ABSTRACT
The PTPRQ gene has been identified as one of the genes responsible for non-syndromic sensorineural hearing loss (SNHL), and assigned as DFNA73 and DFNB84. To date, about 30 causative PTPRQ variants have been reported to cause SNHL. However, the detailed clinical features of PTPRQ-associated hearing loss (HL) remain unclear. In this study, 15,684 patients with SNHL were enrolled and genetic analysis was performed using massively parallel DNA sequencing (MPS) for 63 target deafness genes. We identified 17 possibly disease-causing PTPRQ variants in 13 Japanese patients, with 15 of the 17 variants regarded as novel. The majority of variants identified in this study were loss of function. Patients with PTPRQ-associated HL mostly showed congenital or childhood onset. Their hearing levels at high frequency deteriorated earlier than that at low frequency. The severity of HL progressed from moderate to severe or profound HL. Five patients with profound or severe HL received cochlear implantation, and the postoperative sound field threshold levels and discrimination scores were favorable. These findings will contribute to a greater understanding of the clinical features of PTPRQ-associated HL and may be relevant in clinical practice.
Subject(s)
Hearing Loss, Sensorineural , Receptor-Like Protein Tyrosine Phosphatases, Class 3 , Humans , Male , Female , Receptor-Like Protein Tyrosine Phosphatases, Class 3/genetics , Child , Child, Preschool , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/pathology , Adult , Japan , Adolescent , Mutation , Infant , High-Throughput Nucleotide Sequencing , Cohort Studies , Middle Aged , East Asian PeopleABSTRACT
BACKGROUND: Our previous research showed that a high rate of secondary carcinogenesis is observed during follow-up after transoral surgery in patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal cancers. We speculate that the contributing factors are alcohol drinking, smoking, and aging; however, we could not provide clear evidence. In this study, we aimed to identify the risk factors for secondary carcinogenesis in patients with these cancers, particularly factors associated with drinking and/or smoking. METHODS: The medical records of all-stage laryngeal, oropharyngeal, and hypopharyngeal cancer patients who had undergone definitive treatment were retrospectively analyzed. Assessments included visual and endoscopic observations of the primary site, enhanced cervical CT or US of the primary site and regional lymph nodes, PET-CT, and enhanced whole-body CT. Clinical characteristics were compared in patients with and without secondary carcinogenesis and in patients with hypopharyngeal cancer and patients with other cancers. RESULTS: Hypopharyngeal cancer was an independent risk factor for secondary cancer. The 5-year incidence rate of secondary cancer was 25.5%, 28.6%, and 41.2% in laryngeal, oropharyngeal, and hypopharyngeal cancers, respectively. Radiotherapy was defined as an independent risk factor in hypopharyngeal cancer patients with secondary cancers. No direct correlation was found between secondary carcinogenesis and alcohol consumption, smoking, or aging. CONCLUSIONS: Patients with hypopharyngeal cancer require close follow-up as they are at high risk of developing secondary cancer, possibly because out-of-field radiation exposure may induce systemic secondary carcinogenesis in hypopharyngeal cancer patients with genetic abnormality induced by alcohol consumption.
Subject(s)
Hypopharyngeal Neoplasms , Laryngeal Neoplasms , Humans , Hypopharyngeal Neoplasms/pathology , Retrospective Studies , Positron Emission Tomography Computed Tomography , Laryngeal Neoplasms/pathology , Risk Factors , CarcinogenesisABSTRACT
BACKGROUND/AIM: This study aimed to identify key molecules associated with the survival of patients with hypopharyngeal squamous cell carcinoma (HpSCC) by combining in silico and in vitro analyses. MATERIALS AND METHODS: Differentially expressed genes (DEGs) were screened using the Gene Expression Omnibus database. For DEGs, we performed functional enrichment and protein-protein interaction network analyses to identify potential biological functions and hub genes. Functional analysis of HpSCC cell lines verified the critical roles of the hub genes. RESULTS: DEGs were associated with the extracellular matrix. Among the hub genes, high expression of prolyl 4-hydroxylase subunit alpha 1 (P4HA1) was significantly associated with shorter survival. In addition, P4HA1 knockdown inhibited cell migration and colonization. Suppression of cell proliferation was demonstrated using P4HA1-selective inhibitors. CONCLUSION: P4HA1 may be a useful therapeutic target for the treatment of HpSCC.
