The pyruvate-GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells.

The intestinal lumen is rich in gut microbial metabolites that serve as signaling molecules for gut immune cells. G-protein-coupled receptors (GPCRs) sense metabolites and can act as key mediators that translate gut luminal signals into host immune responses. However, the impacts of gut microbe-GPCR interactions on human physiology have not been fully elucidated. Here, we show that GPR31, which is activated by the gut bacterial metabolite pyruvate, is specifically expressed on type 1 conventional dendritic cells (cDC1s) in the lamina propria of the human intestine. Using human induced pluripotent stem cell-derived cDC1s and a monolayer human gut organoid coculture system, we show that cDC1s extend their dendrites toward pyruvate on the luminal side, forming transepithelial dendrites (TED). Accordingly, GPR31 activation via pyruvate enhances the fundamental function of cDC1 by allowing efficient uptake of gut luminal antigens, such as dietary compounds and bacterial particles through TED formation. Our results highlight the role of GPCRs in tuning the human gut immune system according to local metabolic cues.

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis.

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer1-3. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals. Mutational profiles vary substantially between colitis-associated cancer and non-dysplastic tissues in ulcerative colitis, which indicates that there are distinct mechanisms of positive selection in both tissues. In particular, mutations in NFKBIZ are highly prevalent in the epithelium of patients with ulcerative colitis but rarely found in both sporadic and colitis-associated cancer, indicating that NFKBIZ-mutant cells are selected against during colorectal carcinogenesis. In further support of this negative selection, we found that tumour formation was significantly attenuated in Nfkbiz-mutant mice and cell competition was compromised by disruption of NFKBIZ in human colorectal cancer cells. Our results highlight common and discrete mechanisms of clonal selection in inflammatory tissues, which reveal unexpected cancer vulnerabilities that could potentially be exploited for therapeutics in colorectal cancer.

Identification of a unique subset of tissue-resident memory CD4+ T cells in Crohn's disease.

T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4+ tissue-resident memory T cell (Trm) subset that is increased in Crohn's disease (CD) showing unique inflammatory properties. Functionally and transcriptionally distinct CD4+ Trm subsets are observed in the inflamed gut mucosa, among which a CD-specific CD4+ Trm subset, expressing CD161 and CCR5 along with CD103, displays previously unrecognized pleiotropic signatures of innate and effector activities. These inflammatory features are further enhanced by their spatial proximity to gut epithelial cells. Furthermore, the CD-specific CD4+ Trm subset is the most predominant producer of type 1 inflammatory cytokines upon various stimulations among all CD4+ T cells, suggesting that the accumulation of this T cell subset is a pathological hallmark of CD. Our results provide comprehensive insights into the pathogenesis of IBD, paving the way for decoding of the molecular mechanisms underlying this disease.

Histological differentiation between sporadic and colitis-associated intestinal cancer in a nationwide study: A propensity-score-matched analysis.

BACKGROUND AND AIM: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. METHODS: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data. RESULTS: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). CONCLUSION: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression.

Association between Sense of Coherence, Disease-Specific Symptoms, and Health-Related Quality of Life among Japanese Patients with Ulcerative Colitis: A Cross-Sectional Study.

