Simulation of Changes in Tensile Strain by Airbag Impact on Eyes After Trabeculectomy by Using Finite Element Analysis.

Purpose: We studied the kinetic phenomenon of an airbag impact on eyes after trabeculectomy using finite element analysis (FEA), a computerized method for predicting how an object reacts to real-world physical effects and showing whether an object will break, to sequentially determine the responses at various airbag deployment velocities. Methods: A human eye model was used in the simulations using the FEA program PAM-GENERISTM (Nihon ESI, Tokyo, Japan). A half-thickness incised scleral flap was created on the limbus and the strength of its adhesion to the outer sclera was set at 30%, 50%, and 100%. The airbag was set to hit the surface of the post-trabeculectomy eye at various velocities in two directions: perpendicular to the corneal center or perpendicular to the scleral flap (30° gaze-down position), at initial velocities of 20, 30, 40, 50, and 60 m/s. Results: When the airbag impacted at 20 m/s or 30 m/s, the strain on the cornea and sclera did not reach the mechanical threshold and globe rupture was not observed. Scleral flap lacerations were observed at 40 m/s or more in any eye position, and scleral rupture extending posteriorly from the scleral flap edge and rupture of the scleral flap resulting from extension of the corneal laceration through limbal damage were observed. Even in the case of 100% scleral flap adhesion strength, scleral flap rupture occurred at 50 m/s impact velocity in the 30° gaze-down position, whereas in eyes with 30% or 50% scleral flap adhesion strength, scleral rupture was observed at an impact velocity of 40 m/s or more in both eye positions. Conclusion: An airbag impact of ≥40 m/s might induce scleral flap rupture, indicating that current airbags may induce globe rupture in the eyes after trabeculectomy. The considerable damage caused by an airbag on the eyes of short-stature patients with glaucoma who have undergone trabeculectomy might indicate the necessity of ocular protection to avoid permanent eye damage.

The usefulness of texture and color enhancement imaging to identify the minor papilla orifice.

In clinical cases of pancreas divisum, endoscopic retrograde cholangiopancreatography often necessitates cannulation of the pancreatic duct through the minor papilla. Nevertheless, this procedure can be challenging because of the small size of the minor papilla and the difficulty in visualizing the ductal orifice. A new image-enhanced endoscopy technique called texture and color enhancement imaging (TXI) has been developed, which enhances texture, brightness, and color compared with white-light imaging, resulting in subtle differences in the surface mucosa. Herein, we describe the case of a 73-year-old man with pancreas divisum in whom TXI was useful in identifying the orifice of the minor papilla. He was referred to our hospital with repetitive acute exacerbation of chronic pancreatitis. Since contrast-enhanced computed tomography revealed a pancreatic stone in the main pancreatic duct, endoscopic retrograde cholangoepancreatography was performed as a therapeutic intervention. Despite the initial difficulty in identifying the orifice of the minor papilla on white-light imaging, TXI enhanced its visibility successfully, enabling dorsal pancreatic duct cannulation via the minor papilla. Subsequently, endoscopic pancreatic sphincterotomy was performed and a 6Fr plastic stent was placed. Post-endoscopic therapy, the patient's abdominal pain was relieved. TXI was useful in identifying the minor papilla orifice and led to successful cannulation.

Finite Element Analysis of Changes in Deformation of Intraocular Segments by Airbag Impact in Eyes of Various Axial Lengths.

Background: We studied the kinetic phenomenon of an airbag impact on eyes with different axial lengths using finite element analysis (FEA) to sequentially determine the physical and mechanical responses of intraocular segments at various airbag deployment velocities. Methods: The human eye model we created was used in simulations with the FEA program PAM-GENERISTM. The airbag was set to impact eyes with axial lengths of 21.85 mm (hyperopia), 23.85 mm (emmetropia) and 25.85 mm (myopia), at initial velocities of 20, 30, 40, 50 and 60 m/s. The deformation rate was calculated as the ratio of the length of three segments, anterior chamber, lens and vitreous, to that at the baseline from 0.2 ms to 2.0 ms after the airbag impact. Results: Deformation rate of the anterior chamber was greater than that of other segments, especially in the early phase, 0.2-0.4 ms after the impact (P < 0.001), and it reached its peak, 80%, at 0.8 ms. A higher deformation rate in the anterior chamber was found in hyperopia compared with other axial length eyes in the first half period, 0.2-0.8 ms, followed by the rate in emmetropia (P < 0.001). The lens deformation rate was low, its peak ranging from 40% to 75%, and exceeded that of the anterior chamber at 1.4 ms and 1.6 ms after the impact (P < 0.01). The vitreous deformation rate was lower throughout the simulation period than that of the other segments and ranged from a negative value (elongation) in the later phase. Conclusion: Airbag impact on the eyeball causes evident deformation, especially in the anterior chamber. The results obtained in this study, such as the time lag of the peak deformation between the anterior chamber and lens, suggest a clue to the pathophysiological mechanism of airbag ocular injury.