Subject(s)
Head and Neck Neoplasms , Protein Interaction Maps , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Cell Proliferation/genetics , Head and Neck Neoplasms/genetics , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Procollagen-Proline Dioxygenase/genetics , Procollagen-Proline Dioxygenase/metabolismABSTRACT
Biphenotypic sinonasal sarcoma is a newly established tumor entity that is associated with distinct clinicopathological findings. Biphenotypic sinonasal sarcoma is a rare, low-grade spindle cell sarcoma that arises in middle-aged females, exclusively in the sinonasal tract. A fusion gene involving PAX3 is detected in most biphenotypic sinonasal sarcomas, which aids in its diagnosis. Here, we report a case of biphenotypic sinonasal sarcoma with its cytological findings. The patient was a 73-year-old woman who presented with purulent nasal discharge and dull pain in the left cheek area. Computed tomography showed a mass extending from the left nasal cavity to the left ethmoid sinus, the left frontal sinus, and the frontal skull base. She underwent a combined transcranial and endoscopic approach for en bloc resection with a safety margin. Histologically, spindle-shaped tumor cells have been thought to proliferate mainly in the subepithelial stroma. Here, nasal mucosal epithelial hyperplasia was noted, and the tumor had invaded the bone tissue accompanying the epithelial cells. Fluorescence in situ hybridization (FISH) analysis showed a PAX3 rearrangement, and next-generation sequencing identified a PAX3::MAML3 fusion. Based on FISH, split signals were observed not in respiratory cells but in stromal cells. This indicated that respiratory cells were non-neoplastic. In the diagnosis of biphenotypic sinonasal sarcoma, the inverted growth of the respiratory epithelium can be a diagnostic pitfall. FISH analysis using a PAX3 break-apart probe is helpful not only for an accurate diagnosis but also for detecting the true neoplastic cells.
Subject(s)
Paranasal Sinus Neoplasms , Sarcoma , Soft Tissue Neoplasms , Middle Aged , Female , Humans , Aged , In Situ Hybridization, Fluorescence , Paranasal Sinus Neoplasms/diagnosis , Paranasal Sinus Neoplasms/genetics , Paranasal Sinus Neoplasms/pathology , Sarcoma/pathology , Respiratory Mucosa/pathology , Bone and Bones/pathologyABSTRACT
BACKGROUND: We previously identified hypopharyngeal cancer as an independent risk factor for the incidence of newly diagnosed secondary cancers after the treatment of early-stage laryngeal, oropharyngeal, and hypopharyngeal cancers. We subsequently used a different patient cohort to validate the usefulness of this factor during the follow-up period in these patients. METHODS: Patients who underwent transoral surgery (TOS) as a definitive treatment between April 1, 2016, and September 30, 2020, were included. The incidence of secondary cancer was evaluated in hypopharyngeal and other cancers. Overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS) outcomes were evaluated. Statistical analyses based on the risk factors were also performed. RESULTS: Incidence of new secondary cancer was 30% in hypopharyngeal cancer patients as compared to 11% in other cancer patients, and the risk was 3.60-fold (95% confidence interval 1.07-12.10) higher after definitive treatment for initial head and neck cancers. The 3-year OS, RFS, and DFS rates were 98%, 86%, and 67%, respectively. CONCLUSIONS: Among patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma, who were initially treated with TOS, hypopharyngeal cancer patients had a higher risk of newly diagnosed secondary cancers as observed during the follow-up period.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Hypopharyngeal Neoplasms , Laryngeal Neoplasms , Carcinoma, Squamous Cell/pathology , Humans , Hypopharyngeal Neoplasms/complications , Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/complications , Laryngeal Neoplasms/surgery , Prospective Studies , Retrospective Studies , Risk FactorsABSTRACT
Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.
