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A 69-year-old woman who had undergone renal transplantation and was receiving sulfamethoxazole/trimethoprim (ST) developed pulmonary nocardiosis. To our knowledge, this is the first report of the identification of Nocardia elegans using nanopore sequencing, supported by 16S rDNA capillary sequencing findings. Chest computed tomography performed after ST initiation revealed significant improvement of the pulmonary shadows compared to previous findings. We herein report the value of nanopore sequencing for rapid identification of rare pathogens, such as Nocardia elegans. Furthermore, our findings suggest that Nocardia may infect even patients receiving ST, which is currently the most effective prophylactic drug.

Background Preoperative portal vein embolization (PVE) stimulates liver hypertrophy and improves the safety of major hepatectomy. It is essential to predict the future remnant liver volume (FRLV) and resection limit following PVE. Previously, we reported that evaluating functional FRLV (fFRLV) using EOB-MRI could predict post-hepatectomy liver failure. In this study, we investigated the usefulness of fFRLV in predicting the achieving of adequate resection limit for safe hepatectomy following PVE. Methods We included 55 patients who underwent PVE and were scheduled for major hepatectomy. We calculated the liver-to-muscle ratio in the remnant liver and fFRLV using EOB-MRI. We investigated the pre-PVE variables in determining the nonachievement of the resection limit. Results The median observation period between PVE and the first evaluation was 21 days, and the median growth rate of FRLV was 26.4%. In 54.5% of patients, the resection limit of fFRLV (615 mL/m2) was achieved. In logistic regression and receiver-operating characteristic analyses, pre-PVE fFRLV (p Conclusion Pre-PVE fFRLV can be useful in predicting the achievement of adequate resection limit following PVE.

Summary Objective To observe and analyze the interaction between excessive mechanical stress (MS) and decreased sex hormones on Temporomandibular Joint Osteoarthritis (TMJ-OA), and to discover TMJ-OA disease susceptibility genes by molecular biological analysis to elucidate part of the mechanism of TMJ-OA onset. Design For experimental groups, orchiectomy (ORX) or ovariectomy (OVX) was performed on sexually mature 8-week-old mice. A metal plate was attached to the posterior surface of the maxillary incisors to apply excessive MS on mandibular condyles. Male mice were divided into control, ORX, MS, and ORX + MS groups, while female mice were divided into control, OVX, MS, and OVX + MS groups. Mandibular condyles were evaluated by histology and molecular biology. Results Histomorphometric analysis of the TMJ in ORX + MS and OVX + MS groups revealed the thinnest chondrocyte layers, highest modified Mankin scores, and significant increases in the number of osteoclasts. Gene expression analysis indicated upregulation of Angptl7 and Car1 genes in the mandibular condyles of mice subjected to the combined effects of excessive MS and reduced sex hormones. In vitro analysis suggested that cartilage-like cells overexpressing Angptl7 enhanced calcification, and osteoblast-like cells overexpression Car1 suppressed cell proliferation and calcification. Conclusions A severe TMJ-OA mouse model was successfully developed by applying excessive MS on the mandibular condyle of male and female mice with reduced sex hormones. Disease-susceptibility genes Angptl7 and Car1 were newly discovered in the experimental groups, suggesting their involvement in the onset mechanism of TMJ-OA.

To evaluate the effect of morphine or morphine equivalents on the risk of bile leakage (BL) after hepatectomy. The subjects of this retrospective study were 379 patients who underwent hepatectomy without biliary reconstruction and biliary decompression tube insertion at Gunma University between 2016 and 2020. Clinical BL was defined as International Study Group of Liver Surgery post-hepatectomy bile leakage Grade B or C. Intra- and post-operative analgesia comprised intravenous patient-controlled analgesia (IV-PCA) with fentanyl (n = 58), epidural analgesia with fentanyl (n = 157), epidural analgesia with morphine (n = 151), and epidural analgesia with ropivacaine or levobupivacaine (n = 13). Clinical BL was diagnosed in 14 of the 379 (3.7%) patients. The significant risk factors for clinical BL were hepatocellular carcinoma (HCC), elevated serum total bilirubin, high indocyanine green retention at 15 min, elevated Mac-2-binding protein glycosylated isomer, prolonged duration of surgery, and a large volume of blood loss. There was no significant correlation of clinical BL with intra- and post-operative analgesia and total oral morphine equivalents. Intra- and post-operative IV-PCA and epidural analgesia were not related to clinical BL after hepatectomy. Based on our data, fentanyl and morphine can be administered safely as epidural or intravenous analgesic agents.

Introduction: The International Study Group of Liver Surgery (ISGLS) definition of bile leakage is an elevated total bilirubin concentration in the drainage fluid after post-operative day (POD) 3, which has been widely accepted. However, there were no reports about direct bilirubin in drainage fluid to predict bile leakage. Methods: Data from 257 patients who underwent hepatectomy were retrospectively reviewed. The optimal cut-off value was investigated using receiver-operating characteristic curves. The predictive power of drainage fluid total bilirubin (dTB) and drainage fluid direct bilirubin (dDB) to predict bile leakage, which was defined using ISGLS grade B or grade C, were compared. Results: ISGLS grade B bile leakage occurred in 16 patients (6.2%). Area under the curve (AUC) of dDB was always higher than that of dTB on each POD. The AUC of dDB was >0.75 on PODs 2, 3, and 5, and then it increased with the increasing POD. The dDB on POD 5 showed the highest accuracy (0.91) and positive predictive value (PPV) (0.67), which was followed by dTB/serum total bilirubin (sTB) on POD 3 (accuracy, 0.91; PPV, 0.33). Because the PPV of dDB increased as the POD increased, dDB was better than dTB for predicting clinically significant bile leakage. dDB on POD 3 showed the highest negative predictive value (0.97). The positive likelihood of dDB increased and the negative likelihood of dDB decreased on the basis of the POD. Among patients with dTB/sTB ≤3 on POD 3, 19.1% of these patients had bile leakage when dDB was >0.44 on POD 3. Conclusions: Measurement of both dDB and dTB, which are easy to perform, can be used to effectively predict clinically significant bile leakage.

