Acute Infectious Purpura Fulminans Complicated by Bacterial Translocation after Rectal Cancer Surgery: A Case Report.

The patient was a man in his 80s who had undergone laparoscopic anterior resection for rectal cancer. Bowel obstruction occurred on the third postoperative day but improved with a decompression tube by the fifth postoperative day. A high fever (in the 38 °C range) was also observed. Blood culture tests detected two sets of the gram-negative bacilli Klebsiella aerogenes within 24 h of collection. On the seventh postoperative day, the patient subsequently went into septic shock with disseminated intravascular coagulation (DIC). On the eighth postoperative day, the fingertips and toes became black, and the palms and dorsal surfaces of both feet were dark purple due to peripheral circulatory failure. This suggested acute infectious purpura associated with sepsis (acute infectious purpura fulminans (AIPF)). Intensive care was provided; however, the necrosis of both middle fingers worsened, both middle fingers were gangrenous, and the patient died on the thirtieth postoperative day. AIPF is rarely reported, especially in early-onset cases after elective surgery. We encountered a rare complication of bacterial translocation from postoperative bowel obstruction, leading to AIPF.

Proportions and characteristics of interval cancer in annual fecal immunochemical test screening and postcolonoscopy colorectal cancer: Results from a Japanese multicenter prospective study using questionnaires, the C-DETECT study.

OBJECTIVES: There are several types of colorectal cancer (CRC) according to the detection methods and intervals, including interval CRC (iCRC) and postcolonoscopy CRC (PCCRC). We aimed to examine their proportions and characteristics. METHODS: We conducted a multicenter prospective study using questionnaires in Japan ("C-DETECT study"), in which differences in CRC characteristics according to detection methods and intervals were examined from consecutive adult patients. Because the annual fecal immunochemical test (FIT) was used in population-based screening, the annual FIT-iCRC was assessed. RESULTS: In total, 1241 CRC patients (1064 with invasive CRC) were included. Annual FIT-iCRC (a), 3-year PCCRC (b), and CRC detected within 1 year after a positive FIT with noncompliance to colonoscopy (c) accounted for 4.5%, 7.0%, and 3.9% of all CRCs, respectively, and for 3.9%, 5.4%, and 4.3% of invasive CRCs, respectively. The comparison among these (a, b, c) and other CRCs (d) demonstrated differences in the proportions of ≥T2 invasion ([a] 58.9%, [b] 44.8%, [c] 87.5%, [d] 73.0%), metastasis ([a] 33.9%, [b] 21.8%, [c] 54.2%, [d] 43.9%), right-sided CRC ([a] 42.9%, [b] 40.2%, [c] 18.8%, [d] 28.6%), and female sex ([a] 53.6%, [b] 49.4%, [c] 27.1%, [d] 41.6%). In metastatic CRC, (a) and (b) showed a higher proportions of BRAF mutations ([a] [b] 12.0%, [c] [d] 3.1%). CONCLUSIONS: Annual FIT-iCRC and 3-year PCCRC existed in nonnegligible proportions. They were characterized by higher proportions of right-sided tumors, female sex, and BRAF mutations. These findings suggest that annual FIT-iCRC and 3-year PCCRC may have biological features different from those of other CRCs.

A Predictive Model for Cancer-Associated Thrombosis in Japanese Cancer Patients: Findings from the J-Khorana Registry.

Background Although the close relationship between cancer and venous thromboembolism (VTE) has been identified, risk stratification for VTE in Japanese patients with cancer remains unclear. Objectives This study aimed to validate the Khorana VTE risk assessment score (KRS) for VTE diagnosis and establish an optimal predictive model for VTE in Japanese patients with cancer. Methods A total of 7,955 Japanese patients with cancer were subdivided into low- (0), intermediate- (1-2), and high-score (3) groups according to the KRS. Using 37 explanatory variables, a total of 2,833 patients with cancer were divided into derivation and validation cohorts (5:5). A risk model for Japanese participants was developed using the derivation cohort data. Results The prevalence of VTE in low-, intermediate-, and high-score patients was 1.2, 2.5, and 4.3%, respectively. Logistic regression analysis demonstrated that cancer stage (III-IV) and KRS ≥ 2 were independent and significant predictors of VTE onset. The risk model for VTE assigned 1 point to body mass index ≥25 kg/m 2 and 2 points each to the prevalence of osteochondral cancer and D-dimer level ≥1.47 µg/mL. The areas under the curve of the risk model were 0.763 and 0.656 in the derivation and validation cohorts, respectively. Conclusion The KRS was useful in Japanese patients, and our new predictive model may be helpful for the diagnosis of VTE in Japanese patients with cancer.