Subject(s)
Deafness , Hearing Loss, Sensorineural , Hearing Loss , Genetic Association Studies , Hearing Loss/genetics , Hearing Loss, Central , Hearing Loss, Sensorineural/genetics , Humans , Japan , Membrane Proteins/genetics , MutationABSTRACT
BACKGROUND: We had previously identified the following risk factors for insufficient control of early T-stage head and neck cancer by transoral surgery (TOS): (1) tumor thickness > 7 mm on enhanced computed tomography (CT), and (2) poor differentiation in pathological examination. We subsequently used a different patient cohort to validate the usefulness of these factors in determining the need for adaptation of TOS. STUDY SETTING: A prospective observational study METHODS: Patients who received TOS as a definitive treatment between April 1, 2016 and September 30, 2020 were included. Primary control rates (by single TOS and TOS alone) in relation to the above-mentioned risk factors were calculated. Overall (O), recurrence-free (RF), and disease-free (DF) survival (S) outcomes were evaluated. A combination analysis based on the number of risk factors was also performed. RESULTS: Patients with tumor thickness > 7 mm had a 2.88-fold [95% confidence interval (CI) 1.01-8.51] higher risk of incomplete primary resection by single TOS, while patients who showed poor differentiation on pathological assessments had a 13.14-fold (95% CI 3.66-47.14) higher risk of insufficient primary control by TOS alone. The 3 year OS, RFS, and DFS rates were 99%, 83%, and 63%, respectively. Patients with both risk factors had a 93.00-fold (95% CI 4.99-1732.00) higher risk of incomplete primary control by TOS alone. CONCLUSIONS: Among patients with early-stage laryngeal, oropharyngeal, and hypopharyngeal squamous cell carcinoma, primary control by TOS alone may not be achieved in patients with both risk factors, that is, tumor thickness > 7 mm as measured by enhanced CT and poor differentiation on pathological examination.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Carcinoma, Squamous Cell/surgery , Humans , Neoplasm Recurrence, Local , Oropharyngeal Neoplasms/surgery , Risk Factors , Squamous Cell Carcinoma of Head and Neck/surgeryABSTRACT
BACKGROUND: Our prospective study of patients with early T-stage head and neck cancer indicated a high incidence of newly diagnosed secondary malignancies during the follow-up period. We aimed to determine the incidence rate and risk factors of secondary malignancies in early-stage head and neck cancer patients. METHODS: We sub-analyzed the patient data of a previous study focusing on secondary cancer incidence. The endpoints were statistical analyses of risk factors and survival and incidence rates. RESULTS: The incidence rate of secondary cancer was 37%, the crude incidence of second primary cancers was 10.6 per 100 person-years, and the 5 year secondary cancer-free survival rate was 63%. The hypopharynx as the primary site was an independent significant predictive factor (odds ratio 3.96, 95% confidence interval 1.07-14.6, p = 0.039). CONCLUSIONS: Early stages of laryngeal, oropharyngeal, and hypopharyngeal cancer had a risk of secondary cancer, especially hypopharyngeal cancer. Attention to the secondary cancer has to be paid during the follow-up period after controlling the early-stage disease. These findings highlight the need for awareness of the incidence of secondary cancer in cases of early-stage primary head and neck cancer.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Hypopharyngeal Neoplasms , Neoplasms, Second Primary , Head and Neck Neoplasms/epidemiology , Head and Neck Neoplasms/surgery , Humans , Hypopharyngeal Neoplasms/epidemiology , Hypopharyngeal Neoplasms/surgery , Incidence , Neoplasms, Second Primary/epidemiology , Prospective StudiesABSTRACT
To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC-derived organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short-term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC-derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC.
