Successful Treatment of Mucus Plug Due to Allergic Bronchopulmonary Aspergillosis Using Dupilumab.

Allergic bronchopulmonary aspergillosis (ABPA) often necessitates treatment with systemic steroids and antifungals, which are associated with relapses and side effects. We report an 82-year-old woman with eosinophilic asthma, experiencing sputum production and dyspnea, who was diagnosed with ABPA based on her chest CT, pulmonary function tests, and elevated blood eosinophils and immunoglobulin E. Due to the presence of osteoporosis and diabetes, standard steroid therapy was considered a high risk. Instead, we administered dupilumab, an interleukin 4 receptor alpha (IL4-Rα) antibody targeting Th2 cytokine signaling. Remarkable improvements were observed within two weeks, including reduced sputum and dyspnea. After 12 weeks, significant enhancements in asthma control and lung function, along with decreased fractional exhaled nitric oxide (FeNO) levels were noted, with chest CT showing resolution of most of the mucus plugs. This case demonstrates dupilumab's potential as a viable ABPA treatment alternative, particularly for patients who are unsuitable for systemic steroids. More research on the long-term effectiveness and safety of such biologics is needed.

Injury prevalence and associated factors among Japanese lacrosse collegiate athletes.

Context: Sports injuries have a substantial impact on athletes' performance and health. To reduce the risk of an injury occurring, the prevalence, localization, and severity need to be established. Objective: To examine the prevalence of sports injuries in collegiate lacrosse athletes. Design: Descriptive epidemiological study using online survey design. Setting: Japanese universities associated with UNIVAS. Participants: A total of 1,689 Japanese collegiate lacrosse athletes, 978 females and 701 males. Main outcome measures: Athletes were surveyed on the injuries within the previous year, their severity, localization, and onset characteristics. The support of an athletic trainer and its association with the odds of sustaining an injury was assessed. Factors related to injuries were explored. Results: One-year prevalence of injuries was 42%. Male sex, higher year at the university, and support from an athletic trainer were identified as factors related to higher odds of sustaining an injury and practicing at least 5 days per week was associated with lower odds of sustaining an injury. Conclusions: Male sex athletes, and athletes at the higher year at university are especially at risk of sustaining a lacrosse injury. The aspects of training (e.g., frequency, volume) should be investigated across the athlete development process to address these findings. Further investigation is needed to determine the extent to which the support of athletic trainers affects both the frequency and severity of injuries in lacrosse athletes.

Prognostic significance of immunohistochemical classification utilizing biopsy specimens in patients with extensive-disease small-cell lung cancer treated with first-line chemotherapy and immune checkpoint inhibitors.

PURPOSE: Although immune checkpoint inhibitors (ICIs), together with cytotoxic chemotherapy (chemoimmunotherapy), have been adapted for the initial treatment of extensive-disease small-cell lung cancer (ED-SCLC), they have achieved limited success. In ED-SCLC, a subtype of SCLC, the expression of immune-related molecules and clinical data are not well understood in relation to ICI treatment efficiency. METHODS: We examined lung biopsy specimens from patients diagnosed with ED-SCLC treated with chemoimmunotherapy or chemotherapy. SCLC subtype, expression of HLA class I, and infiltration of CD8-positive cells were examined using immunohistochemistry (IHC). Subsequently, the association between clinical factors, IHC results, and progression-free survival or overall survival was assessed. RESULTS: Most of the cases showed the achaete-scute homolog 1 (ASCL1) subtype. Among the 75 SCLC cases, 29 expressed high levels of HLA class I, while 46 showed low levels or a negative result; 33 patients were characterized as CD8-high, whereas 42 were CD8-low. In the chemoimmunotherapy cohort, multivariate analysis revealed a correlation between CD8-high and improved survival. Specifically, patients in the CD8-high group of the chemoimmunotherapy cohort experienced enhanced survival compared to those in the chemotherapy cohort, which was attributed to ICI addition. IHC subtype analysis demonstrated a survival advantage in the SCLC-I and SCLC-A groups when ICI was combined with chemotherapy compared to chemotherapy alone. CONCLUSION: Our study highlights the predictive value of IHC-classified subtypes and CD8-positive cell infiltration in estimating outcomes for patients with ED-SCLC treated with chemoimmunotherapy as a first-line therapy. These findings have practical implications for daily clinical assessments and treatment decisions.

