A method of transferring the subgingival contour of interim restorations to definitive restorations by using zirconia copings customized with casting wax.

Establishing continuous and symmetric gingival levels is essential to achieving optimal gingival esthetics. Adjustment of the subgingival contour of the interim prosthesis is useful for managing gingival levels. This article illustrates how to accurately and predictably transfer the adjusted subgingival contour of interim restorations to the definitive restorations by using zirconia copings customized with casting wax.

Pediatric sepsis cases diagnosed with group B streptococcal meningitis using next-generation sequencing: a report of two cases.

BACKGROUND: Group B Streptococcus (GBS) is an important cause of invasive infection in neonates and infants. Cerebrospinal fluid (CSF) findings and culture may not show evidence of infection early in GBS meningitis. Next-generation sequencing (NGS) has the potential to detect microbial genetic material in patients with infectious diseases. We report two cases of infantile sepsis of GBS meningitis with negative results for CSF culture tests, but positive results for NGS analysis. CASE PRESENTATION: Patient 1 was a 22-day-old male infant diagnosed with sepsis and meningitis. His CSF findings showed pleocytosis, decreased glucose, and increased protein levels. However, CSF and blood culture results at admission were negative. He received a total of 3 weeks of treatment with ampicillin and cefotaxime, and showed clinical improvement. GBS was detected through NGS analysis of CSF collected at admission. Patient 2 was a 51-day-old male infant with sepsis. CSF findings on admission were normal, and blood and CSF cultures were also negative. Intravenous ampicillin and cefotaxime treatment were initiated. Treatment was de-escalated to ampicillin alone because Enterococcus faecalis was cultured from urine. He was discharged after a total of 1 week of antibiotic treatment. Six days after discharge, he was re-hospitalized for sepsis. Blood and CSF cultures were negative, and E. faecalis was again cultured from urine. He received a total of 3 weeks of ampicillin treatment for enterococcal-induced nephritis and did not relapse thereafter. NGS pathogen searches were retrospectively performed on both blood and CSF collected at the first and second admission. GBS was detected in the CSF collected at the first admission, but no significant pathogen was detected in the other samples. Inadequate treatment for GBS meningitis at the first admission may have caused the recurrence of the disease. CONCLUSION: Infantile sepsis may present bacterial meningitis that is not diagnosed by either culture testing or CSF findings. NGS analysis for CSF may be useful for confirming the diagnosis of bacterial meningitis.

Evaluation of Proteins and Cells that Adsorb to Dialysis Membranes Used in Continuous Hemodiafiltration: Comparison of AN69ST, Polymethylmethacrylate, and Polysulfone Membranes.

OBJECTIVE: In intensive care medicine, continuous renal replacement therapy (CRRT) is important for critically ill patients. Various types of dialysis membranes are currently used in clinical settings, each having unique structures and characteristics. This study aimed to perform a detailed analysis of the characteristics of polysulfone (PS), polymethylmethacrylate (PMMA), and polyacrylonitrile (AN69ST) membranes, and to determine differences in the adsorption of proteins and blood cells by membrane material. METHODS: Subjects were patients undergoing CRRT in the ICU of the Kokura Memorial Hospital. After use, membranes were collected and analyzed. Semi-quantitative analysis of the membrane surface was performed by scanning electron microscopy. We determined the identity of proteins adsorbed to the surface of membranes by TOF/MS analysis, and measured the amount of adsorbed chemical mediators. RESULTS: Electron microscopy revealed that, compared to PS and PMMA membranes, AN69ST membranes had a greater amount of adsorbed activated white blood cells (WBCs). A large amount of platelets was adsorbed to PMMA membranes. In terms of the amount of adsorbed protein, significantly more proteins adsorbed to AN69ST membranes compared to PS and PMMA membranes. Moreover, TOF/MS analysis revealed a difference in the types of adsorbed proteins by membrane. Chemokines were particularly prevalent among adsorbed proteins for all 3 membranes. CONCLUSION: Compared to PS and PMMA membranes, AN69ST membranes had a higher capacity to remove activated WBCs. Moreover, apparent differences were noted in the types of proteins that adsorbed to each type of membrane. These differences in membrane properties may impact clinical outcomes.