An organized hematoma is a cystic lesion characterized by superficial fibrotic encapsulation. While an organized hematoma is benign, making a differential diagnosis from a malignant lesion is difficult, as both exhibit invasive behavior and cause bone resorption. The objective of this study was to describe a rare case of organized hematoma in the cheek of a 28-year-old male. The swelling in the cheek developed following the extraction of the right mandibular third molar. The extraction site did not show any signs of inflammation and the patient did not have any systemic risk factors. A preoperative magnetic resonance image revealed characteristic findings associated with organized hematoma. Clarithromycin was administered for 2 months before the lesion was surgically removed. The results of this case suggested that antibiotic administration prior to surgical removal was important, as the cause of the organized hematoma was mild inflammation.

Intraductal tubulopapillary neoplasm is a rare pancreatic tumor. The purpose of this study was to clarify the recurrence type and prognosis in recurrent cases after intraductal tubulopapillary neoplasm resection. PubMed was searched for previous reports on surgical resection of intraductal tubulopapillary neoplasm of the pancreas that were published from 2009 to July 2020. The clinical features obtained from these reports were summarized and analyzed. The clinicopathological data of 35 intraductal tubulopapillary neoplasm cases were obtained. Of these, 21 were males, and 14 were females, with an average age of 57.9 years old. Invasive findings were observed in 21 of 35 patients (60%). Recurrence was observed in 11 of the 35 cases (31.4%), including remnant pancreatic recurrence in 6 cases (17.1%) and liver metastasis in 5 cases (14.3%). The tumor size was significantly larger in the liver metastasis group than in the remnant pancreas recurrence group (P = 0.04), and patients with liver metastases tended to have a poorer prognosis than those with remnant pancreas recurrence. The recurrence type of intraductal tubulopapillary neoplasm resection was mainly remnant pancreatic recurrence and liver metastasis recurrence. Total pancreatectomy for remnant pancreatic recurrence may be suitable because of its good prognosis.

A 88-year-old female who was being treated for end-stage pseudoexfoliation syndrome was referred to our hospital for treatment of dislocated intraocular lens (IOL) and the elevated intraocular pressure (IOP) and in the right eye (RE). At the first visit to our hospital, best-corrected visual acuity (BCVA) was 0.2 in the RE and 0.02 in the left eye (LE). IOP was 47 mm Hg in the RE and 21 mm Hg in the LE. Slit-lamp examination showed no abnormalities in anterior segments and dislocated IOL in the RE. Fundus photograph showed optic disc pallor in both eyes. We performed the combined therapy of flanged intrascleral IOL fixation with the double-needle technique and trabeculectomy. Throughout the follow-up period, BCVA slightly improved from 0.2 to 0.4 in the RE. The angle of tilt of the IOL was 6.6, 7.9, and 8.7° as measured by swept-source optical coherence tomography at 1, 4, and 6 months after the surgery, respectively. The IOP remained less than 10 mm Hg without having to administer any other glaucoma medications. Furthermore, any complications associated with the surgery were not confirmed.

BACKGROUND Tumor invasion is the most significant prognostic factor in ampullary cancer and is thus a crucial factor in decision making for treatment. Endoscopic ultrasound can be performed to evaluate tumor invasion, but its diagnostic accuracy varies depending on the endoscopist. This study aimed to assess the usefulness of fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperatively predicting tumor invasion in ampullary cancer. METHODS We retrospectively evaluated 44 patients with ampullary cancer (adenoma, n = 6; adenocarcinoma, n = 38) who underwent surgical resection. The SUVmax of the ampullary tumor site was assessed using FDG-PET, and the correlation among tumor invasion, lymph node metastasis, and other clinicopathological factors was evaluated. RESULTS The SUVmax of the ampullary tumor site gradually increased depending on the extent of tumor invasion (p = 0.0075). Moreover, the SUVmax was significantly different between ≤T1a and ≥T1b, which is an indication for endoscopic papillectomy or surgical resection (p = 0.0015). The SUVmax of the ampullary section was significantly correlated with lymph node metastasis (p = 0.035). CONCLUSION The SUVmax of the ampullary tumor site is correlated with tumor invasion and lymph node metastasis in ampullary cancer. Thus, FDG-PET can be a useful modality for preoperative staging and treatment strategy.

Hirotsugu Takashina,1 Akira Watanabe,2 Koji Komatsu,1 Tadashi Nakano2 1Department of Ophthalmology, Tokyo Rosai Hospital, Tokyo, Japan; 2Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, JapanCorrespondence: Hirotsugu TakashinaDepartment of Ophthalmology, Tokyo Rosai Hospital, 4-13-21 Omori-Minami, Ota-ku, Tokyo, 143-0013, Japan, Tel +81-3-3742-7301 ext 8116Fax +81-3-3744-9310Email two-shina@s7.dion.ne.jpBackground: Subthreshold photocoagulation is one of the treatments for diabetic macular edema. However, the range of adequate laser energy that can be used for subthreshold photocoagulation is very restricted. Therefore, determination of the titration settings for the threshold energy is an essential part of the subthreshold-photocoagulation procedure. This study examined factors influencing the threshold energy used in subthreshold photocoagulation for diabetic macular edema.Methods: For 20 consecutive cases (29 eyes) who had received treatment using Endpoint Management (EpM) between April 2019 and June 2020 for persistent diabetic macular edema after completion of panretinal photocoagulation, multiple regression analysis was used to examine factors influencing threshold energy.Results: Analysis evaluating all the surgical procedures (n=150) determined there was statistical significance for a history of vitrectomy and cataract surgery, central macular thickness, interval from completion of panretinal photocoagulation, superior 6 mm subfield, and nasal 6 mm subfield. Further analysis examined surgical procedures that had been done in patients with a history of vitrectomy and cataract surgery (n=116). This analysis showed that central macular thickness, axial length, interval from completion of panretinal photocoagulation, and HbA1c were all statistically significant factors.Conclusion: Threshold energy for diabetic macular edema was significantly influenced by a history of vitrectomy and cataract surgery, central macular thickness, and interval between the completion of panretinal photocoagulation and initial EpM. Transparency of ocular media and intraocular inflammation were speculated to be associated with these results.Keywords: diabetic macular edema, subthreshold photocoagulation, panretinal photocoagulation, vitrectomy, cataract surgery