Sputum colour: An indicator of Legionella pneumophila pneumonia.

The sputum colour in patients with severe pneumonia needs to be considered during diagnosis.

Transbronchial cryobiopsy for small peripheral pulmonary lesions using endobronchial ultrasonography and an ultrathin bronchoscope.

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.

Do standardization of the procedure reduce measurement variability of the sonographic anterior drawer test of the ankle?

BACKGROUND: In quantitative ankle stress sonography, different examiners use different techniques, which may cause measurement variability. This study aimed to clarify whether standardizing stress sonography techniques reduces variability in the quantitative measurement of anterior talofibular ligament length change. METHODS: Fourteen examiners with a mean ultrasound experience of 8.7 years participated in this study. Each examiner performed stress ultrasonography of the ankle using their preferred method on one patient with an intact anterior talofibular ligament (Patient 1) and on two patients with chronic ankle instability (Patient 2 and 3). Changes in the ligament length between the resting and stressed positions were determined. A consensus meeting was then conducted to standardize the sonographic technique, which was used by the examiners during a repeat stress sonography on the same patients. The variance and measured values were compared between the preferred and standardized techniques using F-tests and paired t-tests, respectively. RESULTS: At a consensus meeting, a sonographic technique in which the examiner pushed the lower leg posteriorly against the fixed foot was adopted as the standardized technique. In Patient 1, the change in the anterior talofibular ligament length was 0.4 (range, -2.3-1.3) mm and 0.6 (-0.6-1.7) mm using the preferred and standardized techniques, respectively, with no significant difference in the variance (P = 0.51) or the measured value (P = 0.52). The length changes in Patient 2 were 2.0 (0.3-4.4) mm and 1.7 (-0.9-3.8) mm using the preferred and standardized techniques, respectively. In Patient 3, the length changes were 1.4 (-2.7-7.1) mm and 0.7 (-2.0-2.3) mm. There were no significant differences between the techniques in either patient group. CONCLUSION: Variability in the quantitative measurement of ankle stress sonography was not reduced despite the standardization of the technique among examiners. Hence, comparing the measured values between different examiners should be avoided.

Modulation of host glutamine anabolism enhances the sensitivity of small cell lung cancer to chemotherapy.

Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of ∼7%. Here, we performed a targeted proteomics analysis of human SCLC samples and thereby identified hypoxanthine phosphoribosyltransferase 1 (HPRT1) in the salvage purine synthesis pathway as a factor that contributes to SCLC malignancy by promoting cell survival in a glutamine-starved environment. Inhibition of HPRT1 by 6-mercaptopurine (6-MP) in combination with methotrexate (MTX), which blocks the de novo purine synthesis pathway, attenuated the growth of SCLC in mouse xenograft models. Moreover, modulation of host glutamine anabolism with the glutamine synthetase inhibitor methionine sulfoximine (MSO) in combination with 6-MP and MTX treatment resulted in marked tumor suppression and prolongation of host survival. Our results thus suggest that modulation of host glutamine anabolism combined with simultaneous inhibition of the de novo and salvage purine synthesis pathways may be of therapeutic benefit for SCLC.

Histological and immunohistochemical prognostic factors of primary angiosarcoma.

Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70 years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p < 0.0001), size ≥ 5 cm (p = 0.0388), no taxane chemotherapy (p = 0.0388), strong nuclear atypia (p = 0.0087), and the presence of luminal structure in ≥ 50% of the tumor volume (p = 0.0009) were independent poor prognostic factors. Among angiosarcomas with luminal formation, mFNCLCC scores were significantly correlated with a poorer prognosis. The overexpression of p16 was associated with less luminal formation (p = 0.0192). Immunohistochemical analysis of C-MYC showed a moderate level of concordance with FISH (Kappa value = 0.45). This study suggested that luminal formation and nuclear atypia may be poor histological prognostic factors of angiosarcoma and that mFNCLCC would be useful for predicting the prognosis of angiosarcoma with luminal formation.

Estimation of maximal lactate steady state using the sweat lactate sensor.

A simple, non-invasive algorithm for maximal lactate steady state (MLSS) assessment has not been developed. We examined whether MLSS can be estimated from the sweat lactate threshold (sLT) using a novel sweat lactate sensor for healthy adults, with consideration of their exercise habits. Fifteen adults representing diverse fitness levels were recruited. Participants with/without exercise habits were defined as trained/untrained, respectively. Constant-load testing for 30 min at 110%, 115%, 120%, and 125% of sLT intensity was performed to determine MLSS. The tissue oxygenation index (TOI) of the thigh was also monitored. MLSS was not fully estimated from sLT, with 110%, 115%, 120%, and 125% of sLT in one, four, three, and seven participants, respectively. The MLSS based on sLT was higher in the trained group as compared to the untrained group. A total of 80% of trained participants had an MLSS of 120% or higher, while 75% of untrained participants had an MLSS of 115% or lower based on sLT. Furthermore, compared to untrained participants, trained participants continued constant-load exercise even if their TOI decreased below the resting baseline (P < 0.01). MLSS was successfully estimated using sLT, with 120% or more in trained participants and 115% or less in untrained participants. This suggests that trained individuals can continue exercising despite decreases in oxygen saturation in lower extremity skeletal muscles.

Pneumocystis Pneumonia Infection Following the Initiation of Pembrolizumab Therapy for Lung Adenocarcinoma.

Pneumocystis pneumonia (PCP) is an opportunistic infection that presents a ground-glass appearance in the lungs on chest radiography. Interstitial lung disease is a commonly reported adverse effect of immune checkpoint inhibitor (ICI) treatment; however, there are few reports of ICI treatment-associated PCP infection. A 77-year-old man with lung adenocarcinoma was administered pembrolizumab and hospitalized for dyspnea 2 weeks after treatment. Chest computed tomography showed bilateral ground-glass opacities in all lung lobes. PCP was therefore diagnosed, and steroids and sulfamethoxazole-trimethoprim were initiated. Following treatment, the patient's condition improved promptly. This report suggests that ICI treatment can cause PCP infection.

Severe heart failure due to peripartum cardiomyopathy.

Perinatal cardiomyopathy presents similarly to dilated cardiomyopathy and should be suspected in perinatal women presenting with dyspnoea, even with no previous history of heart disease.

Comparison of Akt/mammalian target of rapamycin/4E-binding protein 1 pathway signal activation in round stromal and surface cells in patients with sclerosing pneumocytoma.

Sclerosing pneumocytoma (SP) is a rare benign epithelial tumor of the lung, and approximately 40 % of patients with SP present with AKT1 E17K mutation. SP cells comprise proliferated surface and round stromal cells. To elucidate the role of signal transductions and to identify the difference between surface and stromal cells, the current study aimed to investigate the activation of the Akt/mammalian target of rapamycin (mTOR)/4E-binding protein 1 signaling pathway in SP. METHODS: The molecular and pathological characteristics of SP in 12 patients were analyzed. AKT1 gene analysis revealed AKT1 E17K mutation in four cases. Immunohistochemical analysis revealed that tumor cells were cytoplasmic positive for pAkt, pmTOR, p4EBP1, and pS6RP. The surface cells had a significantly higher expression of pmTOR (p = 0.002) and a significantly lower expression of p4EBP1 (p = 0.017) than stromal cells. SP without AKT1 E17K mutation had a higher positive correlation with pacts, p4EBP1, pmTOR, and pS6RP expression than SP with AKT1 E17K mutation. These findings may be attributed to the aberrant activation of the Akt/mTOR pathway due to AKT1 E17K mutations. Hence, both surface and round stromal cells have tumorigenic characteristics, and differences in these characteristics may contribute to variations in tumor growth and the morphology and angiogenesis of SP.

