Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

[A Case of Lymphorrhea after Radical Cystectomy Treated by Ultrasound-Guided Inguinal Intranodal Lymphangiography].

A 76-year-old woman was diagnosed with invasive bladder cancer and underwent cystectomy, bilateral external iliac, internal iliac and obturator lymph node dissection, and bilateral cutaneous ureterostomy. Pathological findings showed no lymph node metastasis ; however, the patient had lower abdominal pain and fever from the 14th postoperative day, and computed tomography (CT) revealed fluid retention in the pelvis. Retrograde pyelography showed no leakage from the urinary tract, and a drain was placed after percutaneous puncture of the pelvic cavity. There was copious drainage fluid and its nature and composition suggested lymphorrhea. Ultrasound-guided intranodal lymphangiography revealed contrast material leakage from the bilateral lymph node dissection sites. After lymphangiography, drainage from the drain decreased. Despite the drainage being minimal yet persistent, sclerotherapy was performed, the drain was removed and the patient was discharged. After discharge, there was leakage from the site of urethral extraction, and CT revealed recurrent lymph leakage. The patient was readmitted, and a second lymphangiography was performed. The leakage from the site of urethral extraction gradually decreased, and the patient was discharged on the 59th postoperative day. CT after discharge confirmed that the lymphorrhea had shrunk in size, and there has been no recurrence since then. Lymphangiography is a promising treatment option for lymphorrhea after pelvic surgery.

Intraoperative EABR Testing Predicts Strength of Cochlear Implant Stimulation Optimized After Long-Term Use in Pediatric Malformation Ears.

OBJECTIVE: This study focused on the intensities of cochlear implant (CI) stimulation in pediatric CI users with inner ear malformation or cochlear nerve deficiency (CND). In this population, CI programming is difficult because a large intensity of CI stimulation is required to achieve sufficient hearing, but the excess CI stimuli often induce facial nerve stimulation. We aimed to assess whether the results of intraoperative electrically evoked auditory brainstem responses (EABRs) testing predict maximum current levels of CI stimuli (cC levels) optimized by a behavioral-based method after long-term CI use. STUDY DESIGN: A retrospective case review. SETTING: A tertiary referral CI center. PATIENTS: A total of 116 ears with malformations (malformation group) and 63 control ears (control group) from patients younger than 18 years who received CI. The malformation group comprised 23 ears with a common cavity (CC), 26 with incomplete partition type 1 (IP-1), 26 with incomplete partition type 2 (IP-2), and 41 with CND. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Correlation between intraoperative EABR results and cC levels determined by the behavioral-based CI programming after long-term CI use. RESULTS: The CC, IP-1, and CND ears required significantly larger cC levels than the IP-2 ears and control groups. However, the cC levels increased to reach the plateau 1 year after surgery in all groups. Among the malformation group, 79 ears underwent intraoperative EABR testing. Greater than 80% of the CC, IP-1, and IP-2 ears and 54.8% of the CND ears exhibited evoked wave V (eV) and were included in the eV-positive category. Myogenic responses but no eV were observed in 18.2, 15.0, and 35.5% of the CC, IP-1, and CND ears, defined as the myogenic category. No eV or myogenic response was elicited in 9.7% of the CND ears. We focused on minimum current levels that elicited eV (eV levels) in the eV-positive category and maximum current levels that did not elicit any myogenic responses (myogenic levels) in the myogenic category. A significant relationship was detected between the eV levels and the cC levels. When analyzed in each malformation type, the eV levels significantly correlate with the cC levels in the CC and CND ears but not in the IP-1 and IP-2 ears, probably because of slight variation within the IP-1 group and the small number of the IP-2 group. The myogenic category did not show a significant relationship between the myogenic levels and cC levels, but the cC levels were similar to or smaller than the myogenic levels in most ears. CONCLUSIONS: This study confirmed that intraoperative EABR testing helps predict the optimal cC levels in malformation ears. EABR-based CI programming immediately after cochlear implantation, followed by behavioral-based CI programming, may allow us to achieve early postoperative optimization of CI maps even in young children with severe malformations.

