Exploring the relationship between plasma substance P and glottal incompetence in the elderly.

We speculated that increased blood-plasma levels of Substance P may serve as an indicator of glottal incompetence, which is usually indicated by reduced maximum phonation time. We performed an initial study to test the plausibility of this hypothesis. Patients with dysphonia caused by glottal incompetence were asked to perform vocal exercises for six months to reduce glottal incompetence and we compared the plasma concentration of Substance P before and after the vocal exercise to detect correlation between maximum phonation time and plasma concentration of Substance P. Based on the results, we further hypothesized that patients exhibiting dysphonia with maximum phonation time less than 14 s, in particular less than 10 sec, caused by glottal incompetence may have increased plasma concentration of Substance P with the results of elevated thresholds of cough reflex associated with subclinical aspiration in airways. Further study is needed on patients with decreased Substance P levels, with low scores on Activities of Daily Living and who are hospitalized with aspiration pneumonia.

Exploration of tumor size measurement methods in preoperative breast cancer assessment using whole-body silicon photomultiplier PET: feasibility and first results.

PURPOSE: Whole-body silicon photomultiplier positron emission tomography (WB SiPM PET) could be used to diagnose breast cancer spread before lumpectomy. We aimed to investigate the method of measuring the tumor size by WB SiPM PET as a basis for diagnosing breast cancer spread in the breast. MATERIALS AND METHODS: We retrospectively reviewed 35 breast cancer lesions in 32 patients who underwent WB SiPM PET/CT in the prone position as preoperative breast cancer examinations from September 2020 to March 2022. In all cases, a 20-mm spherical VOI was placed in the normal mammary gland to measure the mean standardised uptake value (SUVmean) and the standard deviation (SD) of 18F-fluorodeoxyglucose (FDG) uptake. We prepared four types of candidates (SUVmean + 2 SD, SUVmean + 3 SD, 1.5 SUVmean + 2 SD, 1.5 SUVmean + 3 SD) for thresholds for delineating tumor contours on PET images. On the semiautomatic viewer soft, the maximum tumor sizes were measured at each of the four thresholds and compared with the pathological tumor sizes, including the extensive intraductal component (EIC). RESULTS: The lesion detection sensitivity was 97% for WB SiPM PET. PET detected 34 lesions, excluding 4-mm ductal carcinomas in situ (DCIS). PET measurements at the '1.5 SUVmean + 2 SD' threshold demonstrated values closest to the pathological tumor sizes, including EIC. Moreover, '1.5 SUVmean + 2 SD' had the highest concordance (63%). CONCLUSIONS: The study demonstrated that among various PET thresholds, the '1.5 SUVmean + 2 SD' threshold exhibited the best performance. However, even with this threshold, the concordance rate was limited to only 63%.

[A case of rectal cancer with immune thrombocytopenic purpura that achieved a complete response to continued chemotherapy with eltrombopag].

A 73-year-old male patient with postoperative recurrent rectal cancer developed thrombocytopenia after XELOX therapy. Thrombocytopenia persisted despite chemotherapy discontinuation;therefore, he was referred to our department for further evaluation. Bone marrow specimen examination revealed increased immature megakaryocytes and blood test results revealed elevated platelet-associated immunoglobulin G (PA-IgG) levels, leading to immune thrombocytopenic purpura diagnosis. His platelet count recovered after prednisolone therapy. Eltrombopag treatment was introduced considering thrombocytopenia secondary to chemotherapy resumption for rectal cancer. FOLFIRI therapy was continued without platelet count reduction, and PA-IgG levels decreased over time. The patient continued chemotherapy with eltrombopag and achieved a complete treatment response.

A case of breast cancer: Suppression of lactation-related FDG uptake 2 days after cabergoline administration.