Introduction Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza. Methods The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system. Results A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67–84), and the patients in the 2015–2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality. Conclusions Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989).

Objective In clinical dentistry, tooth extraction is one of the most fundamental techniques learned during mandatory dentist clinical internships. However, there are fewer opportunities for students to perform this procedure on actual patients. Hence, a tooth extraction simulator was developed based on clinical experience to evaluate the appropriate load and magnitude of the three- dimensional forces (x, y, and z axes) applied while using forceps for tooth extraction. Methods Twenty-three subjects were divided into five groups according to experience (i.e., fifth-year dental students, clinical intern dentists, early-career oral surgeons, board-certified members of the Japanese Society of Oral and Maxillofacial Surgeons [JSOMS], and JSOMS specialists and clinical instructors). The simulator was developed with Osada Electric Co. Ltd. using electromagnets and load cells. The magnitude of the three-directional load applied in actual tooth extractions was used as basis for the simulator. Results With increasing clinical experience, a consistent trend in terms of lower variation in loading, stable initial movements, and low directional variability was observed. On determination of the appropriate standards from the measurements of this study, users can not only gauge the amount of force needed to grasp the teeth and tear the periodontal ligament by dislocation but also appreciate the orientation and force required for tooth extractions. Conclusion This study demonstrated the utility of a tooth extraction simulator in evaluating the generated loads and movements during tooth extraction procedures.

Aggressive periodontitis during adolescence has a poor prognosis due to rapid alveolar bone resorption. Few studies have investigated long-term follow-up after surgical orthodontic treatment performed in conjunction with that for invasive periodontitis. Here, we report a case of mandibular prognathism accompanied by generalized aggressive periodontitis and crowding. A 31-year-old woman was referred to our department for treatment of masticatory dysfunction due to reverse overjet. The patient exhibited a class III molar relationship, protrusion of the ANB of －6.0°, and severe maxillary crowding. Initial periodontal examination revealed deep periodontal pockets and extensive inflammation. Mandibular prognathism accompanied by generalized aggressive periodontitis and crowding was diagnosed. Therefore, it was necessary to adopt an interdisciplinary approach involving surgical, orthodontic, and periodontal treatment. Prior to commencement of orthodontic treatment, plaque control, scaling, and root planing of all teeth were performed by a periodontist to suppress inflammation and reduce probing depth. During pre-surgical orthodontic treatment, the maxillary first premolars were extracted to reduce crowding of the maxillary incisors. To correct the mandibular prognathism, the mandible was repositioned by sagittal split ramus osteotomy. Proper occlusion of the incisors and maximum intercuspation were achieved by post-surgical orthodontic treatment. After completion of active orthodontic treatment, acceleration of inflammation was observed together with aggravated resorption of the alveolar bone surrounding the molars. However, reduction of probing depth and inflammation were observed after scaling and root planing. The surgical-orthodontic treatment time was 1 year and 11 months, which was followed by a 2-year retention period. There was no tooth loss due to periodontitis, and an overall satisfactory outcome was achieved.

Differences in vocal tract lengths (VTLs) in individual speakers cause variations in acoustic features of phonemes. In this paper, a simple method to estimate speaker-specific VTLs and to quantitatively evaluate some speaker-normalization effects of the VTLs is proposed. We employed accumulated means of formant trajectories to estimate the VTLs of speakers ranging from children to adults. For the formant estimation, the inverse-filter control (IFC) system was used. In the system, the decision of analysis order, which means number of formants to be estimated, is automated. Moreover, to evaluate the speaker-normalization effect of VTLs, we proposed the data reduction method, which can reasonably find dense areas of ellipses from distributions in the formant space. Using these ellipse areas, we evaluated the three normalization effects of VTLs: normalization by the mean of all VTLs as the standard, by speaker-categorical means of VTLs, and by individual VTLs. The area reduced from the standard area of the original data by 39.5% and 46.6% in the case of the categorical means and individual VTLs, respectively. As a result, our proposed method was used to provide a “normalized vowel map (NVM)” that visualizes universal vowel-distributions as a core image of linguistic information. Finally, we compared the estimated VTLs with those by another method based on magnetic resonance imaging (MRI) data, using the proposed methods.

Purpose Multifocal intraocular lenses (IOLs) can potentially affect the intraoperative view of the retina. We investigated the suitability of different lenses for viewing the macular area through two multifocal intraocular lenses in a human eye model. Methods This study compared the image quality of graduated index (0.1 mm) in a model eye when viewed through refractive or diffractive multifocal IOLs with a meniscus or flat contact lens, and a wide field 60 diopter non-contact lens or wide field contact lens (Super Macula®). Results Images acquired through the meniscus contact lens or flat contact lens via the central optical zone of the refractive multifocal IOL or the diffractive multifocal IOL were well focused. However, images viewed through these lenses near the center were warped and out of focus. All images viewed through a wide-field 60 diopter non-contact lens at the central optical zone and near the center were slightly out of focus. All images viewed through the Super Macula at the central optical zone and near the center were well focused. Conclusion A wide field contact lens (Super Macula®) made it possible to obtain clear images of the macular area at multiple focal points through refractive or diffractive multifocal IOLs.

