Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Population Pharmacokinetic-Pharmacodynamic Target Attainment Analysis of Flomoxef in the Serum and Liver Tissue of Patients Undergoing Hepatic Resection.

The purpose of this study was to investigate the population pharmacokinetics of prophylactic flomoxef based on serum and liver tissue concentrations and to demonstrate a pharmacodynamic target concentration in the serum and liver tissue exceeding the MIC in order to design an effective dosing regimen. Serum samples (n = 210) and liver tissue samples (n = 29) from 43 individuals were analyzed using a nonlinear mixed-effects model. The pharmacodynamics index target value was regarded as the probability of maintaining flomoxef serum trough and liver tissue concentrations exceeding the MIC90 values, 0.5 mg/L and 1.0 mg/L, for Escherichia coli and methicillin-susceptible Staphylococcus aureus, respectively. The final population pharmacokinetic model was a two-compartment model with linear elimination. Creatinine clearance (CLCR) was identified as a significant covariate influencing total clearance when CLCR was less than 60 mL/min. The probability of achieving concentrations in the serum and liver tissue exceeding the MIC90 for E. coli or methicillin-susceptible S. aureus for a 1 g bolus dose was above 90% at 2 h after the initial dose. Our findings suggest that population pharmacokinetic parameters are helpful for evaluating flomoxef pharmacokinetics and determining intraoperative flomoxef redosing intervals.

Preliminary study regarding the predicted body weight-based dexamethasone therapy in patients with COVID-19 pneumonia.

BACKGROUND: The RECOVERY clinical trial reported that 6 mg of dexamethasone once daily for up to 10 days reduces the 28-day mortality in patients with coronavirus disease 2019 (COVID-19) receiving respiratory support. In our clinical setting, a fixed dose of dexamethasone has prompted the question of whether inflammatory modulation effects sufficiently reduce lung injury. Therefore, preliminary verification on the possibility of predicted body weight (PBW)-based dexamethasone therapy was conducted in patients with COVID-19 pneumonia. METHODS: This single-center retrospective study was conducted in a Japanese University Hospital to compare the treatment strategies/management in different periods. Consecutive patients (n = 90) with COVID-19 pneumonia requiring oxygen therapy and were treated with dexamethasone between June 2020 and May 2021 were analyzed. Initially, 60 patients administered a fixed dexamethasone dose of 6.6 mg/day were defined as the conventional group, and then, 30 patients were changed to PBW-based therapy. The 30-day discharged alive rate and duration of oxygen therapy were analyzed using the Kaplan-Meier method and compared using the log-rank test. The multivariable Cox regression was used to evaluate the effects of PBW-based dexamethasone therapy on high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), or mechanical ventilation (MV). RESULTS: In the PBW-based group, 9, 13, and 8 patients were administered 6.6, 9.9, and 13.2 mg/day of dexamethasone, respectively. Additional respiratory support including HFNC, NIV, or MV was significantly less frequently used in the PBW-based group (P = 0.0046), with significantly greater cumulative incidence of being discharged alive and shorter oxygen demand within 30 days (92 vs. 89%, log-rank P = 0.0094, 90 vs. 92%, log-rank P = 0.0002, respectively). Patients treated with PBW-based therapy significantly decreased the use of additional respiratory support after adjusting for baseline imbalances (adjusted odds ratio, 0.224; 95% confidence interval, 0.062-0.813, P = 0.023). Infection occurred in 13 (21%) and 2 (7%) patients in the conventional and PBW-based groups, respectively (P = 0.082). CONCLUSIONS: In patients with COVID-19 pneumonia requiring oxygen therapy, PBW-based dexamethasone therapy may potentially shorten the length of hospital stay and duration of oxygen therapy and risk of using HFNC, NPPV, or MV without increasing serious adverse events or 30-day mortality.

Pancreas-contactless gastrectomy for gastric cancer prevents postoperative inflammation.