We present a case of a 35-year-old woman with breast cancer in lactation 3 months after childbirth, in which a lactation inhibitor was useful for 18F-FDG PET/CT examination. Via ultrasonography and biopsy with histopathology, we diagnosed the lesion in the upper region of the left breast as invasive ductal carcinoma. She stopped breastfeeding and was administered cabergoline to suppress lactation. Two days after the administration, 18F-FDG PET/CT revealed segmental uptake (10 cm in diameter) and no lactation-related uptakes. Dynamic MRI also revealed a segmental enhancement of the same size as 18F-FDG PET/CT. The lactation inhibitor was useful to delineate the extent of the lesion during the 18F-FDG PET/CT examination.

The Incidence of Serious/Invasive Bacterial Diseases in Infants 90 Days Old or Younger at an Emergency Hospital in Japan.

Background The incidence of severe bacterial infections (SBIs) in infants aged ≤90 days is thought to have decreased because of widespread vaccination programs. However, relevant epidemiological data in Japan are scarce. Materials and methods This observational, single-center study investigated the epidemiology of fever in infants aged ≤90 days. SBI was defined as the presence of meningitis, urinary tract infections (UTIs), or bacteremia. Invasive bacterial infection (IBI) was defined as the presence of meningitis, bacteremic UTI, or bacteremia. We determined the incidence of UTIs, bacteremia, meningitis, SBIs, and IBIs in the following three age groups: 0-28, 29-60, and 61-90 days. We subsequently calculated the relative incidence for the groups aged 29-60 and 61-90 days, using the group aged 0-28 days as the reference group.  Results Herein, 58, 124, and 166 infants were included in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. Of the total number of patients, 15.5%, 8.9%, and 16.9% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with SBI. The relative incidences were 1 for the 0-28 days group (reference group), 0.67 for the 29-60 days group (95% confidence interval [CI], 0.39-1.15), and 1.08 for the 61-90 days group (95% CI, 0.58-2.00). Of the total number of patients, 10.3%, 3.2%, and 0.6% in the 0-28 days, 29-60 days, and 61-90 days age groups, respectively, were diagnosed with IBI. Relative incidences were 1 (reference group), 0.50 (95% CI, 0.29-0.88), and 0.28 (95% CI, 0.19-0.41) for the 0-28 days, 29-60 days, and 61-90 days age groups, respectively. All cases of IBI were caused by Group B streptococcus (GBS), except for two cases of bacteremia, which were caused by Haemophilus influenzae.  Conclusion The incidence of SBI was similar in the 0-28 days and 61-90 days age groups. However, the incidence of IBI decreased with increasing age. The incidence of UTIs was highest in the 61-90 days age group, and that of meningitis and bacteremia decreased with increasing age.

Cardiac features of Noonan syndrome in Japanese patients.

BACKGROUND: Cardiovascular disease is one of the most important problems in long-term follow-up for Noonan syndrome. We examined cardiovascular issues and clinical manifestations, with a focus on the cardiovascular disease and prognosis of patients with Noonan syndrome. METHODS: This single-centre study evaluated patients who were clinically and genetically diagnosed with Noonan syndrome. RESULTS: Forty-three patients diagnosed with Noonan syndrome were analysed. The most prevalent responsible mutation was found in PTPN11 (25/43). The second and third most prevalent causative genes were SOS1 (6/43) and RIT1 (5/43), respectively, and 67.4% of genetically diagnosed patients with Noonan syndrome had structural cardiovascular abnormalities. Pulmonary valve stenosis was prevalent in patients with mutations in PTPN11 (8/25), SOS1 (4/6), and RIT1 (4/5). Hypertrophic cardiomyopathy was found in two of three patients with mutations in RAF1. There was no difference in the cardiovascular events or cardiovascular disease prevalence in patients with or without PTPN11 mutations. The proportion of RIT1 mutation-positive patients who underwent intervention due to cardiovascular disease was significantly higher than that of patients with PTPN11 mutations. Patients who underwent any intervention for pulmonary valve stenosis exhibited significantly higher pulmonary flow velocity than patients who did not undergo intervention, when they visited our hospital for the first time. All patients who underwent intervention for pulmonary valve stenosis had a pulmonary flow velocity of more than 3.0 m/s at first visit. CONCLUSIONS: These findings suggest that genetic information can provide a clinical prognosis for cardiovascular disease and may be part of genotype-based follow-up in Noonan syndrome.

