Diagnostic yields and safety of thoracoscopic cryobiopsies in Japan: A single-center retrospective observational study.

BACKGROUND: Thoracoscopy is useful for diagnosing unexplained pleural effusions. A sufficient specimen volume is often difficult to obtain using forceps biopsies (FBs) but can be obtained with pleural cryobiopsies (CBs). This study aimed to assess the utility and safety of CB during thoracoscopy in the Japanese population. METHODS: Patients who underwent thoracoscopic CBs at the Japanese Red Cross Medical Center between January 2017 and August 2023 were included in the study. Data were retrospectively analyzed, including clinical data, thoracoscopic findings, specimen size, diagnostic yield, and complications. The number of collected specimens and the freezing time were left to the discretion of the attending physician. RESULTS: Twenty-six patients underwent thoracoscopic CB. Specimens obtained by CB were larger than those obtained by FB. Primary lung cancer was the most common cause of pleural effusion, followed by malignant pleural mesothelioma. CB contributed to the diagnosis in 24 of 26 cases (92.3%) and FB contributed to the diagnosis in 11 of 18 cases (61.1%). Severe fibrosis could be diagnosed in all 3 cases by CB, but not by FB. The common complications of CB included bleeding at the biopsy site and atelectasis, but no severe complications occurred. CONCLUSIONS: The utility and safety of thoracoscopic CB for diagnosing pleural effusions in Japan were verified. The diagnostic yield, specimen size, and safety profile of CB support the diagnostic utility of this method.

Two cases of airway-centered fibroelastosis treated with an antifibrotic agent and corticosteroids.

Airway-centered fibroelastosis is characterized by peribronchovascular fibroelastosis, predominantly in the upper lobes, with little-to-no pleural involvement. In this study, we describe two cases of airway-centered fibroelastosis diagnosed based on radiological and pathological findings. The first case comprised a 44-year-old man whose forced vital capacity improved over three months following treatment with nintedanib. The second case involved a 50-year-old woman who was treated with oral corticosteroids but yielded an unfavorable outcome. An effective treatment for airway-centered fibroelastosis has not yet been identified; therefore, this study may help contribute to a more thorough discussion regarding treatment strategies for this disease.

Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

Diagnostic accuracy of direct reverse transcription-polymerase chain reaction using guanidine-based and guanidine-free inactivators for SARS-CoV-2 detection in saliva samples.

This study aimed to evaluate diagnostic accuracy of SARS-CoV-2 RNA detection in saliva samples treated with a guanidine-based or guanidine-free inactivator, using nasopharyngeal swab samples (NPS) as referents. Based on the NPS reverse transcription-polymerase chain reaction (RT-PCR) results, participants were classified as with or without COVID-19. Fifty sets of samples comprising NPS, self-collected raw saliva, and saliva with a guanidine-based, and guanidine-free inactivator were collected from each group. In patients with COVID-19, the sensitivity of direct RT-PCR using raw saliva and saliva treated with a guanidine-based and guanidine-free inactivator was 100.0%, 65.9%, and 82.9%, respectively, with corresponding concordance rates of 94.3% (κ=88.5), 82.8% (κ=64.8), and 92.0% (κ=83.7). Among patients with a PCR Ct value of <30 in the NPS sample, the positive predictive value for the three samples was 100.0%, 80.0%, and 96.0%, respectively. The sensitivity of SARS-CoV-2 RNA detection was lower in inactivated saliva than in raw saliva and lower in samples treated with a guanidine-based than with a guanidine-free inactivator. However, in individuals contributing to infection spread, inactivated saliva showed adequate accuracy regardless of the inactivator used. Inactivators can be added to saliva samples collected for RT-PCR to reduce viral transmission risk while maintaining adequate diagnostic accuracy.

Imaging of 17O-labeled Water Using Fast T2 Mapping with T2-preparation: A Phantom Study.

17O-labeled water is a T2-shortening contrast agent used in proton MRI and is a promising method for visualizing cerebrospinal fluid (CSF) dynamics because it provides long-term tracking of water molecules. However, various external factors reduce the accuracy of 17O-concentration measurements using conventional signal-intensity-based methods. In addition, T2 mapping, which is expected to provide a stable assessment, is generally limited to temporal-spatial resolution. We developed the T2-prepared based on T2 mapping used in cardiac imaging to adapt to long T2 values and tested whether it could accurately measure 17O-concentration in the CSF using a phantom. The results showed that 17O-concentration in a fluid mimicking CSF could be evaluated with an accuracy comparable to conventional T2-mapping (Carr-Purcell-Meiboom-Gill multi-echo spin-echo method). This method allows 17O-imaging with a high temporal resolution and stability in proton MRI. This imaging technique may be promising for visualizing CSF dynamics using 17O-labeled water.