BACKGROUND: Pancreas-related complications after laparoscopic gastrectomy (LG) for gastric cancer can be fatal. We developed a gastrectomy procedure with no pancreas contact to prevent such complications and herein report the surgical outcomes. METHODS: We retrospectively reviewed 182 consecutive patients with gastric cancer who underwent LG at Kitasato University Hospital from January 2017 to January 2020. These patients were divided into a pancreas-contact group (C group) and pancreas-contactless group (CL group) for comparison of postoperative complications, and inflammatory parameters such as body temperature (BT) and C-reactive protein (CRP). RESULTS: Postoperative complications of CDc grade ≧ IIIa were significantly fewer in the CL group than in the C group [0/76 (0%) vs. 6/106 (5.7%), P = 0.035]. The median drain amylase (drain-AMY) on postoperative day 1 (POD1) was significantly lower in the CL group than in the C group (641 vs. 1162 IU/L, P = 0.02), as was BT at POD1 (37.4 °C vs. 37.7 °C, P = 0.04), the patient group with a BT above 37.5 °C at POD3 [5/76 (6.5%) vs. 18/106 (17%), P = 0.037], and those showing a CRP above 20.0 mg/dL at POD3 [5/76 (6.5%) vs. 20/106 (19%), P = 0.018]. CONCLUSIONS: Our technique to prevent pancreas contact during supra-pancreatic lymph node dissection during LG could minimize the inflammatory response and prevent further postoperative complications. Further large-scale, prospective studies are now required.

Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN).

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) involves adenoma (IPMA), a precancerous lesion, cancer (IPMC) including high-grade dysplasia (HGD), and invasive carcinoma (IC). DNA markers of IPMN are required for detection of invasive disease, and cysteine dioxygenase 1 (CDO1) gene promoter hypermethylation is a potential candidate. However, it has never been investigated in the context of IPMN. PATIENTS AND METHODS: A total of 107 IPMN tumor tissues, including 41 IPMC and 66 IPMA, were studied. CDO1 promoter methylation was quantified using TaqMan quantitative methylation-specific polymerase chain reaction (qMSP) in patients with IPMN and other pancreatic cystic disorders after pancreatectomy. RESULTS: The methylation values (TaqMeth Vs) of CDO1 increased when noncancerous pancreas tissues were compared with IPMA and HGD (p < 0.0001). Among IPMC, the TaqMeth Vs in IC were not significantly higher than in HGD. The TaqMeth Vs of the solid tumors were higher than those of the cystic tumors (p = 0.0016), which were in turn higher than the corresponding noncancerous tissues (p < 0.0001). Prognostic analysis revealed that high TaqMeth Vs (≥ 14.1) resulted in a poorer prognosis than low TaqMeth Vs (< 14.1) (p < 0.0001). In other pancreatic cystic diseases, only malignant mucinous cystic neoplasm showed DNA hypermethylation of its promoter. A pilot study in pancreatic juice confirmed methylation in all IPMN samples but not in benign pancreatic diseases (p = 0.0277). CONCLUSIONS: CDO1 promoter hypermethylation is extremely specific to IPMN and may accumulate with IPMN tumor progression during the adenoma-carcinoma sequence. It might be a promising candidate as a diagnostic marker of pancreatic cystic diseases.

Neoadjuvant chemotherapy plus surgery for high-risk advanced gastric cancer: long-term results of KDOG1001 trial.

PURPOSE: The purpose of this study is to evaluate the long-term survival outcomes of KDOG1001 trial after a minimum follow-up of 3 years. METHODS: Patients with bulky N2 lymph nodes, linitis plastica (type 4), or large ulcero-invasive-type tumors (type 3) received up to four 28-day cycles of DCS neoadjuvant chemotherapy (docetaxel at 40 mg/m2, cisplatin at 60 mg/m2 on day 1, and S-1 at 40 mg/m2 twice daily for 2 weeks) followed by gastrectomy with D2 lymphadenectomy plus adjuvant S-1 therapy for 1 year. The final preplanned analysis of long-term outcomes including overall survival and relapse-free survival was conducted after minimum follow-up of 3 years. This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry, number UMIN 000003642, and has been completed. RESULTS: From May 2010 through January 2017, 40 patients were enrolled. All included patients underwent neoadjuvant chemotherapy with DCS followed by gastrectomy with D2 lymphadenectomy, and 32 (80%) completed adjuvant S-1 therapy for 1 year. After a median follow-up for surviving patients of 68 months at the last follow-up in January 2020, 3-year overall survival rate was 77.5% (95% confidence interval 62.1-87.9%), while 3-year relapse-free survival rate was 62.5% (95% confidence interval 46.8-76.0%). CONCLUSION: Neoadjuvant chemotherapy with 4 cycles of DCS followed by D2 gastrectomy plus adjuvant S-1 was associated with relatively good long-term oncologic outcomes for patients with the high-risk gastric cancer.

