Identification of microbial antigens in liver tissues involved in the pathogenesis of primary biliary cholangitis using 16S rRNA metagenome analysis.

BACKGROUND: Multiple factors are involved in the pathogenesis of primary biliary cholangitis (PBC), a chronic cholestatic liver disease, characterized by intrahepatic cholangiopathy. In particular, studies have suggested that environmental factors such as the presence of granulomas in the portal vein region are important for the development of PBC. This study aimed to comprehensively analyze and identify foreign-derived antigens in PBC liver tissue to confirm their involvement in PBC pathogenesis. METHODS: Portal areas and hepatocyte regions were selectively dissected from formalin-fixed paraffin-embedded PBC liver tissue samples using the microlaser method, followed by total DNA extraction. We then validated whether the bacterial strains identified through 16S rRNA metagenomic analysis were detected in PBC liver tissues. RESULTS: The most frequently detected bacterial genera in the PBC liver tissue samples were Sphingomonas panacis, Providencia, and Cutibacterium. These bacterial genera were also detected in the other PBC samples. Validation for the detection of S. panacis, the most abundant genus, revealed polymerase chain reaction bands extracted from the portal areas of all samples. They were also more highly expressed than bands detected in the hepatocyte region. CONCLUSION: S. panacis antigen was specifically detected in the portal areas of PBC liver tissues. The introduction of foreign-derived antigens into the liver as an environmental factor could be a possible mechanism for the development of PBC.

Appraising mandibular prognathism in class III malocclusion following orthognathic surgery: Patient-reported and cephalometry-based outcomes.

Patients with class III malocclusion often exhibit mandibular prognathism and complain of "prognathic appearance". The overall positive effects of orthognathic surgery on facial appearance have been demonstrated using patient-reported outcome measures (PROMs), but studies investigating the correlation between subjective PROMs results and objective measurements of imaging studies are sparse in the literature. This study recruited consecutive patients with skeletal class III malocclusion who underwent two-jaw orthognathic surgery between January 2016 and January 2021. The PROMs survey was conducted focusing on subjective perception of mandibular appearance. Lateral cephalometric images were measured to examine the correlation with the PROMs results. A total of 96 patients were eligible for this study. Of these, 74 patients (77.1%) reported complete correction of prognathic appearance postoperatively, whereas 22 patients (22.9%) perceived residual prognathic appearance. In a comparison of postoperative measurements between completely and incompletely satisfied patients, there were significant differences in SNB, ANB, convexity, facial angle, Nv-B, Nv-Pog, SN'B', soft tissue facial angle, lip-chin-throat angle, N'v-B', and N'v-Pog'. The PROM results were significantly associated with the objective measurements of imaging studies. Investigating the correlation between PROMs and objective measurements enables integration of patients' perception of the outcomes into future therapeutic strategy and surgical planning, contributing to the enhancement of patient satisfaction.

Outcome of patients with complete cleft lip and alveolus: 20-year follow-up.

BACKGROUND: Patients with cleft have functional and aesthetic impairment, and typically require several interventions as they grow. Long-term evaluation following a treatment protocol is essential, but such reports on patients with complete cleft lip and alveolus (CLA) are sparse in the literature. METHODS: A retrospective review was conducted to all patients with complete CLA born between January 1995 and August 2002 and treated at our center. Patients who received continuous multidisciplinary team care until 20 years of age were included, and patients with cleft palate and syndromic abnormalities were excluded. Facial bone growth was evaluated using cephalometric analysis. RESULTS: Eighty-seven and 11 patients with unilateral and bilateral CLA (UCLA and BCLA) were included respectively. All patients received one-stage cheiloplasty with primary rhinoplasty. Revisional lip/nose surgery was performed in 21.8 and 27.3% during growing age, and in 51.7 and 72.7% after skeletal maturity. Orthognathic surgery was performed in 20.7 and 27.3%. Compared with UCLA patients, BCLA had larger number of operations (3.0 versus 3.7, p = 0.03) and higher chance of receiving alveolar bone grafting twice (1.1% versus 36.4%, p < 0.01). Patients with complete CLA had less hypoplastic maxilla, and received smaller number of operations than complete cleft lip and palate. CONCLUSION: Complete CLA is a less severe form of cleft, but the patients still require multiple interventions. This review revealed certain suboptimal results, and modifications have been made in the treatment protocol. Longitudinal follow-up and periodic assessment help to establish an ideal therapeutic strategy and improve overall cleft care.