Electrocardiographic Changes with Age in Japanese Patients with Noonan Syndrome.

Little information is available on age-related electrocardiographic changes in patients with Noonan syndrome. This single-center study evaluated the electrocardiograms of patients with Noonan syndrome. We divided the patients (n = 112; electrocardiograms, 256) into four groups according to age: G1 (1 month-1 year), G2 (1-6 years), G3 (6-12 years), and G4 (>12 years). Typical Noonan syndrome-related electrocardiographic features such as left-axis deviation, abnormal Q wave, wide QRS complex, and small R wave in precordial leads were detected. A high percentage of QRS axis abnormalities was found in all groups. Significant differences in right-axis deviation (RAD) were noted among the groups: 56.5% of G1 patients showed RAD compared with 33.3% of G2, 21.1% of G3, and 19.2% of G4 patients. The small R was also significantly different among the groups: 32.6% of G1 patients showed a small R wave compared with 14.9% of G2, 8.5% of G3, and 15.4% of G4 patients. Of the 53 patients with Noonan syndrome aged 1 month to 2 years, 18 had T-positive V1 with a higher prevalence of pulmonary stenosis and cardiac interventions. QRS axis abnormalities, small R in V6, and T-positive V1 could help diagnose Noonan syndrome in infants or young children.

[Angioimmunoblastic T-cell lymphoma after immune checkpoint inhibitor-combined chemotherapy for lung cancer].

A 68-year-old male patient with lung adenocarcinoma, who was treated with chemotherapy and immune checkpoint inhibitors (ICIs), developed lymphadenopathy during treatment. His para-aortic lymph nodes increased to 2.0 cm in diameter. Both inguinal lymph nodes were 1.5 cm in diameter, and multiple hepatic masses appeared. After the ICI readministration, both inguinal lymph nodes increased to 2.0 cm in diameter, but the para-aortic lymph nodes and hepatic masses remained. Angioimmunoblastic T-cell lymphoma (AITL) diagnosis was established after the right inguinal lymph node biopsy, which was accompanied by an infiltration of Epstein-Barr virus (EBV)-encoded small ribonucleic acid-positive B-cells. After the ICI discontinuation, the inguinal lymph nodes decreased to 1.5 cm in diameter, but the para-aortic lymph nodes remained, and hepatic masses increased. Hepatic lesions were possibly lung cancer metastasis. The ICI administration and EBV reactivation were potentially associated with AITL development in the present case. The natural shrinkage of lymphoma after the ICI cessation implied the immunological mechanism like that of the methotrexate-related lymphoproliferative disease.

Association between a single mother family and childhood undervaccination, and mediating effect of household income: a nationwide, prospective birth cohort from the Japan Environment and Children's Study (JECS).

BACKGROUND: Although childhood undervaccination among single mother families is a concern for child healthcare, their association is still under debate. This study aimed to investigate the association between maternal marital status and the risk of childhood undervaccination and determine the mediating effect of household income. METHODS: We utilised prospective birth cohort from the Japan Environment and Children's Study (JECS). Of 104,062 foetal records (children) from 97,413 mothers, 82,462 that included mothers recruited between 2011 and 2014, were analysed. Childhood undervaccination was defined as not having been vaccinated with at least one routine vaccine. A log-binomial regression analysis was used to estimate the risk ratio (RR) for the association between maternal marital status and the risk of childhood undervaccination. A causal mediation analysis was further performed to investigate the proportion of the association mediated by household income. RESULTS: Among 82,462 children, 3188 and 79,274 had unmarried and married mothers, respectively. Childhood undervaccination was observed in 1053 (33.0%) and 16,901 (21.3%) children of unmarried and married mothers, respectively. Maternal marital status was associated with a higher risk of childhood undervaccination (adjusted risk ratio [aRR], 1.34; 95% confidence interval [CI], 1.27 to 1.41). Compared with married and older mothers, both unmarried and older (aRR, 1.54; 95% CI, 1.35 to 1.77) and unmarried and younger (aRR, 1.66; 95% CI, 1.54 to 1.79) mothers were associated with a higher risk of childhood undervaccination. The causal mediation analysis showed that the proportion mediated by household income was 10.5% (95% CI, 9.9 to 11.0%). CONCLUSIONS: This nationwide, prospective, large-scale birth cohort study found that a household with a single mother was associated with an increased risk of childhood undervaccination, and 10% of this association was explained by household income. These findings underscore the importance of improving the social environment among single mother families, including not only poverty but also working conditions.