The positive effect of student-oriented clinical clerkship rounds employing role-play and peer review on the clinical performance and professionalism of clerkship students.

Background: Role-play (RP) and peer review (PR) are occasionally used in training and evaluating communication skills in clinical clerkship (CC). Thus, we evaluated the effect of combining RP and PR during student-oriented CC rounds.Methods: Clerkship students conducted medical interviews with and performed physical examinations on their patients, which were reviewed by five peer students who observed their performance while role-playing as senior physicians or patients' families. The peer reviewers then provided feedback to the students. The performance of the students was evaluated based on a mini-clinical evaluation exercise (Mini-CEX) and a professionalism mini-evaluation exercise (P-MEX) before and after the rounds by two attending physicians. After the CC, the students responded to questionnaires about the rounds.Results: Seventy-five students completed the rounds, and the duration of each round was 41.7 ± 7.1 min. Their communication skills and professionalism abilities on Mini-CEX and P-MEX showed significant improvement after the rounds. Improvements in medical interviewing and physical examinations were also noted. Additionally, the students recognized the importance of multiple viewpoints in patient care through experiences of the rounds.Conclusions: Combining RP and PR with CC rounds improves the students' clinical performance and professionalism and promotes their awareness of the importance of multiple viewpoints in patient care.

Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer.

DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene (CDO1) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation-specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound-fine needle aspiration (EUS-FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS-FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS-FNA cytology.

Factors affecting the performance of activities of daily living in patients with advanced cancer undergoing inpatient rehabilitation: results from a retrospective observational study.

[Purpose] Many clinicians believe that rehabilitation for patients with advanced cancer is futile. We determined factors affecting the performance of activities of daily living in patients with advanced cancer based on age, gender, marital status, living arrangement, rehabilitation intensity, type of cancer, impairment, metastasis, and active cancer treatment. [Participants and Methods] We assessed the Barthel Index to evaluate the performance of activities of daily living. Of the 120 adult patients with cancer who underwent inpatient rehabilitation, we analyzed the Barthel Index scores, consisting of 10 items, and reviewed the clinical characteristics from the medical records of 48 patients who completed supportive or palliative rehabilitation according to Dietz and showed an increased or maintained total Barthel Index score at final evaluation. [Results] The median total Barthel Index score increased from 45 (5-95) to 72.5 (5-100); the rehabilitation intensity was 320 (40-1,240) minutes. The analytical results showed that the increase of total Barthel Index score was positively associated with rehabilitation intensity (ß=0.350) and negatively associated with the initial grooming score (ß=-0.277). [Conclusion] Adequate rehabilitation positively affects performance of activities of daily living, especially in patients with advanced cancer who lost their grooming ability at the onset of rehabilitation. Importantly, rehabilitation may be beneficial for patients with advanced cancer.

[A Patient Who Underwent Resection of Liver Metastases after Receiving Systemic Chemotherapy for Advanced Rectal Cancer and Multiple Liver Metastases].

The patient was a 52-year-old man who had a positive fecal occult-blood test on a medical check-upi n April 2015 and was referred to our hospital in June. Detailed preoperative examinations resulted in a diagnosis of cancer of the lower rectum, multiple liver metastases, and clinical Stage IV . A biopsy showed moderately differentiated tubular adenocarcinoma. All-RAS was wild type, and the patient was asymptomatic. Unresectable advanced rectal cancer was diagnosed, and the patient was scheduled to receive systemic chemotherapy. The patient received a total of 16 courses of combination chemotherapy with 5- fluorouracil, Leucovorin, and oxaliplatin(FOLFOX)plus panitumumab, starting in October 2015. In July 2016, Colonoscopy showed scar findings at the site of the primary rectal cancer lesion. A biopsy revealed no cancer cells. It was difficult to identify the primary lesion on computed tomography, and there was no evidence of clinically significant lymphadenopathy. Positronemission tomography and computed tomography showed shrinkage of the liver metastases, with no accumulation of tracer in the primary lesion or lymph nodes. The primary lesion had a clinical complete response(CR), and the metastatic lesions had a clinical partial response(PR). In October 2016, laparoscopic partial hepatectomy was performed to treat the liver metastases. Histologic examination showed that the liver metastases were from rectal cancer. It is currently under observation.

