Individuals with problem gambling and obsessive-compulsive disorder learn through distinct reinforcement mechanisms.

Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are accompanied by deficits in behavioural flexibility. In reinforcement learning, this inflexibility can reflect asymmetric learning from outcomes above and below expectations. In alternative frameworks, it reflects perseveration independent of learning. Here, we examine evidence for asymmetric reward-learning in OCD and PG by leveraging model-based functional magnetic resonance imaging (fMRI). Compared with healthy controls (HC), OCD patients exhibited a lower learning rate for worse-than-expected outcomes, which was associated with the attenuated encoding of negative reward prediction errors in the dorsomedial prefrontal cortex and the dorsal striatum. PG patients showed higher and lower learning rates for better- and worse-than-expected outcomes, respectively, accompanied by higher encoding of positive reward prediction errors in the anterior insula than HC. Perseveration did not differ considerably between the patient groups and HC. These findings elucidate the neural computations of reward-learning that are altered in OCD and PG, providing a potential account of behavioural inflexibility in those mental disorders.

Lyn Kinase Suppresses the Transcriptional Activity of IRF5 in the TLR-MyD88 Pathway to Restrain the Development of Autoimmunity.

Interferon regulatory factor-5 (IRF5), a transcription factor critical for the induction of innate immune responses, contributes to the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) in humans and mice. Lyn, a Src family kinase, is also implicated in human SLE, and Lyn-deficient mice develop an SLE-like disease. Here, we found that Lyn physically interacted with IRF5 to inhibit ubiquitination and phosphorylation of IRF5 in the TLR-MyD88 pathway, thereby suppressing the transcriptional activity of IRF5 in a manner independent of Lyn's kinase activity. Conversely, Lyn did not inhibit NF-κB signaling, another major branch downstream of MyD88. Monoallelic deletion of Irf5 alleviated the hyperproduction of cytokines in TLR-stimulated Lyn(-/-) dendritic cells and the development of SLE-like symptoms in Lyn(-/-) mice. Our results reveal a role for Lyn as a specific suppressor of the TLR-MyD88-IRF5 pathway and illustrate the importance of fine-tuning IRF5 activity for the maintenance of immune homeostasis.

Inferences regarding oneself and others in the human brain.

The human brain can infer one's own and other individuals' mental states through metacognition and mentalizing, respectively. A new study in PLOS Biology has implicated distinct brain regions of the medial prefrontal cortex (PFC) in metacognition and mentalizing.

Continuous decision to wait for a future reward is guided by fronto-hippocampal anticipatory dynamics.

Deciding whether to wait for a future reward is crucial for surviving in an uncertain world. While seeking rewards, agents anticipate a reward in the present environment and constantly face a trade-off between staying in their environment or leaving it. It remains unclear, however, how humans make continuous decisions in such situations. Here, we show that anticipatory activity in the anterior prefrontal cortex, ventrolateral prefrontal cortex, and hippocampus underpins continuous stay-leave decision-making. Participants awaited real liquid rewards available after tens of seconds, and their continuous decision was tracked by dynamic brain activity associated with the anticipation of a reward. Participants stopped waiting more frequently and sooner after they experienced longer delays and received smaller rewards. When the dynamic anticipatory brain activity was enhanced in the anterior prefrontal cortex, participants remained in their current environment, but when this activity diminished, they left the environment. Moreover, while experiencing a delayed reward in a novel environment, the ventrolateral prefrontal cortex and hippocampus showed anticipatory activity. Finally, the activity in the anterior prefrontal cortex and ventrolateral prefrontal cortex was enhanced in participants adopting a leave strategy, whereas those remaining stationary showed enhanced hippocampal activity. Our results suggest that fronto-hippocampal anticipatory dynamics underlie continuous decision-making while anticipating a future reward.

BRCA1/2 reversion mutations in a pan-cancer cohort.