Mega-Enhancer Bodies Organize Neuronal Long Genes in the Cerebellum.

Dynamic regulation of gene expression plays a key role in establishing the diverse neuronal cell types in the brain. Recent findings in genome biology suggest that three-dimensional (3D) genome organization has important, but mechanistically poorly understood functions in gene transcription. Beyond local genomic interactions between promoters and enhancers, we find that cerebellar granule neurons undergoing differentiation in vivo exhibit striking increases in long-distance genomic interactions between transcriptionally active genomic loci, which are separated by tens of megabases within a chromosome or located on different chromosomes. Among these interactions, we identify a nuclear subcompartment enriched for near-megabase long enhancers and their associated neuronal long genes encoding synaptic or signaling proteins. Neuronal long genes are differentially recruited to this enhancer-dense subcompartment to help shape the transcriptional identities of granule neuron subtypes in the cerebellum. SPRITE analyses of higher-order genomic interactions, together with IGM-based 3D genome modeling and imaging approaches, reveal that the enhancer-dense subcompartment forms prominent nuclear structures, which we term mega-enhancer bodies. These novel nuclear bodies reside in the nuclear periphery, away from other transcriptionally active structures, including nuclear speckles located in the nuclear interior. Together, our findings define additional layers of higher-order 3D genome organization closely linked to neuronal maturation and identity in the brain.

[Impact of COVID-19 on cancer treatment: Results from 18 hospital-based cancer registries in Tochigi prefecture].

Objectives　To show the impact of COVID-19 on cancer treatment in Tochigi prefecture.Methods　The number of cancer cases registered in Tochigi prefecture before (2019) and after (2020) COVID-19 was compared using cancer registry data from 18 member hospitals of the Tochigi Prefecture Cancer Care Collaboration Council. Data were compared by sex, age, patient's address at the time of diagnosis, month of diagnosis, cancer site, cancer stage, and treatment. Data on screenings for stomach, colorectum, lung, female breast, cervix, and prostate cancers were investigated in detail.Results　The total number of registered cancer cases was 19,748 in 2019 and 18,912 in 2020 (a decrease of 836 cases [-4.2%]). Among the total cases, there were 11,223 and 10,511 males in 2019 and 2020, respectively (a decrease of 712 cases [-6.3%]) and 8,525 and 8,401 females in 2019 and 2020, respectively (a decrease of 124 cases [-1.5%]). The decrease was greater among males than among females. There was no decrease in the number of registered patients aged <40 years between 2019 and 2020. Based on the patients' address at the time of diagnosis, there was no decrease in the number of cases from outside of the Tochigi prefecture. Regarding the month of diagnosis, there was a notable decrease in the number of registered patients in May and August of 2020. Among the decrease of 836 cases detected by screening, 689(82.4%) were cases of stomach, lung, colorectum, female breast, cervix, and prostate cancer. The number of registered cases of malignant lymphoma, leukemia, and cancer of the oral cavity and pharynx, pancreas, bone and soft tissue, corpus uteri, and bladder did not decrease between 2019 and 2020. In terms of stage of cancer, the number of registered cases of carcinoma in situ, localized cancer, and regional lymph node metastases was lower in 2020 than in 2019, but there was no decrease in the number of registered cases of distant metastases or regional extension.Conclusion　The number of cancer cases registered in 2020 was lower than in 2019, and the degree of change varied by age, hospital, site, whether the case was detected by screening, and stage of cancer. In particular, a marked decrease was observed in the number of cases detected by screening. Furthermore, the decrease in the number of cancer cases registered in May and August of 2020 were believed to be due to the peak in the spread of COVID-19 and the associated declaration of a state of emergency.

Impact of correlations between prioritized outcomes on the net benefit and its estimate by generalized pairwise comparisons.