INTRODUCTION: We examined the associations among disease-related symptoms, health-related quality of life (HRQOL), and sense of coherence (SOC) in Japanese patients with ulcerative colitis (UC). METHODS: This cross-sectional survey involved patients and physicians at 23 hospitals specializing in UC treatment in Japan (December 2019-December 2020). Multiple linear regression analysis was performed using scores on the Mental Health and General Health subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey as outcomes and SOC as the main independent variable. Scores on the Inflammatory Bowel Disease Questionnaire (IBDQ) and Fecal Incontinence Quality of Life Scale (FIQL) were used to measure the effect of disease-related symptoms. The moderating effect of symptoms on the association between HRQOL and SOC was also tested. RESULTS: SOC was positively and independently associated with HRQOL (Mental Health: ß = 0.43, 95% confidence interval [CI] = 0.24-0.61, p < 0.001; General Health: ß = 0.41, 95% CI = 0.23-0.59, p < 0.001). The association of SOC with Mental Health scores did not differ by symptoms, whereas its association with General Health was attenuated by symptoms (interaction term of IBDQ by SOC: ß = -0.0082, 95% CI = -0.017 to 0.00064, p = 0.07; that of FIQL by SOC: ß = -0.0052, 95% CI = -0.011 to 0.0010, p = 0.10). CONCLUSIONS: SOC affected mental health independently, and its protective association with general health perception was affected by symptoms. Further research is required to determine the most effective use of SOC in interventions to improve HRQOL in patients with UC.

Subcutaneous emphysema associated with laparoscopic or robotic abdominal surgery: a retrospective single-center study.

BACKGROUND: Subcutaneous emphysema (SCE) is a common complication in laparoscopic surgery. However, its precise incidence and impact on the clinical course are partially known. In this study, the incidence and risk factors of SCE were retrospectively analyzed. METHODS: Patients who underwent laparoscopic/robotic abdominal surgery (e.g., gastrointestinal, hepatobiliary, gynecologic, and urologic surgery) between October 2019 and September 2022 were retrospectively analyzed. The presence of SCE was confirmed by either conclusive findings obtained through chest/abdominal X-ray examination immediately after operation, or intraoperative palpation conducted by nurses. X-ray examination was performed in the operation room before extubation. RESULTS: A total of 2503 patients treated with laparoscopic/robotic abdominal surgery between October 2019 and September 2022 were identified and all of them were included in the analysis. SCE was confirmed in 23.1% of the patients (i.e., 577/2503). SCE was identified by X-ray examination in 97.6% of the patients. Extubation failure was observed in 10 patients; however, pneumothorax was not observed. Female sex (odds ratio [OR]: 2.09; 95% confidence interval [95%CI]: 1.69-2.57), age ≥ 80 years (OR 1.63; 95%CI 1.19-2.22), body mass index < 20 (OR 1.32; 95%CI 1.06-1.65), operation time > 360 min (OR 1.97; 95%CI 1.53-2.54), robotic surgery (OR 2.54; 95%CI 1.91-3.38), maximum intraabdominal pressure with CO2 > 15 mmHg (OR 1.79; 95%CI 1.02-3.16), and endo-tidal CO2 > 50 mmHg (OR 1.32; 95%CI 1.08-1.62)were identified as independent factors of SCE. Regarding the extubation failure due to SCE, age (OR 5.84; 95%CI 1.27-26.8) and maximum intraabdominal pressure with CO2 (OR 21.7; 95%CI 4.76-99.3) were identified as risk factors. CONCLUSION: Although the presence of SCE is associated with a low risk of severe complications, monitoring of the perioperative intraabdominal pressure is essential for performing safe laparoscopic/robotic surgery, particularly in elderly patients.

Crohn's Disease-Associated Anorectal Cancer Has a Poor Prognosis With High Local Recurrence: A Subanalysis of the Nationwide Japanese Study.