Comparison of modified Furlow palatoplasty using small double-opposing Z-plasty and conventional Furlow palatoplasty: A long-term outcome study.

BACKGROUND: The aim of palatoplasty is to create a functional palate to achieve normal speech, while minimizing post-operative complications. This study aimed to compare the long-term outcomes of modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ) and conventional Furlow palatoplasty (conventional-DOZ) performed in a single center. METHODS: A retrospective review of consecutive patients who underwent Furlow palatoplasty between May 2007 and March 2014 was executed. Non-syndromic patients subjected to palatoplasty prior to 24 months of age and followed-up until at least 9 years of age were included. RESULTS: A total of 196 small-DOZ and 280 conventional-DOZ palatoplasty patients were included in this study. Overall, 14 patients (2.9%) developed oronasal fistula, and 40 patients (8.4%) received velopharyngeal insufficiency (VPI) surgery. In comparisons, oronasal fistula rate was significantly higher in conventional-DOZ (0.5% vs. 4.6%, p = 0.01), and the VPI prevalence was not significantly different (9.2% vs. 7.9%, p = 0.62). Patients who developed fistula had a significantly higher likelihood of developing VPI than patients without oronasal fistula (50.0% vs. 7.1%, respectively; p < 0.01), with an odds ratio of 13.0. CONCLUSION: Both modalities of palatoplasty yielded commendable velopharyngeal function in the long-term follow-up. The small-DOZ with reduced tension lowered the risk of oronasal fistula.

The Relationships Among Chronic Pain Subtypes, Motor Function, and Physical Activity in Community-Dwelling Japanese Older Adults: A Cross-Sectional Study.

PURPOSE: We investigated the relationships among motor function, physical activity, and the characteristics of chronic pain (the number of pain sites, pain intensity, and pain-type). DESIGN: Cross-sectional study. SETTING: An ongoing community-based prospective study conducted in Itoshima, Japan. SUBJECTS: Community-dwelling Japanese aged 65-75 years (n = 805; 401 men, 404 women). MEASURES: Chronic pain subtypes were examined in terms of the number of pain sites, pain intensity, and pain type. Motor function was evaluated by handgrip strength, walking speed, and the 5 Times Stand-up and Sit Test (FTSST). Locomotive activity, non-locomotive activity, and sedentary time were evaluated by a tri-axial accelerometer as physical-activity parameters. ANALYSIS: Multiple regression model adjusting for age, sex, education level, employment status, subjective economic status, body mass index, cognitive function, comorbidity, current tobacco use, current alcohol consumption, and regular exercise. RESULTS: In a multivariate analysis, the subjects' walking speed was negatively associated with multisite, moderate-to-severe, and neuropathic-like pain. The FTSST was positively associated with single-site, moderate-to-severe, and neuropathic-like pain. There was no significant association between handgrip strength and any chronic pain subtypes. Locomotive activity was negatively related to multisite, moderate-to-severe, and neuropathic-like pain, but there was no clear association between the amount of non-locomotive activity, sedentary time, and chronic pain subtypes. CONCLUSION: Severe chronic pain was associated with decreased locomotion-related motor function and physical activity.

New risk stratification for adjuvant nivolumab for high-risk muscle-invasive urothelial carcinoma.