Combined home and clinic-based therapy versus home-based exercise programme after distal radial fracture: a randomized controlled study.

We investigated outcomes of clinic-based hand therapy combined with a home-based exercise programme after anterior plating for distal radial fractures. A total of 102 patients were randomly assigned to one of three groups: a home-based exercise programme alone; a home-based exercise programme combined with four hand therapy sessions in the clinic; and a home-based exercise programme with seven sessions in the clinic. Mean Patient-Rated Wrist Evaluation scores at 6 weeks were significantly better for the group of patients with seven sessions in the clinic than in those with only home exercises (12 vs. 30), but the difference was no longer significant at 12 weeks. Grip strength was significantly better at 6 and 12 weeks. Combined home- and clinic-based hand therapy may facilitate an earlier return of function after anterior plating for distal radius fractures.Level of evidence: II.

Comparison of cold snare polypectomy for sessile serrated lesions ≥10 mm between experienced and trainee endoscopists: A propensity score matching cohort study.

Objectives: Previous studies of cold snare polypectomy (CSP) for sessile serrated lesions (SSLs) ≥10 mm were performed by experienced endoscopists, and therefore their skills might have significantly influenced results. In this study, we compared the efficacy and safety of CSP for SSLs ≥10 mm between experienced and trainee endoscopists. Methods: In a 1:1 propensity score matched retrospective cohort study, we compared the complete resection rate, en-bloc resection rate, adverse event rate, and procedure time between experienced and trainee groups. Thirteen endoscopists performed CSP, and we defined the experienced group as endoscopists with board certification from the Japan Gastroenterological Endoscopy Society. Results: We examined 616 lesions with SSLs ≥10 mm resected by CSP between February 2018 and May 2022. We excluded 61 lesions from the analysis because they had simultaneously undergone hot snare polypectomy (n = 57) or had been taken over by experienced endoscopists from trainees in the CSP procedure (n = 4). Finally, we identified 217 propensity score-matched pairs (n = 434). Between experienced and trainee groups, the results were complete resection rate (100 vs. 100%; p = 1.00), en-bloc resection rate (73.2 vs. 75.6%; p = 0.24), adverse event rate (3.2 vs. 2.8%; p = 0.77), or procedure time (6.2 vs. 5.9 min; p = 0.64). Conclusions: We have demonstrated the safety and efficacy of CSP for SSLs ≥10 mm performed by experienced and trainee endoscopists.

Endoscopic management of gastric ectopic pancreas with repeated ulcerations and bleeding: A case report.

A 25-year-old man was referred to our center for investigation of a gastric submucosal tumor and an ulcer that had developed on its oral side. Endoscopic ultrasonography findings suggested the presence of an ectopic pancreas, and treatment with an oral proton pump inhibitor was planned for the ulcer. Over the subsequent 3 years, the patient endured recurring epigastric pain and episodes of passing black stools. Emergency endoscopy revealed that the morphology of the gastric submucosal tumor had transformed into a pedunculated polyp-like morphology with a bleeding ulcer at the apex of the lesion. Endoscopic hemostasis using hemostatic forceps was performed. However, the patient continued to pass black stools. In light of the persistent symptoms and unique morphology of the lesion, endoscopic resection was attempted as a curative approach. The lesion was excised by hot snare polypectomy. Post-treatment, the patient exhibited no signs of recurrence, marking a successful resolution. Three months later, a gastroduodenal endoscopy showed that the excised site had undergone scar formation without recurrence of the lesion. This case holds significant clinical value as it demonstrates the efficacy of a minimally invasive treatment strategy in managing repeated bleeding ulcerations of an ectopic pancreas, ultimately achieving a complete cure.

Novel Cytochrome P450 2C119 Enzymes in Cynomolgus and Rhesus Macaques Metabolize Progesterone, Diclofenac, and Omeprazole.