INTRODUCTION: Colorectal cancer (CRC) is one of the major life-threatening complications in patients with Crohn's disease (CD). Previous studies of CD-associated CRC (CD-CRC) have involved only small numbers of patients, and no large series have been reported from Asia. The aim of this study was to clarify the prognosis and clinicopathological features of CD-CRC compared with sporadic CRC. METHODS: A large nationwide database was used to identify patients with CD-CRC (n = 233) and sporadic CRC (n = 129,783) over a 40-year period, from 1980 to 2020. Five-year overall survival (OS), recurrence-free survival (RFS), and clinicopathological characteristics were investigated. The prognosis of CD-CRC was further evaluated in groups divided by colon cancer and anorectal cancer (RC). Multivariable Cox regression analysis was used to adjust for confounding by unbalanced covariables. RESULTS: Compared with sporadic cases, patients with CD-CRC were younger; more often had RC, multiple lesions, and mucinous adenocarcinoma; and had lower R0 resection rates. Five-year OS was worse for CD-CRC than for sporadic CRC (53.99% vs 71.17%, P < 0.001). Multivariable Cox regression analysis revealed that CD was associated with significantly poorer survival (hazard ratio 2.36, 95% confidence interval: 1.54-3.62, P < 0.0001). Evaluation by tumor location showed significantly worse 5-year OS and RFS of CD-RC compared with sporadic RC. Recurrence was identified in 39.57% of CD-RC cases and was mostly local. DISCUSSION: Poor prognosis of CD-CRC is attributable primarily to RC and high local recurrence. Local control is indispensable to improving prognosis.

Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study.

INTRODUCTION: The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS: The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS: In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION: Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

Transanal Minimally Invasive Surgical Approach to Total Pelvic Exenteration.

BACKGROUND: Total pelvic exenteration, a surgical procedure for patients with highly advanced primary and recurrent rectal cancer, is technically demanding. IMPACT OF INNOVATION: We report the utility of a transanal minimally invasive surgical approach to total pelvic exenteration. TECHNOLOGY MATERIALS AND METHODS: A 2-team approach with a laparoscopic transabdominal approach and transanal minimally invasive surgery was adopted. During the transabdominal approach in the pelvis, dissection was performed to remove the pelvic organs and visceral branches of the internal iliac vessels. The dissection goal via the transabdominal approach is the levator ani. During the transperineal approach, dissection is performed along the levator ani, and the tendinous arch of the levator ani is penetrated at the lateral side to achieve rendezvous between the 2 approaches. The levator ani is then dissected circumferentially, with identification of the internal pudendal vessels passing through the levator ani at the 4 o'clock and 8 o'clock positions, known as Alcock's canal. The anterior wall of Alcock's canal is formed by the coccygeus muscle and sacrospinous ligament, which are dissected by the transperineal approach to open Alcock's canal, thus obtaining a clear view of the internal pudendal vessels. On the anterior side, the urethra is divided with a laparoscopic linear stapler via the transperineal approach. PRELIMINARY RESULTS: Eight patients with rectal cancer underwent this procedure. The median (range) blood loss was 200 (120-1520) mL and operating time was 467 (321-833) minutes. Reoperation was performed in 1 internal hernia case; however, there were no mortalities, and there were no cases with severe complications or conversion to open surgery. CONCLUSIONS AND FUTURE DIRECTIONS: When performing total pelvic exenteration, transanal minimally invasive surgery offers direct visualization behind the tumor from the anal side and shows the deep pelvic structures, including the retroperitoneal space of the pelvic sidewall.

Risk factors for the postoperative recurrence of ulcerative colitis-associated colorectal cancer.

PURPOSE: Although ulcerative colitis-associated colorectal cancer (UC-CRC) has been described, there are few reports regarding recurrent cases of UC-CRC. In this study, we investigated the risk factors for UC-CRC recurrence. METHODS: Recurrence-free survival (RFS) was determined for 144 stage I to III cancer patients among 210 UC-CRC patients from August 2002 to August 2019. The Kaplan‒Meier method was used to obtain the cumulative RFS rate, and the Cox proportional hazard model was used to extract recurrence risk factors. The interaction term between cancer stage and prognostic factors specific to UC-CRC was evaluated using the Cox model. The Kaplan‒Meier method was applied by cancer stage to the UC-CRC-specific prognostic factors for which interaction effects were indicated. RESULTS: There were 18 cases of recurrence involving patients with stage I to III cancer, and the recurrence rate was 12.5%. The cumulative 5-year RFS rate was 87.5%. Multivariable analysis showed that age at surgery (hazard ratio (HR): 0.95, 95% CI: 0.91-0.99, p = 0.02), undifferentiated carcinoma (HR: 4.42, 95% CI: 1.13-17.24, p = 0.03), lymph node metastasis (HR: 4.11, 95% CI: 1.08-15.69, p = 0.03), and vascular invasion (HR: 8.01, 95% CI: 1.54-41.65, p = 0.01) were significant risk factors for recurrence. Patients with stage III CRC in the young adult (age < 50 years) group had a significantly worse prognosis than those in the adult (age ≥ 50 years) group (p < 0.01). CONCLUSION: Age at surgery was identified as a risk factor for UC-CRC recurrence. Young adult patients with stage III cancer may have a poor prognosis.