Objectives: We aim to evaluate the risk of recurrence after neoadjuvant chemotherapy followed by radical cystectomy, particularly in ypT2 disease in patients with urothelial carcinoma, because it is not clear if all eligible patients with high-risk muscle-invasive urothelial carcinoma should be treated with adjuvant nivolumab. Materials and Methods: We analysed the radiological and clinicopathological features, including cT and ypT stages, of 197 patients who had undergone two to four cycles of cisplatin-based neoadjuvant chemotherapy and radical cystectomy without adjuvant chemotherapy. We stratified the risk of postoperative recurrence by these factors. Results: The median observation period was 29.6 (interquartile range, 11.4-71.7) months, and disease recurrence was observed in 58 patients. Multivariate analysis revealed that ypT stage (P = 0.019) and lymphovascular invasion (P = 0.015) were independent risk factors for postoperative recurrence. The ypT2 group (n = 38) had significantly better recurrence-free survival than the ypT3 group (n = 41) (median recurrence-free survival: not reached vs. 13.4 months, respectively, P = 0.005). In ypT2 disease, the cT2 and ypT2 group (n = 15), which was diagnosed as cT2 preoperatively and then diagnosed as ypT2 postoperatively, had significantly better recurrence-free survival than the cT3/4 and ypT2 group (n = 23) (median recurrence-free survival: not reached vs. 63.1 months, respectively, P = 0.034). There was no significant difference in recurrence-free survival between the ypT ≤ 1 (n = 106) and the cT2 and ypT2 groups (median recurrence-free survival: not reached in both, P = 0.962). Conclusion: Patients with cT2 and ypT2 stage have a relatively low risk of recurrence and thus have a lower need for adjuvant nivolumab, particularly those with ypT2.

Elucidation of pericholangitis and periductal fibrosis in cholestatic liver diseases via extracellular vesicles released by polarized biliary epithelial cells.

Cholestatic liver diseases causes inflammation and fibrosis around bile ducts. However, the pathological mechanism has not been elucidated. Extracellular vesicles (EVs) are released from both the basolateral and apical sides of polarized biliary epithelial cells. We aimed to investigate the possibility that EVs released from the basolateral sides of biliary epithelial cells by bile acid stimulation induce inflammatory cells and fibrosis around bile ducts, and they may be involved in the pathogenesis of cholestatic liver disease. Human biliary epithelial cells (H69) were grown on cell culture inserts and stimulated with chenodeoxycholic acid + IFN-γ. Human THP-1-derived M1-macrophages, LX-2 cells, and KMST-6 cells were treated with the extracted basolateral EVs, and inflammatory cytokines and fibrosis markers were detected by RT-PCR. Highly expressed proteins from stimulated EVs were identified, and M1-macrophages, LX-2, KMST-6 were treated with these recombinant proteins. Stimulated EVs increased the expression of TNF, IL-1ß, and IL-6 in M1-macrophages, TGF-ß in LX-2 and KMST-6 compared with the corresponding expression levels in unstimulated EVs. Nucleophosmin, nucleolin, and midkine levels were increased in EVs from stimulated cells compared with protein expression in EVs from unstimulated cells. Leukocyte cell-derived chemotaxin-2 (LECT2) is highly expressed only in EVs from stimulated cells. Stimulation of M1-macrophages with recombinant nucleophosmin, nucleolin, and midkine significantly increased the expression of inflammatory cytokines. Stimulation of LX-2 and KMST-6 with recombinant LECT2 significantly increased the expression of fibrotic markers. These results suggest that basolateral EVs are related to the development of pericholangitis and periductal fibrosis in cholestatic liver diseases.NEW & NOTEWORTHY Our research elucidated that the composition of basolateral EVs from the biliary epithelial cells changed under bile acid exposure and the basolateral EVs contained the novel inflammation-inducing proteins NPM, NCL, and MK and the fibrosis-inducing protein LECT2. We report that these new results are possible to lead to the potential therapeutic target of cholestatic liver diseases in the future.

Secondary Bilateral Cleft Rhinoplasty: Achieving an Aesthetic Result.