Tumor sensitivity to platinum (Pt)-based chemotherapy and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors is increased by homologous recombination deficiency-causing mutations; in particular, reversion mutations cause drug resistance by restoring protein function. Treatment response is predicted by breast cancer susceptibility gene 1/2 (BRCA1/2) mutations; however, BRCA1/2 reversion mutations have not been comprehensively studied in pan-cancer cohorts. We aimed to characterize BRCA1/2 reversion mutations in a large pan-cancer cohort of Japanese patients by retrospectively analyzing sequencing data for BRCA1/2 pathogenic/likely pathogenic mutations in 3738 patients with 32 cancer types. We identified somatic mutations in tumors or circulating cell-free DNA that could restore the ORF of adverse alleles, including reversion mutations. We identified 12 (0.32%) patients with somatic BRCA1 (n = 3) and BRCA2 (n = 9) reversion mutations in breast (n = 4), ovarian/fallopian tube/peritoneal (n = 4), pancreatic (n = 2), prostate (n = 1), and gallbladder (n = 1) cancers. We identified 21 reversion events-BRCA1 (n = 3), BRCA2 (n = 18)-including eight pure deletions, one single-nucleotide variant, six multinucleotide variants, and six deletion-insertions. Seven (33.3%) reversion deletions showed a microhomology length greater than 1 bp, suggesting microhomology-mediated end-join repair. Disease course data were obtained for all patients with reversion events: four patients acquired mutations after PARP-inhibitor treatment failure, two showed somatic reversion mutations after disease progression, following Pt-based treatment, five showed mutations after both treatments, one patient with pancreatic cancer and BRCA1 reversion mutations had no history of either treatment. Although reversion mutations commonly occur in BRCA-associated cancers, our findings suggest that reversion mutations due to Pt-chemotherapy might be correlated with BRCA1/2-mediated tumorigenesis even in non-BRCA-associated histologies.

Identification of putative noncanonical driver mutations in patients with essential thrombocythemia.

Essential thrombocythemia (ET) cases without canonical JAK2, CALR, or MPL mutations, that is, triple-negative (TN) ET, have been found in 10%-20% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical JAK2/CALR/MPL mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): MPL S204P, MPL L265F, JAK2 R683G, and JAK2 T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a THPO splicing site mutation, MPL*636Wext*12, and MPL E237K. Four of the seven identified driver mutations were germline. Functional studies on MPL*636Wext*12 and MPL E237K revealed that they are gain-of-function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis.

CD98 expression can be a predictive factor of resistance to radiotherapy in head and neck squamous cell carcinoma.

CD98 is a marker of cancer stem cells, and it regulates radiosensitivity in head and neck squamous cell carcinoma (HNSCC). The current study aimed to investigate whether CD98 can be used as a prognostic factor and marker of radioresistance. CD98 immunostaining was performed using biopsy specimens collected from patients diagnosed with HNSCC. The average period of postoperative monitoring was 31.6 months. The treatment options were radiation therapy with either cisplatin or cetuximab, and surgery. The participants were divided into groups of low and high fluorescence intensity. CD98 was an independent prognostic factor of radioresistance. In total, 103 patients were treated with chemoradiotherapy or bioradiotherapy. The overall survival rates of patients receiving chemoradiotherapy or bioradiotherapy were 69.2% in the low group and 36.2% in the high group. The progression-free survival rates were 60.0% and 24.6%, respectively. CD98 expression was considered an independent prognostic factor of overall survival and progression-free survival. In total, 99 patients underwent surgical treatment. The surgery group did not differ according to CD98 expression. Via CD98 immunostaining, sensitivity to radiotherapy can be determined in advance. In HNSCC, knowledge about sensitivity to radiotherapy can significantly improve prognosis.

Gamma-secretase inhibitor does not induce cytotoxicity in adult T-cell leukemia cell lines despite NOTCH1 expression.

