Hiroshi Sekiguchi's research while affiliated with Society of Critical Care Medicine and other places

Background Critical care ultrasonography (CCUS) has become a daily diagnostic tool for intensivists. While the effective training measures for ultrasound novices are discussed widely, the best curriculum for the novices to retain a long-term proficiency is yet to be determined. Methods Critical care medicine fellows who underwent an introductory CCUS workshop were randomly allocated into the standard training (ST) or the intensive training (IT) group. The IT group received an 8-h training besides the standardized fellowship education that the ST group received. Participant improvement in CCUS proficiency tests (maximum score, 200) after a 6-month training intervention was compared between the groups. CCUS examinations performed in patient care were observed over 2 years. Results Twenty-one fellows were allocated into the ST ( n = 10) or the IT ( n = 11) group. No statistically significant difference was observed in the median (interquartile range [IQR]) improvement in CCUS proficiency tests between the ST group and the IT group: 18 (3.8–38) versus 31 (21–46) ( P = .09). Median (IQR) test scores were significantly higher in postintervention than preintervention for both groups: ST, 103 (87–116) versus 124 (111–143) ( P = .02), and IT, 100 (87–113) versus 143 (121–149) ( P < .01). Participating fellows performed 226 examinations over the 2 years of observation. Conclusions Fellows improved their CCUS proficiency significantly after 6-month training intervention. However, an additional 8-h training did not provide further benefits.

Background Exogenous lipoid pneumonia (ELP) develops when lipid-containing substances enter the airways through aspiration or inhalation, and incite an inflammatory response. The diagnosis of ELP is often difficult as findings may be nonspecific. ELP’s clinical course has not been well-characterized. Research Question What are the presenting clinico-radiologic features of ELP, its causative agents, and clinical course? Study Design and Methods We searched the Mayo Clinic electronic medical records for patients diagnosed with ELP between 1998 and 2020. Inclusion diagnostic criteria were: 1) lipoid pneumonia on histopathology, 2) lipid-laden macrophages in bronchoalveolar lavage fluid, or 3) fatty-attenuation of parenchymal opacities on chest CT. Additionally, all patients were required to have a clinician diagnosis of lipoid pneumonia in the absence of conditions known to cause endogenous lipoid pneumonia. Results Thirty-four patients were identified. Mean age was 71 years, with no gender predominance; one-half were asymptomatic. The diagnosis was confirmed by lung biopsy (including 3 lobectomies for suspected malignancy) in 71%, CT in 24%, and bronchoalveolar lavage in 5% of patients. Most patients manifested bilateral parenchymal opacities that commonly involved the lower lobes; fatty-attenuation was identifiable in only 41% of patients. A causative substance was identified in 79% of cases, in most cases after the diagnosis was established. Over a median follow-up of 1.2-years, only 20% of patients with chronic respiratory symptoms improved, while 50% worsened. Over a median follow-up interval of 1 year, CT abnormalities improved/resolved in 33%, and progressed in 39%. Patients who deteriorated were older, with a higher prevalence of gastrointestinal disorders than those who remained stable or improved. Interpretation ELP is often asymptomatic and may not manifest fatty-attenuation on chest CT. Clinical and radiologic abnormalities persist or worsen in the majority of affected patients, even when the causative agent is discontinued.

Background Intrathoracic involvement with lymphomas is common and manifests lymphadenopathy as well as a wide spectrum of imaging abnormalities in the lungs. Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal subtype of large B-cell lymphoma that typically involves small blood vessels and is difficult to detect. Methods Using a computer-assisted search, we identified patients with histopathologically proven IVLBCL in the lungs at Mayo Clinic from 2001 through 2018. Medical records, imaging studies, and pathologic specimens were reviewed. Results Five patients were diagnosed with a median age at diagnosis of 68 years (range, 44-73); four patients were male. The diagnosis of IVLBCL was achieved by surgical lung biopsy in 3 and at autopsy in 2. At presentation, all 5 patients had dyspnea and systemic symptoms including fever, fatigue, night sweats, and/or weight loss. Chest radiography and CT failed to demonstrate the diffuse infiltrative process; PET scan performed in 2 patients did not show fluorodeoxyglucose (FDG) uptake in the lungs. Pulmonary function tests obtained in 3 patients showed reduced diffusing capacity in all; transthoracic echocardiography yielded evidence of pulmonary hypertension in 2 of 4 patients. Three patients diagnosed antemortem underwent chemotherapy with one patient remaining alive at 4 years after diagnosis. Conclusions IVLBCL is difficult to diagnose given variable and nonspecific clinical presentations. Microvascular disease processes such as IVLBCL should be kept in mind in cases of undiagnosed progressive dyspnea accompanied by systemic symptoms even when imaging studies are unrevealing.