Subject(s)
Carcinoma, Adenoid Cystic/pathology , Primary Cell Culture/methods , Salivary Gland Neoplasms/pathology , Animals , Carcinoma, Adenoid Cystic/genetics , Carcinoma, Adenoid Cystic/surgery , Female , Humans , Male , Mice , Oncogene Proteins, Fusion/genetics , Organoids , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-myb/genetics , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/surgery , Salivary Glands/pathology , Salivary Glands/surgery , Trans-Activators/genetics , Xenograft Model Antitumor AssaysABSTRACT
Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. We selected 1,336 autosomal dominant hearing loss patients among 7,408 unrelated Japanese hearing loss probands and performed targeted genome enrichment and massively parallel sequencing of 68 target genes for all patients. Clinical information of cases with mutations in EYA4 was gathered and analyzed from medical charts. Eleven novel EYA4 variants (three frameshift variants, three missense variants, two nonsense variants, one splicing variant, and two single-copy number losses) and two previously reported variants were found in 12 probands (0.90%) among the 1,336 autosomal dominant hearing loss families. The audiometric configuration of truncating variants tends to deteriorate for all frequencies, whereas that of non-truncating variants tends to show high-frequency hearing loss, suggesting a new correlation between genotype and phenotype in DFNA10. The rate of hearing loss progression caused by EYA4 variants was considered to be 0.63 dB/year, as found in this study and previous reports.
Subject(s)
Hearing Loss, Sensorineural/epidemiology , Hearing Loss, Sensorineural/genetics , Mutation , Trans-Activators/genetics , Cohort Studies , Female , Humans , Japan/epidemiology , Male , PrevalenceABSTRACT
Complete or partial tetrasomy 21 has been reported only in rare cases. We report a Japanese female patient with tetrasomy 21 due to an extra chromosome derived from chromosome 21 (Chr21). The patient had severe psychomotor retardation without Down syndrome (DS) phenotype; she showed short stature, microcephaly, round face, cleft lip and palate, and other dysmorphic features. The chromosome analyses for the patient detected an extra dicentric Chr21 consisting of two partial Chr21 copies fused together within their long arms. Her karyotype was revealed to be 47,XX,+dic(21;21). Allelic ratios of heterozygous SNPs observed in the patient indicated the maternal origin of the extra Chr21. Copy number and structural variant analyses using whole genome sequencing data indicated that the distal breakpoint of the dicentric Chr21 was located within 21q21.3 and that the extra Chr21 did not simply consist of inverted duplications of the pterâq21.3 region, but likely contained multiple partial deletions, duplications, and inversions within it. Fluorescence in situ hybridization results were consistent with the karyotype and genomic analyses. The patient's lack of DS phenotype turned out to be due to the normal copy number of the DS critical region (21q22.13-22.3). A possible molecular mechanism leading to the complex genomic rearrangements in the tetrasomic region consists mainly of breakage-fusion-bridge cycles with an unequal crossing-over event.
Subject(s)
Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 21/genetics , Intellectual Disability/genetics , Tetrasomy , Child , Cleft Lip/genetics , Cleft Palate/genetics , Female , Humans , In Situ Hybridization, Fluorescence , Karyotype , Karyotyping , Microcephaly/genetics , Phenotype , Whole Genome SequencingABSTRACT
OBJECTIVE: In this study, we examine the relationship between developmental insufficiency of mastoid air cells and abnormal morphology of the paranasal sinuses in patients with chronic otitis media (COM) and acquired middle ear cholesteatoma (AMEC) using precise image assessment, in order to evaluate whether the anatomical features of paranasal sinuses has any impact on the pathogenesis in COM and AMEC. METHODS: A total of 127 patients, including 45 COM patients and 82 AMEC patients, were enrolled for this study. The existence of nasal septal deviation, the existence of paranasal sinus opacification, the modified Lund-Mackay score, the diameters of the paranasal sinuses, the Vidic classification, mastoid development, and cranial size were assessed by CT examination. A further 76 adult patients who underwent high-resolution CT imaging of their skull bone for other diseases were enrolled as the control. RESULTS: The AMEC group showed a significantly shorter sphenoid length (P < 0.01) and lower Vidic classification score (P < 0.01) compared to the control group in this study. In addition, we observed that patients with AMEC had less pneumatization of the mastoid air cells compared to the control individuals, and that the sphenoid length of the poor MC score group was significantly shorter than that of the good MC score group. CONCLUSION: Our results suggested that the developmental deficiency in sphenoid length caused by long-standing pediatric rhinosinusitis might indicate the potential of chronic middle ear inflammation in childhood and impact the pneumatization of mastoid air cells. Therefore, chronic rhinosinusitis during the childhood and adolescence might play a role in the pathophysiology of AMEC.