BACKGROUND: Activated mutations in NOTCH1 are drivers of T-cell type acute lymphoblastic leukemia/lymphoma. The γ-secretase inhibitor (GSI), which suppresses the function of NOTCH1, is expected to be a molecular-targeted agent. NOTCH1 is also expressed in other malignant neoplasms. We aimed to determine the function of NOTCH1 expression and the effects of GSI on adult T-cell leukemia/lymphoma (ATL) caused by long-term human T-cell leukemia virus type I (HTLV-1) infection. METHODS: We analyzed the expression of NOTCH1 in six ATL- and HTLV-1-infected cell lines and investigated the influence of activated NOTCH1 (i.e., the cleaved form of NOTCH1) together with GSI on cell proliferation. RESULTS: Activated NOTCH1 found in ATL- and HTLV-1-infected cell lines was undetectable after incubation with GSI, regardless of Tax expression (HTLV-1-coded protein). Whole-exome sequencing revealed that activated NOTCH1 mutations were undetectable in six ATL- and HTLV-1-infected cell lines, regardless of abundant NOTCH1 expression. Moreover, GSI did not suppress the growth of ATL cell lines. CONCLUSIONS: These findings suggested that NOTCH1 protein is constitutively activated but is likely a passenger during NOTCH1-mutation-negative ATL cell proliferation.

Self-Controlled Choice Arises from Dynamic Prefrontal Signals That Enable Future Anticipation.

Self-control allows humans the patience necessary to maximize reward attainment in the future. Yet it remains elusive when and how the preference to self-controlled choice is formed. We measured brain activity while female and male humans performed an intertemporal choice task in which they first received delayed real liquid rewards (forced-choice trial), and then made a choice between the reward options based on the experiences (free-choice trial). We found that, while subjects were awaiting an upcoming reward in the forced-choice trial, the anterior prefrontal cortex (aPFC) tracked a dynamic signal reflecting the pleasure of anticipating the future reward. Importantly, this prefrontal signal was specifically observed in self-controlled individuals, and moreover, interregional negative coupling between the prefrontal region and the ventral striatum (VS) became stronger in those individuals. During consumption of the liquid rewards, reduced ventral striatal activity predicted self-controlled choices in the subsequent free-choice trials. These results suggest that a well-coordinated prefrontal-striatal mechanism during the reward experience shapes preferences regarding the future self-controlled choice.SIGNIFICANCE STATEMENT Anticipating future desirable events is a critical mental function that guides self-controlled behavior in humans. When and how are the self-controlled choices formed in the brain? We monitored brain activity while humans awaited a real liquid reward that became available in tens of seconds. We found that the frontal polar cortex tracked temporally evolving signals reflecting the pleasure of anticipating the future reward, which was enhanced in self-controlled individuals. Our results highlight the contribution of the fronto-polar cortex to the formation of self-controlled preferences, and further suggest that future prospect in the prefrontal cortex (PFC) plays an important role in shaping future choice behavior.

Testing the reinforcement learning hypothesis of social conformity.

Our preferences are influenced by the opinions of others. The past human neuroimaging studies on social conformity have identified a network of brain regions related to social conformity that includes the posterior medial frontal cortex (pMFC), anterior insula, and striatum. Since these brain regions are also known to play important roles in reinforcement learning (i.e., processing prediction error), it was previously hypothesized that social conformity and reinforcement learning have a common neural mechanism. However, although this view is currently widely accepted, these two processes have never been directly compared; therefore, the extent to which they shared a common neural mechanism had remained unclear. This study aimed to formally test the hypothesis. The same group of participants (n = 25) performed social conformity and reinforcement learning tasks inside a functional magnetic resonance imaging (fMRI) scanner. Univariate fMRI data analyses revealed activation overlaps in the pMFC and bilateral insula between social conflict and unsigned prediction error and in the striatum between social conflict and signed prediction error. We further conducted multivoxel pattern analysis (MVPA) for more direct evidence of a shared neural mechanism. MVPA did not reveal any evidence to support the hypothesis in any of these regions but found that activation patterns between social conflict and prediction error in these regions were largely distinct. Taken together, the present study provides no clear evidence of a common neural mechanism between social conformity and reinforcement learning.