BACKGROUND: Secondary rhinoplasty in patients with bilateral cleft lip poses ongoing challenges and requires a reliable method for achieving optimal outcomes. OBJECTIVES: The purpose of this study was to establish a safe and effective method for secondary bilateral cleft rhinoplasty. METHODS: A consecutive series of 92 skeletally matured patients with bilateral cleft lip and nasal deformity were included. All had undergone secondary open rhinoplasty, performed by a single surgeon with a bilateral reverse-U flap and septal extension graft, between 2013 and 2021. Medical records of these 92 patients were reviewed to assess the clinical course. A 3-dimensional (3D) anthropometric analysis and panel assessment of 32 patients were performed to evaluate the aesthetic improvement, with an age-, sex-, and ethnicity-matched normal control group for comparisons. RESULTS: The methods showed statistically significant improvement in addressing a short columella (columellar height), short nasal bridge (nasal bridge length), de-projected nasal tip (nasal tip projection, nasal dorsum angle), poorly defined nasal tip (nasal tip angle, dome height, and panel assessment), and transversely oriented nostrils (columellar height, alar width, nostril type). Importantly, these improvements were accompanied by a low complication rate of 4%. However, upper lip deficiency over the upper lip angle and labial-columellar angle remained without significant improvement. CONCLUSIONS: In this study we described effective secondary rhinoplasty, which was composed of a bilateral reverse-U flap and septal extension graft, with acceptable outcome. The 3D anthropometric analysis and panel assessment clarified that our rhinoplasty procedure could bring the nasal morphology in these patients closer to the normal data.

Primary rhinoplasty in patients with bilateral cleft lip: Longitudinal results and comparison between closed and semi-open approaches.

BACKGROUND: Although several studies have shown that primary rhinoplasty in patients with cleft lip provides good outcomes with limited effect on nasal growth, the surgical procedure remains to be standardized. The purpose of this study was to evaluate the long-term outcome of primary semi-open rhinoplasty with Tajima reverse-U incision, compared with that of closed rhinoplasty. METHODS: Consecutive nonsyndromic patients with complete bilateral cleft lip and palate (n = 52) who underwent primary semi-open rhinoplasty between 2001 and 2016 were reviewed. Patients who underwent primary closed rhinoplasty (n = 61) and control group individuals were recruited for comparison. Computer-based standardized measurements of 2D photographs and panel assessments by laypersons were collected and statistically analyzed. RESULTS: In the comparative analysis at preschool age, semi-open rhinoplasty significantly improved the typical nasal deformities, including transversely oriented wide nostrils, short columella, and de-projected nasal tip, more effectively than closed rhinoplasty. Without major drawbacks, these parameters in the semi-open group were well maintained closer to those in the control group till skeletal maturity. After primary rhinoplasty, 54% of patients in the closed group and 4% in the semi-open group underwent intermediate rhinoplasty at preschool age. CONCLUSION: This study showed that the patients who underwent primary semi-open rhinoplasty achieved long-term and persistent outcomes that were closer to the normal nasal morphology compared with the patients treated with closed rhinoplasty, while avoiding intermediate rhinoplasty during the preschool to adolescent periods.

Prognostic impact of tumor ureteral invasion on recurrence after radical cystectomy.

PURPOSE: Several preoperative factors have been suggested to be risk factors of disease recurrence after radical cystectomy. There is no study focusing on the impact on prognosis of bladder tumor ureteral invasion in preoperative imaging. METHODS: The study population consisted of 136 patients, all of whom underwent radical cystectomy during the period between 2007-2019. We excluded patients with concurrent or a history of upper tract urothelial carcinoma and who underwent radical cystectomy for other cancers or nononcologic reasons. The starting point of this study was the timing of neoadjuvant chemotherapy or radical cystectomy and the endpoint was the timing of disease recurrence. To identify the factors influencing recurrence, univariate and multivariate analyses were performed using the Cox proportional hazard model. Recurrence-free survival curves were constructed using the Kaplan-Meier method. RESULTS: Ureteral invasion was observed in 20 (14.7%) patients. Disease recurrence was observed in 11 (55.0%) of 20 ureteral invasion positive patients and 35 (30.2%) of 116 ureteral invasion negative patients, respectively. In the ureteral invasion positive group, clinical T and N stage were higher and hydronephrosis were more common than in the ureteral invasion negative group. According to the multivariate analysis, ureteral invasion (hazard ratio: 2.307, p = 0.016) and clinical N stage ≥ 1 (hazard ratio: 2.140, p = 0.028) were independent risk factors for postoperative recurrence. In the ureteral invasion positive group, more local recurrences were observed. CONCLUSION: This study suggested that ureteral invasion in preoperative imaging is a significant risk factor for postoperative recurrence.