Atelocollagen-associated autologous chondrocyte implantation for the repair of large cartilage defects of the knee: Results at three to seven years.

BACKGROUND: Recently, various types of engineered autologous chondrocyte implantation (ACI) have been developed. Atelocollagen-associated ACI (A-ACI) is the only ACI procedure covered by Japanese Health Insurance since 2013. The indications of the A-ACI are traumatic cartilage defects and osteochondral dissecans (OCD) for knee joints. PURPOSE: To evaluate midterm clinical results after A-ACI for the treatment for full-thickness cartilage defects of the knee. METHODS: Thirteen consecutive patients who underwent A-ACI between 2014 and 2018 had been prospectively enrolled in this study. There were 11 men and 2 women with a mean age of 34 years at the time of surgery. The causes of the cartilage defect were trauma in 10 knees and OCD in 3 knees. The total number of lesions was 15, which were comprised of the medial femoral condyle in 5 knees, the lateral femoral condyle in 5 knees, and the femoral trochlea in 5 knees. The mean size of the lesion was 5.3 cm2. Each knee was clinically and radiologically evaluated preoperatively and postoperatively. RESULTS: The mean Lysholm score improved significantly from 74.0 points to 94.0 points (p = 0.008) and each subscale in Knee injury and Osteoarthritis Outcome Score improved significantly (p < 0.001) at the mean final follow-up period of 51 months (range, 36-84 months). The magnetic resonance observation of cartilage repair tissue 2.0 score at the mean follow-up of 38 months was significantly higher than that at 2 months postoperatively (p = 0.014). According to the International Cartilage Repair Society (ICRS) grading scale, 3 knees were graded as normal, 3 knees as nearly normal, and 1 knee as severely abnormal in second-look arthroscopic evaluation at a mean of 22 months (range, 8-41 months) after A-ACI. CONCLUSION: The present study showed a significant subjective and objective clinical improvement in the A-ACI for large cartilage defects of the knee at a mean follow-up of 51 months (range, 36-84 months).

Triplet dynamic nuclear polarization of pyruvate via supramolecular chemistry.

Dynamic nuclear polarization (DNP) significantly improves the sensitivity of magnetic resonance imaging, and its most important medical application is cancer diagnosis via hyperpolarized 13C-labeled pyruvate. Unlike cryogenic DNP, triplet-DNP uses photoexcited triplet electrons under mild conditions. However, triplet-DNP of pyruvate has not been observed because of incompatibility of the hydrophobic polarizing agent with hydrophilic pyruvate. This work demonstrates that supramolecular complexation with ß-cyclodextrin can disperse 4,4'-(pentacene-6,13-diyl)dibenzoate (NaPDBA), a pentacene derivative with hydrophilic substituents, even in the presence of high sodium pyruvate concentrations. The polarization of photoexcited triplet electron spins in NaPDBA was transferred to the 13C spins of sodium pyruvate via triplet-DNP of 1H spins in water and 1H-to-13C cross-polarization. This provides an important step toward the widespread use of ultra-sensitive MRI for cancer diagnosis.

Polarizing agents beyond pentacene for efficient triplet dynamic nuclear polarization in glass matrices.

Triplet dynamic nuclear polarization (triplet-DNP) is a technique that can obtain high nuclear polarization under moderate conditions. However, in order to obtain practically useful polarization, large single crystals doped with a polarizing agent must be strictly oriented with respect to the magnetic field to sharpen the electron spin resonance (ESR) spectra, which is a fatal problem that prevents its application to truly useful biomolecular targets. Instead of this conventional physical approach of controlling crystal orientation, here, we propose a chemical approach, i.e., molecular design of polarizing agents; pentacene molecules, the most typical triplet-DNP polarizing agent, are modified so as to make the triplet electron distribution wider and more isotropic without loss of the triplet polarization. The thiophene-modified pentacene exhibits a sharper and stronger ESR spectrum than the parent pentacene, and state-of-the-art quantum chemical calculations revealed that the direction of the spin polarization is altered by the modification with thiophene moieties and the size of D and E parameters are reduced from parent pentacene due to the partial delocalization of spin densities on the thiophene moieties. The triplet-DNP with the new polarizing agent successfully exceeds the previous highest 1H polarization of glassy materials by a factor of 5. This demonstrates the feasibility of a polarizing agent that can surpass pentacene, the best polarizing agent for more than 30 y since triplet-DNP was first reported, in the unoriented state. This work provides a pathway toward practically useful high nuclear polarization of various biomolecules by triplet-DNP.