Benefit-risk balance is gaining interest in clinical trials. For the comprehensive assessment of benefits and risks, generalized pairwise comparisons are increasingly used to estimate the net benefit based on multiple prioritized outcomes. Although previous research has demonstrated that the correlations between the outcomes impact the net benefit and its estimate, the direction and magnitude of this impact remain unclear. In this study, we investigated the impact of correlations between two binary or Gaussian variables on the true net benefit values via theoretical and numerical analyses. We also explored the impact of correlations between survival and categorical variables on the net benefit estimates based on four existing methods (Gehan, Péron, Gehan with correction, and Péron with correction) in the presence of right censoring via simulation and application to actual oncology clinical trial data. Our theoretical and numerical analyses revealed that the true net benefit values were impacted by the correlations in various directions depending on the outcome distributions. With binary endpoints, this direction was governed by a simple rule with a threshold of 50% for a favorable outcome. Our simulation showed that the net benefit estimates based on Gehan's or Péron's scoring rule could be substantially biased in the presence of right censoring, and that the direction and magnitude of this bias were associated with the outcome correlations. The recently proposed correction method greatly reduced this bias, even in the presence of strong outcome correlations. The impact of correlations should be carefully considered when interpreting the net benefit and its estimate.

Mid-term outcomes of intracorporeal versus extracorporeal anastomosis after laparoscopic colectomy: a propensity score-matched cohort study from a single institution.

PURPOSE: There is still insufficient discussion of the mid- to long-term safety of the intracorporeal anastomosis (IA) method of reconstruction after laparoscopic colectomy (LAC) for colon cancer. The present study clarified the postoperative mid-term results of IA based on recurrence and the incidence of incision hernia. METHODS: This single-institution observational retrospective study included 268 patients with colon cancer who underwent IA or extracorporeal anastomosis (EA) after LAC at our institution between 2018 and 2021. The mid-term results of the IA group were compared with those of the EA group using a propensity score matching method. RESULTS: The median follow-up periods were 36 and 25 months in the EA and IA groups, respectively (p < 0.0001). In this matched cohort study, the recurrence-free survival (RFS) rates were comparable between the IA and EA groups (each group, n = 72; 3-year RFS: IA, 92.1%; EA, 88.2%; hazard ratio, 0.78; 95% confidence interval, 0.25-2.40; p = 0.66). The cumulative incisional hernia rates were 9.8% and 9.9% (p = 0.99) for the IA and EA groups, respectively. CONCLUSION: The safety of IA after LAC was demonstrated in this study, as IA after LAC showed good mid-term results, including with regard to the rates of recurrence and incisional hernia.

[Usefulness of Nutritional Evaluation in Adjuvant Chemotherapy for Colorectal Cancer in Older Patients].

OBJECTIVE: To clarify the usefulness of Onodera's prognostic nutritional index(OPNI)in adjuvant chemotherapy(AC)for older patients with colorectal cancer. MATERIALS AND METHODS: This study included 39 patients aged over 70 years who underwent AC for colorectal cancer from August 2009 to February 2018. We evaluated the association of OPNI with AC toxicities and prognosis. RESULTS: OPNI was an independent predictor of toxicities of Grade 3 or higher(OR: 0.18, 95%CI: 0.043-0.75, p=0.019). The 3-year recurrence-free survival rate was significantly better in the higher OPNI group than in the lower OPNI group(89.9% and 66.7%, respectively; HR: 0.19, 95%CI: 0.04-0.92, p=0.038). There was a positive correlation with Spearman's rank correlation coefficient of 0.66 in OPNI before and after AC(p<0.001). CONCLUSION: OPNI could be one of the valuable predictors of AC toxicities and the prognosis. There was a high correlation between OPNI before and after AC. These findings suggest the importance of early nutritional support for patients with lower OPNI.

High expression of Sam68 contributes to metastasis by regulating vimentin expression and a motile phenotype in oral squamous cell carcinoma.