Increasing Patients With HPV-positive Oropharyngeal Squamous Cell Carcinoma and its Oncologic Outcomes in the Rural Region in Northern Japan.

BACKGROUND/AIM: Despite the global rise in the incidence of human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC) in recent years, its prevalence and oncological outcomes in patients living in rural areas of Northern Japan has not been explored and should be investigated. PATIENTS AND METHODS: A total of 105 patients with oropharyngeal squamous cell carcinoma who underwent HPV screening and received first-line treatment were included in this study. The annual changes in the number of patients, survival rates, and clinical factors affecting prognosis were examined. RESULTS: The HPV-positive rate in patients with OPC was low, with the lowest rate of 10.0% in 2013 and the highest rate of 46.7% in 2020. The number of HPV-negative cases remained almost unchanged, whereas the overall number of cases increased with the increasing number of HPV-positive cases. Additionally, HPV-positive cases exhibited a fairly good prognosis. CONCLUSION: The number of OPC cases increased not only in urban areas, but also in rural areas. HPV-positive cases had better outcomes than HPV-negative cases.

Risk assessment of metachronous gastric cancer after endoscopic submucosal dissection based on endoscopic intestinal metaplasia.

Background and Aim: The incidence of metachronous gastric cancer (MGC) after endoscopic treatment for early gastric cancer (EGC) is high, but a method of risk assessment for MGC based on endoscopic findings has not been established. In this study, we focused on endoscopic intestinal metaplasia (IM) and investigated the risk for MGC after endoscopic submucosal dissection (ESD) for EGC. Methods: This retrospective observational study involved patients who underwent curative ESD for EGC from April 2015 to January 2021. We assessed endoscopic IM using the pretreatment endoscopic examination images. The severity of endoscopic IM was classified into four levels: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Four different gastric areas were evaluated. We divided the patients into a low-score group and a high-score group, and compared the cumulative incidence of MGC. Results: In total, 156 patients who met the inclusion criteria were followed up for at least 12 months after ESD, and MGC developed in 14 patients during a mean period oof 41.5 months. The endoscopic IM scores in the lesser curvature of the antrum, lesser curvature of the corpus, and greater curvature of the corpus were higher in patients with MGC than in those without MGC. In the corpus, the 5-year cumulative incidence of MGC was significantly higher in the high-score group than in the low-score group (29.8% vs 10.0%, P = 0.004). Conclusion: The severity of endoscopic corpus IM was associated with MGC. Thus, patients with severe corpus IM at the time of ESD require careful examination and intensive follow-up.

Appropriate Preconception Corticosteroid-Free Remission Period in Pregnant Women With Ulcerative Colitis.

BACKGROUND: In women with inflammatory bowel disease, at least 3 months of preconception corticosteroid-free remission (CFREM) is recommended by experts in current consensus statements. However, data are lacking on the appropriate preconception remission period. We investigated the appropriate preconception CFREM period in women with ulcerative colitis to reduce maternal disease activity and adverse pregnancy outcomes (ie, preterm birth, low birth weight, and small for gestational age). METHODS: We retrospectively examined 141 pregnancies in women with ulcerative colitis at 2 institutions. We categorized the patients into 3 subgroups by their preconception CFREM period (≥3 months, >0 to <3 months, and non-CFREM). We also investigated disease activity during pregnancy and postpartum and adverse pregnancy outcomes in each group. RESULTS: During pregnancy, the rate of active disease was significantly lower in the ≥3 months and >0 to <3 months CFREM groups compared with that in the non-CFREM group (P < .001 and P = .0257, respectively). Postpartum, the rate of active disease was significantly lower in the ≥3 months CFREM group compared with that in the non-CFREM group (P = .0087). The preconception CFREM period of ≥3 months was an independent inhibitory factor for active disease during pregnancy and postpartum (adjusted odds ratio, 0.15; P = .0035; and adjusted odds ratio, 0.33; P = .027, respectively). Adverse pregnancy outcomes were less common in the >3 months CFREM group compared with those in the other groups, but this difference was not significant. CONCLUSIONS: A preconception CFREM period of more than 3 months may be appropriate for better maternal and adverse pregnancy outcomes, as recommended in consensus statements.