Cynomolgus and rhesus macaques are used in drug metabolism studies due to their evolutionary and phylogenetic closeness to humans. Cytochromes P450 (P450s or CYPs), including the CYP2C family enzyme, are important endogenous and exogenous substrate-metabolizing enzymes and play major roles in drug metabolism. In cynomolgus and rhesus macaques, six CYP2Cs have been identified and characterized, namely, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2C76, and CYP2C93. In this study, CYP2C119, a new CYP2C, was identified and characterized in cynomolgus and rhesus macaques. Cynomolgus and rhesus CYP2C119 contained open reading frames of 489 amino acids with high sequence identities to human CYP2C8 and to cynomolgus and rhesus CYP2C8. Phylogenetic analysis showed that cynomolgus and rhesus CYP2C119 were closely related to cynomolgus and rhesus CYP2C8. In cynomolgus and rhesus genomes, CYP2C genes, including CYP2C119, form a cluster. Among the tissues analyzed, cynomolgus CYP2C119 mRNA was predominantly expressed in liver. Hepatic expressions of CYP2C119 mRNA in four cynomolgus and two rhesus macaques varied, with no expression in one rhesus macaque. Among the CYP2C mRNAs, CYP2C119 mRNA was expressed less abundantly than CYP2C8, CYP2C9, CYP2C19, and CYP2C76 mRNAs but more abundantly than CYP2C18 mRNA. Recombinant cynomolgus and rhesus CYP2C119 catalyzed progesterone 16α-, 17α-, and 21-hydroxylation and diclofenac and omeprazole oxidations, indicating that CYP2C119 is a functional enzyme. Therefore, the novel CYP2C119 gene, expressed in macaque liver, encodes a functional enzyme that metabolizes human CYP2C substrates and is likely responsible for drug clearances. SIGNIFICANCE STATEMENT: Cytochrome P450 2C119 was found in cynomolgus and rhesus macaques, in addition to the known P450 2C8, 2C9, 2C18, 2C19, 2C76, and 2C93. Cynomolgus and rhesus CYP2C119 contain open reading frames of 489 amino acids with high sequence identity to human CYP2C8. Cynomolgus CYP2C119 mRNA is predominantly expressed in the liver. Recombinant CYP2C119 catalyzed progesterone hydroxylation and diclofenac and omeprazole oxidations. Therefore, the novel CYP2C119 gene expressed in the macaque liver encodes a functional enzyme that metabolizes human CYP2C substrates.

Efficacy and safety of cap-assisted endoscopic mucosal resection for superficial duodenal epithelial neoplasia ≤ 10 mm.

Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs.

Synovial fluid and plasma concentrations of tedizolid in patients with osteoarthritis infected with Staphylococcus aureus effectively determined with fluorescence detection.

BACKGROUND: Tedizolid is a new oxazolidinone antibiotic with high potency for the treatment of infections caused by methicillin-resistant Staphylococcus aureus and other species. CASE PRESENTATION: Two patients with osteoarthritis (women aged 79 and 73 years, cases 1 and 2, respectively) infected with S. aureus were successfully treated with tedizolid after administration of 200 mg once daily via intravenous infusion. The synovial fluid and plasma concentrations of tedizolid during surgery in case 1 at day 7 were 2.1 and 1.6 µg/mL, respectively, yielding a ratio of synovial fluid/plasma of 130%. Those in case 2 at day 2 were 2.9 and 3.3 µg/mL, respectively, corresponding to a ratio of synovial fluid/plasma of 88%. CONCLUSIONS: These results imply very similar concentrations of tedizolid in the synovial fluid and plasma of osteoarthritis patients with acute S. aureus infection.

Two-Staged Reconstruction of Extensor Tendons After Wide Resection of Clear Cell Sarcoma at the Anterior Ankle: A Case Report.

CASE: A 23-year-old woman sustained a skin defect in the anterior ankle involving the extensor retinaculum (ER) and 10 cm of extensor tendons (ETs) after a wide resection of clear cell sarcoma. The skin defect was reconstructed with free latissimus dorsi flap, ER with tensor fascia lata, and ETs with 2-staged tendon reconstruction using silicone rod interposition, followed by semitendinosus and gracilis tendon grafts. Four years postoperatively, she achieved 92% of ankle and 70% of great toe motion of the contralateral side. CONCLUSION: This reconstruction technique was useful for a large soft-tissue defect at the anterior ankle.