Convergent evolutionary counterion displacement of bilaterian opsins in ciliary cells.

Opsins are universal photoreceptive proteins in animals. Vertebrate rhodopsin in ciliary photoreceptor cells photo-converts to a metastable active state to regulate cyclic nucleotide signaling. This active state cannot photo-convert back to the dark state, and thus vertebrate rhodopsin is categorized as a mono-stable opsin. By contrast, mollusk and arthropod rhodopsins in rhabdomeric photoreceptor cells photo-convert to a stable active state to stimulate IP3/calcium signaling. This active state can photo-convert back to the dark state, and thus these rhodopsins are categorized as bistable opsins. Moreover, the negatively charged counterion position crucial for the visible light sensitivity is different between vertebrate rhodopsin (Glu113) and mollusk and arthropod rhodopsins (Glu181). This can be explained by an evolutionary scenario where vertebrate rhodopsin newly acquired Glu113 as a counterion, which is thought to have led to higher signaling efficiency of vertebrate rhodopsin. However, the detailed evolutionary steps which led to the higher efficiency in vertebrate rhodopsin still remain unknown. Here, we analyzed the xenopsin group, which is phylogenetically distinct from vertebrate rhodopsin and functions in protostome ciliary cells. Xenopsins are blue-sensitive bistable opsins that regulate cAMP signaling. We found that a bistable xenopsin of Leptochiton asellus had Glu113 as a counterion but did not exhibit elevated signaling efficiency. Therefore, our results show that vertebrate rhodopsin and L. asellus xenopsin regulate cyclic nucleotide signaling in ciliary cells and displaced the counterion position from Glu181 to Glu113 via convergent evolution, whereas subsequently only vertebrate rhodopsin elevated its signaling efficiency by acquiring the mono-stable property.

Efficacy, safety, and pharmacokinetics of teduglutide in adult Japanese patients with short bowel syndrome and intestinal failure: two phase III studies with an extension.

PURPOSE: The short- and long-term efficacy, safety, and pharmacokinetics of teduglutide were analyzed in adult Japanese patients with short bowel syndrome and intestinal failure (SBS-IF). METHODS: Patients received teduglutide 0.05 mg/kg/day in clinical trials (TED-C14-004, SHP633-306, and extension SHP633-307). Data were analyzed at 24 weeks and an interim data cut-off of 4.5 years. RESULTS: The parenteral support (PS) volume decreased by ≥ 20% for 9/18 patients at 24 weeks and in all 11 patients by data cut-off in SHP633-307. The mean (standard deviation) PS volume decreased from baseline at 24 weeks in TED-C14-004 (-30.1 ± 25.9%) and SHP633-306 (-25.6 ± 25.5%), and at data cut-off in SHP633-307 (-57.08 ± 28.49%). Teduglutide was absorbed quickly. The adverse events were consistent with the underlying disease and known adverse drug reactions. Anti-teduglutide antibody titers declined with long-term treatment. CONCLUSIONS: In Japanese adults with SBS-IF, teduglutide treatment was associated with clinically meaningful reductions in PS requirements, similar to findings in prior international studies. No new safety concerns specific to the Japanese SBS-IF patient population were identified with short- or long-term teduglutide treatment. Anti-teduglutide antibody titers disappeared in most Japanese adults with long-term treatment. These results constitute the longest evaluation of teduglutide treatment within clinical trials reported to date.