Modified Furlow palatoplasty using small double-opposing Z-plasty: Long-term outcome and comparison with two-flap palatoplasty.

BACKGROUND: The post-palatoplasty velopharyngeal function needs to be evaluated through long-term follow-up, but such reports are limited in the literature and there has been no consensus as to which surgical technique yields optimal velopharyngeal function with minimum complication rate. This study aimed to evaluate the long-term outcome of the modified Furlow palatoplasty using small double-opposing Z-plasty (small-DOZ). METHODS: A retrospective review of consecutive patients who received palatoplasty performed by the senior author between January 2000 and March 2014 was conducted. Non-syndromic patients who underwent palatoplasty before the age of 18 months and followed-up until at least 9 years of age were included. Comparisons between the small-DOZ and two-flap methods for soft palate repair were made. RESULTS: A total of 196 small-DOZ and 167 two-flap palatoplasty patients were eligible in the study. Among the small-DOZ palatoplasty patients, 1 patient (0.5%) developed oronasal fistula, and 18 patients (9.2%) received velopharyngeal insufficiency (VPI) surgery (10 patients at preschool age and 8 at nine years of age). Compared with the small-DOZ palatoplasty, the oronasal fistula rate, VPI surgery rate, and the need for myringotomy tube insertion were significantly higher in the two-flap group (p =0.01, <0.01, <0.01, respectively). Patients who developed oronasal fistula had significantly higher likelihood of having velopharyngeal insufficiency (p < 0.01). CONCLUSION: The small-DOZ provided successful palatal repair with low rates of oronasal fistula and VPI in the long-term. Wound closure under minimal tension facilitated to avoid oronasal fistula. Reconstruction of the functional muscle sling enabled to achieve normal velopharyngeal function with favorable speech outcome and middle ear function.

Septal extension graft in cleft rhinoplasty: Patients with secondary unilateral cleft lip nasal deformity.

BACKGROUND: Tip refinement procedure is still controversial in secondary unilateral cleft rhinoplasty. The aim of this study was to assess whether septal extension graft improved nasal and tip deformity and achieved a normal profile with clinical and 3D morphometric analyses. METHODS: A consecutive series of 194 skeletally mature patients with unilateral cleft were included and analyzed. All had undergone secondary open rhinoplasty, performed by a single surgeon, with the use of septal extension graft between 2013 and 2021. Clinical data were collected, and 3D morphometric measurements were performed. An age-, sex-, and ethnicity-matched normal group was included for comparisons. RESULTS: Our standard procedures included open approach combining reverse U incision, septal extension graft, dorsal augmentation, lip revision, and vermilion augmentation. The postoperative outcome showed significantly increased numerical values (nasal bridge length, nasal height, nasal tip projection, nasal dorsum angle, columellar angle, columellar-lobule angle, nostril height ratio, nasal surface area, nasal volume) and decreased numerical values (alar width, tip/middle deviation, nasal tip angle, labial-columellar angle) than the preoperative morphology. The postoperative measurement showed significantly higher numerical values (nasal protrusion, tip/middle deviation, nasal dorsum angle), and lower numerical values (columellar-lobule angle, nostril height ratio, alar width ratio) than the control group. CONCLUSION: This study revealed that our secondary cleft rhinoplasty significantly improved the under-projected, up-rotated, deviated, and poorly defined tip as well as short nasal bridge deformities. The technique could result in the nose of the patients with cleft lip nasal deformity being closer to that of the normative profile.