Liver microsomal cytochrome P450 3A-dependent drug oxidation activities in individual dogs.

Drug oxidations are mediated mainly by cytochromes P450 (P450s or CYPs). CYP3As are an important P450 subfamily and include liver-specific CYP3A12 and intestine-specific CYP3A98 in dogs. Individual differences in drug oxidation activities were investigated, including correlations with immunoreactive CYP3A protein intensities and CYP3A mRNA expression levels in livers.Pooled and individual dog liver microsomes showed activities towards nifedipine, midazolam, alprazolam, and estradiol, but the levels of catalytic activities varied approximately twofold among the individual dogs. One dog harboured a CYP1A2 variant causing protein deletion but showed higher activities than the other dogs towards nifedipine oxidation, midazolam 1'-hydroxylation, alprazolam 4-hydroxylation, estradiol 16α-hydroxylation activities, and caffeine C8-hydroxylation; the latter is used as a reference reaction for CYP1A.In individual dog liver microsomes, the intensities of the immunochemical bands with anti-human CYP3A4 and anti-rat CYP3A2 antibodies along with CYP3A12 and CYP3A26 mRNA expression levels showed good correlations (p < 0.05) with nifedipine oxidation, midazolam 1'- and 4-hydroxylation, alprazolam 1'- and 4-hydroxylation, and estradiol 16α-hydroxylation activities.These results suggest that the oxidation activities of dog liver microsomes towards nifedipine and other typical CYP3A-catalyzed drugs exhibit approximately twofold individual differences and were predominantly mediated by liver-specific CYP3A12 in the dogs.

US regulations to curb alleged cancer causes are ineffectual and compromised by scientific, constitutional and ethical violations.

The 1958 Delaney amendment to the Federal Food Drug and Cosmetics Act prohibited food additives causing cancer in animals by appropriate tests. Regulators responded by adopting chronic lifetime cancer tests in rodents, soon challenged as inappropriate, for they led to very inconsistent results depending on the subjective choice of animals, test design and conduct, and interpretive assumptions. Presently, decades of discussions and trials have come to conclude it is impossible to translate chronic animal data into verifiable prospects of cancer hazards and risks in humans. Such conclusion poses an existential crisis for official agencies in the US and abroad, which for some 65 years have used animal tests to justify massive regulations of alleged human cancer hazards, with aggregated costs of $trillions and without provable evidence of public health advantages. This article addresses suitable remedies for the US and potentially worldwide, by critically exploring the practices of regulatory agencies vis-á-vis essential criteria for validating scientific evidence. According to this analysis, regulations of alleged cancer hazards and risks have been and continue to be structured around arbitrary default assumptions at odds with basic scientific and legal tests of reliable evidence. Such practices raise a manifold ethical predicament for being incompatible with basic premises of the US Constitution, and with the ensuing public expectations of testable truth and transparency from government agencies. Potential remedies in the US include amendments to the US Administrative Procedures Act, preferably requiring agencies to justify regulations compliant with the Daubert opinion of the Daubert ruling of the US Supreme Court, which codifies the criteria defining reliable scientific evidence. International reverberations are bound to follow what remedial actions may be taken in the US, the origin of current world regulatory procedures to control alleged cancer causing agents.

Large Palatal Pleomorphic Adenoma Complicated by Dysphagia: A Case Report.

A 60-year-old Japanese woman presented with a palatal pleomorphic adenoma measuring 5 cm in size. In addition to impairments during the oral preparatory and oral transport phases, dysphagia with nasopharyngeal closure disorder was observed in the pharyngeal phase. After resection of the tumor, dysphagia resolved, and the patient was immediately able to eat a standard meal. A videofluoroscopic swallowing study confirmed improvement in the movement of the soft palate compared with the pre-operative condition.

Common Peroneal Nerve Injury Due to an All-Inside Repair of the Posterior Horn of Lateral Meniscus: A Case Report.