Subject(s)
Cholesteatoma, Middle Ear/complications , Otitis Media/complications , Rhinitis/complications , Sinusitis/complications , Sphenoid Sinus/growth & development , Adult , Aged , Aged, 80 and over , Cholesteatoma, Middle Ear/diagnostic imaging , Cholesteatoma, Middle Ear/pathology , Chronic Disease , Ethmoid Sinus/diagnostic imaging , Ethmoid Sinus/pathology , Female , Humans , Male , Middle Aged , Otitis Media/pathology , Sphenoid Sinus/diagnostic imaging , Sphenoid Sinus/pathology , Tomography, X-Ray Computed , Young AdultABSTRACT
BACKGROUND: Transoral surgery (TOS) has been widely applied for early T-stage head and neck cancer (HNC). The resection is performed with a minimum safety margin for function preservation under a limited surgical field; therefore, it is difficult to have a strong conviction about the complete resection. This study aims to evaluate the completeness of the initial TOS procedure; possibility of primary control by TOS alone; and predictive factors in patients with early T-stage laryngeal, oropharyngeal, and hypopharyngeal cancer. METHODS: Patients were treated by TOS at the primary site with or without neck dissection. The patients were divided into two groups based on the pathological evaluation of their surgical specimens: the control (observation) group, in that the resection was considered complete and the intervention (second-look procedure) group, in that incomplete tumor resection was suspected. The predictive factors for the possibility and/or limitations of complete resection by TOS were then analyzed. RESULTS: The study enrolled 26 and 25 patients in the control and intervention group, respectively. The success rate for single resection was 66% and the predictive factor was tumor depth obtained by enhanced computed tomography (CT) examination (odds ratio, 7.870, P = .0243). The success rate for definitive therapy by TOS alone was 83% and the predictive factor was poor differentiation observed on pathological examination (odds ratio, 6.800, P = .0248). CONCLUSIONS: TOS has the potential for both definitive resection and function preservation with minimal invasiveness. Identification of the risk factors for TOS is advantageous for accurate treatment selection in patients with early T-stage HNC.
Subject(s)
Hypopharyngeal Neoplasms/surgery , Laryngeal Neoplasms/surgery , Margins of Excision , Natural Orifice Endoscopic Surgery/methods , Oropharyngeal Neoplasms/surgery , Reoperation/methods , Aged , Aged, 80 and over , Disease-Free Survival , Female , Follow-Up Studies , Humans , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neck Dissection , Neoplasm Staging , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Prospective Studies , Risk FactorsABSTRACT
The OTOF gene (Locus: DFNB9), encoding otoferlin, is reported to be one of the major causes of non-syndromic recessive sensorineural hearing loss, and is also reported to be the most common cause of non-syndromic recessive auditory neuropathy spectrum disorder (ANSD). In the present study, we performed OTOF mutation analysis using massively parallel DNA sequencing (MPS). The purpose of this study was to reveal the frequency and precise genetic and clinical background of OTOF-related hearing loss in a large hearing loss population. A total of 2,265 Japanese sensorineural hearing loss (SNHL) patients compatible with autosomal recessive inheritance (including sporadic cases) from 53 otorhinolaryngology departments nationwide participated in this study. The mutation analysis of 68 genes, including the OTOF gene, reported to cause non-syndromic hearing loss was performed using MPS. Thirty-nine out of the 2,265 patients (1.72%) carried homozygous or compound heterozygous mutations in the OTOF gene. It is assumed that the frequency of hearing loss associated with OTOF mutations is about 1.72% of autosomal recessive or sporadic SNHL cases. Hearing level information was available for 32 of 39 patients with biallelic OTOF mutations; 24 of them (75.0%) showed profound hearing loss, 7 (21.9%) showed severe hearing loss and 1 (3.1%) showed mild hearing loss. The hearing level of patients with biallelic OTOF mutations in this study was mostly severe to profound, which is consistent with the results of past reports. Eleven of the 39 patients with biallelic OTOF mutations had been diagnosed with ANSD. The genetic diagnosis of OTOF mutations has significant benefits in terms of clinical decision-making. Patients with OTOF mutations would be good candidates for cochlear implantation; therefore, the detection of OTOF mutations is quite beneficial for patients, especially for those with ANSD.