Short-term recurrence of takotsubo syndrome with phenotypic variation: a case report.

Background: Takotsubo syndrome (TTS) is an acute and usually reversible heart failure syndrome characterized as an uncommon left ventricular (LV) cardiomyopathy. Recurrence of TTS is rare, estimated to be 1-6%. We report a rare case of TTS that occurred three times in 2 months but manifested various phenotypes. Case summary: A 68-year-old woman was admitted to our hospital with acute-onset chest pain and hypertension. The coronary angiography findings were normal, although left ventriculography revealed inferior wall hypokinesis, leading to a mid-ventricular TTS diagnosis. She was discharged on Day 3 after her symptoms improved and vitals stabilized. The patient's condition remained uneventful until 2-week post-discharge, when acute chest pain and hypertension recurred. She was admitted again with the same diagnosis. However, LV morphology revealed an apical ballooning pattern, with inferior LV wall hypokinesis. She was discharged on Day 7 after her symptoms and electrocardiography findings improved but was readmitted again 2 weeks later after acute chest pain and hypertension recurred. Left ventriculography performed a third time demonstrated mid-ventricular TTS. The patient was prescribed additional medications and discharged on Day 12. Her electrocardiography findings normalized, and the patient remained asymptomatic without recurrence 4 months after the initial presentation. Discussion: Recurrence and phenotypic change of TTS are rare. Some cases have been reported but occurring months to years after initial diagnosis. Combined treatment with ß-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists may be more effective to prevent the recurrence than monotherapies.

Relationship Between Chronic Pain Types (Nociceptive and Neuropathic-Like Symptoms) and Frailty in Community-Dwelling Japanese Older Adults: A Cross-Sectional Study.

Purpose: Chronic pain may accelerate the development of frailty in older adults through a variety of mechanisms. There are no published investigations of the influence of neuropathic-like symptoms on physical frailty. We investigated the association between chronic pain types (nociceptive and neuropathic-like symptoms) and frailty in community-dwelling Japanese older adults. Participants and Methods: This was a population-based cross-sectional study conducted in 2017 in the city of Itoshima, Japan of 917 participants aged 65-75 years, not in need of long-term care, who had completed the physical function tests and questionnaires administered at measurement sessions held at community centers at three sites over a 1- to 2-month period. Their chronic pain types were classified as no-chronic pain, nociceptive pain, and neuropathic-like symptoms according to their painDETECT scores. Frailty phenotypes were defined by the following five components: unintentional weight loss, low grip strength, exhaustion, slow gait speed, and low physical activity. A logistic regression model was used to compute the odds ratios (ORs) and 95% confidence interval (CIs) for frailty status outcomes. Results: The prevalence of pre-frailty was 51.9%, and that of frailty was 5.1%. In multinomial logistic regression analyses, compared to the no-chronic pain group, the OR for the presence of pre-frailty among the participants with nociceptive pain was 1.54 (95% CI: 1.04-2.30, p=0.03), and the OR for the presence of frailty among the participants with neuropathic-like symptoms was 4.37 (95% CI: 1.10-17.37, p=0.04). The neuropathic sensory symptoms of burning, tingling/prickling, and numbness were each associated with frailty, but not with the risk of pre-frailty. Conclusion: Neuropathic-like symptoms were significantly associated with the presence of frailty in community-dwelling Japanese older adults. Chronic pain types might have different effects on frailty status.

Effective correction of columellar base deviation in primary unilateral cleft lip repair: A muscle-driven method.

