Risk Factors of Postoperative Complication and Hospital Mortality after Colorectal Perforation Surgery.

Objectives: Colorectal perforation is associated with high morbidity and mortality rates after surgery. We investigated various clinical features of patients who underwent emergency surgery for colorectal perforation and explored the risk factors for postoperative complications and hospital mortality. Methods: Data from 147 patients who underwent surgery for colorectal perforation were retrospectively reviewed. We investigated various clinical and operative factors, including inflammation-based prognostic scores (IBPSs), and evaluated the risk factors for postoperative complications and hospital mortality due to colorectal perforation. Results: Among 147 patients, the most frequent postoperative complication was wound infection (32 cases, 21.8%), followed by intra-abdominal abscesses (27 cases, 18.4%) after surgery for colorectal perforation. Time from onset to surgery ≥ 2 days (Hazard ratio [HR] = 2.810, p = 0.0383) and prognostic nutritional index (PNI) < 30 (HR = 3.190, p = 0.0488) were identified as risk factors for intra-abdominal abscess, while neutrophil-lymphocyte ratio (NLR) < 6.15 (HR = 5.020, p = 0.0009) was identified as a risk factor for wound infection. Time from onset to surgery ≥ 2 days (HR = 7.713, p = 0.0492), severe postoperative complications (Clavien-Dindo grade ≥ IIIa) (HR = 10.98, p = 0.0281), and platelet-lymphocyte ratio (PLR) < 144 (HR = 18.84, p = 0.0190) were independent predictive factors for hospital mortality. Conclusions: Time from onset to surgery and IBPSs such as PNI, NLR, and PLR, may be associated with postoperative complications and hospital mortality due to colorectal perforation.

Efficacy and histologic frequencies of endoscopic ultrasonography-guided tissue acquisition using conventional fine-needle aspiration needles for gastric subepithelial hypoechoic mass.

Introduction/Purpose: For gastric subepithelial lesions (GSELs) showing a hypoechoic mass (HM) on endoscopic ultrasonography (EUS) imaging, the utility of EUS-guided tissue acquisition using conventional fine-needle aspiration needles (EUS-TA-CFNAN) and the frequency of histological types remain unclear. This study aimed to examine this issue. Methods: This prospective observational study enrolled 291 consecutive patients who underwent EUS-TA-CFNAN for GSELs showing an HM (GSELHM) on EUS imaging. Immunohistochemical analysis was performed for all EUS-TA-CFNAN and surgically resected specimens. The main outcome measures were the technical results of EUS-TA-CFNAN and the frequency of histological types in GSELHM. Results: The endoscopic ultrasound-guided tissue acquisition using conventional fine-needle aspiration needle diagnosis rate for GSELHM was 80.1% (95% confidence interval [CI]: 75.0-84.5, 233/291). It was significantly lower for antrum (P = 0.004) and lesions smaller than 2 cm (P = 0.003). There were no adverse events. The immunohistochemical diagnoses of EUS-TA-CFNAN included 149 cases of gastrointestinal stromal tumour (GIST) (51.2%), 48 cases of leiomyoma (16.5%), 11 cases of schwannoma (3.8%), 8 cases of the ectopic pancreas (2.7%), 5 cases of subepithelial lesion like cancer (1.7%), 12 cases of other lesions (4.1%), and 58 cases of undiagnosable lesions (19.9%). The frequency of malignant or potentially malignant tumour in GSELHM was 55.0% (95% CI: 49.1-60.8, 160/291). Surgery was performed in 149 patients according to the conclusive EUS-TA-CFNAN results, in which the diagnostic accuracy of EUS-TA-CFNAN was 97.3% (95% CI: 94.7-99.9, 145/149). Conclusion: The use of EUS-TA-CFNAN for GSELHMs is safe and accurate. Gastric subepithelial lesions showing a hypoechoic mass have a reasonably high possibility of containing malignant or potentially malignant tumours, including GISTs.

Endoscopic Ultrasonography-Guided Fine-Needle Aspiration for Duodenal Subepithelial Lesions Showing a Hypoechoic Mass on Endoscopic Ultrasound Imaging.