The present study aimed to investigate the clinical and biological significance of Src­associated in mitosis 68 kDa (Sam68) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis was performed on tissue samples obtained from 77 patients with OSCC. Univariate analysis revealed that the high expression of Sam68 was significantly correlated with advanced pathological T stage (P=0.01), positive lymphovascular invasion (P=0.01), and pathological cervical lymph node metastasis (P<0.01). Moreover, multivariate analysis demonstrated that the high expression of Sam68 was an independent predictive factor for cervical lymph node metastasis (odds ratio, 4.39; 95% confidence interval, 1.49­14.23; P<0.01). These results indicated that high Sam68 expression contributed to tumor progression, especially cervical lymph node metastasis, in OSCC. mRNA sequencing was also performed to assess the changes in the transcriptome between OSCC cells with Sam68 knockdown and control cells with the aim of elucidating the biological roles of Sam68. Gene Ontology enrichment analysis revealed that downregulated differentially expressed genes (DEGs) were concentrated in some biological processes related to epithelial­mesenchymal transition. Among these DEGs, it was established that vimentin was particularly downregulated in these cells. It was also confirmed that Sam68 knockdown reduced the motility of OSCC cells. Furthermore, the immunohistochemical study of vimentin identified the association between vimentin expression and Sam68 expression as well as cervical lymph node metastasis. In conclusion, the present study suggested that the high expression of Sam68 may contribute to metastasis by regulating vimentin expression and a motile mesenchymal phenotype in OSCC.

Laparoscopic Colectomy for a Patient with Situs Inversus Totalis: The Usefulness of Preoperative Assessment.

BACKGROUND Situs inversus totalis (SIT) is a rare congenital anomaly in which the patient's internal organs are positioned in a mirror image of their normal locations. Laparoscopic surgery for a patient with SIT requires modification of the standard procedure. Several studies have recently reported surgical techniques for laparoscopic colectomy in patients with SIT. Herein, we present the case of a patient with congenital SIT who underwent laparoscopic colectomy for transverse colon cancer with intracorporeal anastomosis and discuss the usefulness of preoperative assessment. CASE REPORT A 63-year-old woman with SIT was referred to our department for surgical intervention following endoscopic submucosal dissection of transverse colon cancer. We performed a successful laparoscopic colectomy with intracorporeal anastomosis. Our team had no prior experience performing laparoscopic surgery on a patient with SIT; however, preoperative image training using a horizontally flipped video of a normal laparoscopic colectomy enabled the operation to be performed safely. Preoperative image training is very useful for gaining an understanding of images similar to the actual field of view before surgery. The patient was discharged without complications on the eighth postoperative day. CONCLUSIONS Careful preoperative assessment that takes into consideration the mirror-image anatomy and the contemplated laparoscopic procedure should allow patients with SIT to fully benefit from minimally invasive surgery.

[Retrospective Analysis of Adjuvant Chemotherapy for Elderly Patients with Stage â ¢ Colorectal Cancer].

OBJECTIVE: To investigate the efficacy and toxicity of adjuvant chemotherapy(AC)in elderly patients with Stage Ⅲ colorectal cancer(CRC). METHODS: We performed a single-institutional retrospective analysis of 84 patients aged≥75 years with Stage Ⅲ CRC who underwent curative resection from August 2009 to February 2018. RESULTS: Thirty-seven(44.0%) patients received AC. Eleven(29.7%)patients required dose reduction at the start of AC. Twenty-three(62.2%)patients accomplished AC, and 13(35.1%)needed dose reduction during AC. Although toxicities of Grade 3 or higher occurred in 56.8% of patients, they were controllable. The 3-year recurrence-free survival rate was significantly better in the AC group than in the non-AC group(70.3% versus 50.5%, respectively; p=0.011). The prognosis tended to be worse in the group that started AC with dose reduction than in the group with the normal dose. CONCLUSION: AC is effective and well tolerated in elderly patients with Stage Ⅲ CRC. When reducing the initial dose, the need for dose reduction should be carefully considered.

Acute cold stress induces transient MuRF1 upregulation in the skeletal muscle of zebrafish.