Successful combination treatment with transcatheter balloon atrioseptostomy and bilateral pulmonary artery banding in a collapsed preterm neonate.

There has been an increase in the use of extracorporeal membrane oxygenation for severe neonatal cardiac failure. However, the frequency of complications is high, particularly in preterm and low-birth-weight neonates. Herein, we present combination treatment with transcatheter balloon atrioseptostomy and bilateral pulmonary artery banding in a collapsed preterm neonate. This strategy can be an alternative to circulatory support using extracorporeal membrane oxygenation.

Real-world Evidence of Diffusion-weighted Imaging Combined With Magnetic Resonance Cholangiopancreatography for Pancreatic Tumor Screening: A Cross-Sectional Diagnostic Accuracy Study.

OBJECTIVES: The aim was to clarify the sensitivity and specificity of diffusion-weighted imaging, as well as of that in combination with magnetic resonance cholangiopancreatography for pancreatic tumor diagnosis in real-world clinical setting. METHODS: Subjects were 217 consecutive patients who underwent both magnetic resonance imaging and contrast-enhanced ultrasound sonography. Cases positive for a pancreatic tumor were confirmed based on pathological diagnosis, whereas negative cases were defined when no solid pancreatic tumor was detected by contrast-enhanced ultrasound sonography or a solid mass was detected but the diagnosis was ultimately denied based on pathological results. Diffusion-weighted imaging-positive was defined as a case with high signals and magnetic resonance cholangiopancreatography-positive when localized main pancreatic duct stenosis with caudal dilation was detected.We calculated sensitivity and specificity of each modality and those in combination based on sequential use for pancreatic tumor diagnosis. RESULTS: Diffusion-weighted imaging showed a sensitivity of 94.4% and specificity of 94.5%, whereas those values for magnetic resonance cholangiopancreatography alone were 83.3% and 99.0%, respectively, and for the modalities in combination were 100% and 94.5%, respectively. CONCLUSIONS: Diffusion-weighted imaging was more sensitive than magnetic resonance cholangiopancreatography, whereas those used in combination resulted in increased sensitivity.

Seroma formation after modified Blalock-Taussig shunt which caused shock due to pulmonary vein compression.

Seroma formation is a relatively rare complication seen after a modified Blalock-Taussig shunt. Herein, we report a rare case of seroma formation on the posterior aspect of the left atrium without it touching the graft, and presenting with shock, due to pulmonary vein compression.

Risk factors and preventive measures for C5 palsy after cervical open-door laminoplasty.