BACKGROUND/AIMS: For duodenal subepithelial lesions showing a hypoechoic mass on endoscopic ultrasound imaging, the utility of endoscopic ultrasound-guided fine-needle aspiration and the frequency of histological types have not been the focus of previous literature. This study aimed to clarify this. MATERIALS AND METHODS: This prospective observational study enrolled 22 consecutive patients who underwent endoscopic ultrasoundguided fine-needle aspiration for duodenal subepithelial lesions with hypoechoic mass on endoscopic ultrasound. Immunohistochemical analysis was performed for all endoscopic ultrasound-guided fine-needle aspiration and surgically resected specimens. The main outcome measures were the technical results of endoscopic ultrasound-guided fine-needle aspiration and the frequency of histological types of duodenal subepithelial lesions with hypoechoic mass. RESULTS: Thirteen fine-needle aspiration specimens were obtained from the duodenal bulb and eight from the descending duodenal region. The puncture was not performed because of intervening vessels in one patient. The diagnostic rate was 81% (95% confidence interval: 58.1-94.6, 17/21 patients). In 12 patients receiving surgical resection (excluding one cancellation of endoscopic ultrasoundguided fine-needle aspiration), the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration was 75% (95% confidence interval: 42.8-94.5, 9/12 patients). No complications were observed. The histopathological diagnoses included 11 cases of gastrointestinal stromal tumor (50%), 2 cases of leiomyoma (9%), 2 cases of metastatic cancer (9%), 2 cases of benign inconclusive, and 1 case each of carcinoid, malignant lymphoma, leiomyosarcoma, gauzeoma, and aberrant pancreas (4.5% each). The frequency of malignant tumors in the duodenal subepithelial lesions with hypoechoic mass group was 73% (16/22 patients). CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration for duodenal subepithelial lesions with hypoechoic mass was safe and accurate. As duodenal subepithelial lesion with hypoechoic mass has a reasonably high possibility of containing malignant tumors, it is desirable to perform endoscopic ultrasound-guided fine-needle aspiration.

Prognostic significance of a novel index score based on the inflammation-based prognostic scores of patients with colorectal cancer.

BACKGROUND AND AIM: This study aimed to clarify the prognostic value of various inflammation-based prognostic scores (IBPSs) in patients who underwent radical surgery for colorectal cancer (CRC) and to develop a novel prognostic index using IBPSs and other predictive factors. METHODS: Data of 1157 patients who underwent radical surgery for CRC were reviewed. The predictive value of various IBPSs in determining the CRC prognosis was compared. A novel index score based on the IBPSs and other parameters that were associated with survival in patients with CRC was established, and its usefulness was evaluated. RESULTS: The patients were randomly divided into the training (n = 694) and validation (n = 463) sets. Male sex (P = 0.0001), age ≥ 75 years (P < 0.0001), a carcinoembryonic antigen (CEA) level of > 5 (P = 0.0009), a C-reactive protein/albumin ratio (CAR) of ≥ 0.04 (P = 0.0033), and a prognostic nutritional index (PNI) of < 43.1 (P = 0.0004) were poor independent prognostic factors of overall survival. The novel index score was calculated based on the scores of these five prognostic factors. The Kaplan-Meier survival curves showed that the CRC patients with higher novel index scores in the training and validation datasets had poorer overall survival. CONCLUSIONS: CAR and PNI were superior to other IBPSs for predicting the prognosis of CRC patients. The novel index score established based on sex, age, CEA level, CAR, and PNI can predict the prognosis of CRC with more precise and clearer stratification than the individual parameters alone.

An Attempt to Replicate Randomized Trials of Diabetes Treatments Using a Japanese Administrative Claims and Health Checkup Database: A Feasibility Study.