Hypertrophic teres minor restores shoulder strength and range of external rotation in posterosuperior rotator cuff tears.

BACKGROUND: In posterosuperior rotator cuff tears (PS-RCT), the progression of infraspinatus (ISP) muscle atrophy seems to induce compensatory hypertrophy of the teres minor (TM) muscles. However, the effect of these changes on shoulder strength and range of external rotation (ER) remains unclear. This study determined the strength and range of ER in patients with PS-RCT with atrophic ISP and hypertrophic TM and compared this with patients with PS-RCT and normal or deficient TM. METHODS: We investigated 35 patients with PS-RCT and atrophic ISP. TM muscles were classified as hypertrophic (type A) in 17, normal (type B) in 10, or deficient (type C) in 8. The strength ratio of the affected shoulder to the healthy contralateral shoulder was calculated, and the active range of motion was measured for both shoulders. RESULTS: The strength ratios of ER in types A, B, and C were 60%, 33%, and 7% (P < .01) with the patient's arm at the side and were 60%, 35%, and 5% (P < .001) at 90° abduction, respectively. The average ranges of ER in types A, B, and C were 22.6°, 15.0°, and -12.5° (P < .001) with the patient's arm at the side and were 71.6°, 44.5°, and 21.9° at 90° abduction (P < .01), respectively. The differences between shoulder types in other measures of strength or ER range were not significant. CONCLUSIONS: In patients with PS-RCT and atrophic ISP, shoulders with compensatory hypertrophy of the TM had greater strength and range of ER than shoulders with normal or atrophic TM.

Hypertrophic changes of the teres minor muscle in rotator cuff tears: quantitative evaluation by magnetic resonance imaging.

BACKGROUND: Few reports have assessed the teres minor (TM) muscle in rotator cuff tears. This study aimed to quantitatively analyze the morphologic changes of the TM muscle in patients with or without rotator cuff tears by magnetic resonance imaging (MRI). METHODS: This retrospective study consisted of 279 subjects classified on the basis of interpretations of conventional MRI observations into 6 groups: no cuff tear; partial-thickness supraspinatus (SSP) tear; full-thickness SSP tear; SSP and subscapularis tears; SSP and infraspinatus (ISP) tears; and SSP, ISP, and subscapularis tears. With use of ImageJ software (National Institutes of Health, Bethesda, MD, USA) for oblique sagittal MRI, we measured the areas of ISP, TM, and anatomic external rotation (ISP + TM) muscles on the most lateral side in which the scapular spine was in contact with the scapular body. The occupational ratios of the TM muscle area to the anatomic external rotation muscle area were calculated. Ratios above the maximum of the 95% confidence intervals of the occupational ratio in the no-tear group were defined as hypertrophy of the TM muscle. RESULTS: Occupational ratios of the TM muscle in the no-tear group followed a normal distribution, and ratios >0.288 were defined as hypertrophic. Hypertrophic changes of the TM muscle were confirmed in rotator cuff tears involving the ISP tendon. A negative correlation was found between the occupational ratios of TM and ISP (P < .001). CONCLUSION: The TM muscle appeared hypertrophic in rotator cuff tears involving the ISP, and the progression of ISP muscle atrophy seemed to induce the development of this compensatory hypertrophy.

Hepatocellular Carcinoma Showing Tumor Shrinkage Due to an Abscopal Effect.

We herein report a 63-year-old man who presented with left lower jaw pain and was diagnosed with hepatocellular carcinoma with bone metastases post-examination. All tumors grew after immunotherapy with atezolizumab and bevacizumab, and his jaw pain worsened. After palliative radiation therapy, however, the tumors shrank markedly, with no recurrence seen after stopping immunotherapy. To our knowledge, this is the first case in which a radiotherapy- and immunotherapy-mediated abscopal effect facilitated tumor shrinkage and immunotherapy discontinuation.

Metastasis from Renal Cell Carcinoma to Ectopic Pancreas Diagnosed after Resection.