Clinical utility of single-shot echo-planar diffusion-weighted imaging using L1-regularized iterative sensitivity encoding in prostate MRI.

We investigated the ability of echo-planar imaging with L1-regularized iterative sensitivity encoding-based diffusion-weighted imaging (DWI) to improve the image quality and reduce the scanning time in prostate magnetic resonance imaging. We retrospectively analyzed 109 cases of prostate magnetic resonance imaging. We compared variables in the quantitative and qualitative assessments among 3 imaging groups: conventional parallel imaging-based DWI (PI-DWI) with an acquisition time of 3 minutes 15 seconds; echo-planar imaging with L1-regularized iterative sensitivity encoding-based DWI (L1-DWI) with a normal acquisition time (L1-DWINEX12) of 3 minutes 15 seconds; and L1-DWI with a half acquisition time (L1-DWINEX6) of 1 minute 45 seconds. As a quantitative assessment, the signal-to-noise ratio (SNR) of DWI (SNR-DWI), the contrast-to-noise ratio (CNR) of DWI (CNR-DWI), and the CNR of apparent diffusion coefficient were measured. As a qualitative assessment, the image quality and visual detectability of prostate carcinoma were evaluated. In the quantitative analysis, L1-DWINEX12 showed significantly higher SNR-DWI than PI-DWI (P = .0058) and L1-DWINEX6 (P < .0001). In the qualitative analysis, the image quality score for L1-DWINEX12 was significantly higher than those of PI-DWI and L1-DWINEX6. A non-inferiority assessment demonstrated that L1-DWINEX6 was non-inferior to PI-DWI in terms of both quantitative CNR-DWI and qualitative grading of image quality with a <20% inferior margin. L1-DWI successfully demonstrated a reduced scanning time while maintaining good image quality.

High-flow nasal cannula for severe COVID-19 patients in a Japanese single-center, retrospective, observational study: 1 year of clinical experience.

High-flow nasal cannula (HFNC) can be effective in treating type 1 respiratory failure by reducing the severity of coronavirus disease 2019 (COVID-19). The purpose of this study was to assess the reduction of disease severity and safety of HFNC treatment in patients with severe COVID-19. We retrospectively observed 513 consecutive patients with COVID-19 admitted to our hospital from January 2020 to January 2021. We included patients with severe COVID-19 who received HFNC for their deteriorating respiratory status. HFNC success was defined as improvement in respiratory status after HFNC and transfer to conventional oxygen therapy, while HFNC failure was defined as transfer to non-invasive positive pressure ventilation or ventilator, or death after HFNC. Predictive factors associated with failure to prevent severe disease were identified. Thirty-eight patients received HFNC. Twenty-five (65.8%) patients were classified in the HFNC success group. In the univariate analysis, age, history of chronic kidney disease (CKD), non-respiratory sequential organ failure assessment (SOFA) ≥ 1, oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) before HFNC ≤ 169.2, were significant predictors of HFNC failure. Multivariate analysis revealed that SpO2/FiO2 value before HFNC ≤ 169.2 was an independent predictor of HFNC failure. No apparent nosocomial infection occurred during the study period. Appropriate use of HFNC for acute respiratory failure caused by COVID-19 can reduce the severity of severe disease without causing nosocomial infection. Age, history of CKD, non-respiratory SOFA before HFNC ≤ 1, and SpO2/FiO2 before HFNC ≤ 169.2 were associated with HFNC failure.

Clinical usefulness of end-tidal CO2 measured using a portable capnometer in patients with respiratory disease.

