Letermovir prophylaxis for cytomegalovirus in lung-transplant recipients: a comprehensive study with literature review of off-label use and real-world experiences.

Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in lung-transplant (LTx) recipients. Given the high susceptibility of LTx recipients to CMV infection, this study explores the effectiveness and safety of letermovir prophylaxis. A retrospective analysis of using letermovir for LTx recipients at Tohoku University Hospital (January 2000 to November 2023) was conducted. Case summaries from other Japanese transplant centers and a literature review were included. Six cases at Tohoku University Hospital and one at Kyoto University Hospital were identified. Prophylactic letermovir use showed positive outcomes in managing myelosuppression and preventing CMV replication. The literature review supported the safety of letermovir in high-risk LTx recipients. Despite limited reports, our findings suggest letermovir's potential as prophylaxis for LTx recipients intolerant to valganciclovir. Safety, especially in managing myelosuppression, positions letermovir as a promising option. However, careful consideration is important in judiciously integrating letermovir into the treatment protocol.

Native-lung complications following single-lung transplantation for interstitial lung disease: an in-depth analysis.

BACKGROUND: Interstitial lung disease (ILD) represents a heterogeneous group of lung disorders characterized by fibrotic lung tissue changes. In regions with severe donor shortages, single-lung transplantation (SLTx) is often preferred over bilateral lung transplantation for advanced ILD. However, temporal changes and complications in the retained native lung remain poorly understood. METHODS: A retrospective analysis of 149 recipients who had undergone SLTx was conducted, including 34 ILD SLTx recipients. Native-lung volume, radiological alterations, and perfusion were assessed at distinct post-SLTx time points. Statistical analyses compared ILD and non-ILD SLTx groups. RESULTS: Our study revealed a progressive reduction in native-lung volume over time, accompanied by radiographic deterioration and declining perfusion. Complications in the retained native lung were observed, such as pneumothorax (29.4%), pulmonary aspergillosis (11.8%), and acute exacerbation (8.9%). Long-term survival rates were similar between ILD and non-ILD SLTx recipients. CONCLUSIONS: This study illuminates the unique challenges and complications with respect to the native lung following SLTx for ILD. Ongoing monitoring and tailored management are essential. Despite limitations, this research contributes to our understanding of the temporal progression of native-lung complications post-SLTx for ILD, underscoring the need for further investigation.

A Single-Center Analysis of How HLA Mismatch and Donor-Specific Antibodies Affect Short-Term Outcome After Lung Transplantation: A Pilot Study Before a Country-Wide Histocompatibility Study in Japan.

BACKGROUND: Analyzing HLA polymorphism in lung transplantation (LTx) is important, given its impact on LTx recipient survival and graft function. Accordingly, we conducted a retrospective study to examine the influence of HLA mismatch and donor-specific antibodies (DSA) on short-term outcomes and early-phase post-LTx complications. METHOD: HLA antigen or eplet mismatch in LTx patients at Tohoku University Hospital from 2018 to 2023 was determined, and DSA was measured on admission for surgery to identify preformed DSA and at weeks 4 to 12 post-LTx for de novo DSA, respectively. RESULTS: The participants were 45 LTx recipients, HLA-A/B/DR antigen mismatch (5-6 of 6) being identified in 57%, HLA-A/B/Cw/DR/DQ mismatch (8-10 of 10) in 57%, and HLA eplet mismatch (>61) in 46%. The prevalence of preformed DSA was 24%, and persistence (uncleared) was 16%. The incidence of de novo DSA was 16% after LTx. During the study,16 recipients experienced grade 3 primary graft dysfunction (PGD), 8 developed acute rejection, and 5 died. No HLA-related variables were significantly associated with post-LTx mortality and were not risk factors for high-grade PGD or acute rejection. CONCLUSION: Despite limitations in sample size, resulting in tentative findings, the study serves as a crucial pilot study for an ongoing multicenter prospective trial in Japan.

Optical Biopsies Using Probe-Based Confocal Laser Endomicroscopy for Autoimmune Pulmonary Alveolar Proteinosis.

INTRODUCTION: Increasing numbers of cases of mild asymptomatic pulmonary alveolar proteinosis (PAP) are being reported with the recent increase in chest computed tomography (CT). Bronchoscopic diagnosis of mild PAP is challenging because of the patchy distribution of lesions, which makes it difficult to obtain sufficient biopsy samples. Additionally, the pathological findings of mild PAP, particularly those that differ from severe PAP, have not been fully elucidated. This study aimed to clarify the pathological findings of mild PAP and the usefulness of optical biopsy using probe-based confocal laser endomicroscopy (pCLE). METHODS: We performed bronchoscopic optical biopsy using pCLE and tissue biopsy in 5 consecutive patients with PAP (three with mild PAP and two with severe PAP). We compared the pCLE images of mild PAP with those of severe PAP by integrating clinical findings, tissue pathology, and chest CT images. RESULTS: pCLE images of PAP showed giant cells with strong fluorescence, amorphous substances, and thin alveolar walls. Images of affected lesions in mild PAP were equivalent to those obtained in arbitrary lung lesions in severe cases. All 3 patients with mild PAP spontaneously improved or remained stable after ≥3 years of follow-up. Serum autoantibodies to granulocyte-macrophage colony-stimulating factor were detected in all 5 cases. CONCLUSION: Optical biopsy using pCLE can yield specific diagnostic findings, even in patients with mild PAP. pCLE images of affected areas in mild and severe PAP showed similar findings, indicating that the dysfunction level of pathogenic alveolar macrophages in affected areas is similar between both disease intensities.