[Conversion Surgery for Initially Unresectable Locally Advanced Pancreatic Cancer Following Gemcitabine plus Nab-Paclitaxel - A Case Report].

We report a case of unresectable locally advanced pancreatic cancer successfully resected after gemcitabine(GEM)plus nab-paclitaxel(PTX)treatment. A 68-year-old man was referred to our institution with jaundice. We diagnosed pancreatic head cancer using computed tomography(CT)and endoscopic retrograde cholangiopancreatography. We initially diagnosed it as locally advanced unresectable pancreatic cancer because of extensive invasion to the portal vein. GEM plus nab- PTX was administered to the patient as systemic chemotherapy. After 9 courses of chemotherapy, a CT scan revealed that the tumor had significantly reduced in size and range of portal vein invasion. Therefore, we performed pancreaticoduodenectomy with resection of the portal vein and achieved R0 resection. Currently, the patient is alive without recurrence. Therefore, conversion surgery after treatment with GEM plus nab-PTX chemotherapy for unresectable pancreatic cancer should be considered.

Effectiveness of Lung Ultrasound Training Utilizing a High-Fidelity Simulator.

Background: The usefulness of lung ultrasound (LUS) has been demonstrated. However, it is unclear whether diagnostic techniques using LUS are accepted by all physicians. A simple simulation-based educational program may improve the LUS skills of beginners, but it has not been fully assessed. Objective: This prospective study was conducted to assess the educational outcomes of LUS training using a high-fidelity simulator. Methods: A simulator-based program for LUS was conducted. All clerkship students at the Department of Respirology at Chiba University Hospital participated in the program from December 2022 to April 2023. The participants watched a 30 minute teaching video on demand before a hands-on session lasting for 1 hour during the first week of the clinical clerkship. The readiness of the participants to learn LUS and the usefulness of the program were assessed using questionnaires administered before and after the program. The LUS skills were assessed using simulator-based tests during Weeks 1 and 4. Data on the accuracy and time required to answer the questions were collected during the tests. Results: Forty clerkship students participated in this study. Thirty-three (82.5%) had received other ultrasound education; however, only two (5.0%) had experience with LUS. Based on the questionnaire responses, the participants perceived LUS as useful (preprogram: 4.6 vs. postprogram: 4.8; P = 0.010; a 5-point Likert scale was used [1: not useful to 5: useful]). The simulator-based tests showed comparable accuracies at Weeks 1 and 4 for pneumothorax (Week 1: 47.5% vs. Week 4: 52.5%; P = 0.623), pulmonary edema (Week 1: 100% vs. Week 4: 100%; P = 1.000), and pleural effusion (Week 1: 37.5% vs. Week 4: 40.0%; P = 0.800). The time required for scanning was the same for each question. In addition, the test results did not differ with prior learning, previous knowledge, or experience during clinical clerkships on LUS. Conclusion: A short educational program consisting of on-demand learning and hands-on sessions with a high-fidelity simulator would be effective in equipping clerkship students with basic LUS skills. However, to increase its educational effectiveness to a practical degree, the program should be improved, and more opportunities for training using simulators should be provided.

Effect of a workplace-based learning program on clerkship students' behaviors and attitudes toward evidence-based medicine practice.

In clinical clerkship (CC), medical students can practice evidence-based medicine (EBM) with their assigned patients. Although CC can be a valuable opportunity for EBM education, the impact of EBM training, including long-term behavioral changes, remains unclear. One hundred and nine fourth- and fifth-year medical students undergoing CC at a medical school in Japan attended a workplace-based learning program for EBM during CC (WB-EBM), which included the practice of the five steps of EBM. The program's effect on the students' attitudes toward EBM in CC was assessed through questionnaires. A total of 88 medical students participated in the program. Responses to the questionnaire indicated high satisfaction with the WB-EBM program. The most common theme in students' clinical problems with their assigned patients was the choice of treatment, followed by its effect. Based on the responses in the post-survey for the long-term effects of the program, the frequency of problem formulation and article reading tended to increase in the 'within six months' group comprising 18 students who participated in the WB-EBM program, compared with the control group comprising 34 students who did not. Additionally, the ability to self-assess problem formulation was significantly higher, compared with the control group. However, among 52 students who participated in the WB-EBM program more than six months later, EBM-related behavioral habits in CC and self-assessments of the five steps of EBM were not significantly different from those in the control group. The WB-EBM program was acceptable for medical students in CC. It motivated them to formulate clinical questions and enhanced their critical thinking. Moreover, the WB-EBM program can improve habits and self-evaluations about EBM. However, as its effects may not last more than six months, it may need to be repeated across departments throughout CC to change behavior in EBM practice.