We experienced a case of follicular cholangitis that was positive on fluorodeoxyglucose-positron emission tomography (18F-FDG-PET). A 70-year-old man was admitted for jaundice. Endoscopic retrograde cholangiography showed stenosis of the middle to upper choledocus. 18F-FDG-PET depicted a localized hot spot at the stenotic lesion (maximum standardized uptake value = 8.2). Although no malignant findings were found in the cytology or on a bile duct biopsy, malignancy could not be excluded, so surgical treatment was performed. Follicular cholangitis is a new, rare disease that causes severe biliary stricture. Only 11 cases of follicular cholangitis have been reported, including the present case.

Aspergillus empyema is treated with either systemic administration of antifungal drugs or surgery, but the mortality rate is very high. Here, we report a case of Aspergillus empyema successfully treated using combined intrathoracic and intravenous administration of voriconazole (VRCZ). Treatment success was achieved by monitoring VRCZ plasma trough concentration. The patient was a 71-year-old Japanese woman diagnosed with Aspergillus empyema whom we started on intravenous administration of VRCZ. Although penetration of VRCZ into the pleural effusion was confirmed, the level was below 1 μg/mL, which is the minimum inhibitory concentration for Aspergillus fumigatus determined by antifungal susceptibility testing in pleural effusion culture. Therefore, we initiated combination therapy with intrathoracic and intravenous administration of VRCZ. VRCZ 200 mg was first dissolved in 50-100 mL of saline and administered into the thoracic cavity via a chest tube. The chest tube was clamped for 5-6 h, and then VRCZ solution was excreted though the chest tube. When a single dose of the VRCZ was administered into the intrathoracic space, the plasma concentration before intravenous administration increased from 1.45 μg/mL on day 27 to 1.53 μg/mL on day 28. Although intravenous administration was continued, the VRCZ plasma trough concentration decreased to 1.36 μg/mL on day 29. We therefore decided on an intrathoracic administration schedule of 2-3 times a week. Intrathoracic administration was performed 14 times in total until fenestration surgery on day 64. Our case suggests that combined intrathoracic and intravenous administration of VRCZ may be a valid treatment option for Aspergillus empyema.

This study aimed to elucidate the association between postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) and clinicopathological factors and intraoperative and postoperative epidural or intravenous patient-controlled analgesia (IV-PCA). We reviewed data of 116 patients who underwent distal pancreatectomy at Gunma University Hospital from October 2000 to October 2019. Clinical POPF was defined as the International Study Group of Pancreatic Fistula grade B or C. Intraoperative and postoperative analgesia included fentanyl-mediated IV-PCA (n = 37, 32%), fentanyl-mediated epidural analgesia (n = 39, 34%), and morphine-mediated epidural analgesia (n = 40, 34%). All patients had received analgesia. Clinical POPF occurred in 34 of the 116 (29%) DP cases. Male sex (P = 0.035) and the length of operation time (P = 0.0070) were significant risk factors of clinical POPF. Furthermore, a thick pancreas was more likely to cause clinical POPF than a thin one (P = 0.052). No statistically significant difference was found between other factors, including intraoperative and postoperative analgesia (P = 0.95), total median oral morphine equivalents (P = 0.23), and clinical POPF. Intraoperative and postoperative epidural analgesia and IV-PCA are not associated with clinical POPF after DP. Our results suggest that morphine and fentanyl can be used as IV-PCA or epidural analgesia.

Background We retrospectively investigated factors predictive for ascites after hepatic resection to treat hepatocellular carcinoma (HCC). Patients and methods The data of 114 patients with HCC who underwent curative hepatic resection were reviewed. The patients were assigned to two groups according to the presence or not of postoperative ascites. Results Ascites occurred in 16 patients (14.0%), and refractory ascites in four (3.5%). A MAC2-binding protein glycosylation isomer (M2BPGi) cutoff index of 1.61 [sensitivity=75.0%, specificity 67.9%, area under the curve (AUC)=0.745] and virtual touch tissue quantification (VTQ) of 2.62 (sensitivity=68.8%, specificity=89.8%, AUC=0.827) were the best cut-off values. Patients with ascites had lower serum albumin levels, higher serum creatinine levels, higher albumin-bilirubin (ALBI) grade, higher M2BPGi, higher VTQ, and longer operative time. ALBI grade 2 and both M2BPGi>1.61 and VTQ>2.62 were independent predictors of postoperative ascites. Conclusion We demonstrated retrospectively that ALBI grade 2 and both high M2BPGi and VTQ were independent predictors of postoperative ascites in patients undergoing hepatic resection for HCC.

Pneumococcal vaccination has been shown to reduce occurrence of invasive pneumococcal diseases in elderly patients. In this study, we investigated the real-world efficacy of pneumococcal vaccination implemented in elderly individuals in Japan. We reviewed the in-patient database of Juntendo University Hospital and selected elderly patients (≥65 years-old) who had received in-patient care in the general medicine department during 2014–2018. A total of 1355 patients were retrospectively enrolled and comprised of 1045 unvaccinated and 315 vaccinated elderly individuals. Prior vaccination was found associated with all-cause shorter hospital stays (adjusted RR = 0.66, 95% CI = 0.57 to 0.76) and less medical expenditure (adjusted RR = 0.76, 95% CI = 0.66 to 0.87) compared with no vaccination, as well as protection for all-cause in-hospital mortality (adjusted OR = 0.42, 95% CI = 0.22 to 0.83). The association of shorter hospital stays and less medical expenditure with vaccination was also observed in the context of pneumonia, although no altered risk in mortality was observed. In conclusion, this study is one of the first reporting real-world data after the initiation of pneumococcal vaccination program in 2014 in Japan. The national PPV23 vaccination program contributed to the reduction of all-cause in-patient days, mortality, and medical expenses in the elderly aged ≥65 years. Further data is warranted to evaluate the contribution from influenza vaccination and protein-conjugate based pneumococcal vaccine.