Availability of Home sleep apnea test equipment LS-140 on a comparison with Polysomnography.

OBJECTIVE: The prevalence of obstructive sleep apnea (OSA) in Japan is 9% among males and 3% among females. Up to 2.5 million patients are estimated to suffer from the disease, but limited number of facilities are capable of carrying out polysomnography (PSG), leaving more than 80% of these individuals are undiagnosed. In recent years, the development of new portable sleep monitoring (PMs) devices has been remarkable. We evaluate the correlation between the results of the LS-140 PMs device (Fukuda Denshi Tech Co. Ltd.), released in 2017, and those of PSG. METHODS: We obtained contemporaneous data from the same patients by equipping 58 patients with PMs (LS-140) devices while they underwent PSG. Our primary outcome was Case 2 of the intraclass correlation coefficient (ICC), i.e., the ICC (2.1). And we used a Bland-Altman analysis to compare the apnea-hypopnea index (AHI) given by PSG and the respiratory event index (REI) given by LS-140 and examined the sensitivity and specificity of the REI relative to the AHI in the diagnosis of OSA. We also carried out the same comparison but in terms of the presence or absence of periodic limb movements (PLMs). RESULTS: The ICC (2.1) between The REI and the AHI was 0.944, a rather high value (p<0.0001). The mean difference between AHI and REI values was -3.6 (p<0.0001), indicating a negative fixed bias. Sensitivity may decrease in groups with PLMs. CONCLUSION: The REI and the AHI are highly correlated, giving LS-140 sufficient diagnostic sensitivity and specificity to screen for OSA.

Diagnostic contribution of cytological examination to endobronchial ultrasound-guided transbronchial biopsy for lung malignancies.

Although endobronchial ultrasound guided transbronchial biopsy (TBB) with a guide sheath (EBUS-GS) is widely used for diagnosis of peripheral pulmonary lesions, the diagnostic contribution of cytology (bronchial brushing, bronchial washing and biopsy forceps rinse) has not been established. To determine the diagnostic contribution of cytological examination to EBUS-GS-TBB, we reviewed medical records of patients with lung malignancies who had undergone TBB with EBUS-GS (EBUS-GS group, n=187) or TBB without EBUS-GS (conventional TBB [CTBB] group, n=197) at Nagoya University Hospital. Although the mean size of target lesions was significantly larger in the CTBB group than the EBUS-GS group, the total diagnostic rate was equivalent between two groups (EBUS-GS: 73.3%, CTBB: 66.0%). In the EBUS-GS group, cytological procedures increased the diagnostic rate by 9.1% (17/137), compared with only 4.1% (8/130) in the CTBB group. Sensitivity of cytology among biopsy-negative patients was significantly higher in EBUS-GS group than CTBB group (P=0.022). Furthermore, in the EBUS-GS group, among 17 patients whose malignant diagnoses could only be established cytologically, bronchial brushing contributed to the malignant diagnosis in 64.7% (11/17). These data may suggest that cytological examination, especially bronchial brushing, may be an important diagnostic contributor in EBUS-GS-TBB.

Prognosis of pulmonary fibrosis presenting with a usual interstitial pneumonia pattern on computed tomography in patients with myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis: a retrospective single-center study.

BACKGROUND: Myeloperoxidase anti-neutrophil cytoplasmic antibody-related nephritis (MPO-ANCA nephritis) is occasionally accompanied by lung abnormalities such as pulmonary fibrosis. However, the clinical features of pulmonary fibrosis in patients with MPO-ANCA nephritis have not been well documented. This study was performed to compare the prognosis of a usual interstitial pneumonia (UIP) pattern of lung fibrosis in patients with MPO-ANCA nephritis with the prognosis of idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively reviewed the medical records of 126 patients with MPO-ANCA nephritis and identified 31 with a UIP pattern of lung fibrosis on high-resolution or thin-slice computed tomography (CT). We compared the characteristics and prognosis of these patients with those of 32 patients with IPF. In 18 patients from both groups, we assessed and compared the decline in lung volume over time using three-dimensional (3D) CT images reconstructed from thin-section CT data. RESULTS: The numbers of male and female patients were nearly equal among patients with MPO-ANCA nephritis exhibiting a UIP pattern; in contrast, significant male dominancy was observed among patients with IPF (p = 0.0021). Significantly fewer smokers were present among the patients with MPO-ANCA nephritis with a UIP pattern than among those with IPF (p = 0.0062). There was no significant difference in the median survival time between patients with MPO-ANCA nephritis with a UIP pattern (50.8 months) and IPF (55.8 months; p = 0.65). All patients with IPF in this cohort received antifibrotic therapy (pirfenidone or nintedanib). Almost half of the deaths that occurred in patients with MPO-ANCA nephritis with a UIP pattern were caused by non-respiratory-related events, whereas most deaths in patients with IPF were caused by respiratory failure such as acute exacerbation. In the 3D CT lung volume analyses, the rate of decline in lung volume was equivalent in both groups. CONCLUSIONS: MPO-ANCA nephritis with a UIP pattern on CT may have an unfavorable prognosis equivalent to that of IPF with a UIP pattern treated with antifibrotic agents.