Oncological outcomes of lateral lymph node dissection (LLND) for locally advanced rectal cancer: is LLND alone sufficient?

BACKGROUND: Lateral lymph node dissection (LLND) has been considered as the standard treatment strategy for locally advanced lower rectal cancer in Japan. Controversy remains around whether all patients require LLND. This study aims to examine the long-term outcomes of patients in which LLND was performed and clarify the value of LLND. METHOD: Consecutive 458 patients with lower rectal cancer who underwent total mesorectal excision (TME) plus LLND from 1992 to 2012 were included. The long-term outcomes and risk factors for recurrent in patients performed TME + LLND were examined. We assessed the impact of LLND on survival using an estimated therapeutic index. RESULTS: The incidence of LLNM was 15.5%. The 5-year RFS and OS rates of patients with LLNM were 40.9% and 47.7%, while patients without LLNM had a good prognosis. The 5-year local recurrence (LR) rate was 9.2%, and independent risk factors for LR were T4 and LLNM. The LR rate of patients with LLNM was high (22.8%). The LLNM rate of the groups with 0, 1, 2, 3, or 4 risk factors (male, tumor location < 4 cm from anal verge, T4, and MLNM) was 3.8%, 9.2%, 18.1%, and 50.0%. The 5-year OS of the groups was 96.2%, 86.1%, 69.7%, and 48.5%. CONCLUSION: Although patients with locally advanced lower rectal cancer who received LLND had a good prognosis, LLND alone was insufficient to control local recurrence in patients with metastatic lateral nodes.

Evaluation of energy density and macronutrients after extremely brief time exposure.

Many food decisions are made rapidly and without reflective processing. The ability to determine nutritional information accurately is a precursor of food decisions and is important for a healthy diet and weight management. However, little is known about the cognitive evaluation of food attributes based on visual information in relation to assessing nutritional content. We investigated the accuracy of visual encoding of nutritional information after brief and extended time exposures to food images. The following questions were addressed: (1) how accurately do people estimate energy and macronutrients after brief exposure to food images, and (2) how does estimation accuracy change with time exposure and the type of nutritional information? Participants were first asked to rate the energy density (calories) and macronutrient content (carbohydrates/fat/protein) of different sets of food images under three time conditions (97, 500 or 1000 ms) and then asked to perform the task with no time constraints. We calculated estimation accuracy by computing the correlations between estimated and actual nutritional information for each time exposure and compared estimation accuracy with respect to the type of nutritional information and the exposure time. The estimated and actual energy densities and individual macronutrient content were significantly correlated, even after a brief exposure time (97 ms). The degree of accuracy of the estimations did not differ with additional time exposure, suggesting that <100 ms was sufficient to predict the energy and macronutrients from food images. Additionally, carbohydrate estimates were less accurate than the estimates of other nutritional variables (proteins, fat and calories), regardless of the exposure time. These results revealed rapid and accurate assessment of food attributes based on visual information and the accuracy of visual encoding of nutritional information after brief and extended time exposure to food imagery.

A nationwide survey on the incidence and characteristics of traumatic spinal cord injury in Japan in 2018.