INTRODUCTION: This study aimed to evaluate the correlation and agreement between end-tidal CO2 (EtCO2 ) measured with the novel portable capnometer (CapnoEye®) and partial pressure of arterial carbon dioxide (PaCO2 ) levels in patients with respiratory diseases and to compare the efficacy of EtCO2 and PvCO2 in predicting PaCO2 levels. METHODS: We analyzed the correlation and the agreement between EtCO2 and PaCO2 and between PvCO2 and PaCO2 using Pearson's moment correlation coefficient in patients with type 1 and type 2 respiratory failure and both groups overall. RESULTS: A total of 100 samples were included that comprised 67 men (67%). The mean age of the subjects was 77 ± 13 years. Chronic obstructive pulmonary disease (COPD) (43%) was the most common disease. There was a high correlation between EtCO2 and PaCO2 (r = 0.88; p < 0.0001). Sixty-six PvCO2 samples were obtained, and there was a high correlation between PvCO2 and PaCO2 (r = 0.81; p < 0.0001). Regarding type 2 respiratory failure, there was a high correlation between EtCO2 and PaCO2 (r = 0.81). The Bland-Altman analysis between PaCO2 and EtCO2 revealed a bias of 5.7 mmHg, with limits of agreement ranging from -5.1 mmHg to 16.5 mmHg. In contrast, the analysis between PaCO2 and PvCO2 revealed a bias of -6.8 mmHg, and the limits of agreement ranged from -22.13 mmHg to 8.53 mmHg. CONCLUSION: EtCO2 measured by CapnoEye® was significantly correlated to PaCO2 levels in patients with respiratory diseases. Moreover, CapnoEye® may be more useful for predicting hypercapnia conditions in which respiratory diseases are compared with measure PvCO2 .

Adult T-cell leukemia/lymphoma complicated by Pneumocystis pneumonia in a non-endemic area.

Adult T-cell leukemia/lymphoma (ATLL) is a human T-cell leukemia virus type 1-inducing unevenly-distributed T-cell malignancy, which is often complicated by opportunistic infections. Here, we discuss the case of a 75-year-old woman presenting with Pneumocystis pneumonia (PCP) who was subsequently diagnosed with ATLL in Tokyo, a non-endemic area of ATLL. In addition to the elevated soluble interleukin-2 receptor and the detection of flower cells in the screening blood test, the high-resolution computed tomography findings, atypical of PCP, were clues to the diagnosis of ATLL. ATLL should be considered as an underlying disease when patients present with PCP, even in non-endemic areas.

Digoxigenin-labeled RNA probes for untranslated regions enable the isoform-specific gene expression analysis of myosin heavy chains in whole-mount in situ hybridization.

Myosin heavy chains (MyHCs), which are encoded by myosin heavy chain (Myh) genes, are the most abundant proteins in myofiber. Among the 11 sarcomeric Myh isoform genes in the mammalian genome, seven are mainly expressed in skeletal muscle. Myh genes/MyHC proteins share a common role as force producing units with highly conserved sequences, but have distinct spatio-temporal expression patterns. As such, the expression patterns of Myh genes/MyHC proteins are considered as molecular signatures of specific fiber types or the regenerative status of mammalian skeletal muscles. Immunohistochemistry is widely used for identifying MyHC expression patterns; however, this method is costly and is not ideal for whole-mount samples, such as embryos. In situ hybridization (ISH) is another versatile method for the analysis of gene expression, but is not commonly applied for Myh genes, partly because of the highly homologous sequences of Myh genes. Here we demonstrate that an ISH analysis with the untranslated region (UTR) sequence of Myh genes is cost-effective and specific method for analyzing the Myh gene expression in whole-mount samples. Digoxigenin (DIG)-labeled antisense probes for UTR sequences, but not for protein coding sequences, specifically detected the expression patterns of respective Myh isoform genes in both embryo and adult skeletal muscle tissues. UTR probes also revealed the isoform gene-specific polarized localization of Myh mRNAs in embryonic myofibers, which implied a novel mRNA distribution mechanism. Our data suggested that the DIG-labeled UTR probe is a cost-effective and versatile method to specifically detect skeletal muscle Myh genes in a whole-mount analysis.

Rheumatologic manifestations with elevated levels of IL-6, IL-17A, and IL-23 in a patient with scurvy.

Symptomatic vitamin C deficiency, scurvy, is a relatively rare disease in developed countries, but it has been reported in patients with autism spectrum disorder or developmental delay who tend to have selective diets. Patients with scurvy often demonstrate musculoskeletal manifestations with unknown pathophysiology. Herein, we report a case of scurvy in an 11-year-old boy who presented with iron-deficiency anaemia, systemic osteomyelitis, myositis predominantly in the lower extremities, and right ventricular volume overload with mild pulmonary hypertension and was diagnosed with scurvy. He had a mild developmental disorder and a selective diet, which resulted in severe vitamin C deficiency. He received intravenous and oral vitamin C supplementation, which relieved his arthralgia and muscle pain in a week. Following 4 months of vitamin C supplementation, he demonstrated no abnormal manifestations on laboratory or imaging examination and recovered without sequelae. Inflammatory cytokine and chemokine evaluations demonstrated elevated levels of interleukin (IL)-6, IL-17A, and IL-23, which are associated with T-helper (Th) 17 cell activation. This study is the first to suggest the association between the inflammation seen in scurvy, rheumatic manifestations in the patient, and Th17 cell activation. Further analysis of the association between the inflammation and vitamin C supplementation may contribute to new insights for the comprehension and treatment of other inflammatory diseases, such as rheumatic diseases.