Pneumonia is the third most common cause of death in Japan. Low vaccination rates are thought to be related to low levels of public subsidy. Since 2014, the Japanese government has offered subsidies through a 5-year national routine vaccination program of the 23-valent pneumococcal polysaccharide vaccine (PPV23) for older adults at age ≥65 years with 5-year age intervals. We previously reported that, 2 years into the 5-year program, the estimated vaccination rate was 40.6% at the end of 2015, a significant increase compared with periods before the program introduced. Here, we present an update on the estimated vaccination coverage of the 5-year national routine vaccination program at the end of 2018. The PPV23 vaccination rates were calculated by dividing the cumulative amount shipped to each municipality by the population aged ≥65 years. At the end of 2018, the completion of the 5-year national immunization program, the estimated cumulative vaccination rate was 74%. Stepwise regression analysis revealed that the annual PPV23 vaccination rate significantly increased after 2014 (from 2 to 5% prior to 2014, to 10-11% after 2014), and remained steady for 2014-2018. Our findings suggest that the 5-year national routine vaccination subsidy program was successful in achieving a steady and higher vaccination rate of PPV23 in Japan.

Background/purpose Right hepatic vein (RHV) drainage area resection is performed for intrahepatic tumors. However, borders of RHV drainage areas are difficult to identify. We evaluated the usefulness of indocyanine green (ICG) fluorescent images to identify the borders for RHV drainage area resection. Methods From January 2016 to May 2019, we included 12 patients who underwent hepatic resection of the RHV drainage area, which was evaluated using ICG fluorescence images after clamping the RHV and with or without clamping the proper hepatic artery (PHA). The resected liver volume was compared with the preoperative simulated resected liver volume by 3-dimensional computed tomography. Results Eleven borders of the RHV drainage area between the middle hepatic vein (MHV) or inferior RHV drainage area were confirmed using ICG fluorescent images in 12 patients. The borders were observable by only clamping the RHV. In one patient, the border could not be identified because there was a shunt between the RHV and MHV at the peripheral area. Resected liver volume was significantly correlated with the results of preoperative simulation. Conclusion The RHV drainage area resection could be one of the options of hepatic resection for the tumor involving the root of the RHV. ICG fluorescent imaging in hepatic resection of the RHV drainage area is useful for determining areas of liver congestion and clamping the PHA is not always necessary.

We investigated the predictors of bile leakage after hepatic resection. The data of 270 consecutive patients who underwent curative hepatic resection in our institute between January, 2016 and April, 2019 were reviewed retrospectively. The patients were assigned to one of two groups according to the presence of bile leakage and the clinicopathological and surgical outcomes were analyzed. Bile leakage was defined by the International Study Group of Liver Surgery (ISGLS) grade. There were no hospital deaths. The median intraoperative blood loss volume was 167 ml. Bile leakage occurred in 12 patients (4.4%), as ISGLS grade A leakage in 1 and as ISGLS grade B leakage in 11. The mean hospital stay was significantly longer for patients with bile leakage. High-risk procedures, hepatocellular carcinoma, and Albumin–Indocyanine Green Evaluation (ALICE) grade 3 were independent predictors of ISGLS grade B or C postoperative bile leakage. In patients with three high-risk factors, the incidence of bile leakage was 53.9%. Based on this retrospective analysis, high-risk procedures, hepatocellular carcinoma, and ALICE grade 3 were independent predictors of bile leakage in patients undergoing hepatic resection. Thus, special care must be taken during surgery to prevent bile leakage in patients with these risk factors.

As the first biologics for psoriasis in Japan, infliximab and adalimumab, anti-tumor necrosis factor-α antibodies, became available in the field of dermatology in 2010, followed by ustekinumab, an anti-interleukin (IL)-12/IL-23p40 antibody, which was launched in Japan in 2011. Since 2015, three IL-17 inhibitors of secukinumab and ixekizumab, anti-IL-17A antibodies, and brodalumab, an anti-IL-17 receptor antibody, and two anti-IL-23p19 antibodies of guselkumab and risankizumab, have also been launched. It is important for physicians to select appropriate biologic therapy for each psoriatic patient after due consideration of disease factors, treatment factors and patient background factors, sharing such information with patients. The following can be listed as points to be considered for the selection of biologics: drug effects (e.g. strength of effectiveness, time to onset of effectiveness, effectiveness against arthritis, primary failure, secondary failure), safety (e.g. infections, administration-related reactions and relationships with other comorbidities), convenience for patients (e.g. hospital visit intervals, self-injection, maintenance therapy at clinics, feasibility of drug discontinuation/re-administration) and payment (medical costs) borne by patients. This guidance has been prepared with the aim of allowing dermatologists experienced in the treatment of psoriasis to use biologics appropriately according to the circumstances of individual patients after consideration of the above-mentioned factors.