We herein report a 68-year-old man who underwent nephrectomy for right renal cell carcinoma 10 years prior. He remained under regular medical observation, and abdominal computed tomography showed tumors in the head and tail of the pancreas. He was diagnosed with pancreatic metastasis from renal cell carcinoma. He underwent surgical excision. The pathologic diagnosis proved that the pancreatic tumors were metastases from renal cell carcinoma and clarified that an ectopic pancreas in the duodenum had metastases as well. To our knowledge, this is the first case of metastasis to an ectopic pancreas.

Lymphatic drainage dysfunction via narrowing of the lumen of cisterna chyli and thoracic duct after luminal dilation.

BACKGROUND: The chronological pattern of extrahepatic lymphatic vessel progression in the course of chronic liver disease has not been clarified. This study aimed to clarify the chronological changes in lymphatic vessels with liver disease progression. METHODS: This was a prospective cross-sectional study that enrolled a total of 199 patients. The maximum diameter of the cisterna chyli (CC) or terminal thoracic duct (tTD) was measured using computed tomography or ultrasonography, respectively. Changes in the maximum diameters of the CC and tTD were evaluated with patients with chronic liver disease as the pilot set (n = 138). Subsequently, we examined whether CC/tTD could be used to re-allocate unclassified patients by the Baveno-VII criteria to appropriately diagnose clinically significant portal hypertension (CSPH) in the pilot and validation sets. RESULTS: In the pilot set, a scatter-plot showed that both CC and tTD were narrowed as terminal features in chronic liver disease after dilation. Because there was a significant correlation between the CC diameter and hepatic venous pressure gradient (r = 0.724) in unclassified patients, the diagnostic value of CC and tTD for CSPH was good (AUC: 0.961 and 0.913, respectively). After re-allocation, 68 and 27 unclassified patients were reduced to 4 and 5 in the pilot and validation sets, respectively. CONCLUSION: Both the CC and tTD narrow in the course of liver disease after dilation. Moreover, the maximum diameter of the CC and tTD can be used to re-allocate patients who are unclassified according to the Baveno-VII criteria. CLINICAL TRIAL NUMBER: UMIN trial no. 000044857.

Deep attenuation transducer to measure liver stiffness in obese patients with liver disease.

PURPOSE: Deep attenuation transducers (DAX) are capable of imaging at diagnostic depths of up to 40 cm. The feasibility of DAX for liver stiffness measurement (LSM) has not been reported clinically. We aimed to assess the feasibility and reliability of DAX for LSM. METHODS: Overall, 219 patients with chronic liver disease were enrolled. The success rate (acquired after ≥ 10 valid measurements) and inadequate measurements (interquartile range/median ≥ 0.3) for DAX were compared with those of conventional convex (c-convex) probes and M and XL probes of vibration-controlled transient elastography. RESULTS: LSM was successfully performed for all patients using DAX through all degrees of skin-to-liver capsular distance (SCD). Especially in patients with an SCD ≥ 30 mm, the difference in the rate of acquisition of 10 valid measurements was remarkable: M probe (8/33, 24.2%), XL probe (26/33, 78.8%), c-convex probe (33/43, 76.7%), and DAX (44/44, 100%). In patients with an SCD ≥ 30 mm, the inadequate measurement rate of M probe (1/8, 12.5%), XL probe (8/26, 30.8%), and c-convex probe (6/33, 18.2%) was higher than that of DAX (1/43, 2.3%). The areas under the curve for diagnosis of F4 with shear wave speed by c-convex and DAX were 0.916 and 0.918, respectively. Between DAX and c-convex probes, the intraclass correlation coefficient of 0.937 (95% CI 0.918-0.952) was excellent. Bland-Altman plots revealed that there was no statistically significant bias. CONCLUSION: Liver stiffness measured by DAX is feasible and reliable for all patient populations, while the XL probe is limited to use in obese patients.

B-mode shear wave elastography can be an alternative method to vibration-controlled transient elastography according to a moderate-scale population study.