Long-term outcomes after spleen-preserving distal pancreatectomy with splenic vessels preservation or resection: A nationwide survey of the Japanese Society of Pancreatic Surgery.

BACKGROUND: Spleen preserving distal pancreatectomy is achieved by either splenic vessel resection or splenic vessel preservation. However, the long-term outcomes of spleen-preserving distal pancreatectomy with splenic vessel resection and spleen-preserving distal pancreatectomy with splenic vessel preservation are not well known. This study aimed to evaluate the long-term outcomes of spleen-preserving distal pancreatectomy with splenic vessel resection and spleen-preserving distal pancreatectomy with splenic vessel preservation. METHODS: The study included a total of 335 patients who underwent spleen-preserving distal pancreatectomy during the study period and underwent computed tomography or magnetic resonance imaging 3 and 5 years after surgery in the Japan Society of Pancreatic Surgery member institutions. We evaluated the diameter of the perigastric and gastric submucosal veins, patency of the splenic vessels, and splenic infarction. Preoperative backgrounds and short- and long-term outcomes were compared between the 2 groups. RESULTS: Forty-four (13.1%) and 291 (86.9%) patients underwent spleen-preserving distal pancreatectomy with splenic vessel resection and spleen-preserving distal pancreatectomy with splenic vessel preservation, respectively. There were no significant differences in short-term outcomes between the 2 groups. Regarding long-term outcomes, the prevalence of perigastric varices was higher (P = .006), and platelet count was lower (P = .037) in the spleen-preserving distal pancreatectomy with splenic vessel resection group. However, other complications, such as gastric submucosal varices, postoperative splenic infarction, gastrointestinal bleeding, reoperation, postoperative splenectomy, and other hematologic parameters, were not significantly different between the 2 groups 5 years after surgery. In terms of the patency of splenic vessels in spleen preserving distal pancreatectomy with splenic vessel preservation cases, partial or complete occlusion of the splenic artery and vein was observed 5 years after surgery in 19 (6.5%) and 55 (18.9%) patients, respectively. CONCLUSION: Perigastric varices and thrombocytopenia were observed more in spleen-preserving distal pancreatectomy with splenic vessel resection, yet late clinical events such as gastrointestinal bleeding and splenic infarction are acceptable for spleen-preserving distal pancreatectomy with splenic vessel preservation.

Mixed-methods education of mechanical ventilation for residents in the era of the COVID-19 pandemic: Preliminary interventional study.

INTRODUCTION: In the current era of the severe acute respiratory syndrome-coronavirus-2 epidemic, the need for respiratory care, including mechanical ventilatory (MV) management, has increased. However, there are no well-developed educational strategies for training medical personnel dealing with respiratory care in MV management. METHODS: A novel mixed-methods hands-on seminar for learning MV management was conducted for the residents at Chiba University Hospital in March 2022. The seminar lasted approximately 2 hours. The learning goal for the residents was to develop skills and knowledge in performing basic respiratory care, including MV, during an outbreak of a respiratory infection. The seminar with a flipped classroom consisted of e-learning, including modules on respiratory physiology and MV management, hands-on training with a low-fidelity simulator (a lung simulator), and hands-on training with a high-fidelity simulator (a human patient simulator). The effectiveness of the seminar was evaluated using closed questions (scored on a five-point Likert scale: 1 [minimum] to 5 [maximum]) and multiple-choice questions (maximum score: 6) at the pre- and post-seminar evaluations. RESULTS: Fourteen residents at Chiba University Hospital participated in the program. The questionnaire responses revealed that the participants' motivation for learning about MV was relatively high in the pre-seminar period (seven participants [50%] selected level 5 [very strong]), and it increased in the post-seminar period (all participants selected level 5) (p = 0.016). The responses to the multiple-choice questions revealed that the participants did not have enough knowledge to operate a mechanical ventilator, while the total score significantly improved from the pre- to post-seminar period (pre-seminar: 3.3 ± 1.1, post-seminar: 4.6 ± 1.0, p = 0.003). CONCLUSIONS: The seminar implemented in this study helped increase the residents' motivation to learn about respiratory care and improved knowledge of MV management in a short time. In particular, the flipped classroom may promote the efficiency of education on MV management.