SUMMARY: Columellar base deviation is a common and challenging deformity in patients with unilateral cleft lip. Debate still continues on its surgical correction without sufficient studies to establish an effective management. This article presents our experience in correcting the columellar base deviation with the muscle-driven method in primary lip repair. The key is to perform extensive muscle dissection and reconstruction. In the medial lip segment, muscle dissection is performed subcutaneously up to the contralateral nostril floor for effective lengthening and rotation. In the lateral lip segment, muscle dissection is executed in both submucosal and subcutaneous planes, and muscle component is extensively separated from the lip skin and buccal mucosa. The lateral muscle flap is advanced and reattached to the contralateral nostril floor and columellar base using a subcutaneous sustaining suture. Cinching suture between columellar base and alar base is performed. These two sutures help to centralize and over-correct the columellar base. Bilateral muscle components are re-oriented and approximated in a Z-plasty format for lengthening of the lip. The patients were followed up for at least 3 years. Quantitative measurements of deviation in columellar base angulation were executed, which revealed 55.8±2.6° (before nasoalveolar molding), 29.6±1.7° (after nasoalveolar molding), and 2.8±0.4° (postoperative follow-up), respectively. The muscle-driven method represents a safe and effective technique to correct columellar base deviation in patients with unilateral cleft lip.

Long-term treatment outcome of patients with complete bilateral cleft lip and palate: a retrospective cohort study.

BACKGROUND: Patients with cleft lip and palate have functional and esthetic impairment and typically require multiple interventions in their life. Long-term evaluation following a treatment protocol, especially for patients with complete bilateral cleft lip and palate (BCLP), is important but was rarely reported in the literature. PATIENTS AND METHODS: A retrospective review was conducted on all patients with complete BCLP born between 1995 and 2002 and treated at our center. Inclusion criteria were having adequate medical records and receiving continuous multidisciplinary team care at least until 20 years of age. Exclusion criteria were lack of regular follow-up and congenital syndromic abnormalities. The medical records and photos were reviewed, and facial bone development was evaluated using cephalometric analysis. RESULTS: A total of 122 patients were included, with a mean age of 22.1 years at the final evaluation in this study. Primary one-stage cheiloplasty was performed in 91.0% of the patients, and 9.0% underwent two-stage repair with an initial adhesion cheiloplasty. All patients underwent two-flap palatoplasty at an average of 12.3 months. Surgical intervention for velopharyngeal insufficiency was required in 59.0% of patients. Revisional lip/nose surgery was performed in 31.1% during growing age and in 64.8% after skeletal maturity. Orthognathic surgery was applied in 60.7% of patients with retruded midface, of which 97.3% underwent two-jaw surgery. The average number of operations to complete the treatment was 5.9 per patient. CONCLUSION: Patients with complete BCLP remain the most challenging group to treat among the cleft. This review revealed certain suboptimal results, and modifications have been made to the treatment protocol. Longitudinal follow-up and periodic assessment help to establish an ideal therapeutic strategy and improve overall cleft care.

Strategy for PSA progression in patients undergoing salvage radiation for biochemical recurrence after radical prostatectomy.

BACKGROUND: The treatment strategy for prostate-specific antigen (PSA) progression in patients who receive salvage radiation therapy (RT) for biochemical recurrence (BCR) after radical prostatectomy (RP) is salvage androgen deprivation therapy (ADT). However, its optimal timing is highly controversial. METHODS: The study sample consisted of 77 men who underwent RP, received salvage RT against BCR, and underwent salvage ADT for PSA progression. The endpoint of this study was development to castration-resistant prostate cancer (CRPC), from the start of salvage RT. RESULTS: The median follow-up time was 9.5 years, and 20 patients experienced CRPC. The multivariable analysis identified PSA-doubling time (PSA-DT) ≤ 12 months (hazard ratio, 3.5) and seminal vesicle invasion (SVI) (hazard ratio, 4.4) as independent risk factors. We defined the high-risk and low-risk groups as those with one or two risk factors and no risk factors, respectively. In the high-risk group, a significant difference in time to CRPC was observed between patients who received salvage ADT at PSA ≤ 1.0 ng/mL (n = 8) and at > 1.0 ng/mL (n = 27) (10-year non-CRPC rate: 100.0% vs. 46.3%, respectively). In contrast, in the low-risk group, no significant difference in CRPC-free survival was observed between patients who received salvage ADT at PSA ≤ 1.0 ng/mL (n = 14) and at > 1.0 ng/mL (n = 28) (10-year non-CRPC rate: 86.4% vs. 80.8%, respectively). CONCLUSION: In high-risk patients (PSA-DT ≤ 12 months and/or SVI), salvage ADT for PSA progression after salvage RT should be started before the PSA levels exceed 1.0 ng/mL.