BACKGROUND: Use of real-world evidence (RWE) has been limited for evaluating effectiveness because of the lack of confidence in its reliability. Examining whether a rigorously designed observational study using real-world data (RWD) can reproduce the results of a randomized controlled trial (RCT) will provide insights into the implementation of high-quality RWE studies that can produce valid conclusions. OBJECTIVE: We aimed to replicate published RCTs using a Japanese claims and health checkup database and examine whether the emulated RWE studies' results agree with those of the original RCTs. METHODS: We selected three RCTs on diabetes medications for replication in patients with type 2 diabetes. The study outcome was either the change or percentage change in HbA1c levels from baseline. We designed three observational studies using the RWD to mimic the critical study elements of the respective RCTs as closely as possible. We performed 1:1 propensity score nearest-neighbor matching to balance the groups for potential confounders. The differences in outcomes between the groups and their 95% confidence intervals (CIs) were calculated in each RWE study, and the results were compared with those of the RCT. RESULTS: Patient characteristics, such as age, sex, and duration of diabetes, differed between the RWE studies and RCTs. In Trial 1 emulation, the percentage changes in HbA1c levels were larger in the treatment group than in the comparator group (difference -6.21, 95% confidence interval (CI) -11.01 to -1.40). In Trial 2, the change in HbA1c level was larger in the treatment group (difference -0.01; 95% CI -0.25 to 0.23), and in Trial 3, it was smaller in the treatment group (difference 0.46; 95% CI -0.01 to 0.94). These results did not show regulatory or estimate agreement with the RCTs. CONCLUSIONS: None of the three emulated RWE studies using this claims and health checkup database reproduced the same conclusions as the RCTs. These discrepancies could largely be attributed to design differences between RWE studies and RCTs, primarily due to the lack of necessary data in the database. This particular RWD source may not be the best fit for evaluating treatment effects using laboratory data as the study outcome.

Cardiometabolic risk reductions in patients with type 2 diabetes mellitus newly treated with a sodium-glucose cotransporter 2 inhibitor versus a dipeptidyl peptidase-4 inhibitor: A real-world administrative database study in Japan.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown beneficial effects on cardiometabolic risk factors (hemoglobin A1c, body mass index, systolic blood pressure) in patients with type 2 diabetes mellitus. We compared combined cardiometabolic effects of SGLT2i on hemoglobin A1c, body mass index and systolic blood pressure versus dipeptidyl peptidase-4 inhibitors (DPP4i) in Japanese patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This Japanese retrospective cohort study used the JMDC claims database. Patients newly treated with an SGLT2i (n = 18,936) or DPP4i (n = 55,484) were enrolled (January 2015-March 2020) and matched 1:1 using the propensity score. The primary end-point was the proportion of patients achieving a composite outcome (i.e., simultaneous absolute/percent reduction in hemoglobin A1c ≥0.5%, body mass index ≥3% and systolic blood pressure ≥2 mmHg) 1 year after first SGLT2i or DPP4i prescription; Mantel-Haenszel common risk difference and its 95% confidence interval were estimated. Other end-points included treatment persistence, with the associated hazard ratio calculated using the Cox proportional hazards model. RESULTS: After matching, patient characteristics were balanced (7,302 patients each). The proportion of patients achieving the composite outcome was significantly greater in patients receiving an SGLT2i than those receiving a DPP4i (31.0% [1,279/4,120] vs 12.9% [524/4,070], risk difference 18.6%, 95% confidence interval 16.3, 20.9, P < 0.001). Risk of treatment discontinuation was significantly lower in the SGLT2i group than in the DPP4i group (hazard ratio 0.85, 95% confidence interval 0.81, 0.90, P < 0.001). CONCLUSIONS: In the present study, SGLT2i showed favorable cardiometabolic risk reduction and longer treatment persistence than DPP4i in Japanese patients with type 2 diabetes mellitus.

Effect of donepezil for dementia prevention in Parkinson's disease with severe hyposmia (The DASH-PD study): A randomized long-term placebo-controlled trial.

Background: Dementia greatly contributes to poor prognosis in patients with Parkinson's disease (PD). We previously reported that severe olfactory dysfunction may be a good predictor of Parkinson's disease dementia (PDD). In this trial, we investigated whether early administration of donepezil to patients with severe hyposmia can reduce the development of PDD. Methods: This was a multi-centre, randomized, double-blind, parallel group, placebo-controlled trial in patients with non-demented PD with severe hyposmia (The Donepezil Application for Severe Hyposmic Parkinson's Disease [DASH-PD] study). A total of 201 patients were randomly allocated to receive donepezil or placebo in addition to standard therapy for PD. Patients were followed up every 6 months until the onset of PDD or for a maximum of 4 years. The primary endpoint was the onset of dementia. The secondary endpoint was cognitive impairment measured by Addenbrooke's Cognitive Examination-Revised (ACE-R) and the Clinical Dementia Rating (CDR).(UMIN000009958: February 2013 to May 2019). Findings: A total of 201 hyposmic patients with PD were randomly assigned to a treatment: 103 to donepezil and 98 to placebo. Overall, 141 (70%) patients completed the 4-year intervention. During follow-up, 7 of 103 (6.8%) patients in the donepezil group and 12 of 98 (12.2%) patients in the placebo group developed PDD; however, the hazard ratio of PDD incidence was not statistically significant (hazard ratio (HR), 0.609; 95% confidence interval, 0.240 to 1.547; p = 0.2969). At week 208, the patients in the donepezil group had better scores on the ACE-R (p < 0.005) and the CDR (p < 0.005) than those taking placebo. Interpretation: Administration of donepezil to PD patients with severe olfactory dysfunction for 4 years did not change the incidence of dementia but had a beneficial effect on neuropsychological function, with good tolerability. Funding: The Ministry of Health Labour and Welfare and the Japan Agency for Medical Research and Development provided funding for this study.