In women with ulcerative colitis, a preconception corticosteroid-free remission period for at least 3 months may be appropriate. This period could reduce disease activity during pregnancy and postpartum and reduce the incidence of adverse pregnancy outcomes.

Treatment Outcomes and Prognostic Factors of Concurrent Chemoradiotherapy With Docetaxel, Cisplatin, and Fluorouracil in Advanced Head and Neck Cancer.

BACKGROUND/AIM: Although the efficacy of docetaxel, cisplatin, and 5-Fluorouracil (TPF) as induction chemotherapy has been confirmed, the therapeutic outcome and prognostic factors of concurrent chemoradiotherapy (CCRT) should be investigated. PATIENTS AND METHODS: Laboratory data of patients who underwent CCRT for advanced squamous cell carcinoma (SCC) of the head and neck were investigated to clarify the grade of side effects. Survival rates and prognostic scores were also calculated. Multivariate analysis was performed to examine the prognostic factors of the patients. RESULTS: Although there were significantly more advanced cases in the TPF group (n=72) than those in the cisplatin group (n=50), there were no significant differences in patient survival rates. In the TPF group, the lymphocyte count, albumin level, and C-reactive protein level of the patients before treatment were significantly correlated with patient outcomes. CONCLUSION: CCRT using the TPF regimen had remarkable treatment effects in advanced head and neck cancer.

[Surgical ulcerative colitis complicated by multiple lung abscesses secondary to septic pulmonary embolism after multidrug immunosuppressive therapies].

This is a case implying a serious infectious complication risk during intensive severe ulcerative colitis treatment. A 26-year-old man developed diarrhea and bloody stool who was diagnosed with ulcerative colitis in 2018. He was managed with 5-aminosalicylic acid, but intolerance reaction resulted in discontinuation of treatment. He relapsed with severe abdominal pain and bloody stools in February 2019. He was referred to our department for intensive therapy. He had been treated with steroids, tacrolimus, granulocyte and monocyte apheresis, infliximab or tofacitinib, which temporarily improved his clinical symptoms. However, his medical condition could not be controlled. Hand-assisted laparoscopic subtotal colectomy was then performed in October 2019. He developed intermittent fever on postoperative day 3. Enhanced computed tomography (CT) revealed multiple deep vein thromboses and pulmonary embolism. Antibiotics and anticoagulation therapy were initiated, but postoperative day 13 CT showed multiple pulmonary cavities containing fluids and air, which were diagnosed as pulmonary abscess. His intermittent fever was over 38.0°C. Severe cough and hemoptysis lasted 3 weeks, the clinical symptoms and laboratory data then gradually improved after the fourth week.

Neurodegeneration-associated mitochondrial proteins, CHCHD2 and CHCHD10-what distinguishes the two?

Coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) and Coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) are mitochondrial proteins that are thought to be genes which duplicated during evolution and are the causative genes for Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal lobe dementia, respectively. CHCHD2 forms a heterodimer with CHCHD10 and a homodimer with itself, both of which work together within the mitochondria. Various pathogenic and disease-risk variants have been identified; however, how these mutations cause neurodegeneration in specific diseases remains a mystery. This review focuses on important new findings published since 2019 and discusses avenues to solve this mystery.

Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson's disease.

Missense variants in leucine-rich repeat kinase 2 (LRRK2) lead to familial and sporadic Parkinson's disease (PD). The pathological features of PD patients with LRRK2 variants differ. Here, we report an autopsy case harboring the LRRK2 G2385R, a risk variant for PD occurring mainly in Asian populations. The patient exhibited levodopa-responsive parkinsonism at the early stage and visual hallucinations at the advanced stage. The pathological study revealed diffuse Lewy bodies with neurofibrillary tangles, amyloid plaques, and mild signs of neuroinflammation. Biochemically, detergent-insoluble phospho-α-synuclein was accumulated in the frontal, temporal, entorhinal cortexes, and putamen, consistent with the pathological observations. Elevated phosphorylation of Rab10, a substrate of LRRK2, was also prominent in various brain regions. In conclusion, G2385R appears to increase LRRK2 kinase activity in the human brain, inducing a deleterious brain environment that causes Lewy body pathology.