Clinical features and surgical selection in colitis-associated colorectal cancer with ulcerative colitis.

PURPOSE: The aim of this study was to compare the clinical characteristics of ulcerative colitis (UC) patients who underwent surgery for cancer/dysplasia with those who underwent surgery for refractory disease and to discuss the preoperative preparation for successful hand-sewn IPAA. METHODS: Patients who underwent surgery for UC between January 2014 and December 2021 at Hyogo Medical University were included in the study. A total of 443 UC surgical cases were included in the study, which comprised 188 cancer/dysplasia patients and 255 refractory patients. Clinical records were compared retrospectively. RESULTS: The proportion of surgical UC cases with cancer/dysplasia has been on the rise, accounting for approximately 40% in recent years. The duration of disease (months) was 186 (2-590) in the cancer/dysplasia group and 48 (1-580) in the refractory group (p = 0.02). UC severity (mild/moderate/severe) was 119/69/0 in the cancer/dysplasia group and 18/157/80 in the refractory group (p < 0.01). The four nutrition factors of weight (55.2 (32.7-99.6) kg: 49.9 (20.3-85.2) kg), body mass index (21.0 (13.9-32.5) kg/m2: 18.3 (11.4-34.1)kg/m2), serum albumin level (4.3 (2.7-5.0)g/dl: 3.4 (1.4-5.2)g/dl) and prognostic nutrition index (49.2 (33.2-61.2): 40.9 (17.4-61.1)) were significantly higher in the cancer/dysplasia group (p < 0.01). The degree of obesity was also significantly higher in the cancer/dysplasia group (p < 0.01). CONCLUSION: UC patients with cancer/dysplasia were more likely than refractory patients to have mild inflammation; they also had a longer duration of UC disease and better nutritional status.

[Questionnaire Survey on the Timing of Comprehensive Genomic Profiling for Advanced Recurrent Colorectal Cancer and Its Impact on Patients].

BACKGROUNDS: Comprehensive genomic profiling(CGP)has been covered by health insurance since June 2019. However, the clinical impact of CGP on patients with metastatic colorectal cancer(mCRC)remains unclear. To date, there are very limited reports regarding patient-oriented outcomes of CGP in mCRC. PATIENTS: A questionnaire was completed by patients with mCRC who had already received their CGP results after April 2021. Eight questions were posed, covering the degree of satisfaction and timing when CGP was conducted. RESULTS: Of the 51 patients with mCRC who had received their CGP test results by August 2021 in our department, 21 patients responded to our questionnaire. In total 66.7% patients with mCRC answered "(very)satisfied"with the CGP testing. 28.6% of the patients already knew about CGP testing before their local doctors informed them. Except for 3 patients who did not answer, 47.6% and 9.5% of patients with mCRC"agreed"and "moderately agreed"with the timing of the CGP test. CONCLUSION: Although most patients with mCRC failed to access promising new treatment via CGP, approximately half of the patients answered that they were satisfied with the CGP testing. Conversely, a few patients already knew about CGP testing before it was proposed by their doctors. Thus, the provision of information at an early stage is necessary.

[Educational Project of Self-Removal of the Intravenous Central Venous Access Port Guided by Patients with Advanced Colorectal Cancer Instructed by a Nurse in the University Hospital].