Diaphragm pacing implantation in Japan for a patient with cervical spinal cord injury: A case report.

RATIONALE: Traumatic cervical spinal cord injury (SCI) is a devastating condition leading to respiratory failure that requires permanent mechanical ventilation, which is the main driver of increased medical costs. There is a great demand for establishing therapeutic interventions to treat respiratory dysfunction following severe cervical SCI. PATIENT CONCERNS AND DIAGNOSIS: We present a 24-year-old man who sustained a cervical displaced C2-C3 fracture with SCI due to a traffic accident. As the patient presented with tetraplegia and difficulty in spontaneous breathing following injury, he was immediately intubated and placed on a ventilator with cervical external fixation by halo orthosis. The patient then underwent open reduction and posterior fusion of the cervical spine 3 weeks after injury. Although the patient showed significant motor recovery of the upper and lower limbs over time, only a slight improvement in lung capacity was observed. INTERVENTIONS AND OUTCOMES: At 1.5 years after injury, a diaphragmatic pacing stimulator was surgically implanted to support the patient's respiratory function. The mechanical ventilator support was successfully withdrawn from the patient 14 weeks after implantation. We observed that both the vital capacity and tidal volume of the patient were significantly promoted following implantation. The patient finally returned to daily life without any mechanical support. LESSONS: The findings of this report suggest that diaphragmatic pacing implantation could be a promising treatment for improving respiratory function after severe cervical SCI. To our knowledge, this is the first SCI patient treated with a diaphragm pacing implantation covered by official medical insurance in Japan.

Prevention of Pemetrexed-Induced Rash Using Low-Dose Corticosteroids: A Phase II Study.

BACKGROUND: Rash eruptions are a common side-effect of pemetrexed, for which the administration of 8 mg/day of dexamethasone for 3 days from the day preceding pemetrexed administration is recommended. This study aimed to prospectively assess the effectiveness of prophylactic administration of low-dose dexamethasone for pemetrexed-induced rashes. METHODS: This single-arm, phase II study recruited patients with non-squamous non-small cell lung cancer and malignant pleural mesothelioma scheduled to receive chemotherapy including pemetrexed. Patients received 2 mg of dexamethasone daily from days 2 to 6 after chemotherapy with pemetrexed. The primary endpoint was the 3-week incidence of rash eruptions. RESULTS: Twenty-five patients were enrolled between September 2017 and May 2019. The incidence of rash after 3 weeks was 16.7%. Rashes erupted mainly on the upper half of the body, such as the chest and neck, and were of grades 1 and 2 in 2 patients each. No rashes of grade 3 or higher were observed, and there were no adverse events associated with additional corticosteroids. CONCLUSION: Prophylactic administration of low-dose dexamethasone for 5 days from the day after pemetrexed administration resulted in a milder incidence and severity of rash. These findings may provide a standard preventative strategy for pemetrexed-induced rashes. (Trial identifier: UMIN000025666).

Bisphosphonate Use May Reduce the Risk of Urolithiasis in Astronauts on Long-Term Spaceflights.