Challenges of Surgical Resection of Carotid Body Tumors - Multiple Feeding Arteries and Preoperative Embolization.

BACKGROUND: Carotid body tumor is a hypervascular tumor with multiple feeding arteries and unique orientation at the carotid bifurcation. Although resection is a radical therapy for this tumor, complete resection is challenging. MATERIALS AND METHODS: Articles reporting carotid body tumor treatment and surgical resection were reviewed including case-control series and review articles. RESULTS: Selected reports were reviewed and discussed focusing on choice of treatment, surgical difficulties and preoperative embolization of feeding arteries. CONCLUSION: Multiple feeding arteries and adhesion of the tumor to the carotid arterial wall are causes of difficulties in carotid body tumor resection. The effectiveness of preoperative embolization remains controversial due to the varied situations in performing surgical resection among the institutions. However, perfect embolization and resection immediately after embolization reduce blood loss and operative time of surgery for carotid body tumor.

Preliminary Study of Chemoradiotherapy Using Modified Docetaxel, Cis-diaminodichloroplatinum, and 5-Fluorouracil for Sinonasal Squamous Cell Carcinoma.

OBJECTIVE: To examine the safety and efficacy of concomitant chemoradiotherapy using a modified TPF regimen (docetaxel + cisplatin + 5-fluorouracil) in patients with advanced sinonasal squamous cell carcinoma (SNSCC). STUDY DESIGN: Retrospective study. SETTING: Tertiary center (university hospital). METHODS: Seven patients with previously untreated T3-T4 SNSCC were enrolled. They underwent radiotherapy once daily (total dose, 70 Gy) with 2 courses of concomitant 120-hour infusion of 5-fluorouracil (600 mg/m2/d), docetaxel (50 mg/m2, day 2), and cisplatin (60 mg/m2, day 2). RESULTS: Grade 4 leukopenia, grade 4 neutropenia, and grade 3 lymphopenia were observed in 1, 3, and 4 patients, respectively. Grade 4 creatinine elevation was observed in 1 patient. However, other grade 3 or 4 adverse events were not common. Complete response was obtained in all patients. At 60 months there was 85.7% disease-free survival and 100% overall. CONCLUSION: Concomitant chemoradiotherapy with a modified TPF regimen may be feasible and effective in patients with advanced SNSCC.

The Influence of Young Age on Difficulties in the Surgical Resection of Carotid Body Tumors.

This study evaluated patient characteristics that affect the complexity and difficulties of performing surgery to resect carotid body tumors (CBTs). We retrospectively reviewed the medical records of 20 patients with 21 CBTs who were enrolled in the study. The median patient age was 46 years and the mean tumor diameter was 37.6 mm. The mean blood loss and operative time were 40.3 mL and 183 min, respectively. Four patients underwent resection of the carotid artery followed by reconstruction. These four patients were between 18 to 23 years of age at the time of surgery. The mean blood loss and operative time in these patients were 166 mL and 394 min, respectively, which differed significantly from those of older patients. Therefore, young age influenced the difficulties faced in surgical resection of CBT, with an increased risk of blood loss and carotid artery resection.

Contrast-enhanced ultrasonography for the differential diagnosis of pleomorphic adenomas and Warthin tumors in salivary glands.

OBJECTIVE: Pleomorphic adenomas have risks of malignant transformation and post operate recurrence. Therefor it is important that diagnosing pleomorphic adenomas or Warthin tumors before an operation. We evaluated the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid for making differential diagnoses between pleomorphic adenomas and Warthin tumors. METHODS: CEUS was performed the day before surgery in 39 patients. We compared the time-intensity curve and capillary density rate of 14 pleomorphic adenomas and 13 Warthin tumors. RESULTS: Pleomorphic adenomas demonstrated a significantly longer time to peak intensity and lower maximum curve gradient of wash-in than Warthin tumors. The capillary density rate of Warthin tumors tended to be greater than that of pleomorphic adenomas. CONCLUSIONS: CEUS and capillary density rate analysis using Sonazoid is helpful for the differential diagnosis of pleomorphic adenomas and Warthin tumors. LEVEL OF EVIDENCE: 3b.