PURPOSE: We aimed to compare vibration-controlled transient elastography (VCTE) with shear wave elastography (SWE) without previous analysis and generate regression equations between VCTE and new point SWE using combination-elastography. METHODS: Overall, 829 patients with chronic liver disease were enrolled in this study. Patients with a skin-liver capsule distance > 25 mm were excluded. The reproducibility of VCTE and SWE was confirmed in a phantom study and a clinical study. Considering that combination-elastography allows measurement based on strain elastography, a similar analysis was performed for the liver fibrosis index (LFI), which is a quantitative value for evaluation of liver fibrosis calculated using strain elastography image features. Regression equations between the VCTE and SWE values were obtained based on linear regression analysis. RESULTS: In the phantom study and clinical study, there was a strong correlation between VCTE and SWE [r = 0.995 (p < 0.001) and r = 0.747 (p < 0.001), respectively). The regression equation between VCTE and SWE was VCTE (kPa) = 1.09 × point SWE (kPa) - 0.17. The Bland-Altman plots revealed no statistically significant bias. Meanwhile, there was no correlation between VCTE and LFI (r = 0.279). There was a statistically significant bias between VCTE and LFI in the Bland-Altman plots. The inter-operator reliability showed a good intraclass correlation coefficient of 0.760 (95% confidence interval: 0.720-0.779). CONCLUSION: Liver stiffness measured using point SWE was comparable to that measured using VCTE.

Survival Improvements in Advanced Hepatocellular Carcinoma with Sequential Therapy by Era.

Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022. The patients were separated into three groups according to systemic therapy commencement. The number of therapy lines, treatment efficacy, and overall survival (OS) were compared. Multivariate analyses of the prognostic factors were analyzed using the Cox proportional hazards model. Overall, 336 patients were included (period 1: 2009-2013, n = 86; period 2: 2014-2018, n = 132; period 3: 2019-2022, n = 118). A significant etiological trend was observed with decreasing viral hepatitis-related HCC and increasing non-viral hepatitis-related HCC. Across periods 1-3, the proportion of patients who were administered >2 lines progressively increased (1.2%, 12.9%, and 17.0%, respectively; p < 0.001) and the median OS was significantly prolonged (14.3, 16.8, and 31.0 months; p < 0.001). The use of <3 lines, the non-complete and partial response of the first line, modified albumin-bilirubin at grade 2b or 3, an intrahepatic tumor number ≥ 5, extrahepatic metastasis, and alpha-fetoprotein at ≥400 ng/mL were the strongest factors associated with shorter OS. Sequential therapies have contributed to significant improvements in HCC prognosis, suggesting that sequential treatment post-progression is worthwhile for better survival.

Simple new clinical score to predict hepatocellular carcinoma after sustained viral response with direct-acting antivirals.

The time point of the most precise predictor of hepatocellular carcinoma (HCC) development after viral eradication with direct-acting antiviral (DAA) therapy is unclear. In this study we developed a scoring system that can accurately predict the occurrence of HCC using data from the optimal time point. A total of 1683 chronic hepatitis C patients without HCC who achieved sustained virological response (SVR) with DAA therapy were split into a training set (999 patients) and a validation set (684 patients). The most accurate predictive scoring system to estimate HCC incidence was developed using each of the factors at baseline, end of treatment, and SVR at 12 weeks (SVR12). Multivariate analysis identified diabetes, the fibrosis-4 (FIB-4) index, and the α-fetoprotein level as independent factors at SVR12 that contributed to HCC development. A prediction model was constructed with these factors that ranged from 0 to 6 points. No HCC was observed in the low-risk group. Five-year cumulative incidence rates of HCC were 1.9% in the intermediate-risk group and 15.3% in the high-risk group. The prediction model at SVR12 most accurately predicted HCC development compared with other time points. This simple scoring system combining factors at SVR12 can accurately evaluate HCC risk after DAA treatment.

Colorectal cancer screening with odour material by canine scent detection.