Cryotherapy is one of the most common treatments for trauma or fatigue in the field of sports medicine. However, the molecular biological effects of acute cold exposure on skeletal muscle remain unclear. Therefore, we used zebrafish, which have recently been utilized as an animal model for skeletal muscle, to comprehensively investigate and selectively clarify the time-course changes induced by cryotherapy. Zebrafish were exposed intermittently to cold stimulation three times for 15 min each. Thereafter, skeletal muscle samples were collected after 15 min and 1, 2, 4, and 6 h. mRNA sequencing revealed the involvement of trim63a, fbxo32, fbxo30a, and klhl38b in "protein ubiquitination" from the top 10 most upregulated genes. Subsequently, we examined the time-course changes of the four genes by quantitative PCR, and their expression peaked 2 h after cryotherapy and returned to baseline after 6 h. Moreover, the proteins encoded by trim63a and fbxo32 (muscle-specific RING finger protein 1 [MuRF1] and muscle atrophy F-box, respectively), which are known to be major genes encoding E3 ubiquitin ligases, were examined by western blotting, and MuRF1 expression displayed similar temporal changes as trim63a expression. These findings suggest that acute cold exposure transiently upregulates E3 ubiquitin ligases, especially MuRF1; thus, cryotherapy may contribute to the treatment of trauma or fatigue by promoting protein processing.

Usefulness of Carcinoembryonic Antigen Doubling Time in Prognosis Prediction after Curative Resection of Locally Recurrent Rectal Cancer: A Retrospective Study.

INTRODUCTION: Given that doubling time is an indicator of tumor growth, we assessed the usefulness of carcinoembryonic antigen doubling time (CEA-DT) in prognosis prediction after curative resection for locally recurrent rectal cancer. METHODS: During January 1986-December 2016, 33 patients with locally recurrent rectal cancer who underwent curative resection at our hospital were retrospectively reviewed. The primary endpoint was the 3-year recurrence-free survival (RFS) rate. The Kaplan-Meier method was used to compare RFS rates and evaluate univariate and multivariate analyses for factors associated with oncologic outcomes, including CEA-DT. CEA-DT was classified into 2 groups: the short and long CEA-DT groups. RESULTS: The 3-year overall survival and RFS rates were 62.6% and 42.4%, respectively. In multivariate analyses, CEA-DT was an independent risk factor for poor RFS. The 3-year RFS rate was significantly better in the long CEA-DT group than in the short CEA-DT group (58.8% vs. 25.0%, p = 0.0063). CONCLUSION: CEA-DT is a useful prognostic factor that can be assessed before surgery for locally recurrent rectal cancer. Long CEA-DT may indicate a favorable prognosis. Contrarily, short CEA-DT is associated with poor prognosis; therefore, further treatment intervention is necessary for patients with short CEA-DT.

Challenges needed to be overcome in multi-institutional surgical trials: accumulated experience in the JCOG Colorectal Cancer Study Group (CCSG).

JCOG-CCSG has been conducting several surgical trials and experienced several challenges. The first point is the appropriate timing of conducting the trial. Once a certain number of surgeons acquire the new technique and its utility is accepted, it suddenly becomes difficult to maintain 'equipoise' between the standard and new treatment, which may lead to poor patient accrual. Smooth preparation and commencement of the trial at an appropriate timing is necessary for its success. Second is the appropriate quality assurance of surgery. High-level quality assurance will strengthen the comparability of randomized control trials and minimize the heterogeneity among hospitals. On the other hand, it may impair the generalizability of the trial. Large observational studies help to bridge the gap of heterogeneity among hospitals. Third is the selection of an appropriate endpoint. Overall survival (OS) is the gold-standard primary endpoint; however, the number of events is much less due to more effective treatment. JCOG0212 and JCOG0404 were unable to demonstrate the non-inferiority of omission of lateral lymph node dissection and laparoscopic surgery partly due to a lack of power. Disease-free survival (DFS) is also a promising candidate for primary endpoint, but as in JCOG0603, special attention must be paid when DFS does not correlate with OS. Although careful discussion is required because the precision of the hazard ratio depends on the number of events, an alternative population-level summary of variables, including restricted mean survival time, can be considered as the primary endpoint. Future surgical trials should be planned considering these points.

Preoperative and postoperative prognostic factors of patients with stage II/III lower rectal cancer without neoadjuvant therapy in the clinical trial (JCOG0212).