BACKGROUND: Fluorouracil infusion for 46±5h from the central venous(CV)port is required for mFOLFOX6, FOLFIRI, and FOLFOXIRI in patients with advanced colorectal cancer(CRC), followed by self-removal of the needle by patients. At our hospital, outpatients were instructed for self-removal of the needle, but the results were unsatisfactory. Therefore, instructions for self-removal of the needle from the CV port have been initiated at the patient ward since April 2019, making use of a hospital stay of 3 days. PATIENTS: We retrospectively enrolled patients with chemotherapy-introduced advanced CRC from the CV port who received instructions for self-removal of the needle in the outpatient department and ward between January 2018 and December 2021. RESULTS: Of all patients with advanced CRC, 21 received instructions at the outpatient department(OP)while 67 at patient ward(PW). Incidences of successful self-removal of the needle without the aid of others were similar: 47% in OP and 52% in PW(p=0.80). However, after several additional instructions involving their families, it was higher in PW than in OP(97.0 vs 76.1%, p=0.005). Incidences of successful self-removal of the needle without the aid of others in those aged≥75/<75, and≥65/<65 years were 0%/61.1%, and 35.4%/67.5%, respectively. OP was as a risk factor for failed self-removal of the needle in the logistic regression analysis(odds ratio: 11.19, 95%CI: 1.86- 67.30). CONCLUSION: Repeated instructions involving patients' families during the hospital stay improved the incidence of successful self-removal of the needle. Involvement of patients' families from the beginning may effectively improve self- removal of the needle, particularly in the elderly patients with advanced CRC.

Effect of Changing Surgical Instruments Before Wound Closure to Prevent Wound Infection in Lower GI Surgery: A Randomized Controlled Trial.

BACKGROUND: Surgical site infection is a major surgical complication and has been studied extensively. However, the efficacy of changing surgical instruments before wound closure remains unclear. OBJECTIVE: The aim of this study was to investigate the efficacy of changing surgical instruments to prevent incisional surgical site infection during lower GI surgery. DESIGN: This was a randomized controlled trial. SETTINGS: This study was conducted at the Hyogo College of Medicine in Japan. PATIENTS: Patients undergoing elective lower GI surgery with open laparotomy were included. INTERVENTIONS: Patients were randomly assigned to 1 of 2 groups. In group A, the surgeon changed surgical instruments before wound closure, and in group B, the patients underwent conventional closure. MAIN OUTCOME MEASURES: The primary end point was the incidence of incisional surgical site infection. The secondary end point was the incidence of surgical site infection restricted to clean-contaminated surgery. RESULTS: A total of 453 patients were eligible for this trial. The incidence of incisional surgical site infection was not significantly different between group A (18/213; 8.5%) and group B (24/224; 10.7%; p = 0.78). In the clean-contaminated surgery group, the incidence of incisional surgical site infection was 13 (6.8%) of 191 in group A and 9 (4.7%) of 190 in group B (p = 0.51). LIMITATIONS: This was a single-center study. CONCLUSIONS: Changing surgical instruments did not decrease the rate of incisional surgical site infection in patients undergoing lower GI surgery in either all wound classes or clean-contaminated conditions. See Video Abstract at http://links.lww.com/DCR/B701. EFECTO DE REALIZAR CAMBIO DE LOS INSTRUMENTOS QUIRRGICOS ANTES DEL CIERRE DE LA INCISIN EN LA INFECCIN DE LA HERIDA DEL SITIO QUIRRGICO EN CIRUGA DEL TUBO DIGESTIVO BAJO ESTUDIO ALEATORIO CONTROLADO: ANTECEDENTES:La infección del sitio quirúrgico es una complicación importante y se ha estudiado ampliamente. Sin embargo, la eficacia de cambiar los instrumentos quirúrgicos antes del cierre de la herida sigue sin estar clara.OBJETIVO:El objetivo de este estudio es investigar la eficacia de cambiar el instrumental quirúrgico en la prevención de la infección del sitio quirúrgico en cirugía gastrointestinal inferior.DISEÑO:Estudio aleatorio controlado.AJUSTE:Este estudio se realizó en la Facultad de Medicina de Hyogo en Japón.PACIENTES:Se incluyeron pacientes sometidos a cirugía electiva de tubo digestivo bajo con laparotomía abierta.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente a uno de dos grupos. En el grupo A, el cirujano cambió el instrumental quirúrgico antes del cierre de la herida, y en el grupo B, los pacientes se sometieron a un cierre convencional.PRINCIPALES MEDIDAS DE RESULTADO:El criterio de valoración principal fue la incidencia de infección del sitio quirúrgico de la incisión. El criterio de valoración secundario fue la incidencia de infección del sitio quirúrgico restringida a la cirugía limpia contaminada.RESULTADOS:Un total de 453 pacientes fueron elegibles para este ensayo. La incidencia de infección del sitio quirúrgico no fue significativamente diferente entre el grupo A (18/213; 8,5%) y el grupo B (24/224; 10,7%) (p = 0,78). En el grupo de cirugía limpia-contaminada, la incidencia de infección del sitio quirúrgico incisional fue 13/191 (6,8%) en el grupo A y 9/190 (4,7%) en el grupo B (p = 0,51).LIMITACIÓN:Estudio de un solo centro.CONCLUSIÓNES:El cambio de instrumentos quirúrgicos no disminuyó la tasa de infección del sitio quirúrgico en todas las clases de heridas o condiciones limpias-contaminadas. Consulte Video Resumen en http://links.lww.com/DCR/B701.