STUDY DESIGN: Retrospective epidemiological study. OBJECTIVES: Since the causes and incidences of traumatic spinal cord injury (TSCI) in each country change over time, up-to-date epidemiological studies are required for countermeasures against TSCI. However, no nationwide survey in Japan has been conducted for about 30 years. The purpose of this study was therefore to investigate the recent incidence and characteristics of TSCI in Japan. SETTING: Japan METHODS: Survey sheets were sent to all hospitals (emergency and acute care hospitals) that treated TSCI persons in Japan in 2018 and case notes were retrospectively reviewed. Frankel grade E cases were excluded from analysis. RESULTS: The response rate was 74.4% (2804 of 3771 hospitals). The estimated annual incidence of TSCI excluding Frankel E was 49 per million, with a median age of 70.0 years and individuals in their 70s as the largest age group. Male-to-female ratio was 3:1. Cervical cord injuries occurred in 88.1%. Frankel D was the most frequent grade (46.3%), followed by Frankel C (33.0%). The most frequent cause was fall on level surface (38.6%), followed by traffic accident (20.1%). The proportion of fall on level surface increased with age. TSCI due to sports was the most frequent cause in teenagers (43.2%). CONCLUSIONS: This nationwide survey in Japan showed that estimated incidence of TSCI, rate of cervical cord injury, and incomplete injury by falls appear to be increasing with the aging of the population.

Psychiatric symptoms influence reward-seeking and loss-avoidance decision-making through common and distinct computational processes.

AIM: Psychiatric symptoms are often accompanied by impairments in decision-making to attain rewards and avoid losses. However, due to the complex nature of mental disorders (e.g., high comorbidity), symptoms that are specifically associated with deficits in decision-making remain unidentified. Furthermore, the influence of psychiatric symptoms on computations underpinning reward-seeking and loss-avoidance decision-making remains elusive. Here, we aim to address these issues by leveraging a large-scale online experiment and computational modeling. METHODS: In the online experiment, we recruited 1900 non-diagnostic participants from the general population. They performed either a reward-seeking or loss-avoidance decision-making task, and subsequently completed questionnaires about psychiatric symptoms. RESULTS: We found that one trans-diagnostic dimension of psychiatric symptoms related to compulsive behavior and intrusive thought (CIT) was negatively correlated with overall decision-making performance in both the reward-seeking and loss-avoidance tasks. A deeper analysis further revealed that, in both tasks, the CIT psychiatric dimension was associated with lower preference for the options that recently led to better outcomes (i.e. reward or no-loss). On the other hand, in the reward-seeking task only, the CIT dimension was associated with lower preference for recently unchosen options. CONCLUSION: These findings suggest that psychiatric symptoms influence the two types of decision-making, reward-seeking and loss-avoidance, through both common and distinct computational processes.

Clinical Outcomes of Cetuximab and Paclitaxel after Progression on Immune Checkpoint Inhibitors in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Background and Objectives: In recent years, the effectiveness of chemotherapy after immune checkpoint inhibitor administration has attracted attention in various cancers, including head and neck cancers. However, individual assessments of the administered chemotherapy regimens are insufficient. This study aimed to evaluate the efficacy and safety of chemotherapy after immune checkpoint inhibitor administration in recurrent metastatic head and neck cancer by focusing on a single regimen. Materials and Methods: We retrospectively reviewed clinical and radiological data from the medical records of 18 patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who received systemic chemotherapy with weekly cetuximab and paclitaxel (Cmab + PTX) after progression following immune checkpoint inhibitor (ICI) therapy. The objective response rate (ORR) and disease control rate (DCR) were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were recorded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: In all patients, the ORR, DCR, median PFS, and median OS were 44.4%, 72.2%, 3.8 months, and 9.6 months, respectively. Regarding AEs, three patients developed grade 3 neutropenia. Grade 3 anemia, paronychia, asthenia, and peripheral neuropathy were observed in one patient each. There were no treatment-related deaths. Conclusions: Cmab + PTX was shown to maintain high efficacy and acceptable safety for R/M HNSCC that progressed after ICI therapy. Further research is needed to establish optimal treatment sequences and drug combinations for recurrent R/M HNSCC.

Computing Social Value Conversion in the Human Brain.