BACKGROUND: The JCOG0212 trial was a randomized controlled trial comparing mesorectal excision alone to mesorectal excision with lateral lymph node dissection for stage II/III lower rectal cancer patients without clinical lateral lymph node enlargement. This study aimed to identify clinicopathological prognostic factors for relapse-free survival and overall survival of lower rectal cancer in the trial. METHODS: Prospective data were selected from 663 patients with complete data. Uni and multivariable Cox regression model was applied to evaluate the preoperative and the combined preoperative and postoperative factors, respectively. Preoperative factors included age, sex, performance status, clinical T, clinical N and operative procedures. Postoperative factors included histological grade, pathological T, number of metastatic lymph nodes and number of dissected lymph nodes. No patient received neoadjuvant treatment. RESULTS: Regarding preoperative factors, multivariable analysis revealed that performance status 1 (vs. 0: HR 2.079, P = 0.0041) and cT4a (vs. cT2-3: HR 2.721, P = 0.0002) were independent risk factors for relapse-free survival, and those for overall survival were male (vs. female: HR 1.660, P = 0.0228) and cT4a (vs. cT2-3: HR 2.486, P = 0.0473). The only independent preoperative risk factor common for relapse-free survival and overall survival was cT4a. Taking preoperative and postoperative factors together, the number of metastatic lymph nodes was the only independent risk factor common for relapse-free survival and overall survival. CONCLUSIONS: Clinical stage II/III lower rectal cancer patients with cT4a should be a target of therapeutic development of neoadjuvant therapy. Postoperatively, intensive chemotherapy should be investigated for patients with more metastatic lymph nodes.

Short-term outcomes of intracorporeal versus extracorporeal anastomosis after laparoscopic colectomy: a propensity score-matched cohort study from a single institution.

PURPOSE: To compare the postoperative short-term results of intracorporeal anastomosis (IA) using overlap anastomosis (OLA), with those of extracorporeal anastomosis (EA) using functional end-to-end anastomosis (FEEA) or hand-sewn anastomosis (HSA), after laparoscopic colectomy (LAC). METHODS: The subjects of this retrospective study were 208 patients with colon cancer who underwent OLA, FEEA, or HSA after LAC at our institution, between 2018 and 2021. The short-term results of the OLA group were compared with those of the FEEA and HSA groups, respectively, using a propensity score-matching method. RESULTS: The mean operative time for anastomosis was longer in the OLA group than in the FEEA and HSA groups (p < 0.0001). The mean blood loss volume was less in the OLA group than in the FEEA and HSA groups (p = 0.0344 and p = 0.0002, respectively). The mean skin incision size was smaller in the OLA group than in the FEEA and HSA groups (p < 0.0001 and p = 0.0031, respectively). None of the patients in the OLA group had surgical site infections. Three to five patients were required for the surgeon to plateau on the learning curve. CONCLUSION: Although IA required more time than EA, the skills appeared to improve with experience and the short-term results were superior to those of EA.

Accuracy of wristwatch-type photoplethysmography in detecting atrial fibrillation in daily life.

Aims: Detection of asymptomatic paroxysmal atrial fibrillation is challenging. Smartphone- or smartwatch-based photoplethysmography is efficient at detecting irregular rhythms using pulse waves but is too complex for older patients. We aimed to evaluate the detection accuracy of atrial fibrillation by a wristwatch-type continuous pulse wave monitor (PWM) in daily life. Methods and results: Patients at high risk of atrial fibrillation but with no history of atrial fibrillation (n = 163; mean CHADS2 score, 1.9) and patients with known atrial fibrillation (n = 123, including 34 with persistent atrial fibrillation) underwent PWM and telemetry electrocardiogram recording for 3 days. Risk of atrial fibrillation was judged using the 'Kyorin Atrial Fibrillation Risk Score', a scoring system based on previously reported atrial fibrillation risk scoring systems. The PWM assessed the presence of atrial fibrillation at 30 min intervals, and the results were compared with the telemetry electrocardiogram findings. The PWMs accurately diagnosed two patients with paroxysmal atrial fibrillation in the high-risk group. The PWMs accurately diagnosed 48 of the 55 patients with atrial fibrillation in the known-atrial fibrillation group. The PWM accuracy in detecting patients with atrial fibrillation was as follows: sensitivity, 98.0%; specificity, 90.6%; positive predictive value, 69.4%; negative predictive value, 99.5%. The respective values for intervals with atrial fibrillation were 86.9%, 98.8%, 89.6%, and 98.5%. Conclusion: The wristwatch-type PWM has shown feasibility in detecting atrial fibrillation in daily life and showed the possibility of being used as a screening tool.