Long-duration spaceflight is associated with an increased risk of urolithiasis, and the pain caused by urinary calculi could result in loss of human performance and mission objectives. The present study investigated the risk of urolithiasis in astronauts during 6 months on the International Space Station, and evaluated whether the suppression of bone resorption by the bisphosphonate, alendronate (ALN), can reduce the risk. A total of 17 astronauts were included into the analysis: exercise using the advanced resistive exercise device (ARED) plus weekly oral 70 mg alendronate (ARED+ALN group, n = 7) was compared to resistive exercise alone (ARED group, n = 10). Urine volume decreased in both groups during spaceflight but recovered after return. The ARED group showed increased urinary calcium excretion from the 15th to 30th day of spaceflight, whereas urinary calcium was slightly decreased in the ARED+ALN group. Urinary N-terminal telopeptide (NTX) and helical peptide (HP) of type I collagen, as bone resorption markers, were elevated in the ARED group during and until 0 days after spaceflight, while there was no elevation in these parameters in the ARED+ALN group. Urinary oxalate and uric acid excretion tended to be higher in the ARED group than in the ARED+ALN group during spaceflight. These results demonstrate that astronauts on long-duration spaceflights may be at high risk for the formation of urinary calcium oxalate and calcium phosphate stones through increased urinary excretion of oxalate and uric acid, from degraded type I collagen, as well as of calcium from enhanced bone resorption. Our findings suggest that increased bone resorption during spaceflight, as a risk factor for urinary calculus formation, could be effectively prevented by an inhibitor of bone resorption. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Cardiovascular risk factors are associated with augmented thrombogenicity in healthy individuals: analysis using the Total Thrombus-formation Analysis System.

BACKGROUND: Rupture of an atherosclerotic plaque and subsequent exposure of the subendothelial prothrombotic matrix to blood cause arterial thrombosis. Circulating platelets play an indispensable role in the growth of arterial thrombi partially owing to their unique ability to adhere to the subendothelial matrix and to aggregate to each other under flow conditions. Recently, the Total Thrombus-formation Analysis System (T-TAS) was developed for ex vivo analysis of the thrombogenic potential of whole blood samples under flow conditions. Despite the potential clinical utility of the T-TAS in assessing the risk for thrombosis and bleeding, reference intervals for T-TAS analysis in healthy individuals have not been determined. METHODS: In total, 122 whole blood samples were collected from healthy volunteers ranging in age from 25 to 45 years. T-TAS analysis and hematological, physiological, and lifestyle assessments were conducted in these subjects. Whole blood samples anticoagulated with hirudin were perfused into a collagen-coated microchip (PL chip). The time to 10 kPa and the area under the flow pressure curve up to 10 min (AUC10) were analyzed as representative variables for thrombogenic potential. Reference intervals, which were defined as 2.5-97.5 percentiles, were determined. Additionally, univariate and multivariate analyses were performed to identify factors associated with the AUC10 in the T-TAS. RESULTS: The time to 10 kPa and the AUC10 widely varied, even in healthy volunteers. The reference intervals were 1.50-4.02 min and 223.4-456.8, respectively, at a shear rate of 1500 s- 1. Univariate and multivariate analyses showed that platelet counts were most significantly associated with the AUC10 of the T-TAS. The presence of one or more cardiovascular risk factors of a high body mass index, a high pulse pressure, high fasting serum glucose levels, high low-density lipoprotein-cholesterol levels, a history of smoking, and no habitual exercise, had the second largest effect on the AUC10 of the T-TAS. CONCLUSIONS: Healthy volunteers who had any cardiovascular risk factors showed augmented thrombogenicity, even in artificial uniform capillaries, compared with those without any risk factors in the T-TAS.

High Pathological Reproducibility of Diet-induced Atherosclerosis in Microminipigs via Cloning Technology.

BACKGROUND/AIM: The reproducibility of athero - sclerotic lesions was evaluated after the production of cloned-microminipigs and their offspring. MATERIALS AND METHODS: Cloned-microminipig-parents were produced by microminipigsomatic cell nuclei. These parents were crossbred and delivered males (F1-offspring) were divided into two groups: normal chow diet (NcD)-fed and high-fat/high-cholesterol diet (HcD)-fed groups. One of the F1-offsprings was subjected to cloning, and delivered males (F1-clones) were fed with HcD. After 8 weeks, all animals were necropsied for patho - physiological studies compared to non-cloned-microminipigs. RESULTS: HcD-fed F1-offspring and F1-clones, but not NcD-fed F1-offspring, exhibited increased serum lipid levels and systemic atherosclerosis, which were comparable to those of HcD-fed non-cloned-microminipigs. Homogeneity of variance analysis demonstrated that standard deviation values of serum lipoprotein and aortic atherosclerosis area from HcD-fed animals decreased in F1-offspring and F1-clones. CONCLUSION: HcD-induced atherogenesis was highly reproducible in F1-offsprings and F1-clones, indicating that the atherosclerosis-prone genomic background was preserved in the cloned-microminipigs, which can be used for studies on human atherosclerosis and related diseases.