Association between preoperative biologic use and surgical morbidity in patients with Crohn's disease.

PURPOSE: We evaluated the influence of preoperative treatments with biologics on surgical morbidity in patients with Crohn's disease (CD). METHODS: We reviewed the surveillance data of patients with CD who underwent surgery between April 2018 and April 2021. The possible risk factors for morbidity were analyzed. RESULTS: A total of 305 surgically treated patients were included. Anti-TNF alpha agents and ustekinumab were used in 92 and 27 patients, respectively, within 12 weeks before surgery. There were no cases of mortality. In total, 70/305 (23.0%) patients developed a complication, and 42/305 (13.8%) patients developed a surgical site infection (SSI) (17 incisional SSIs and 35 organ/space SSIs). Current smoking status (OR 3.44), emergent/urgent surgery (OR 6.85), and abdominoperineal resection (APR) (OR 14.93) were identified as risk factors for total complications. Penetrating disease (OR 14.55) was identified as a risk factor for incisional SSIs. Current smoking status (OR 7.09), an American Society of Anesthesiologists (ASA) score greater than 3 (OR 5.85), a postoperative blood sugar level over 155 mg/dL (OR 4.37), and APR (OR 207.95) were identified as risk factors for organ/space SSIs. CONCLUSIONS: No correlation between preoperative treatment with biologics and surgical mortality or morbidity was found. However, we should perform further analyses on a larger number of patients because the analyses may be limited by selection bias for treatment and several confounding factors.

Being Elderly Is Associated with Infectious and Fatal Postoperative Complications in Ulcerative Colitis Patients.

INTRODUCTION: It is well known that the infectious complications and mortality rates are increased among elderly individuals with ulcerative colitis (UC) during medical treatment. However, there have been few reports on surgery in elderly individuals with UC, and some cohort studies have reported surgical complication and mortality rates similar to those in nonelderly individuals. METHODS: UC patients who underwent colectomy at the Hyogo College of Medicine between April 2012 and March 2020 were included in this study. The patients were classified as elderly (≥65) or nonelderly (<65). Characteristics and postoperative complications were analyzed and compared between the groups; possible risk factors for infectious and fatal complications were also analyzed. RESULTS: In all, 136/599 (22.7%) elderly patients were included. The incidence of infectious and fatal complications was 177/599 (29.5%) and 18/599 (3%), respectively. These complication rates were significantly higher in the elderly than the nonelderly group (p < 0.01). Age ≥65 years at surgery (OR = 2.92, 95% CI: 1.87-4.57, p < 0.01) was identified as an independent risk factor for infectious complications. Age ≥65 years at surgery (OR = 8.03, 95% CI: 2.16-29.83, p < 0.01), American Society of Anesthesiologists score ≥3 (OR = 6.00, 95% CI: 1.40-25.6 p = 0.02), and urgent/emergent surgery (OR = 16.24, 95% CI: 1.70-154.95, p = 0.02) were identified as independent risk factors for fatal complications. DISCUSSION/CONCLUSION: Age ≥65 years was identified as a risk factor for infectious and fatal complications. It is important to avoid urgent/emergent surgery in elderly patients with an ASA score >3 by emphasizing surgical and medical collaboration and optimizing the timing of surgery.