Subject(s)
DNA Mutational Analysis , Hearing Loss, Sensorineural/genetics , High-Throughput Nucleotide Sequencing , Membrane Proteins/genetics , Mutation , Adult , Female , Hearing Loss, Sensorineural/diagnosis , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: Preoperative frailty affects the progression of cardiac rehabilitation (CR) after cardiovascular surgery. Different frailty assessment measures are available. However, it remains unclear which tool most likely predicts the progress of CR. Our aim was to evaluate preoperative frailty using different methods and to identify the predictors in the progress of postoperative CR. METHODS: Eighty-nine patients underwent elective cardiovascular surgery at our institution between May 2016 and April 2018. Mortality cases and patients without evaluation of preoperative frailty were excluded. This study included the remaining 78 patients. We divided the patients into two groups: 47 patients who achieved 100 m walking within 7 days after surgery (successful CR group) and 31 patients who achieved 100 m walking later than 8 days after surgery (delayed CR group). Preoperative frailty was assessed using the Kaigo-Yobo Check-List, Cardiovascular Health Study, Short Physical Performance Battery, and Clinical Frailty Scale. RESULTS: The prevalence of frailty defined by these four measures was higher in the delayed CR group. The delayed CR group had lower nutritional status, serum hemoglobin level, serum albumin level, and psoas muscle index. Multivariable analysis demonstrated the Kaigo-Yobo Check-List score as an independent predictor for delayed CR (odds ratio 1.53, 95% confidence interval 1.18-1.98, p = 0.001) and Clinical Frailty Scale as an independent predictor for discharge to a health care facility (odds ratio 3.70, 95% confidence interval 1.30-10.51, p = 0.014). CONCLUSIONS: Among the various tools for assessing frailty, the Kaigo-Yobo Check-List was most likely to predict the progress of postoperative CR after elective cardiovascular surgery.