Effect of Cycling Exercise Resisting Electrically Stimulated Antagonist Muscle Contractions in Healthy Males.

A hybrid training system (HTS) combining antagonist muscle electrical stimulation and voluntary muscle contraction has been developed using eccentric antagonist muscle contractions with electrical stimulation as resistance to voluntary muscle contractions. We devised an exercise method using HTS combined with a cycle ergometer (HCE). The purpose of this study was to compare the muscle strength, muscle volume, aerobic functions and lactate metabolism of HCE and a volitional cycle ergometer (VCE). A total of 14 male participants performed exercise on a bicycle ergometer for 30 min per session, 3 times per week for 6 weeks. We divided 14 participants into an HCE group (7 participants) and a VCE group (7 participants). The workload was set at 40% of each participant's peak oxygen uptake (V.O2peak). Electrodes were placed over each motor point on the quadriceps and hamstrings. The V.O2peak and anaerobic threshold significantly increased before and after training when using HCE rather than VCE. The HCE group had significantly increased extension and flexion muscle strength at 180 degrees/s in post-training measurements over pre-training measurements. Knee flexion muscle strength at 180 degrees/s tended to increase in the HCE group compared to the VCE group. The quadricep muscle cross-sectional area was significantly increased in the HCE group compared to the VCE group. Additionally, the HCE group had significantly decreased maximal lactate, measured every 5 min during exercise at the end of study, between pre and post-training. Thus, HCE may be a more effective training method for muscle strength, muscle mass and aerobic functions at 40% of each participant's V.O2peak than conventional cycling exercise. HCE could be applied not only as aerobic exercise but also as resistance training.

The effects of simple graphical and mental visualization of lung sounds in teaching lung auscultation during clinical clerkship: A preliminary study.

INTRODUCTION: The study aimed to evaluate visualization-based training's effects on lung auscultation during clinical clerkship (CC) in the Department of Respiratory Medicine on student skills and confidence. METHODS: The study period was December 2020-November 2021. Overall, 65 students attended a lecture on lung auscultation featuring a simulator (Mr. Lung™). Among them, 35 (visualization group) received additional training wherein they were asked to mentally visualize lung sounds using a graphical visualized lung sounds diagram as an example. All students answered questions on their self-efficacy regarding lung auscultation before and after four weeks of CC. They also took a lung auscultation test with the simulator at the beginning of CC (pre-test) and on the last day of the third week (post-test) (maximum score: 25). We compared the answers in the questionnaire and the test scores between the visualization group and students who only attended the lecture (control group, n = 30). The Wilcoxon signed-rank test and analysis of covariance were used to compare the answers to the questionnaire about confidence in lung auscultation and the scores of the lung auscultation tests before and after the training. RESULTS: Confidence in auscultation of lung sounds significantly increased in both groups (five-point Likert scale, visualization group: pre-questionnaire median 1 [Interquartile range 1] to post-questionnaire 3 [1], p<0.001; control group: 2 [1] to 3 [1], p<0.001) and was significantly higher in the visualization than in the control group. Test scores increased in both groups (visualization group: pre-test 11 [2] to post-test 15 [4], p<0.001; control group: 11 [5] to 14 [4], p<0.001). However, there were no differences between both groups' pre and post-tests scores (p = 0.623). CONCLUSION: Visualizing lung sounds may increase medical students' confidence in their lung auscultation skills; this may reduce their resistance to lung auscultation and encourage the repeated auscultation necessary to further improve their long-term auscultation abilities.