Correction of thrombocytopenia caused by linezolid with scheduled sequential tedizolid use in patients with vertebral osteomyelitis by antibiotic resistant Gram-positive organisms.

INTRODUCTION: Because of thrombocytopenia, linezolid treatment tends to be stopped before the completion of therapy for complicated infections that require prolonged antimicrobial administration. In contrast, tedizolid shows a favorable hematologic profile. The primary end-point of this study was to evaluate the efficacy of switching treatment to tedizolid in patients who developed thrombocytopenia during linezolid therapy. METHODS: This retrospective study was conducted in patients with vertebral osteomyelitis (VO) caused by antibiotic-resistant Gram-positive bacteria. Treatment failure was defined as the reappearance of infection signs within 2 weeks after stopping tedizolid and discontinuation of tedizolid because of continued thrombocytopenia or other adverse effects. RESULTS: Eight patients with native VO (n = 3) and postoperative VO (n = 5) were included in the study. The causative organisms were MRSA in all patients except one. Platelet counts decreased from 35.2 ± 11.5 × 104/mm3 to 17.8 ± 6.2 × 104/mm3 during linezolid therapy and improved without washout period in all patients after switching to tedizolid on days 5-7 (28.6 ± 4.9 × 104/mm3, p = 0.002). Tedizolid therapy was completed and treatment failure was not observed in any patient. The duration of treatment was 20.0 ± 11.2 days for linezolid and 30.3 ± 9.5 days for tedizolid (total, 50.3 ± 10.7 days). One patient died because of underlying disease, and there was no recurrence in the remaining 7 patients (median follow-up 501 days). CONCLUSIONS: Switching therapy to tedizolid improved thrombocytopenia that occurred during linezolid therapy, and it enabled the completion of therapy for VO patients.

Enhanced loading dose of teicoplanin for three days is required to achieve a target trough concentration of 20 µg/mL in patients receiving continuous venovenous haemodiafiltration with a low flow rate.

INTRODUCTION: Because of its lower risk of renal toxicity than vancomycin, teicoplanin is the preferred treatment for methicillin-resistant Staphylococcus aureus infection in patients undergoing continuous venovenous haemodiafiltration (CVVHDF) in whom renal function is expected to recover. The dosing regimen for achieving a trough concentration (Cmin) of ≥20 µg/mL remains unclear in patients on CVVHDF using the low flow rate adopted in Japan. METHODS: The study was conducted in patients undergoing CVVHDF with a flow rate of <20 mg/kg/h who were treated with teicoplanin. We adopted three loading dose regimens for the initial 3 days: the conventional regimen, a high-dose regimen (four doses of 10 mg/kg), and an enhanced regimen (four doses of 12 mg/kg). The initial Cmin was obtained at 72 h after the first dose. RESULTS: Overall, 60 patients were eligible for study inclusion. The proportion of patients achieving the Cmin target was significantly higher for the enhanced regimen than for the high-dose regimen (52.9% versus 8.3%, p = 0.003). In multivariate analysis, the enhanced regimen (odds ratio [OR] = 39.93, 95% confidence interval [CI] = 5.03-317.17) and hypoalbuminaemia (OR = 0.04, 95% CI = 0.01-0.44) were independent predictors of the achievement of Cmin ≥ 20 µg/mL. CONCLUSIONS: An enhanced teicoplanin regimen was proposed to treat complicated or invasive infections by methicillin-resistant Staphylococcus aureus in patients receiving CVVHDF even with a low flow rate.