Efficacy and safety of sotrovimab for vaccinated or unvaccinated patients with mild-to-moderate COVID-19 in the omicron era.

Although sotrovimab, one of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies has been shown to be effective in patients with mild-to-moderate coronavirus disease 2019 (COVID-19) with risk factors, their efficacy in mRNA COVID-19 vaccinated patients in omicron era is unknown. To evaluate the effectiveness of sotrovimab clinical data from both COVID-19 vaccinated and unvaccinated patients who were hospitalized and receiving sotrovimab at the Japanese Red Cross Medical Center were compared. The efficacy and adverse events were evaluated. Of the total 60 patients enrolled in this study, 45 had received the mRNA COVID-19 vaccine and 15 were unvaccinated. The clinical progression with low nasal cannula or face mask was not significantly different between groups (occurring in one patient in each group; p = 0.44), with no further progression in both groups. The duration of hospitalization was eight days for both groups (p = 0.90). Two patients in each group experienced adverse events (7%, p = 0.26). The results suggested that the efficacy and safety of sotrovimab against mild-to-moderate COVID-19 with risk factors in the omicron era might not be different regardless of the vaccination status. The results of the present study are encouraging; however, further randomized clinical studies are needed.

Pulmonary amyloidosis diagnosed via transbronchial lung cryobiopsy without surgical lung biopsy: A case series.

Pulmonary amyloidosis is a rare disease characterized by abnormal extracellular deposition of amyloid fibril in the lung tissue, and the identification of amyloid deposits is essential for its diagnosis. Surgical lung biopsy (SLB) is a standard diagnostic method for pulmonary amyloidosis. However, it has a relatively high post-procedural mortality rate. Recently, transbronchial lung cryobiopsy (TBLC) has been gradually used for diagnosing interstitial lung disease. However, its diagnostic efficacy for pulmonary amyloidosis has not yet been validated. Here, we describe two cases of pulmonary amyloidosis with deposition of amyloid light chain detected via TBLC. Since SLB is a high-risk procedure for the patients due to age and complications, TBLC was performed. Both patients presented with Congo red-positive amyloid deposits. One patient with localized pulmonary amyloidosis had a good clinical course without therapeutic intervention and was followed up. The other with systemic amyloidosis received chemotherapy and presented with a stable clinical course. TBLC can collect a larger pulmonary specimen for pulmonary amyloidosis than forceps biopsy and has fewer complications and a lower mortality rate than SLB. Thus, it can be a diagnostic method for pulmonary amyloidosis.

Nuclear protein of the testis midline carcinoma of the thorax.

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor that typically presents in the head, neck, and chest region. NMC is characterized by rearrangement of the NUTM1 gene. It mainly affects children and young adults and is rapidly progressive and lethal. Reportedly, the prognoses of NMCs of the head and neck improve following aggressive initial surgical resection +/- postoperative chemoradiotherapy (CRT) or radiotherapy (RT). However, as NMC of the thorax was identified later, treatments to improve its prognosis are yet to be identified. Our review reveals that NMC is an extremely rare cancer, and most patients remain undiagnosed. Furthermore, this review outlines the clinical characteristics of NMC of the thorax and the prospects for its treatment.

Clinical outcomes of corticosteroids for COVID-19 patients at the National Center for Global Health and Medicine during the first wave of infections.

BACKGROUND: Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2, has been a significant concern worldwide since its outbreak in December 2019. Various treatments are being researched and developed, and there are reports that dexamethasone has reduced the mortality rate and improved the clinical course of critically ill patients with COVID-19. In this study, we examined the clinical efficacy of corticosteroid therapy for patients with COVID-19 in our hospital during the first wave of infections. METHODS: We retrospectively reviewed the medical records of patients with COVID-19 who were treated with or without corticosteroid therapy at the National Center for Global Health and Medicine in Japan between February and April 2020. The primary outcome was improvement in the patients' clinical course using a seven-category ordinal scale. We collected data on patient characteristics, treatment, and clinical course, and compared them between two groups: the steroid-using group and the non-steroid-using group. RESULTS: Between February and April 2020, 110 patients were diagnosed with COVID-19. Despite poor conditions during admission into the steroid group, there were no statistical differences in clinical course between both groups, as measured using the scale. There were no statistical differences between the two groups in the number of days to fever resolution or negative polymerase chain reaction results. CONCLUSIONS: There was no difference in the clinical course between both groups. Because of the difference in background, corticosteroids may potentially make the clinical course of severely ill patients similar to that of mildly ill patients.