Association between the number of chronic pain sites and neuropathic-like symptoms in community-dwelling older adults with chronic pain: a cross-sectional study.

OBJECTIVES: We investigated the relationship between the number of chronic pain sites and the prevalence and severity of neuropathic-like symptoms in community-dwelling older Japanese adults with chronic pain. DESIGN: Cross-sectional study. SETTING: The data analysed are from a study conducted in the city of Itoshima, Japan in 2017. PARTICIPANTS: The study population was 988 participants (age 65-75 years) not in need of long-term care who completed questionnaires assessing sociodemographic factors, psychological factors and chronic pain. PRIMARY OUTCOME MEASURES: The primary outcome was the participants' neuropathic-like symptoms evaluated by the PainDETECT Questionnaire (PD-Q). We classified the participants into mild and moderate-to-severe pain groups according to the pain intensity on the PD-Q. The number of chronic pain sites was categorised into groups with 1, 2-3 and ≥4 sites. RESULTS: The age-adjusted and sex-adjusted prevalence of neuropathic-like symptoms was significantly higher among the participants with 2-3 or ≥4 sites compared with the single-site group. In the binomial logistic regression analyses, the multivariable-adjusted ORs and 95% CIs for neuropathic-like symptoms among the participants with 2-3 and ≥4 sites were 1.94 (1.13 to 3.33) and 3.90 (2.22 to 6.85), respectively compared with the participants with single-site pain. The ORs for moderate-to-severe neuropathic-like symptoms increased significantly with the increase in the number of chronic pain sites. CONCLUSIONS: The number of chronic pain sites was positively associated with the presence and severity of neuropathic-like symptoms in community-dwelling older Japanese adults with chronic pain.

Family dysfunction is associated with chronic pain in a community-dwelling Japanese population: The Hisayama study.

BACKGROUND: Poor family functioning has been reported to be associated with the severity of chronic pain in outpatients, but the association has not been fully addressed in general populations. The present study aimed to examine the association between family dysfunction levels and the presence of chronic pain in a community-dwelling Japanese population. METHODS: A total of 2598 participants aged ≥40 years were classified as having healthy, borderline or unhealthy family functioning. Chronic pain was defined as subjective pain for three months or longer, and further classified by pain intensity, the number of chronic pain sites, pain duration and the extent of pain spread. A logistic regression model was used to compute the odds ratios (ORs) for chronic pain outcomes. RESULTS: The prevalence of chronic pain was 49%. The age- and sex-adjusted prevalence of total and severe chronic pain were increased significantly with increasing family dysfunction levels (all p for trend <0.01). After adjusting for sociodemographic, physical, social and family structure factors, the ORs (95% confidence intervals [CI]) for having chronic pain among borderline and unhealthy groups were 1.20 (1.01-1.44) and 1.43 (1.15-1.79), respectively, as compared with a healthy family function group. The association was stronger among people who were employed and those who were living with their children. In addition, the ORs for severe chronic pain increased significantly with increasing levels of family dysfunction. CONCLUSIONS: The family dysfunction level was positively associated with the presence as well as the severity of chronic pain in a community-dwelling population. SIGNIFICANCE: A biopsychosocial burden due to family relationships could worsen the clinical presentation of pain. Social support or family therapy for dysfunctional families would be a potential initiative for the prevention or management of chronic pain.

Pathological Analysis of Medial and Intimal Calcification in Lower Extremity Artery Disease: Impact of Hemodialysis.

Background: The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated. Objectives: The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification. Methods: Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification. Results: The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group (P < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; P = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque (P = 0.02). The prevalence of severe bone formation was more common in the HD patients (P = 0.01). Conclusions: Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.