CASE: An 18-year-old man sustained a peroneal nerve (PN) injury during an all-inside repair of the posterior horn of the lateral meniscus from the medial portal. Although he could dorsiflex his ankle actively after emergence from general anesthesia, he had a foot drop on the day after surgery. Exploration of the PN at 5 months postoperatively revealed that the nerve was entrapped by the suture. Fifteen months after a nerve repair using a sural nerve graft, he recovered from the foot drop. CONCLUSION: This case report highlights the risk of PN injury during an all-inside repair of the posterior horn of the lateral meniscus.

Newly identified cytochrome P450 3A genes of tree shrews and pigs are expressed and encode functional enzymes.

Novel cytochrome P450 3A5 (CYP3A5) cDNA in tree shrews (which are non-rodent primate-like species) and pig CYP3A227 cDNA were identified, along with known pig CYP3A22, CYP3A29, and CYP3A46 cDNAs. All five cDNAs contained open reading frames encoding a polypeptide of 503 amino acids that shared high sequence identity (72-78 %) with human CYP3A4 and were more closely related to human CYP3As than rat CYP3As by phylogenetic analysis. CYP3A5 was the only CYP3A in the tree shrew genome, but pig CYP3A genes formed a CYP3A gene cluster in the genomic region corresponding to that of human CYP3A genes. Tree shrew CYP3A5 mRNA was predominantly expressed in liver and small intestine, among the tissues analyzed, whereas pig CYP3A227 mRNA was most abundantly expressed in jejunum, followed by liver. Metabolic assays established that tree shrew CYP3A5 and pig CYP3A proteins heterologously expressed in Escherichia coli metabolized typical human CYP3A4 substrates nifedipine and midazolam. These results suggest that novel tree shrew CYP3A5 and pig CYP3A227 were functional enzymes able to metabolize human CYP3A4 substrates in liver and small intestine, similar to human CYP3A4, although pig CYP3A227 mRNA was minimally expressed in all tissues analyzed.

Management of Already Inserted Ventilation Tubes During Pediatric Cochlear Implantation: To Remove or Leave the Tube?

OBJECTIVE: Ventilation tube (VT) insertion is usually recommended before cochlear implantation (CI) in pediatric cochlear implant candidates with recurrent acute otitis media (AOM) or chronic otitis media with effusion (OME). However, there is no consensus on whether the VT is beneficial even after CI, that is, whether the tube should be removed or left in place during CI. This study aimed to assess the effect of tube placement after CI, especially on the incidence of post-CI AOM, in pediatric cochlear implant recipients who had undergone VT insertion before CI because of recurrent AOM or chronic OME. STUDY DESIGN: A retrospective medical record review. SETTING: A tertiary referral cochlear implant center. PATIENTS: This study recruited 58 consecutive ears of children who underwent VT insertion followed by CI at age 7 years or younger between 2004 and 2021. Before October 2018, we removed the VT simultaneously with CI (removed group, 39 ears), while since then, the tube has remained in place during CI (retained group, 19 ears). INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE: The primary outcome was the proportion of ears that developed AOM at post-CI 6 months in the removed and retained groups. RESULTS: The age at CI was significantly higher in the removed group than in the retained group (mean [standard deviation]: the removed group, 2.9 [1.2] yr; the retained group: 1.5 [0.8] yr; p < 0.001). The removed group showed a significantly higher proportion of ears with post-CI AOM (8 of 39 ears; 20.5%) than the retained group (none of 19 ears; 0%) 6 months after CI ( p = 0.044). The AOM-free proportion at post-CI 12 months was 76.9% in the removed group and 83.3% in the retained group, demonstrating no significant difference ( p = 0.49), probably because the VT was spontaneously extruded in the retained group at a median of 6.5 months after CI. Throughout the study period, 17 ears (13 from the removed group) were affected by post-CI AOM. Of these, three ears in the removed group and two in the retained group after spontaneous extrusion of the VT were hospitalized and treated with intravenous antibiotics for AOM that had failed to respond to oral antibiotic therapy. Only one ear in the removed group required an explanation of the infected implant. None suffered from chronic perforation of the tympanic membrane or secondary cholesteatoma after VT insertion or meningitis associated with post-CI AOM. CONCLUSION: Our results suggest that in CI for children who already have a VT because of a recurrent AOM or chronic OME, retaining the tube in position, rather than removing the tube, may decrease the incidence of AOM at least within 6 months after CI, during which most cochlear implant device infection was reported in the pediatric population.