Favorable effects of burosumab on tumor-induced osteomalacia caused by an undetectable tumor: A case report.

RATIONALE: Tumor-induced osteomalacia (TIO) is curable by tumor resection, but detection of the tumor can be challenging. Overproduction of fibroblast growth factor 23 (FGF23) by the tumor causes hypophosphatemia and consequently induces inappropriate bone turnover. Conventionally oral phosphate supplementation was the only treatment for TIO, but had risks of hypercalciuria and nephrocalcinosis. Burosumab, a human monoclonal anti-FGF23 antibody, was recently post-marketed in Japan against for FGF23-related hypophosphatemia. Herein, we present a case of TIO with undetectable tumor that was successfully treated with burosumab. PATIENT CONCERNS: A 47-year-old woman was forced to use a wheelchair because of pain in both feet. DIAGNOSIS: Laboratory findings showed hypophosphatemia, elevated bone markers, and high serum FGF23 without renal tubular defects. Imaging studies revealed bone atrophy in the feet, decreased bone density, and multiple pseudofractures in the talar, sacral, and L5 vertebral regions. After excluding drug-induced and hereditary osteomalacia, we diagnosed her as TIO. INTERVENTIONS: Comprehensive imaging studies and stepwise venous sampling failed to localize the tumor, and we started to administer subcutaneous burosumab. OUTCOMES: After administration of burosumab, her serum phosphate was normalized without phosphate supplementation within 2 months. Improvement of pseudofractures, relief of pain evaluated by a visual analog scale, and normalization of bone biomarkers were observed. The patient was able to stand by herself after 6 months administration of burosumab. LESSONS: This is the first report in clinical practice to demonstrate favorable effects of burosumab, including not only normalization of serum phosphate but also improvements of pseudofractures and subjective pain, in a patient with TIO and undetectable tumor.

Usefulness of Jackson mask ventilation during bronchoscopy in patients with acute respiratory failure: A retrospective review.

ABSTRACT: Bronchoscopy is a procedure for diagnosis and treatment decision-making in patients with lung disease, especially those with acute respiratory failure. However, the optimal bronchoscopic method for patients with acute respiratory failure is not known. Therefore, in the real world, we sometimes hesitate to perform bronchoscopy in such patients because of safety and have experienced treating patients without bronchoscopy. To address this problem, we evaluated the usefulness and safety of Jackson mask ventilation, a novel noninvasive method of bronchoscopy performed under mask ventilation using the Jackson Rees circuit, in patients with acute respiratory failure.We retrospectively reviewed patients with acute respiratory failure who underwent bronchoscopy at our institution between January 2015 and May 2018. We compared patients who received Jackson mask ventilation (Jackson group) and those who received conventional oxygen administration (conventional group). Mean percutaneous oxygen saturation (SpO2) and mean oxygen flow rate were compared between the groups by the Wilcoxon signed-rank test. We excluded patients who were intubated and those without acute respiratory failure who received Jackson mask ventilation preventively.Of 1262 patients who underwent bronchoscopy, 12 were classified into the Jackson group and 13 into the conventional group. Proper oxygenation was maintained in the Jackson group, with SpO2 increasing after Jackson mask ventilation (89.4% to 96.8%, P = .03). Mean SpO2 was significantly higher in the Jackson group than in the conventional group (96.8% vs 95.2%, P = .03). Mean oxygen flow rate was significantly lower in the Jackson group (4.0 L/min vs 7.9 L/min, P < .001). There was no significant difference in safety.Our findings suggest that Jackson mask ventilation is safe and effective when performing bronchoscopy in patients with acute respiratory failure. Jackson mask ventilation maintained proper oxygenation and decreased the oxygen flow rate compared with the conventional method. Using Jackson mask ventilation, we could perform bronchoscopy safely and effectively in patients with acute respiratory failure, including some who had unstable respiratory status. (UMIN000038481).