Highlights • Dermoid cysts arising from the upper lip are relatively rare. • Dermoid cysts have been histopathologically classified as epidermoid, dermoid and teratoid cysts. • The diagnosis and management of dermoid cysts can be improved with the combined use of ultrasonography., Introduction Generally, dermoid cysts commonly arise from the anus and ovaries. Oral and maxillofacial lesions are most commonly observed in the midline of the floor of the mouth, and lesions arising from the upper lip are relatively rare. Presentation of case A 50-year-old man was referred to our hospital due to swelling of the left upper lip. Clinical examination revealed an elevated alar base, Gerber protrusion and nasal deformity. Ultrasonography revealed a clearly defined 30-mm lesion with more hypoechoic bands. Meanwhile, magnetic resonance imaging revealed a 30-mm mass below the orbicularis oris of the left upper lip. The lesion had a homogeneous, low-signal intensity on T1-weighted imaging. Thus, based on these findings, a dermoid cyst was suspected. The lesion was then removed en bloc without the overlying skin while the patient was under general anaesthesia. Histopathological examination revealed a cystic cavity lined by an orthokeratinised stratified squamous epithelium. However, skin appendages were not found. Based on the clinical and histopathological features of the lesion, a diagnosis of epidermoid cyst was made. Swelling of the left upper lip, nasal deformity and Gerber protrusion significantly improved after surgery. Conclusion Although dermoid cysts arising from the upper lip are rare, the diagnostic accuracy for dermoid cyst can be improved with the combined use of ultrasonography and other imaging modalities even though these lesions are difficult to distinguish from differential diagnosis.

While orthognathic surgery is now a safe and established procedure, it poses associated complications, similarly to every surgical procedure. Aseptic necrosis is an ischemic complication associated with orthognathic surgery. Although aseptic necrosis is a serious complication, treatment protocol has not yet been established. Herein we reported a case of aseptic necrosis occurring in the maxilla following Le Fort I (LFI) osteotomy. The patient was a 25-year-old woman referred to our hospital with a chief complaint of maxillary alveolar bone exposure. She had been submitted to horseshoe-type LFI osteotomy and bilateral sagittal split ramus osteotomy two months earlier. At initial visit, osseous non-union of the maxilla and exposure of the right anterior maxillary alveolar bone were observed. At first surgery, necrotic alveolar bone and soft tissue were debrided, titanium plates were removed, and a new titanium plate was provided for adequate osteosynthesis in left-side bone gap under general anesthesia. At second surgery, 11.12.13.14 were extracted and alveolus was reconstructed by iliac crest graft. In addition, 21 was extracted under local anesthesia owing to tooth mobility, and root canal treatment to 22.23 was performed. After 6 months, the plates were removed, and four implants were placed. At third surgery, oral vestibular extension operation was performed. Five years following the initial procedure, the patient achieved normal occlusion and dentofacial appearance.

Aim Few reported studies examine the relationship between zinc (Zn) deficiency and short- and long-term outcomes in patients with hepatocellular carcinoma (HCC) undergoing hepatic resection. Methods We retrospectively reviewed data from 179 consecutive patients who had undergone curative hepatic resection for HCC in our institute between January 2016 and May 2019. Zn deficiency was defined in accordance with the Japanese Society of Clinical Nutrition guidelines. We allocated the participants into two groups according to Zn deficiency status and analyzed the clinicopathological and short- and long-term outcomes. Results In this series, 32 patients (17.8%) had Zn deficiency. Zn deficiency was significantly associated with older age, lower serum albumin, higher aspartate aminotransferase, lower hemoglobin, higher creatinine, lower prognostic nutritional index, higher liver fibrosis markers, albumin-bilirubin 2, portal hypertension, larger amount of estimated blood loss, larger amount of maximum ascites, longer hospital stay, postoperative complications, and liver-related complications. Concentrations of liver fibrosis markers were negatively correlated with serum Zn concentrations. Zn deficiency, albumin-bilirubin 2 and non-laparoscopic approach were identified as independent predictors of postoperative complications. Multivariate analyses revealed that the overall survival rate decreased in parallel with decreasing Zn concentrations. Conclusions In this study, Zn deficiency was significantly associated with poorer liver function, more severe liver fibrosis, higher incidence of postoperative complications, and worse overall survival according to multivariate analysis. Serum Zn status could serve as a new surrogate marker for predicting short- and long-term outcomes in patients undergoing hepatic resection for HCC. This article is protected by copyright. All rights reserved.

Invasive fungal disease (IFD) in patients with haematological disorders is a fatal disease, making rapid identification and treatment crucial. However, the identification of the causative fungus is often difficult, sometimes even impossible. There have been few reports concerning the causative species of IFD. This study aimed to investigate the epidemiology and causative organism of IFD in patients with haematological diseases in Japan. We analyzed the IFD cases among the patients with haematological malignancies identified at the Medical Mycological Research Center, Chiba University, between 2013 and 2019. The most common underlying disease was acute myeloid leukaemia (34.3%). Forty-six point one percent of IFD patients received haematopoietic stem cell transplantation (HSCT). The major pathogens were Aspergillus, Candida, and Fusarium. Aspergillus fumigatus was the most common Aspergillus species, and Candida fermentati and Fusarium petroliphilum were the most common Candida and Fusarium species, respectively, in this analysis. Furthermore, various cryptic species and non-albicans Candida were identified. The drug susceptibility of such relatively rare strains suggests that analysis of the causative fungi should provide valuable information for therapeutic options. Therefore, our study indicated that it is clinically significant to identify the organism in as much detail as possible.

The efficacy and prognosis of adjuvant chemotherapy for resected pancreatic cancer remain unclear. We investigated the utility and risk factors of S-1 adjuvant chemotherapy in patients with pancreatic cancer undergoing pancreatectomy. This study comprised 80 patients, including 58 patients who received S-1 adjuvant chemotherapy. Skeletal muscle loss was defined using cutoff values of skeletal muscle mass index. In total, 16 (20%) octogenarian patients underwent pancreatectomy. Skeletal muscle loss was present in 56 (70%) patients. The entire course of S-1 adjuvant chemotherapy for 6 months was completed in 33 patients (41%). S-1 adjuvant chemotherapy &lt, 6 months was an independent prognostic indicator of poor overall survival. Patients who completed S-1 adjuvant chemotherapy exhibited significantly longer overall and relapse-free survival rates than those did not complete the chemotherapy (p &lt, 0.0001 and p = 0.0003, respectively). Being an octogenarian and skeletal muscle loss were independent variables associated with the discontinuation of S-1 adjuvant chemotherapy. Finally, the S-1 adjuvant chemotherapy rates were 6.3% (1/16) and 28.6% (16/56) in octogenarian patients and those with skeletal muscle loss, respectively. S-1 adjuvant chemotherapy completion was associated with improved prognosis in patients with pancreatic cancer. Skeletal muscle loss and octogenarian status predicted the failure of S-1 adjuvant chemotherapy completion.