Newly Identified Tree Shrew Cytochrome P450 2A13 is Expressed in Liver and Lung and Encodes a Functional Drug-Metabolizing Enzyme Similar to Dog Cytochrome P450 2A13 and Pig Cytochrome P450 2A19.

The tree shrew, a non-rodent primate-like species, is used in various fields of biomedical research, including hepatitis virus infection, myopia, depression, and toxicology. Recent genome analysis found that the numbers of cytochrome P450 (P450 or CYP) genes are similar in tree shrews and humans and their sequence identities are high. Although the P450s are a family of important drug-metabolizing enzymes, they have not yet been fully investigated in tree shrews. In the current study, tree shrew CYP2A13 cDNA was isolated from liver, and its characteristics were compared with those of pig, dog, and human CYP2As. Tree shrew CYP2A13 amino acid sequences were highly identical (87-92%) to the human CYP2As and contained sequence motifs characteristic of P450s. Phylogenetic analysis revealed that tree shrew CYP2A13 was more closely related to human CYP2As than to rat CYP2As, similar to dog and pig CYP2As. Among the tissue types analyzed, tree shrew CYP2A13 mRNA was preferentially expressed in liver and lung, similar to dog CYP2A13 mRNA, whereas dog CYP2A25 and pig CYP2A19 mRNAs were predominantly expressed in liver. Tree shrew liver microsomes and tree shrew CYP2A13 proteins heterologously expressed in Escherichia coli catalyzed coumarin 7-hydroxylation and phenacetin O-deethylation, just as human, dog, and pig CYP2A proteins and liver microsomes do. These results demonstrate that tree shrew CYP2A13 is expressed in liver and lung and encodes a functional drug-metabolizing enzyme. SIGNIFICANCE STATEMENT: Novel tree shrew cytochrome P450 2A13 (CYP2A13) was identified and characterized in comparison with human, dog, and pig CYP2As. Tree shrew CYP2A13 isolated from liver had high sequence identities and close phylogenetic relationships to its human homologs and was abundantly expressed in liver and lung at the mRNA level. Tree shrew CYP2A13 metabolized coumarin and phenacetin, human selective CYP2A6 and CYP2A13 substrates, respectively, similar to dog and pig CYP2As, and is a functional drug-metabolizing enzyme likely responsible for drug clearances.

Changes in the Functional Range of Motion of the Thumb Metacarpophalangeal Joint After Trapeziometacarpal Arthrodesis for Patients With Advanced Trapeziometacarpal Osteoarthritis.

PURPOSE: Advanced-stage trapeziometacarpal (TMC) osteoarthritis of the thumb often presents with concomitant hyperextension deformity of the metacarpophalangeal (MCP) joint. Although several studies have reported simultaneous procedures to correct this deformity, the indication for these procedures remains controversial. The purpose of this study was to evaluate changes in the range of motion (ROM) of the thumb MCP joint before and after TMC arthrodesis. METHODS: We evaluated the functional flexion and extension and functional ROM of the MCP joints during the performance of 10 activities of daily living tasks before and after TMC arthrodesis in 10 thumbs of 9 patients with Eaton stage III TMC osteoarthritis and hyperextension deformity of the MCP joint. RESULTS: The mean functional flexion of the MCP joint increased from 26° to 38°, and the mean functional extension of the MCP joint decreased from 16° to 5° of hyperextension. There was no change in the mean total arc of functional ROM of the MCP joint. CONCLUSIONS: The MCP joint motion shifted from extension to flexion after TMC arthrodesis, and the total arc of functional ROM of the MCP joint was similar before and after arthrodesis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Novel cytochrome P450 1 (CYP1) genes in tree shrews are expressed and encode functional drug-metabolizing enzymes.