Evaluation and comparison of oral function after resection of cancer of the upper gingiva in patients who underwent reconstruction surgery versus those treated with a prosthesis.

BACKGROUND: We retrospectively analyzed the articulation, mastication, and swallowing function of patients who underwent reconstruction or used a prosthesis after resection of the upper gingiva. METHODS: This study included patients who underwent resection of cancer of the upper gingiva from January 2014 to December 2018. Articulatory function was evaluated with Hirose's conversational function evaluation criteria. Mastication function was evaluated with the Yamamoto's occlusion table. Swallowing function was assessed with the MTF (Method of intake, Time, Food) score. RESULTS: The mean articulatory function score was 8 points in the Reconstruction Surgery Group (RSG) and 8.8 points in the Prosthesis Group (PG). The mean mastication function score was 2.8 points in the RSG and 3.3 points in the PG. The mean swallowing function score was M3T4F4 in the RSG and M4T4F4.3 in the PG. CONCLUSIONS: The prosthesis depends on the remaining occlusal support area. Our study suggest that prosthesis is better indication when there is more than one occlusal support area.

Genetic analysis of ATP10B for Parkinson's disease in Japan.

Compound heterozygosity of ATP10B is thought to be a risk factor for young-onset Parkinson's disease (PD). We genetically screened 245 patients with young-onset sporadic PD and 33 patients with autosomal recessive PD for ATP10B. All 13 identified gene variants were heterozygous with little evidence of the pathogenicity.

Homeostatic p62 levels and inclusion body formation in CHCHD2 knockout mice.

Inactivation of constitutive autophagy results in the formation of cytoplasmic inclusions in neurones, but the relationship between impaired autophagy and Lewy bodies (LBs) remains unknown. α-Synuclein and p62, components of LBs, are the defining characteristic of Parkinson's disease (PD). Until now, we have analyzed mice models and demonstrated p62 aggregates derived from an autophagic defect might serve as 'seeds' and can potentially be a cause of LB formation. P62 may be the key molecule for aggregate formation. To understand the mechanisms of LBs, we analyzed p62 homeostasis and inclusion formation using PD model mice. In PARK22-linked PD, intrinsically disordered mutant CHCHD2 initiates Lewy pathology. To determine the function of CHCHD2 for inclusions formation, we generated Chchd2-knockout (KO) mice and characterized the age-related pathological and motor phenotypes. Chchd2 KO mice exhibited p62 inclusion formation and dopaminergic neuronal loss in an age-dependent manner. These changes were associated with a reduction in mitochondria complex activity and abrogation of inner mitochondria structure. In particular, the OPA1 proteins, which regulate fusion of mitochondrial inner membranes, were immature in the mitochondria of CHCHD2-deficient mice. CHCHD2 regulates mitochondrial morphology and p62 homeostasis by controlling the level of OPA1. Our findings highlight the unexpected role of the homeostatic level of p62, which is regulated by a non-autophagic system, in controlling intracellular inclusion body formation, and indicate that the pathologic processes associated with the mitochondrial proteolytic system are crucial for loss of DA neurones.

The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1.

To investigate the prevalence and genotype-phenotype correlations of phosphatase and tensin homolog induced putative kinase 1 (PINK1) variants in Parkinson's disease (PD) patients, we analyzed 1700 patients (842 familial PD and 858 sporadic PD patients from Japanese origin). We screened the entire exon and exon-intron boundaries of PINK1 using Sanger sequencing and target sequencing by Ion torrent system. We identified 30 patients with heterozygous variants, 3 with homozygous variants, and 3 with digenic variants of PINK1-PRKN. Patients with homozygous variants presented a significantly younger age at onset than those with heterozygous variants. The allele frequency of heterozygous variants in patients with age at onset at 50 years and younger with familial PD and sporadic PD showed no differences. [123I]meta-iodobenzylguanidine (MIBG) myocardial scintigraphy indicated that half of patients harboring PINK1 heterozygous variants showed a decreased heart to mediastinum ratio (12/23). Our findings emphasize the importance of PINK1 variants for the onset of PD in patients with age at onset at 50 years and younger and the broad spectrum of clinical symptoms in patients with PINK1 variants.