Dyslipidemia is correlated with the prognosis of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder characterized pathologically by TAR DNA binding protein (TDP-43) inclusions. We investigated molecular mechanisms of lipid metabolism regulated by TDP-43 in ALS. Expression microarray and RNA deep sequencing (RNA-Seq) were performed using cell lines expressing doxycycline-inductive TDP-43. Gene expression and transcriptome profiling identified 434 significantly altered genes under high levels of TDP-43 (Tukey’s test, P

Highlights • The complication of percutaneous transhepatic gallbladder aspiration. • Inappropriate aspiration may cause an abdominal wall biloma. • We should consider alternative therapy when aspiration was not sufficiently., Background Abdominal wall biloma is an uncommon entity. We herein report an extremely rare case of cholecystitis with abdominal wall biloma after percutaneous transhepatic gallbladder aspiration (PTGBA). Presentation of case A 69-year-old woman was diagnosed with acute cholecystitis, and PTGBA was performed on Day 1. PTGBA was performed a second time because of re-expansion of the gallbladder and an increased CRP level on Day 3. Computed tomography was performed on Day 9 because we suspected recurrence of cholecystitis. It revealed a well-circumscribed fluid collection between the abdominal wall or the diaphragm and the liver. Based on these intraoperative findings, we diagnosed her with cholecystitis with abdominal wall biloma. Cholecystectomy and drainage of the abdominal wall biloma were performed on Day 10. The postoperative course was uneventful, and she was discharged on Day 18. Discussion Early cholecystectomy is the gold-standard treatment for acute cholecystitis, but cholecystectomy is not performed in some cases. PTGBA is much more convenient, quicker, and less costly, but inappropriate aspiration during the second PTGBA session might have spread the infected bile to the abdominal wall through the PTGBA route. Conclusion This case represents the first reported case of a biloma within the abdominal wall after PTGBA. To prevent this complication, we should aspirate gallbladder bile sufficiently during PTGBA. In addition, we should consider performing alternative therapy, such as percutaneous transhepatic gallbladder drainage or an operation, when we fail to appropriately aspirate.

Background We assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza. Methods This open-label study administered 1 weight-adjusted dose of baloxavir to 107 children aged 1–11 years with laboratory-confirmed, febrile influenza virus infection of ≤48 hours duration. Results Adverse events (AEs) were reported in 34.6% of patients, most commonly vomiting (7.5%); no serious AEs or AEs causing discontinuation occurred. The median time to alleviation of influenza illness was 44.6 hours (95% confidence interval, 38.9–62.5 hours), to resolution of fever was 21.4 hours, and to sustained cessation of infectious viral shedding was 24.0 hours. However, viruses with amino acid substitutions in the viral polymerase acidic protein at position I38 (PA/I38T/M) emerged in 18 of 77 (23.4%) patients. Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses). Among patients with PA/I38T/M-substituted virus emergence, those with baseline hemagglutinin inhibition (HAI) antibody titer, A single, oral dose of baloxavir marboxil was well tolerated and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children.

In this retrospective study, we aimed to analyze 2640 cases of orthognathic surgery performed in the Department of Oral and Maxillofacial Surgery, Tokyo Dental College, Suidobashi Hospital between April 1990 and March 2017. We also, analyzed the incidence of bad splits in bilateral sagittal split osteotomy (BSSRO) and massive blood loss exceeding 1000 g, between January 2012 and December 2016.The aim was to gain insight into the circumstances surrounding orthognathic surgery cases and to identify potential trends in jaw deformity treatment. The study included 952 males (35.9%) and 1688 females (64.1%). The majority of patients were 10–30 years old. Mandibular osteotomy was performed in 1820 and double-jaw surgery was performed in 787 cases, including the Le Fort I osteotomy and bilateral sagittal splitting ramus osteotomy (BSSRO). The annual number of orthognathic surgeries increased gradually, while the average operating time and blood loss decreased. Massive blood loss occurred in three cases, and bad splits following BSSRO were occurred in 13 cases between January 2012 and December 2016.There was a significant correlation between operating time and blood loss; operating times and blood loss improved over the 27-year study period.

Background Recent studies have shown that the systemic inflammatory response induced by cancer leads to cancer progression. Neutrophil-to-lymphocyte ratio (NLR) is the most reliable marker to detect systemic inflammation. In this study, we investigated the significance of NLR in patients with well-differentiated pancreatic neuroendocrine tumors (PanNETs) according to the World Health Organization 2017 classification. Methods We retrospectively collected data for patients with PanNET who underwent pancreatic resection with curative intent between January 2008 and December 2017 at six institutions. Clinicopathological factors, recurrence, and immunohistochemical staining of tumor-associated macrophages (TAMs) were analyzed in a total of 55 patients in this study. Results High NLR (>3.41) in patients was significantly associated with higher white blood cell count, higher Ki-67 index, higher mitotic count, higher grade, higher incidence of lymph node metastasis, higher incidence of lymphatic and neural invasion, massive blood loss, and a large number of CD163-expressing TAMs. Recurrence-free survival of patients with high NLR was significantly poorer than that of patients with low NLR. Multivariate analysis identified high NLR, NET Grade 2 (G2) or Grade 3 (G3), and synchronous hepatic resection as independent risk factors for recurrence after curative resection. Conclusions NLR is a promising predictor of recurrence after pancreatectomy that needs to be further investigated and that accumulation of TAMs in the tumor could be one of the causes of NLR elevation.