Social signals play powerful roles in shaping self-oriented reward valuation and decision making. These signals activate social and valuation/decision areas, but the core computation for their integration into the self-oriented decision machinery remains unclear. Here, we study how a fundamental social signal, social value (others' reward value), is converted into self-oriented decision making in the human brain. Using behavioral analysis, modeling, and neuroimaging, we show three-stage processing of social value conversion from the offer to the effective value and then to the final decision value. First, a value of others' bonus on offer, called offered value, was encoded uniquely in the right temporoparietal junction (rTPJ) and also in the left dorsolateral prefrontal cortex (ldlPFC), which is commonly activated by offered self-bonus value. The effective value, an intermediate value representing the effective influence of the offer on the decision, was represented in the right anterior insula (rAI), and the final decision value was encoded in the medial prefrontal cortex (mPFC). Second, using psychophysiological interaction and dynamic causal modeling analyses, we demonstrated three-stage feedforward processing from the rTPJ and ldPFC to the rAI and then from rAI to the mPFC. Further, we showed that these characteristics of social conversion underlie distinct sociobehavioral phenotypes. We demonstrate that the variability in the conversion underlies the difference between prosocial and selfish subjects, as seen from the differential strength of the rAI and ldlPFC coupling to the mPFC responses, respectively. Together, these findings identified fundamental neural computation processes for social value conversion underlying complex social decision making behaviors.SIGNIFICANCE STATEMENT In daily life, we make decisions based on self-interest, but also in consideration for others' status. These social influences modulate valuation and decision signals in the brain, suggesting a fundamental process called value conversion that translates social information into self-referenced decisions. However, little is known about the conversion process and its underlying brain mechanisms. We investigated value conversion using human fMRI with computational modeling and found three essential stages in a progressive brain circuit from social to empathic and decision areas. Interestingly, the brain mechanism of conversion differed between prosocial and individualistic subjects. These findings reveal how the brain processes and merges social information into the elemental flow of self-interested decision making.

Comprehensive Comparative Analysis of Prognostic Value of Systemic Inflammatory Biomarkers for Patients with Stage II/III Colon Cancer.

BACKGROUND: Among numerous systemic inflammatory biomarkers, it remains unclear which is the most prognostic for patients with stage II/III colon cancer. We aimed to compare the prognostic significance of systemic inflammatory biomarkers among patients with stage II/III colon cancer. METHODS: We included 1303 patients with stage II/III colon cancer who underwent potentially curative resection from July 2004 to December 2013. Sixteen systemic inflammatory biomarkers-derived from combinations of neutrophils, lymphocytes, monocytes, platelets, C-reactive protein (CRP), and albumin-were compared to identify the biomarker most associated with overall survival (OS) and disease-free survival (DFS) using receiver operating characteristic (ROC) curve analysis. RESULTS: Nine inflammatory biomarkers were predictive for OS, among which lymphocyte-to-CRP ratio (LCR), CRP-to-albumin ratio (CAR), neutrophil × CRP, monocyte × CRP, and platelet × CRP were also predictive for DFS. Among these five inflammatory biomarkers, the area under the curve (AUC) value was highest (0.630) for LCR, being significantly higher than that for neutrophil × CRP (P = 0.010), monocyte × CRP (P = 0.007), or platelet × CRP (P = 0.010) for OS. When the prognostic impact of LCR and CAR were analyzed by multivariate analysis, only LCR was an independent predictor of both OS [hazard ratio (HR), 1.77; 95% confidence interval (CI), 1.23-2.60; P = 0.002] and DFS (HR, 1.29; 95% CI, 1.00-1.66; P = 0.048). CONCLUSIONS: LCR may be the most useful predictive factor for OS and DFS in patients with stage II or III colon cancer.

Risk factors of chemotherapy-induced nausea and vomiting in patients with metastatic colorectal cancer: a prospective cohort study (YCOG1301).