Laparoscopic treatment of median arcuate ligament syndrome without ganglionectomy of the celiac plexus in the hybrid operating room: Report of a case.

INTRODUCTION: Median arcuate ligament syndrome (MALS) is a rare condition in which the median arcuate ligament (MAL) causes compression of the celiac artery (CA) and plexus. Although 13-50 % of healthy population exhibit radiologic evidence of the CA compression, the majority remains asymptomatic. With or without symptoms, MALS have a risk of developing collateral circulation that leads to pancreaticoduodenal artery (PDA) aneurysms that have high risk of rupture. The treatment of MALS is the surgical release of the MAL. However, the necessity of ganglionectomy of the celiac plexus is still unclear. PRESENTATION OF CASE: A 60-year-old man with a ruptured PDA aneurysm caused by MALS was admitted to our hospital for an emergency. After treatment for the ruptured PDA aneurysm by transcatheter arterial coil embolization, he underwent elective laparoscopic MAL release in the hybrid operation room to check blood flow of the CA intraoperatively. The angiography of the CA immediately after MAL release without ganglionectomy of the celiac plexus showed the antegrade blood flow to the proper hepatic artery instead of the retrograde flow via the pancreaticoduodenal arcade. The postoperative course was uneventful and the follow-up computed tomography revealed no residual CA stenosis. DISCUSSION: Unlike symptomatic MALS, it might be enough to just release the MAL without ganglionectomy of the celiac plexus for asymptomatic MALS, especially that with the treated PDA aneurysm. CONCLUSION: Laparoscopic treatment of MALS in hybrid operating room could allow for adequate MAL release without ganglionectomy of the celiac plexus using the intraoperative angiography of the CA.

Effects of Cardiac Massage and ß-Blocker Pretreatment on the Success Rate of Cardiopulmonary Resuscitation Assessed by the Canine Ischemia/Reperfusion-Induced Ventricular Fibrillation Model.

BACKGROUND: Effects of rapid electrical defibrillation and ß-blockade on coronary ischemia/reperfusion-induced ventricular fibrillation (VF) during cardiopulmonary resuscitation (CPR) remain unknown.Methods and Results:After induction of VF by 30 min of ischemia followed by reperfusion, animals were treated with defibrillation alone (Group A, n=13), 2 min of open-chest cardiac massage followed by defibrillation (Group B, n=11), or the same therapy to Group B with propranolol (1 mg/kg, i.v.) treatment before ischemia/reperfusion (Group C, n=11). If return of spontaneous circulation (ROSC) was not attained, each therapy was repeated ≤3 times (Set-1). When ROSC was not obtained within Set-1, cardiac massage was applied to all animals followed by defibrillation, which was repeated ≤3 times (Set-2). ROSC after Set-1 was 8% in Group A, 82% in Group B and 82% in Group C, whereas that after Set-2 was 62% in Group A, 100% in Group B and 82% in Group C. Each animal with ROSC in Groups A (n=8) and B (n=11) showed sinus rhythm, whereas those in Group C (n=9) had sinus rhythm (n=5), atrial fibrillation (n=1), accelerated idioventricular rhythm (n=2) and atrioventricular block (n=1). Post ROSC heart rate and mean arterial pressure were significantly lower in Group C. CONCLUSIONS: Cardiac massage increased the likelihood of ROSC vs. rapid defibrillation, but ß-blocker pretreatment may worsen hemodynamics and electrical stability after ROSC.

Percutaneous intestinal drainage for a refractory enterocutaneous fistula: A case report.