Endoscope images of Schönlein-Henoch purpura.

BACKGROUND/AIMS: Schönlein-Henoch purpura (SHP) is a systemic condition characterized by purpura associated with leukocytoclastic vasculitis. SHP diagnosis is more difficult in infrequent cases where gastrointestinal (GI) symptoms precede purpura. This report examines 11 cases of SHP at our hospital with specific regard to the incidences and details of GI symptoms. METHODS: The clinical manifestations and endoscopic findings were investigated for their utility in SHP diagnosis. RESULTS: Among the 11 cases, 3 showed GI symptoms prior to other manifestations. In terms of GI symptoms, abdominal pain was reported in all 11 cases, diarrhea in 4 cases, and bloody stools in 3 cases. Endoscopic findings were seen in the stomach in 7/10 cases, in the small intestine including the duodenum in 10/11 cases, and in the large intestine in 6/10 cases. The frequency of ulcer formation was significantly higher in the small intestine (including the duodenum) than in the stomach. Multiple specific erythematosus lesions were observed in the stomach and large intestine. CONCLUSION: Familiarity with characteristic endoscopic findings and careful observation of all GI findings are essential for diagnosing SHP in cases in which GI tract symptoms precede cutaneous findings.

Treatment outcome of breast-conserving therapy in patients with positive or close resection margins: Japanese multi institute survey for radiation dose effect.

BACKGROUND: The relationship between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) is controversial. To evaluate the radiation dose and other factors influencing the ipsilateral breast tumor control (IBTC) in patients with positive or close resection margins after breast conserving surgery (BCS), the Japanese Radiation Oncology Study Group (JROSG) S-99-3 study group conducted a multi-institute survey of these patients. METHODS: The patients with less than 5 mm tumor-free margins after BCS were eligible for this study. A total of 971 patients from 18 institutes were enrolled in the analysis. The final pathological margin status was classified into 3 groups. Radiation doses to the tumor bed were less than 60 Gy in 252 patients, 60 Gy in 456 patients and more than 60 Gy in 233 patients. RESULTS: IBTR was observed in 55 patients (5.8%). The IBTC rates at 5 and 10 years by the Kaplan Meier method were 95.6% and 87.3%, respectively. There was no significant difference in 10-year IBTC rates according to marginal status; 85.9% in positive margin patients, 91.0% in equal or less than 2 mm margin patients and 87.0% in 2.1-5 mm margin patients. Radiation dose to the tumor bed was a marginally significantly associated with the 10-year IBTC rate (> or = 60 Gy 90.8% vs < 60 Gy 84.2%, p = 0.057). In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better (p = 0.039). The other factors influencing the IBTC were age (> or = 35 years vs < 35 years: p < 0.0001), menopausal status (p < 0.0001) and tumor size (p = 0.023). CONCLUSIONS: In patients with positive margins, IBTC with radiation dose equal to or more than 60 Gy was significantly better than the others. We recommend that the tumor bed be irradiated with at least 60 Gy in the patients with positive margins. Further follow-up is necessary to draw final conclusions.

[Imaging of gastrointestinal stromal tumor (GIST): relation between CT findings and grade of malignancy].

PURPOSE: To report the relation between CT findings and the grade of malignancy in gastrointestinal stromal tumor (GIST), especially the uncommitted type of GIST. MATERIALS AND METHODS: A total of 14 patients with histologically proven GIST (uncommitted type) underwent CT. Tumors were divided into three grades. HISTOLOGICALLY: Benign (mitotic index [MI] < 2/10 high-power fields [HPF]), borderline (2/10 HPF < or = MI < or = 5/10 HPF), and malignant (5/10 HPF < MI). We evaluated tumor size, cystic component, margin, and early enhancement. RESULTS: All benign tumors were smaller than 5 cm, and most malignant tumors reached 5 cm. The size of borderline tumors was between the sizes of benign and malignant tumors. No benign tumors had cystic components, whereas all borderline and malignant tumors except for one case had cystic components. Only two huge malignant tumors had unclear margins. The relation between early enhancement and the grade of malignancy showed no tendency, but all duodenal tumors showed marked early enhancement irrespective of grade. CONCLUSION: The grade of malignancy of GIST (uncommitted type) and size, presence of cystic components, and margin were highly correlated. That is, 1) tumors smaller than 5 cm with no cystic components can be diagnosed as benign, whereas 2) tumors that have cystic components are borderline or malignant. 3) Tumors that have cystic components and unclear margin can be diagnosed as actively malignant.