OBJECTIVE: Early detection and early treatment are of vital importance to the successful treatment of various cancers. The development of a novel screening method that is as economical and non-invasive as the faecal occult blood test (FOBT) for early detection of colorectal cancer (CRC) is needed. A study was undertaken using canine scent detection to determine whether odour material can become an effective tool in CRC screening. DESIGN: Exhaled breath and watery stool samples were obtained from patients with CRC and from healthy controls prior to colonoscopy. Each test group consisted of one sample from a patient with CRC and four control samples from volunteers without cancer. These five samples were randomly and separately placed into five boxes. A Labrador retriever specially trained in scent detection of cancer and a handler cooperated in the tests. The dog first smelled a standard breath sample from a patient with CRC, then smelled each sample station and sat down in front of the station in which a cancer scent was detected. RESULTS: 33 and 37 groups of breath and watery stool samples, respectively, were tested. Among patients with CRC and controls, the sensitivity of canine scent detection of breath samples compared with conventional diagnosis by colonoscopy was 0.91 and the specificity was 0.99. The sensitivity of canine scent detection of stool samples was 0.97 and the specificity was 0.99. The accuracy of canine scent detection was high even for early cancer. Canine scent detection was not confounded by current smoking, benign colorectal disease or inflammatory disease. CONCLUSIONS: This study shows that a specific cancer scent does indeed exist and that cancer-specific chemical compounds may be circulating throughout the body. These odour materials may become effective tools in CRC screening. In the future, studies designed to identify cancer-specific volatile organic compounds will be important for the development of new methods for early detection of CRC.

A case of walled-off necrosis extending into the pelvic cavity successfully treated by endoscopic necrosectomy using a lumen-apposing metal stent.

A 31-year-old man developed massive walled-off necrosis extending into the pelvic cavity following severe acute alcoholic pancreatitis. Endoscopic ultrasound-guided fistula drainage was performed using a lumen-apposing metal stent, but this was insufficiently effective, and endoscopic necrosectomy was also performed, after which the patient improved. Percutaneous drainage and surgery are other options for the treatment of walled-off necrosis extending into the pelvic cavity, but a valuable case in which the patient improved with endoscopic treatment alone is presented.

Vitamin D Supplementation Regulates Postoperative Serum Levels of PD-L1 in Patients with Digestive Tract Cancer and Improves Survivals in the Highest Quintile of PD-L1: A Post Hoc Analysis of the AMATERASU Randomized Controlled Trial.

Because vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to stage III digestive tract cancer from the esophagus to the rectum was conducted. Postoperative serum PD-L1 levels were measured by ELISA and divided into quintiles (Q1-Q5). Serum samples were available for 396 (95.0%) of the original trial. Vitamin D supplementation significantly (p = 0.0008) up-regulated serum PD-L1 levels in the lowest quintile (Q1), whereas it significantly (p = 0.0001) down-regulated them in the highest quintile (Q5), and it did not either up- or down-regulate them in the middle quintiles (Q2-Q4). Significant effects of vitamin D supplementation, compared with placebo on death (HR, 0.34; 95% CI, 0.12-0.92) and relapse/death (HR, 0.37; 95% CI, 0.15-0.89) were observed in the highest quintile (Q5) of serum PD-L1, whereas significant effects were not observed in other quintiles (Pinteraction = 0.02 for death, Pinteraction = 0.04 for relapse/death). Vitamin D supplementation significantly reduced the risk of relapse/death to approximately one-third in the highest quintile of serum PD-L1.

Involvement of non­triple helical type VI collagen α1 chain, NTH α1(VI), in the proliferation of cancer cells.