INTRODUCTION: Enterocutaneous fistulas (ECFs) that occur following gastrointestinal surgery require long-term hospitalization, and treatment may be difficult in rare cases. Although the morbidity and mortality associated with ECF have decreased with modern medical, the overall mortality is still surprisingly high, up to 30.4 %. PRESENTATION OF CASE: The patient was a 79-year-old male who had undergone laparoscopic sigmoidoscopy for sigmoid colon cancer 5 years previously. He was newly diagnosed with sigmoid colon cancer 5 years following surgery. A laparoscopic high anterior resection was performed. On the 4th postoperative day, he was diagnosed with a suture failure which was treated conservatively; however, the fistula could not be closed, and ileostomy construction was performed. Intestinal fluid leaked from the median surgical incision, leading to the formation of a small intestinal fistula on the proximal side from the ileostomy. Conservative treatment did not improve the condition and skin erosion worsened. Two months after the stoma was constructed, a urethral balloon catheter was percutaneously inserted into the intestinal tract from the small intestinal fistula to drain the intestinal fluid. Following the maneuver, the problem of skin erosion was improved, with the resulting closure of the fistula. DISCUSSION: The basic principles underlying treatment for ECFs are essentially fasting, drainage, and adequate nutritional management. Some studies reported that the average period of negative pressure therapy was four weeks. It seems that four weeks is the breakpoint. CONCLUSION: Percutaneous intestinal drainage for refractory ECFs following gastrointestinal surgery is minimally invasive and is likely to be extremely useful.

The Effect of Prone Positioning as Postoperative Physiotherapy to Prevent Atelectasis After Hepatectomy.

BACKGROUND: The incidences of postoperative pulmonary complications (PPCs) such as atelectasis, pneumonia and pleural effusion after major surgery range from <1 to 23%. Atelectasis after abdominal surgery increases the duration of hospitalization and short-term mortality rate, but there are few reports about atelectasis after hepatectomy. The effectiveness of prone position drainage as physiotherapy has been reported, but it remains unclarified whether prone positioning prevents atelectasis after hepatectomy. This study aimed to evaluate the effect of the prone position on the incidence of atelectasis after hepatectomy. METHODS: We retrospectively analyzed the incidence of PPCs after hepatectomy at a single center. Patients were divided into two cohorts. The earlier cohort (n = 165) underwent hepatectomy between January 2016 and March 2018 and was analyzed to identify the risk factors for atelectasis and short-term outcomes; the later cohort (n = 51) underwent hepatectomy between April 2018 and March 2019 and underwent prone position drainage in addition to regular mobilization postoperatively. The incidences of PPCs were compared between the two cohorts. RESULTS: Independent risk factors for atelectasis were anesthetic duration (P = 0.016), operation time (P = 0.046) and open surgery (P = 0.011). The incidence of atelectasis was significantly lower in the later cohort (9.8%) than the earlier cohort (34.5%, P < 0.001). Moreover, the later cohort had a significantly shorter duration of oxygen support (P < 0.001) and postoperative hospitalization (P < 0.001). After propensity score-matching, the incidence of atelectasis remained significantly lower in the later cohort (P = 0.027). CONCLUSION: Prone position drainage may decrease the incidence of atelectasis after hepatectomy and improve the short-term outcomes.

Perioperative complications of abdominal surgery in smokers.

PURPOSE: This study examined the association between smoking and perioperative complications of laparoscopic abdominal surgery and whether these complications were reduced with ≥ 4 weeks of preoperative smoking cessation. METHODS: A total of 555 patients who underwent gastric and colorectal cancer surgeries under general anesthesia were divided into the following groups retrospectively: 290 individuals without smoking history (NS group), 144 previous smokers (stopped smoking more than 8 weeks before surgery, PS group), and 121 current smokers (CS group) divided to two groups according to preoperative smoking cessation for < 4 (CS1, n = 76) and 4-8 weeks (CS2, n = 45). RESULTS: When compared with the NS group, postoperative hospitalization duration was significantly longer in the CS1 group (p < 0.01), whereas differences between the CS2 or PS groups and NS group were not significant. The total number of postoperative complications was higher in all groups of smoking than in NS group, independent on preoperative smoking cessation; however, suture failure was significantly more frequent only in CS1 group. Although pack-years did not significantly affect complication rates in smokers, duration of smoking cessation time in PS group was a negative predictor of postoperative complications. CONCLUSION: Providing more than 4 weeks of smoking cessation before gastrointestinal surgery can reduce the duration of hospitalization and rate of suture failure.

Exposure-response analysis of drug-induced QT interval prolongation in telemetered monkeys for translational prediction to human.