PURPOSE: Although the effectiveness of antiemetic therapy for colorectal cancer chemotherapy has improved with further drug development, some patients still suffer from chemotherapy-induced nausea and vomiting (CINV) even with only 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. The present study investigated the risk factors of CINV in patients who received chemotherapy for colorectal cancer and clarified which patients need additional neurokinin 1 receptor antagonist. METHODS: Patients with colorectal cancer receiving moderate-emetic-risk chemotherapy (MEC) were enrolled in this prospective single-arm study with intravenous palonosetron 0.75 mg and dexamethasone 9.9 mg before chemotherapy and with paroral dexamethasone 8 mg on days 2 and 3. The primary endpoint was the complete response (CR) rate for delayed-phase CINV. RESULTS: A total of 179 patients were eligible for this study. The delayed CR rate was 84.9% (152/179). There were no significant differences in any risk factors, but women with a low body mass index (BMI) (a combination of "female sex" and "BMI < 20") showed a significantly lower rate of CC (complete control) (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.17-1.13; p = 0.039), and young patients with a low BMI (combination of "age < 65" and "BMI < 20") showed a significantly lower rate of CR (OR = 0.34, 95% CI = 0.13-0.88; p = 0.022) than the other patients. CONCLUSIONS: This study failed to identify any single risk factors associated with delayed CINV in patients who received chemotherapy for advanced colorectal cancer. However, combinations of "thin and women" or "young and thin patients" might be possible predictive conditions, thus, candidates for NK1 receptor antagonist administration in MEC. Further investigations are required to develop criteria for the supplementation of NK1 receptor antagonist.

Efficacy and safety of enoxaparin for preventing venous thromboembolic events after laparoscopic colorectal cancer surgery: a randomized-controlled trial (YCOG 1404).

PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of postoperative enoxaparin for the prevention of venous thromboembolism (VTE) after laparoscopic surgery for colorectal cancer (LAC) in Japanese patients. METHODS: The subjects of this multicenter, open-label randomized-controlled trial were 121 patients who underwent LAC between September 2015 and May 2017. The patients were randomly allocated to receive intermittent pneumatic compression (IPC) with enoxaparin (20 mg, twice daily), started 24-36 h after surgery and continued until discharge (Enoxaparin group; n = 61), or IPC alone (IPC group; n = 60). The primary endpoint was the incidence of VTE on day 28 after surgery. The safety outcome was the incidence of any bleeding during treatment and follow-up. RESULTS: The incidence of VTE on day 28 after surgery was 12.3% (7/57 patients) in the enoxaparin group and 11.9% (7/59 patients) in the IPC group ((p = 1.00). One of the 57 patients (1.8%) in the enoxaparin group and none in the IPC group experienced a bleeding event. CONCLUSIONS: It may be unnecessary to give enoxaparin to all Japanese patients for the prevention of VTE after LAC. The UMIN Clinical Trials Registry number was UMIN000018633.

Unilateral chronic subdural hematoma due to spontaneous intracranial hypotension: a report of four cases.

Background: Chronic subdural hematoma (CSDH) is a common neurosurgical disease. A subset of patients with CSDH may exhibit underlying spontaneous intracranial hypotension (SIH). Bilateral CSDH has a causal relationship with SIH, but there is no known causal relationship between unilateral CSDH and SIH.Case description: We encountered four cases of unilateral CSDH due to SIH. The patients' age ranged between 44 and 64 years; there were three males and one female. All patients presented with headache as their initial symptom, and then became comatose. Computed tomography demonstrated unilateral CSDH and transtentorial herniation in all patients. Treatments were emergency epidural blood patch (EBP) and evacuation of CSDH. The site of cerebrospinal fluid leak could not be identified in three patients; therefore, EBP was performed at upper and lower spine. All patients recovered from SIH; however, one patient experienced poor outcome due to Duret hemorrhage and ischemic complications of transtentorial herniation. Cranial asymmetry was present in all four patients, and unilateral CSDH was located on the side of the most curved cranial convexity.Conclusions: Unilateral CSDH, asymmetric cranial morphology, and transtentorial herniation in relatively young patients may indicate underlying SIH.