporadic ALS, decreased mRNA expression of FGF1 and THSD7A and the viability of iPSC-MNs from patients. The iPSC-MN model reflects the association between patient prognosis and genotype and can contribute to target screening and validation for therapeutic intervention.

IL-33 Induces Sema4A Expression in Dendritic Cells and Exerts Antitumor Immunity.

Cancer immunotherapy has shown great promise as a new standard therapeutic strategy against cancer. However, the response rate and survival benefit remain unsatisfactory because most current approaches, such as the use of immune checkpoint inhibitors, depend on spontaneous antitumor immune responses. One possibility for improving the efficacy of immunotherapy is to promote antitumor immunity using adjuvants or specific cytokines actively. IL-33 has been a candidate for such cytokine therapies, but it remains unclear how and in which situations IL-33 exerts antitumor immune effects. In this study, we demonstrate the potent antitumor effects of IL-33 using syngeneic mouse models, which included marked inhibition of tumor growth and upregulation of IFN-γ production by tumor-infiltrating CD8+ T cells. Of note, IL-33 induced dendritic cells to express semaphorin 4A (Sema4A), and the absence of Sema4A abolished the antitumor activity of IL-33, indicating that Sema4A is intrinsically required for the antitumor effects of IL-33 in mice. Collectively, these results not only present IL-33 and Sema4A as potential therapeutic targets but also shed light on the potential use of Sema4A as a biomarker for dendritic cell activation status, which has great value in various fields of cancer research, including vaccine development.

Safety and Clinical Benefits of Laryngeal Closure in Patients with Amyotrophic Lateral Sclerosis.

This study evaluated the safety of laryngeal closure and post-surgical changes in swallowing function of patients with amyotrophic lateral sclerosis (ALS) and proposed an appropriate surgical strategy for patients with ALS. Clinical and surgical data of 26 consecutive patients with ALS who underwent laryngeal closure at Nagoya University Hospital in Japan between 2003 and 2020 were retrospectively analyzed. Changes in swallowing functions were evaluated before and approximately 1 month post-surgery using Neuromuscular Disease Swallowing Status Scale (NdSSS), and Functional Oral Intake Scale (FOIS). The median operation time was 126 min (range, 51-163 min), and the median intraoperative blood loss was 20 mL (range, 0-88 mL). Among the 26 ALS patients who underwent laryngeal closure, grade 1 (mild) complications occurred in three patients (12%); however, no severe complications were observed. After surgery, 25 patients (96%) maintained the swallowing function and only one patient (4%) had deteriorating NdSSS and FOIS scores. No patients were referred to our hospital due to severe aspiration pneumonia after the surgery. Two patients did not require a feeding tube after the surgery and returned to oral intake. Laryngeal closure may be a safe surgical procedure for preventing chronic aspiration and may also maintain swallowing function of patients with ALS. Further multicenter prospective studies using the gold standard videofluoroscopic swallowing examination are required to support our findings.

The influence of serum cholinesterase levels and sarcopenia on postoperative infectious complications in colorectal cancer surgery.

PURPOSE: Cholinesterase is a nutritional marker associated with sarcopenia. The present study evaluated the relationship between cholinesterase and postoperative infectious complications in patients undergoing colorectal resection for colorectal cancer. METHODS: The study involved 231 patients who had undergone colorectal resection for colorectal cancer. We retrospectively investigated the relationship between preoperative serum cholinesterase levels and postoperative infectious complications. Univariate and multivariate analyses were performed to identify independent risk factors for postoperative infectious complications. We then performed stratified analyses to assess the interaction between cholinesterase and clinical variables to predict postoperative infectious complications. RESULTS: In the multivariate analysis, the body mass index (P = 0.010), serum cholinesterase levels (P = 0.005), sarcopenia (P = 0.003) and blood loss (P < 0.001) were independent risk factors for postoperative infectious complications. In stratified analyses, the association between serum cholinesterase levels and postoperative infectious complications differed by the sarcopenia status (Pinteraction = 0.006). CONCLUSION: Preoperative serum cholinesterase levels may be useful for predicting postoperative infectious complications in colorectal cancer surgery. The association differs by the sarcopenia status, suggesting a potential interaction between nutritional markers and sarcopenia.