Diagnostic utility of ERG immunostaining in dermatofibroma.

AIMS: Dermatofibroma/fibrous histiocytoma (DF/FH) is a common cutaneous mesenchymal neoplasm exhibiting benign biological behaviour. However, the immunohistochemical utility of erythroblast transformation-specific-related gene (ERG) for diagnosing DF remains unknown. The authors reviewed the immunohistochemical status of ERG in different subtypes of DF and in its differential diagnoses. METHODS: Overall, 97 cases of ordinary DF/FH, 6 cases of aneurysmal FH, 10 cases of cellular FH, 5 cases of angiomatoid FH, 2 cases of epithelioid FH, 64 cases of dermatofibrosarcoma protuberans (DFSP) and 52 cases of fibrous scar were retrieved. As the other histological types of cutaneous neoplasms, 6 cases of myxofibrosarcoma, 4 cases of undifferentiated pleomorphic sarcoma, 11 cases of atypical fibroxanthoma, 19 cases of malignant melanoma, 20 cases of nevocellular nevus, 20 cases of neurofibroma, 19 cases of schwannoma, 8 cases of angioleiomyoma and 1 case of pilar leiomyoma were included. RESULTS: Immunohistochemical positivity for ERG was demonstrated in 87 of 97 cases (89.6%) of ordinary DF/FH, 7 of 10 cases (70%) of cellular FH, 3 of 6 cases (50%) of aneurysmal FH, 1 of 5 cases (20%) of angiomatoid FH and 1 of 52 cases (0.1%) of fibrous scar. All cases of DFSP, epithelioid FH and other types of cutaneous neoplasms included in the current investigation were negative for ERG. The intensity of ERG immunohistochemical staining in spindle-shaped cells appeared weaker than that in endothelial cells. CONCLUSIONS: DF/FH was frequently positive for ERG immunostaining. ERG immunostaining may thus be useful to distinguish DF/FH from DFSP.

Cerebral Glucose Metabolism in Patients with Chronic Disorders of Consciousness.

OBJECTIVE: To measure regional cerebral metabolic rate of glucose (CMRGlu) in patients with chronic disorders of consciousness (DOCs) using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: This retrospective cohort study examined 50 patients (mean age: 40.9 ± 20.1 years) with traumatic brain injury (TBI)-induced chronic DOCs [minimally conscious state (MCS)+, n = 20; MCS-, n = 15 and vegetative state (VS), n = 15]. We measured FDG-PET-based CMRGlu values in 12 regions of both brain hemispheres and compared those among MCS+, MCS - and VS patients. RESULTS: In both hemispheres, the regional CMRGlu reduced with consciousness deterioration in 11 of 12 regions (91.7%). In seven right hemisphere regions, CMRGlu values were markedly higher in MCS+ patients than in MCS- patients. Furthermore, CMRGlu was suggestively higher in the left occipital region in MCS- patients than in VS patients. CONCLUSION: Functional preservation in the left occipital region in patients with chronic DOCs might reflect an awareness of external environments, whereas extensive functional preservation in the right cerebral hemisphere might reflect communication motivation.

Expression of SATB2, RUNX2, and SOX9 and possible osteoblastic and chondroblastic differentiation in chondroblastoma.