It has been reported that a polypeptide encoded by collagen type VI alpha 1 chain (COL6A1), one of the three α chains of type VI collagen, is strongly associated with the migration and invasion of highly metastatic human pancreatic cancer BxPC­M8 cells and excessive proliferation of LNCaP cells. We previously reported that non­triple helical type VI collagen α1 chain, NTH α1(VI), a non­triple helical polypeptide encoded by COL6A1, is not derived from type VI collagen and exists in cancer cell­conditioned media. Therefore, NTH α1(VI) may be involved in cancer cell migration, invasion, and proliferation. The active entity that promotes cellular behaviors in cancer remains unclear. Thus, we predicted that NTH α1(VI) has cancer­promoting activity, such as the ability to induce cell proliferation. This study was conducted to examine whether NTH α1(VI) and/or its derived peptides are involved in cancer cell proliferation. Highly metastatic human pancreatic S2­VP10 cells were used to explore the potential of COL6A1 knockdown in reducing cell proliferation. Moreover, S2­VP10 conditioned medium was assessed after molecular size­fractionation to determine whether the inhibitory effect of COL6A1 knockdown could be rescued by the medium. We showed that S2­VP10­conditioned medium contained COL6A1 polypeptide, but not COL6A2, suggesting that COL6A1 in the conditioned medium of S2­VP10 cells reflects the presence of NTH α1(VI). COL6A1 knockdown repressed S2­VP10 cell proliferation and this repression was rescued using the conditioned medium of S2­VP10 cells. The fraction of conditioned medium containing peptides smaller than 10 kDa rescued the inhibitory effect; however, the fraction containing polypeptides larger than 10 kDa, including NTH α1(VI), did not show rescue activity, indicating that NTH α1(VI) fragmentation is necessary for enhanced cancer cell proliferation. In conclusion, fragmentation of NTH α1(VI) into peptides <10 kDa is required for its cancer cell proliferation­promoting activity.

Identification of a common epitope in the sequences of COL4A1 and COL6A1 recognized by monoclonal antibody #141.

Identification of a type IV collagen α1 polypeptide in non-triple helical form [NTH α1(IV)], possibly involved in angiogenesis, introduces the further possibility of the existence of non-triple helical forms of other collagen chains. We previously reported that an anti-NTH α1(IV) monoclonal antibody #141 recognizes not only NTH α1(IV) but also a novel non-triple helical collagen polypeptide NTH α1(VI) encoded by COL6A1. In this study, we identified the recognition sequence in order to better understand the properties of antibody #141 and provide clues regarding the biological function of the two non-triple helical molecules. Additionally, we determined the common epitope between COL4A1 and COL6A1 as PXXGXPGLRG, with surface plasmon resonance analyses revealing KD values for the COL4A1 epitope as 5.56±1.81×10-9 M and for the COL6A1 epitope as 7.15±0.44×10-10 M. The specific recognition of NTH α1(IV) and NTH α1(VI) by antibody #141 can be explained by the common epitope sequence. Moreover, epitope localization supports previous finding that NTH α1(IV) and NTH α1(VI) differ in conformation from the α1 chains in triple-helical type IV and type VI collagen. These findings suggest that antibody #141 might be useful for diagnosis of type VI collagen myopathies.

[Case of gastric cancer with recurrence of carcinomatous lymphangiosis of the lung 7.6 years after surgery and successfully treated with S-1/low-dose CDDP/Lentinan combination therapy].

A 78-year-old woman underwent gastrectomy for type 3 gastric cancer with pyloric stenosis, which was detected in November 1997. Thoracic and abdominal CT and other diagnostic procedures were conducted regularly for 5 years after surgery. The patient was recurrence-free and her clinical course was satisfactory. Starting in early May 2005, however, she began to experience respiratory difficulty at exertion, which exacerbated rapidly thereafter. Examination at a department of respiratory physiology led to a diagnosis of a recurrence of stomach cancer and carcinomatous lymphangiosis+lymphatic metastasis to the peritoneal cavity. She was referred to us for palliative care. The accentuated respiratory difficulty was eased with oxygen inhalation and opioid administration. With improvement in her respiratory condition, a combination of S-1 80 mg/day, CDDP 10 mg x once/week and Lentinan 1 mg x twice/week, was initiated. Within about 2 weeks, her respiratory difficulty was eliminated and after 4 weeks x 2 courses, the tumor images were no longer recognized in the thoracic and abdominal CTs. The combination therapy of S-1/low-dose CDDP/Lentinan is free of evident adverse effects and may be a potent therapeutic alternative as a palliative therapy for malignant stomach cancers in elderly patients or those in a poor systemic condition.