A Pilot Study of miRNA Expression Profile as a Liquid Biopsy for Full-Marathon Participants.

Exosomal microRNA (miRNA) in plasma and urine has attracted attention as a novel diagnostic tool for pathological conditions. However, the mechanisms of miRNA dynamics in the exercise physiology field are not well understood in terms of monitoring sports performance. This pilot study aimed to reveal the miRNA dynamics in urine and plasma of full-marathon participants. Plasma and urine samples were collected from 26 marathon participants before, immediately after, 2 h after, and one day after a full marathon. The samples were pooled, and exosomal miRNAs were extracted and analyzed using next-generation sequencing. We determined that the exosomal miRNA expression profile changed under time dependency in full marathon. New uncharacterized exosomal miRNAs such as hsa-miR-582-3p and hsa-miR-199a-3p could be potential biomarkers reflecting physical stress of full marathon in plasma and urine. In addition, some muscle miRNAs in plasma and urine have supported the utility for monitoring physical stress. Furthermore, some inflammation-related exosomal miRNAs were useful only in plasma. These results suggest that these exosomal miRNAs in plasma and/or urine are highly sensitive biomarkers for physical stress in full marathons. Thus, our findings may yield valuable insights into exercise physiology.

Proof of Gene Doping in a Mouse Model with a Human Erythropoietin Gene Transferred Using an Adenoviral Vector.

Despite the World Anti-Doping Agency (WADA) ban on gene doping in the context of advancements in gene therapy, the risk of EPO gene-based doping among athletes is still present. To address this and similar risks, gene-doping tests are being developed in doping control laboratories worldwide. In this regard, the present study was performed with two objectives: to develop a robust gene-doping mouse model with the human EPO gene (hEPO) transferred using recombinant adenovirus (rAdV) as a vector and to develop a detection method to identify gene doping by using this model. The rAdV including the hEPO gene was injected intravenously to transfer the gene to the liver. After injection, the mice showed significantly increased whole-blood red blood cell counts and increased expression of hematopoietic marker genes in the spleen, indicating successful development of the gene-doping model. Next, direct and potentially indirect proof of gene doping were evaluated in whole-blood DNA and RNA by using a quantitative PCR assay and RNA sequencing. Proof of doping could be detected in DNA and RNA samples from one drop of whole blood for approximately a month; furthermore, the overall RNA expression profiles showed significant changes, allowing advanced detection of hEPO gene doping.

Risk factors for surgical site infection and association of surgical site infection with survival of lower rectal cancer patients without clinical lateral pelvic lymph node metastasis (clinical Stage II/III): Analysis of data from JCOG0212.

This study aimed to examine the risk factors for surgical site infection (SSI) and the association of that with recurrence in JCOG0212. The results for secondary endpoints showed that compared with the mesorectal excision (ME) alone group, ME with lateral lymph node dissection (LLND) group showed significantly longer operative time and significantly higher blood loss. These results suggested that LLND was a risk factor for SSI. All 701 patients registered in JCOG0212 were analyzed in this study. Wound infection was defined as incisional/deep SSI, and pelvic abscess and anastomotic leakage were defined as organ/space SSI. The risk factors for the incidence of SSI and the effect of SSI on relapse-free survival (RFS) were investigated. Multivariable odds ratio of Grade 2 or higher all SSI was 0.58 [95% Confidence interval: 0.36-0.93] for female (vs. male) and that of Grade 2 or higher incisional/deep SSI was 2.24 [1.03-4.86] for blood infusion. For RFS, patients with Grade 3 or higher all SSI showed poor prognosis (multivariable hazard ratio: 1.66 [1.03-2.68]). LLND is not significant factor for the incidence of all SSI. Male sex might be a risk factor of Grade 2 or higher SSI, and blood transfusion is a possible risk factor of Grade 2 or higher incisional/deep SSI. Grade 3 or higher all SSI might be a significant worse prognostic factor for lower rectal cancer.