A low-intensity 10-min resistance exercise program that ameliorated hepatic fibrosis indices and altered G-CSF/IP-10/PDGF-BB in a patient with nonalcoholic fatty liver disease: A case report.

We developed a low-intensity 10-min resistance exercise program for nonalcoholic fatty liver disease (NAFLD). We report a case of NAFLD with elevated hepatic fibrosis indices, which were improved by a 60-week daily exercise program. A 71-year-old female patient with NAFLD whose hepatic fibrosis stage corresponded to F2 was referred to our hospital. She performed the exercise once a day with no changes in other lifestyle habits and medications. The homeostasis model assessment-insulin resistance value and NAFLD-liver fat score, the Hepamet fibrosis score, and the enhanced liver fibrosis score decreased. The FIB-4 index and serum levels of Mac-2 binding protein glycosylation isomer decreased to the reference values. We investigated the changes in chemokines/cytokines. The serum granulocyte-colony stimulating factor level was increased, and serum interferon-gamma-induced protein-10 and platelet-derived growth factor-BB levels were decreased. Our program may be beneficial for improving hepatic fibrosis in patients with NAFLD.

Combination therapy with predicted body weight-based dexamethasone, remdesivir, and baricitinib in patients with COVID-19 pneumonia: A single-center retrospective cohort study during 5th wave in Japan.

BACKGROUND: Dexamethasone, remdesivir, and baricitinib reduce mortality in patients with coronavirus disease 2019 (COVID-19). A single-arm study using combination therapy with all three drugs reported low mortality in patients with severe COVID-19. In this clinical setting, whether dexamethasone administered as a fixed dose of 6 mg has sufficient inflammatory modulation effects of reducing lung injury has been debated. METHODS: This single-center retrospective study was conducted to compare the treatment strategies/management in different time periods. A total of 152 patients admitted with COVID-19 pneumonia who required oxygen therapy were included in this study. A predicted body weight (PBW)-based dose of dexamethasone with remdesivir and baricitinib was administered between May and June 2021. After this period, patients were administered a fixed dose of dexamethasone at 6.6 mg/day between July and August 2021. The additional respiratory support frequency of high-flow nasal cannula, noninvasive ventilation, and mechanical ventilation was analyzed. Moreover, the Kaplan-Meier method was used to analyze the duration of oxygen therapy and the 30-day discharge alive rate, and they were compared using the log-rank test. RESULTS: Intervention and prognostic comparisons were performed in 64 patients with PBW-based and 88 with fixed-dose groups. The frequency of infection or additional respiratory support did not differ statistically. The cumulative incidence of being discharged alive or oxygen-free rate within 30 days did not differ between the groups. CONCLUSIONS: In patients with COVID-19 pneumonia who required oxygen therapy, combination therapy with PBW-based dexamethasone, remdesivir, and baricitinib might not shorten the hospital stay's length or oxygen therapy's duration.

Comparison of infectious complications after spleen preservation versus splenectomy during laparoscopic distal pancreatectomy for benign or low-grade malignant pancreatic tumors: A multicenter, propensity score-matched analysis.

BACKGROUND: Previous studies have reported contrasting results regarding the advantages of spleen preservation during laparoscopic distal pancreatectomy (LDP) for preventing infectious complications. METHODS: A total of 3787 patients who underwent LDP for benign or low-grade malignant pancreatic disease in 92 centers across Korea and Japan were included in this retrospective study. Postoperative infectious complications and other complications were compared between LDP with splenectomy (LDPS) and LDP with spleen preservation (LSPDP) by propensity score matching (PSM) analysis. RESULTS: After PSM, the LSPDP group had a lower rate of overall infectious complications (P = .079) and a significantly lower rate of intra-abdominal abscess (P = .014) compared with the LDPS group. Within the LSPDP group, the vessel preservation subgroup had a significantly higher rate of infectious complications (P = .002) compared with the vessel resection subgroup. Low-volume centers had a higher rate of intra-abdominal abscess than high-volume centers in the LSPDP group (P = .001) and the splenic vessel preservation subgroup (P = .003). CONCLUSIONS: Spleen preservation in LDP for benign or borderline malignant pancreatic diseases was advantageous in lowering the risk of infectious complications, specifically intra-abdominal abscess. However, the risk of intra-abdominal abscess may differ according to the level of surgeon's experience.