OBJECTIVE: The pathomechanism of C5 palsy after cervical open-door laminoplasty is unknown despite the relatively common occurrence of this condition postoperatively. The aim of this study was to review clinical and imaging findings in patients with C5 palsy and to propose countermeasures for prevention of this complication. METHODS: Between 2001 and 2018, 326 patients with cervical myelopathy underwent cervical laminoplasty at the authors' hospital, 10 (3.1%) of whom developed C5 palsy. Clinical features and radiological findings of patients with and without C5 palsy were analyzed. RESULTS: In patients with C5 palsy, the width of the C5 intervertebral foramen was narrower and the position of the bony gutter was wider beyond the medial part of the C5 facet joint. The distance between the lateral side of the spinal cord and bony gutter was significantly greater in patients with C5 palsy. Patient characteristics, disease, cervical alignment, spinal canal expansion rate, anterior protrusion of the C5 superior articular process, high-intensity area in the spinal cord on T2-weighted MR images, posterior shift of the spinal cord, and operative time did not differ significantly between patients with and without C5 palsy. CONCLUSIONS: The position of the bony gutter may have a central role in the pathomechanism of postoperative C5 palsy, especially in patients with a narrow C5 intervertebral foramen. Making an excessively lateral bony gutter might be a cause of C5 nerve root kinking at the intervertebral foramen. To prevent the occurrence of C5 palsy, it is important to confirm the medial line of the facet joint on the preoperative CT scan, and a high-speed burr should be started from inside of the facet joint and manipulated in a direction that allows the ligamentum flavum to be identified.

Exploring the Relation between Glottal Closure and Plasma Substance P: A Study Protocol.

Glottal incompetence, i.e., reduced ability to produce effective glottal closure, is a problem often associated with aging. The study protocol is presented to determine whether blood substance P (SP) serves as an indicator of glottal closure function among the elderly. SP is involved in the neuromuscular mechanisms of cough; reduced concentration of SP may be a marker for increased risk of aspiration pneumonia. The antihypertensive angiotensin-converting enzyme inhibitor, which also inhibits degradation of SP, has been found to be effective in preventing aspiration pneumonia by strengthening the cough reflex. In this study, we will employ National Hospital Organization self-controlled vocal exercise (NHOEx), which has been shown to improve glottal closure by strengthening the laryngeal adduction muscles. We hypothesize that improved glottal closure by NHOEx may lead to the increase in the plasma concentration of SP, which reflects effective cough reflex. Maximum phonation time (MPT), an indicator of glottal closure, will be measured to assess improvement of glottis-closing function. The study will include 180 patients over 65 years old with dysphonia, dysphagia, or MPT of less than 15 seconds. Based on the speculation that the improved MPT may be associated with changes in SP expression, we will measure the plasma SP before and after 6-month treatment of glottal incompetence using NHOEx. The goal is to verify the reliability of SP as an indicator for glottal closure and swallowing function. Measurement of plasma SP may be helpful for earlier detection of subjects with higher risk of aspiration pneumonia among the elderly.

Feasibility of the imatinib stop study in the Japanese clinical setting: delightedly overcome CML expert stop TKI trial (DOMEST Trial).

BACKGROUND: Treatment-free remission (TFR), the ability to maintain a molecular response (MR), occurs in approximately 50% of patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs). METHODS: A multicenter phase 2 trial (Delightedly Overcome CML Expert Stop TKI Trial: DOMEST Trial) was conducted to test the safety and efficacy of discontinuing imatinib. Patients with CML with a sustained MR of 4.0 or MR4.0-equivalent for at least 2 years and confirmed MR4.0 at the beginning of the study were enrolled. In the TFR phase, the international scale (IS) was regularly monitored by IS-PCR testing. Molecular recurrence was defined as the loss of MR4.0. Recurrent patients were immediately treated with dasatinib or other TKIs including imatinib. RESULTS: Of 110 enrolled patients, 99 were evaluable. The median time from diagnosis to discontinuation of imatinib was 103 months, and the median duration of imatinib therapy was 100 months. Molecular recurrence-free survival rates were 69.6%, 68.6% and 64.3% at 6, 12, and 24 months, respectively. After discontinuation of imatinib therapy, 26 patients showed molecular recurrence, and 25 re-achieved deep MR after dasatinib treatment. Molecular response MR4.0 was achieved in 23 patients within 6 months and 25 patients within 12 months. Multivariate analysis revealed that a longer time from diagnosis to discontinuation of imatinib therapy (p = 0.0002) and long duration of imatinib therapy (p = 0.0029) predicted a favorable prognosis. CONCLUSIONS: This DOMEST Trial showed the feasibility of TKI discontinuation in a Japanese clinical setting.