INTRODUCTION: The preclinical in vivo assay for QT prolongation is critical for predicting torsadogenic risk, but still difficult to extrapolate to humans. This study ran preclinical tests in cynomolgus monkeys on seven QT reference drugs containing the drugs used in the IQ-CSRC clinical trial and applied exposure-response (ER) analysis to the data to investigate the potential for translational information on the QT effect. METHODS: In each of six participating facilities in the J-ICET project, telemetered monkeys were monitored for 24 h following administration of vehicle or 3 doses of test drugs, and pharmacokinetic profiles at the same doses were evaluated separately. An individual rate-corrected QT interval (QTca) was derived and the vehicle-adjusted change in QTca from baseline (∆∆QTca) was calculated. Then the relationship of concentration to QT effect was evaluated by ER analysis. RESULTS: For QT-positive drugs in the IQ-CSRC study (dofetilide, dolasetron, moxifloxacin, ondansetron, and quinine) and levofloxacin, the slope of the total concentration-QTca effect was significantly positive, and the QT-prolonging effect, taken as the upper bound of the confidence interval for predicted ∆∆QTca, was confirmed to exceed 10 ms. The ER slope of the negative drug levocetirizine was not significantly positive and the QTca effect was below 10 ms at observed peak exposure. DISCUSSION: Preclinical QT assessment in cynomolgus monkeys combined with ER analysis could identify the small QT effect induced by several QT drugs consistently with the outcomes in humans. Thus, the ER method should be regarded as useful for translational prediction of QT effects in humans.

Factors Affecting the Absorption of Midazolam to the Extracorporeal Membrane Oxygenation Circuit.

Sedatives are administered during extracorporeal membrane oxygenation (ECMO) therapy to ensure patient safety, reduce the metabolic rate and correct the oxygen supply-demand balance. However, the concentrations of sedatives can be decreased due to absorption into the circuit. This study examined factors affecting the absorption of a commonly used sedative, midazolam (MDZ). Using multiple ex vivo simulation models, three factors that may influence MDZ levels in the ECMO circuit were examined: polyvinyl chloride (PVC) tubing in the circuit, use of a membrane oxygenator in the circuit, and heparin coating of the circuit. We also assessed changes in drug concentration when MDZ was re-injected in a circuit. The MDZ level decreased to approximately 60% of the initial concentration in simulated circuits within the first 30 minutes. The strongest factor in this phenomenon was contact with the PVC tubing. Membrane oxygenator use tended to increase MDZ loss, whereas heparin circuit coating had no influence on MDZ absorption. Similar results were obtained when a second dose of MDZ was injected to the second-use circuits.

Use of a Healthcare Claims Database for Post-Marketing Safety Assessments of Eribulin in Japan: A Comparative Assessment with a Prospective Post-Marketing Surveillance Study.

BACKGROUND: To understand the extent to which a large-scale healthcare claims database (DB) captures the safety profile of eribulin mesylate (Halaven®, Eisai Co., Ltd., Japan), we compared patient characteristics, drug use, and adverse events (AEs) between data for patients treated with eribulin retrieved from a DB and data for metastatic breast cancer patients from a conventional prospective post-marketing surveillance (PMS). METHODS: We descriptively summarized patient characteristics and AEs of 551 and 951 patients retrieved from DB and PMS, respectively, during 2011‒2013. Using 2814 patient data from the DB during 2011‒2016, the drug use and AE incidence over time were assessed. RESULTS: In both datasets, 99.8% were females, and the mean age was 57.8 ± 10.7 years. The mean number of eribulin administration was 11.1 ± 10.9 and 10.1 ± 7.8 in DB and PMS, respectively. Although, overall, the difference in AE incidence between the two datasets was moderate, gaps were larger for nausea (DB: 73.32% vs. PMS: 15.77%), neutropenia (20.87% vs. 66.67%), stomatitis (37.39% vs. 10.94%), and alopecia (0.36% vs. 12.09%). During 2011‒2016, the observed incidence of anemia or pyrexia significantly decreased (trend test, p = 0.0009 for both). CONCLUSION: Generally, patient characteristics, drug use, and AE incidence between the DB and PMS were comparable; however, AEs such as neutropenia may require defining based on the laboratory data to achieve more comparable results in DBs. Besides the usefulness of healthcare claims DBs for long-term assessments, they may also serve as a good complementary to PMS in the pharmacovigilance of eribulin.