INTRODUCTION Intercostal port is useful for the superior segments in laparoscopic liver resection, but optimal indications for its use remain unclear. This study analyzed the surgical outcomes in patients undergoing laparoscopic partial liver resection for superior segments to determine the optimal indications. METHODS A total of 30 cases of laparoscopic partial liver resection for superior segments were retrospectively reviewed. First, comparison of cases according to use of the intercostal port was performed. Second, cases were classified into two groups according to the branch of the hepatic vein in the superior segments: superior-ventral group (S4a/S8vent: Svent group, n = 18) and superior-dorsal group (S7/S8dor: Sdor group: n = 12). The surgical outcomes were then compared to assess the performance of intercostal ports. RESULTS No differences in surgical outcomes were observed between patients with or without intercostal port. In this series, no complication due to the intercostal port, and no major complication were observed. In the comparison between Svent and Sdor, similar values of the operation time (Svent: 275 minutes vs Sdor: 316 minutes, P = .161) and blood loss (Svent: 30 mL vs Sdor: 17 mL, P = .718) were observed in both groups. The tumor size tended to be smaller in Sdor (Svent: 20 mm vs Sdor: 17 mm, P = .018), but use of the intercostal port was significantly more frequent in Sdor (58%) compared to Svent (33%) (P

Pancreatic cancer tissue contains abundant stromal components, including extracellular matrix proteins such as tenascin C (TNC), which exists as large (TNC-L) and non-large splice variants. Here, we examined human pancreatic cancer specimens for the expression of total TNC (TNC-ALL) and TNC-L in the stroma and annexin A2 (ANXA2), a cell surface receptor for TNC, and evaluated their significance as prognostic markers for pancreatic cancer. Expression of ANXA2, TNC-ALL, and TNC-L was examined in 106 pancreatic cancer tissues from patients who underwent curative resection and who had not received prior therapy or surgery. Protein expression was measured by immunohistochemistry and scored on a semi-quantitative scale. The relationships between protein expression, clinicopathological factors, and prognosis were evaluated by Cox proportional hazards analysis. TNC-ALL and TNC-L were detected mainly in the stroma, whereas ANXA2 was predominantly expressed in cancer cell membranes. TNC-ALL was also expressed in non-tumor pancreatic tissue. High levels of stromal TNC-L and membranous ANXA2, but not stromal TNC-ALL, were independently associated with cancer progression and poor prognosis. Moreover, high co-expression of stromal TNC-L and membranous ANXA2 was a superior indicator of poor prognosis compared with detection of TNC-ALL, TNC-L, or ANXA2 alone. Our data suggest that co-expression of stromal TNC-L and membranous ANXA2 is a poor prognostic marker compared with detection of TNC-L or ANXA2 alone for pancreatic cancer patients. Additionally, targeting of crosstalk between stromal TNC and cancer cell ANXA2 could be a promising therapeutic strategy to overcome refractory pancreatic cancer.

Background Pleomorphic leiomyosarcomas (PLMSs) are extremely rare tumors. We present the first case of hepatic primary PLMS after surgery for gastric gastrointestinal stromal tumor (GIST). Case presentation The patient was a 62-year-old man who was referred to our hospital for resection of a hepatic tumor arising after gastric GIST surgery that was resistant to imatinib and sunitinib. A 40-mm tumor in the left lobe of the liver and three small nodules in the right lobe were detected. We performed hepatic left lobectomy and partial resections for three lesions. According to the histopathological and immunohistochemical findings and c-kit gene mutations analysis, the main tumor was diagnosed as a PLMS. Conclusion It is necessary to consider the possibility that imatinib-resistant GIST recurrence lesions are a different kind of soft-tissue sarcoma. Accurate diagnosis is required to not miss the opportunity for radical excision of PLMS.

During the period from January to December 2015, 104 Streptococcus pneumoniae strains, 129 Haemophilus influenzae strains and 54 Moraxella catarrhalis strains isolated from clinical specimens of pediatric infections in the national 16 institutions, studied susceptibilities of total 28 antibiotics, the capsular serotype for S. pneumoniae, the capsular b type and β-lactamase production capability for H. influenzae, and the β-lactamase production capability for M. catarrhalis were measured. In S. pneumoniae, the results showed that 68 strains (65.4%) were PSSP, 32 (30.8%) were PISP, and 4 (3.8%) were PRSP. The susceptibilities of TBPM and GRNX among oral antibiotics, and PAPM among injectable antibiotics demonstrated the lowest value with MIC90 ≤ 0.06 μg/mL. The most frequent distribution of S. pneumoniae serotypes was seen in 15B, followed by 19A, and 35B. Serotype strains contained in 13-valent pneumococcal conjugate vaccine (PCV13) were 19 strains (18.3%). In H. influenzae, the results showed that BLNAS accounted for 40 strains (31.0%), BLNAI for 28 strains (21.7%), BLNAR for 47 strains (36.4%), β-lactamase producing for 14 strains (10.8%). The susceptibilities of quinolones demonstrated the lowest outcome among oral antibiotics with MIC90 ≤ 0.06 μg/mL, and CTRX and TAZ/PIPC (TAZ4 fixed) among injectable antibiotics with MIC of 0.25 μg/mL. There was no detection of capsular type b strains. In M. catarrhalis, all the isolates were β-lactamase producing strains. The susceptibilities of TBPM, CPFX, TFLX and GRNX among oral antibiotics, and TAZ/PIPC (TAZ4 fixed), PAPM, MEPM and DRPM among injectable antibiotics demonstrated the lowest outcome with MIC of ≤0.06 μg/mL.