Tree shrews (Tupaia belangeri) are a non-rodent primate-like species sometimes used for biomedical research involving hepatitis virus infections and toxicology. Genome analysis has indicated similarities between tree shrews and humans in the numbers of cytochromes P450 (P450 or CYP), which constitute a family of important drug-metabolizing enzymes; however, P450s have not been fully investigated in tree shrews. In this study, we identified CYP1A1, CYP1A2, CYP1B1, and CYP1D1 cDNAs from tree shrew liver and compared their characteristics with dog, pig, and human CYP1As. The deduced amino acid sequences of tree shrew CYP1s were highly identical (82-87 %) to human CYP1s. In tree shrews, CYP1A1 and CYP1A2 mRNAs were preferentially expressed in liver, whereas CYP1D1 mRNA was preferentially expressed in kidney and lung. In contrast, CYP1B1 mRNA was expressed in various tissues, with the most abundant expression in spleen. Among the tree shrew CYP1 mRNAs, CYP1A2 mRNA was most abundant in liver, and CYP1B1 mRNA was most abundant in kidney, small intestine, and lung. All tree shrew CYP1 proteins heterologously expressed in Escherichia coli catalyzed caffeine and estradiol in a similar manner to tree shrew liver microsomes and human, dog, and pig CYP1 proteins. These results suggest that tree shrew CYP1A1, CYP1A2, CYP1B1, and CYP1D1 genes, different form human pseudogene CYP1D1P, are expressed in liver, small intestine, lung, and/or kidney and encode functional drug-metabolizing enzymes important in toxicology.

A multicenter study to investigate the positive rate of SARS-CoV-2 in middle ear and mastoid specimens from otologic surgery patients.

OBJECTIVE: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus, causes coronavirus disease 2019 (COVID-19). Otologic surgeries with drilling by powered instruments induce significant aerosols, which may induce SARS-CoV-2 transmission to medical staff if SARS-CoV-2 exists in the middle ear and mastoid cavity. During a COVID-19 pandemic, therefore, confirming a negative COVID-19 test prior to otologic surgery is recommended. However, previous coronavirus studies demonstrated that coronavirus was detected in the middle ear in some patients even though the polymerase chain reaction (PCR) test using their nasopharyngeal swab was negative. This study aimed to elucidate the probability of a positive SARS-CoV-2 PCR test in the middle ear or mastoid specimens from otologic surgery patients in whom SARS-CoV-2 was not detected by preoperative PCR test using a nasopharyngeal swab. METHODS: We conducted a prospective, multicenter clinical study. Between April 2020 and December 2021, during the COVID-19 pandemic, 251 ears of the 228 participants who underwent otologic surgery were included in this study. All participants had no symptoms suggesting COVID-19 or close contact with a confirmed COVID-19 patient two weeks prior to the surgery. They were also negative in the SARS-CoV-2 PCR tests using a nasopharyngeal swab before surgery. We collected mucosa, granulation, bone dust with mucosa or fluid from the middle ear or mastoid for the SARS-CoV-2 PCR tests during each otologic surgery. RESULTS: The median age of the participants at surgery was 31.5 years old. Mastoidectomy using a powered instrument was conducted in 180 of 251 otologic surgeries (71.8%). According to intraoperative findings, active inflammation in the middle ear or mastoid cavities was evident in 20 otologic surgeries (8.0%), while minor inflammation was observed in 77 (30.7%). All SARS-CoV-2 PCR tests of otologic specimens showed a negative result. No patient suffered from COVID-19 within two months after otologic surgery. Furthermore, no hospital-acquired infections associated with otologic surgery occurred in our institutions CONCLUSIONS: Our results showed that PCR testing did not detect SARS-CoV-2 in middle ear and mastoid specimens, suggesting that the risk of transmission of SARS-CoV-2 is not high in otologic surgeries even using powered instruments when both clinical and laboratory tests are confirmed to be negative for COVID-19.