Chondroblastoma (CB) is histologically characterized by oval to polygonal-shaped mononuclear neoplastic cells, multinucleated osteoclastic giant cells, and eosinophilic matrix with occasional calcification. Genetically, the majority of CBs harbor H3F3B p.K36M mutation. Despite the historical nomenclature, it has been reported that the matrix of CB is similar to osteoid rather than true cartilage; however, it remains unclear whether neoplastic cells in CB have the potential for osteoblastic differentiation. To clarify this issue, we immunohistochemically examined the expression of osteogenic and chondrogenic markers (SATB2, RUNX2, p63, and SOX9) as well as H3K36M mutant protein in 33 cases of CB. All 33 cases of CB were positive for H3K36M, while SATB2, RUNX2, p63, and SOX9 were expressed in 30/33 (91%), 33/33 (100%), 29/33 (88%), and 31/32 (97%) CB cases, respectively. Our immunohistochemical results suggest that neoplastic cells in CB frequently express both osteogenic and chondrogenic markers and may have an intermediate feature of osteoblastic and chondroblastic nature.

Prevalence of and Factors Associated with Sports Injuries in 11,000 Japanese Collegiate Athletes.

BACKGROUND: To establish the 1-year prevalence of sports injuries and explore associations of various factors with a sports injury in Japanese collegiate athletes. METHODS: The data were collected through a web-based survey of Japanese collegiate athletes associated with UNIVAS (Japan Association for University Athletics and Sport). The survey questions asked about athletes' personal characteristics, sports participation, and injuries sustained within the previous year. Follow-up questions on the details regarding the three most serious injuries were asked. Differences in proportions of athlete characteristics between males and females and between injured and uninjured were explored with the chi-square test. Factors associated with sustaining an injury were determined with regression analysis. RESULTS: The prevalence of injuries among Japanese collegiate athletes is high, and most of the sustained injuries require athletes to take a considerable time off training and competition indicating their severity. Athletes from year two and higher at the university, overweight or obese, training more often per week, and with longer sports experience were more likely to sustain an injury within the previous year. CONCLUSIONS: There is compelling evidence to suggest that excessive training and insufficient recovery may be contributing to their increased risk of injury. These findings underscore the importance of implementing evidence-based training programs and recovery strategies to mitigate injury risk and optimize performance outcomes among this population.

Relation of overall tumor burden with severe immune-related adverse events in nivolumab plus ipilimumab treatment for lung cancer.

Compared to chemotherapy alone, monoclonal antibodies like ipilimumab and nivolumab, with or without chemotherapy, improve the prognosis of patients with non-small cell lung cancer (NSCLC), albeit with a higher incidence of immune-related adverse events (irAEs) than those with immune checkpoint inhibitor (ICI) monotherapy. Therefore, we aimed to investigate if baseline overall tumor burden was associated with the development of Grade ≥ 3 irAEs (severe irAEs) when treated with first-line ipilimumab plus nivolumab with or without chemotherapy.We retrospectively examined consecutive patients with advanced NSCLC who received nivolumab plus ipilimumab with or without chemotherapy at Hakodate Goryoukaku Hospital between December 2020 and December 2021. Baseline overall tumor burden was measured as the sum of unidimensional diameters of up to five target lesions according to the Response Evaluation Criteria in Solid Tumors, version 1.1. We defined irAEs as ICI therapy-related toxicities according to the Common Terminology Criteria for Adverse Events, version 5.0.A significant difference in tumor burden was observed between patients with and without severe irAEs (100 mm vs. 67.5 mm, p = 0.001). We evaluated various clinical parameters, including baseline overall tumor burden, before treatment initiation. Of the various parameters, only high tumor burden correlated with severe irAEs, independent of complementary chemotherapy. The multivariate odds ratio of severe irAEs and high tumor burden was 6.62.Conclusively, baseline overall tumor burden may be a risk factor for severe irAEs in patients treated with first-line combination ICI therapy. Therefore, patients with large tumor burden should be carefully monitored to prevent irAEs.