Verification of a false positive in a two-year rat carcinogenicity study using dual control groups.

There is sometimes controversy over whether or not statistically significant responses produced in carcinogenicity studies have biologically significance. Ambiguous results from our previous two-year oral carcinogenicity study on acotiamide hydrochloride hydrate (acotiamide-HH), a prokinetic drug for functional dyspepsia, in rats made it unclear whether the drug may exhibit uterine carcinogenicity. To check this finding, we performed a second long-term carcinogenicity study using two identical control groups to more accurately evaluate uterine carcinogenesis by considering the incidence of spontaneous neoplasms. Female Fischer 344 rats were divided into three groups: the two control groups (control 1 and 2) were administered vehicle (0.5% w/v methylcellulose) and the acotiamide-HH-treated group was administered 2,000 mg/kg/day of acotiamide-HH by oral gavage for two years. Among all groups, the incidence of endometrial adenocarcinoma (EmA) was highest in the control 2 group, followed by the acotiamide-HH-treated group and the control 1 group. Moreover, acotiamide-HH did not affect the incidence of precursor lesions of EmA. In cases where an ambiguous difference is observed, the use of two control groups allows for a more informed interpretation of the findings in the drug-treated groups. The outcomes in this study strongly support the hypothesis that the increase in EmA in rats treated with acotiamide-HH in our previous study is unrelated to administration of the drug.

Vocal Hygiene Education Program Reduces Surgical Interventions for Benign Vocal Fold Lesions: A Randomized Controlled Trial.

OBJECTIVES/HYPOTHESIS: Vocal fold polyps and nodules are common benign laryngeal lesions. Currently, the Japanese health insurance system covers surgical interventions. However, the establishment of more cost-effective conservative methods is required, because healthcare costs are viewed as a major concern, and the government and taxpayers are demanding more economical, effective treatments. In this situation, more suitable vocal hygiene education may be important for the success of cost-effective conservative treatment. In this study, we developed a novel reinforced vocal hygiene education program and compared the results of this program with those of previous methods of teaching vocal hygiene. STUDY DESIGN: Multicenter randomized controlled trial. METHODS: Patients who visited a National Hospital Organization (NHO) hospital for the surgical indication of hoarseness were included in the study. Before undergoing surgery, 200 patients with benign vocal fold lesions (vocal fold polyps/nodules) were enrolled and randomly allocated to the NHO-style vocal hygiene educational program (intervention group) or control education program (control group). Two months after enrollment, the patients in both groups underwent laryngeal fiberscopic examinations to determine whether the benign lesions had resolved or whether surgery was indicated for the vocal fold polyps/nodules. RESULTS: After 2 months, in the intervention group, the proportion of lesion resolution (61.3%) was significantly greater than that in the control group (26.3%) (P < .001, Fisher exact test). CONCLUSIONS: Our results clearly indicate that the quality and features of the education program could affect the outcome of the intervention. We found that a reinforced vocal hygiene education program increased the rate of the resolution of benign vocal fold polyps and nodules in a multicenter randomized clinical trial. LEVEL OF EVIDENCE: 1b Laryngoscope, 2593-2599, 2018.

Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia.

OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89.0%, respectively. Patients with comorbidities (46.4%) and aged ≥60 years (50.4%) at diagnosis had significantly inferior OS to those without comorbidities and aged <60. Patients achieved higher rates of major molecular response (MMR) at 6 and 12 months after initial treatment with dasatinib or nilotinib compared to imatinib, but final MMR rates were almost the same. Sixty-six percent of patients required treatment modifications from first-line TKI therapy; the main reasons were AEs (48.4%) and failure (18%). Grade III-IV AEs in first-line TKI therapy were significantly correlated to inferior OS/EFS compared to grade 0-II AEs. CONCLUSION: Although long-term outcomes were similar in CML-CP patients treated with each TKI regardless of first-line TKI selection, severe AEs in first-line TKI therapy decreased their survival rates. Early change in TKIs is recommended, when faced with severe AEs of specific TKIs.