Subject(s)
Cardiac Rehabilitation , Cardiovascular Surgical Procedures/rehabilitation , Checklist , Frailty/diagnosis , Geriatric Assessment/methods , Aged , Aged, 80 and over , Cardiovascular Surgical Procedures/adverse effects , Elective Surgical Procedures/adverse effects , Elective Surgical Procedures/rehabilitation , Female , Frail Elderly , Frailty/complications , Hemoglobins/metabolism , Humans , Male , Middle Aged , Nutritional Status , Patient Discharge , Postoperative Complications/etiology , Postoperative Period , Psoas Muscles , Serum Albumin/metabolism , Time Factors , Walk TestABSTRACT
The average lifespan of individuals with Down syndrome has approximately doubled over the past three decades to 55-60â¯years. To reveal the pathogenic process of Alzheimer-type dementia in individuals with Down syndrome, we immunohistochemically examined senile plaque formation in the cerebral cortex in the autopsy brain and compared findings with our previous studies. We described a 52-year-old female with Down syndrome who developed progressively more frequent myoclonus following cognitive decline and died at the age of 59â¯years. Her karyotype [46XX, inv(9)(p12q13), i(21)(q10)] included triplication of the gene for amyloid precursor protein and the Down syndrome critical region. On microscopy, very few gamma-aminobutyric acid-ergic (GABAergic) neurons, in the form of small granular cells, in the cortex and Purkinje cells in the cerebellum were visible. In our previous study, amyloid precursor protein immunoreactivity was first noted in senile plaques at the age of 32â¯years. In this patient, even though amyloid ß immunoreactivity was detected in the cores of senile plaques and diffuse plaques, amyloid precursor protein immunoreactivity was not noted in senile plaques in the frontal cortex. Amyloid precursor protein and its derivative amyloid-ß play an important role in the formation of senile plaques and the time course of immunoreactive expression may be related to the pathogenic process of Alzheimer-type dementia.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/metabolism , Brain/metabolism , Down Syndrome/metabolism , Plaque, Amyloid/metabolism , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Alzheimer Disease/pathology , Brain/diagnostic imaging , Brain/pathology , Down Syndrome/diagnostic imaging , Down Syndrome/genetics , Down Syndrome/pathology , Epilepsies, Myoclonic/diagnostic imaging , Epilepsies, Myoclonic/genetics , Epilepsies, Myoclonic/metabolism , Epilepsies, Myoclonic/pathology , Fatal Outcome , Female , Humans , Middle Aged , Plaque, Amyloid/diagnostic imaging , Plaque, Amyloid/genetics , Plaque, Amyloid/pathologyABSTRACT
BACKGROUND: We confirmed the safety of postoperative bio-chemoradiotherapy using cetuximab and docetaxel in a small number of patients with cis-platinum-intolerant core high-risk head and neck cancer. OBJECTIVE: To assess treatment efficacy, we planned a phase 2 study of postoperative bio-chemoradiotherapy for patients with cis-platinum-intolerant core high-risk head and neck cancer and will compare the results to those of previously collected radiotherapy data. METHODS: Patients who underwent definitive surgery for oral cavity, laryngeal, oropharyngeal, or hypopharyngeal advanced cancer, whose postoperative pathological results indicated core high risk for recurrence (eg, positive margin in the primary site or extranodal extension) and who were cis-platinum-intolerant, will undergo postoperative bio-chemoradiotherapy. The primary end point is 2-year disease-free survival. RESULTS: The expected 2-year disease-free survival is set at 55%, and the calculated sample size is 35 patients, according to a statistical analysis based on previous reports. CONCLUSIONS: This treatment method is expected to improve the survival rate of patients with severe head and neck cancer. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000031835; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000036355 (Archived by WebCite at http://www.webcitation.org/71fejVjMr).
ABSTRACT
OBJECTIVE: Progression of cardiac rehabilitation after cardiovascular surgery can be affected by frailty. The nutritional status of the patient has been proposed as an indicator of frailty. In this study, we aimed to evaluate the influence of preoperative nutritional status on the progress of postoperative cardiac rehabilitation. METHODS: This study included 146 patients (82 males, 64 females, average age 71.9 ± 12.0 years) who underwent elective cardiovascular surgery. In-hospital mortality cases were excluded to focus on postoperative cardiac rehabilitation. We classified patients with a Geriatric Nutritional Risk Index of 92 or higher as the good nutrition group and those with a Geriatric Nutritional Risk Index less than 92 as the malnutrition group. Preoperative patient characteristics and postoperative cardiac rehabilitation progress were compared between the good nutrition (n = 93) and malnutrition (n = 53) groups. RESULTS: The patients in the good nutrition group had an earlier progression to walking after postoperative rehabilitation (p = 0.002), a shorter postoperative hospital stay (p = 0.004), and a higher rate of discharge home (p = 0.028) than those in the malnutrition group. Multivariable analysis demonstrated preoperative malnutrition to be an independent predictor for the day to 100 m walking (p = 0.010). CONCLUSIONS: Preoperative nutritional status was associated with progression of postoperative cardiac rehabilitation.