Assessment of liver function-related mRNA expression and fluorescence imaging in outflow-obstructed regions in rats.

PURPOSE: The liver function in outflow-obstructed regions is reportedly impaired; however, the functional decrease has not been quantitatively assessed. We therefore evaluated the uptake of indocyanine green (ICG) into hepatocytes and the mRNA expression associated with the liver function in outflow-obstructed regions using rat models. METHODS: A total of 20 rats with the ligation of the right median hepatic vein to induce outflow obstruction were studied. Five rats each were grouped by the time of re-laparotomy, and the fluorescence intensity (FI) values of ICG. The mRNA expression, including that of Albumin, Cytochrome P450 (Cyp) 1a2, Cyp3a1, Cyp7a1, and Gamma-glutamylcysteine synthetase, in outflow-obstructed (mRNAOut-Ob) and non-outflow-obstructed (mRNANon) regions was assessed. RESULTS: Microscopic fluorescence imaging showed that the FI values were significantly lower in outflow-obstructed regions than in non-outflow-obstructed regions at 12 h, 24 h, and 3 days after ligation of the hepatic vein. The mRNAOut-Ob/mRNANon ratios decreased to approximately 30% at 12 h after the outflow obstruction and increased to approximately 70-80% at 7 days. CONCLUSIONS: The liver function in outflow-obstructed regions was impaired in terms of the uptake of ICG and the mRNA expression. Our findings may help estimate the postoperative functional remnant liver volume by considering the decrease in the liver function in outflow-obstructed regions.

Impacts of increases and decreases of drugs on rehabilitation outcomes of subacute stroke patients.

OBJECTIVE: To examine changes in drugs for subacute stroke patients and elucidate the impact of medications on rehabilitation outcomes. MATERIALS AND METHODS: A total of 295 subacute stroke patients who were admitted to the convalescent rehabilitation ward between June 2018 and May 2019 were included. Polypharmacy was defined as five or more drugs at admission. The primary outcome was the Functional Independence Measure Total score (FIM-T) at discharge. Multiple regression analysis was performed to examine the relationships between the FIM-T at discharge and drug changes or other factors. This study was conducted in two stages. The first analysis included all stroke patients, and the second analysis included only stroke patients with polypharmacy. RESULTS: On multiple regression analysis, the number of drugs at admission (ß=-0.628) was associated with FIM-T at discharge of all stroke patients. Furthermore, the number of additional drugs during hospitalization (ß=-1.964) was associated with FIM-T at discharge in the 176 stroke patients with polypharmacy. CONCLUSION: This study suggested that the number of drugs at admission and the addition of drugs during hospitalization might have a negative impact on the rehabilitation outcomes of subacute stroke patients.

[Minimally Invasive Direct Coronary Artery Bypass in a Patient with Osteopetrosis and Symptomatic Ischemic Heart Disease:Report of a Case].

Osteopetrosis is a heterogeneous group of heritable conditions. It varies greatly in severity, and fracture treatment remains a matter of controversy due to altered responses to fixation and the risk of osteomyelitis. Therefore, sternotomy outcomes in this condition are unclear. We report the case of a patient with osteopetrosis and coronary artery disease (CAD). A 78-year-old man with osteopetrosis presented with frequent chest pain. Coronary angiography revealed two-vessel CAD. Percutaneous coronary intervention was contraindication because of coronary aneurysm in the left main trunk. Considering risks in median sternotomy, we performed minimally invasive cardiac surgery through left minithoracotomy for coronary artery bypass grafting( CABG). But we needed to break the left fourth rib to obtain sufficient surgical views. To the best of our knowledge, this is the first case report on CABG for a patient with osteopetrosis and endoscopic surgery without rib retractor is recommended.