Introduction: Short telomere syndromes (STS) are accelerated aging syndromes affecting hematopoietic, pulmonary, hepatobiliary and/or immunological systems. Clinical assessment of age-appropriate telomere length (TL) is performed using flow cytometry & fluorescence in-situ hybridization (flowFISH). Screening for germline variants in STS-related genes is guided by flowFISH-determined centile categories of TL, with screening recommended for TL <1st centile or 1-10th centile in lymphocytes (L) or granulocytes (G). However, the utility of genetic testing for patients with TL >10th centile and integration of clinical phenotype with flowFISH data in predictive algorithms is currently unclear. Methods: FlowFISH testing was done at reference laboratories in Vancouver (Repeat Diagnostics; Canada) & Johns Hopkins University (JHU, USA). Salient clinical features were pre-determined as, personal history of premature hair greying (onset at age < 30 years), idiopathic pulmonary fibrosis (IPF) or IPF/emphysema overlap (in smokers), cryptogenic cirrhosis or NRH, unexplained cytopenias &/or immunodeficiency, & family history of the above (in >1 1st or 2nd degree relatives). Clinical likelihood score (CLS) was assigned as low (1), intermediate (int, 2) or high (>2), based on the number of aforementioned clinical features present prior to flowFISH testing. Genetic testing was performed using either an in-house or commercial bone marrow failure-specific next generation sequencing (NGS) panel or whole exome sequencing (WES), and data for known variants affecting telomerase or telomeric function (TERT, TERC, DKC1, TINF2, NHP2, NOP10, TCAB1, NAF1, & RTEL1) was recorded. Results: One hundred forty-nine patients at our institution underwent TL assessment at Repeat diagnostics (n=38) and JHU (n=111) laboratories, respectively. Median age was 56 (range: 7-79) years; 88 (59%) being males. Significant family history was present in 40 (27%) patients, while premature greying of hair was present in 13 (9%) patients. Organ-specific clinical features included unexplained cytopenias (n=89, 60%) IPF (n=71, 48%), cryptogenic cirrhosis or NRH (n=21, 14%), & unexplained immunodeficiency (n=14, 9%). CLS stratification included low (n=74, 50%), int (n=54, 36%), & high (n=21, 14%), with higher CLS significantly correlating with lower delta TL for L (p=0.0005) but not G (p=0.3). Genetic testing was performed in 51 (35%) patients (NGS-51, WES-1) among which 13 (26%) patients had a telomere-associated variant; 5 (10%) pathogenic (pv, all TERT). CLS alone was unable to predict likelihood of finding a telomere-associated variant (p=0.4). Based on age-appropriate centile categorization of L & G TL (information for both available in 134 patients), patients were stratified into six groups (table 1). TL <1st centile in L: This group was further divided into two groups; TL<1st centile in both L & G [A1, n=7, CLS low-3 (43%), int-2 (29%), & high-2 (29%)] and TL <1st centile in L and 1-50th centile in G (A2, n=2, CLS low & high) patients. Among the 4 (57%) patients who underwent genetic (NGS-3, WES-1) testing, 3 (75%) had TERTpv in A1 subgroup and 1 A2 subgroup patient had a VUS in TERT.TL <1st centile in G, 1-10th centile in L (n=18): This group included 9 (50%) low, 8 (44%) int and 1 (6) high CLS patients, of which only 1 of 8 NGS-tested patients had TERTpv.TL 1-10th centile in L or G: This group was divided into; 1-10th centile in both L & G [C1, n=28, CLS low-3 (11%), int-14 (50%), high-11(39%)] of whom 8 (22%) underwent NGS with no pathogenic variants but 3 VUS in RTEL1, NAF1 & PARN genes, and 1-10th centile in L, >1-90th centile in G [C2, n=36, CLS low-19 (53%), 16 (44%), 1 (3%)] of whom 8 (22%) underwent NGS with 1 TERTpv and 2 VUS in TINF2TL >10th centile in L & 1-90th centile in G (n=43, 32%): CLS stratification in this group included 27 (63%) low, 12 (28%) int, 4 (9%) high. NGS testing was done in 13 (30%) patients [CLS low-9(69%), int 2(15%), high 2 (15%)], of whom only 2 (15%) had VUS in TINF2 and TERT gene, but no pathogenic variants (figure 1). Conclusion: Our study demonstrates the importance of using a flowFISH assay based predictive algorithm to screen patients with suspected STS for telomere-related genetic alternations, in comparison to a clinical likelihood score. We also demonstrate a limited role for genetic testing in patients with lymphocyte TL >10th centile, regardless of the clinical likelihood score. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees.

Purpose The objective of this study was to determine if long term itraconazole use, as antifungal prophylaxis, in lung transplant recipients is an independent risk factor for skin cancer. Methods We retrospectively reviewed patients who received a lung transplant at Mayo Clinic Rochester from 2002 to 2010. The antifungal prophylaxis protocol at our institution is triazole therapy, itraconazole or voriconazole, for a minimum of 3 years. Patients who died within 6 months of initial transplant were excluded. Characteristics to help assess independent risk for the development of cutaneous cancers and type of antifungal prophylaxis were noted. Patients who were exposed to both voriconazole and more than 6 months of itraconazole were analyzed separately. Results We identified 102 patients who underwent lung transplant at Mayo Clinic from 2002 to 2010; 11 patients died within 6 months of transplant and were excluded. Of the remaining 91 patients, 44 received only itraconazole prophylaxis, 10 received only voriconazole prophylaxis, and 37 received both itraconazole and voriconazole. No statistically significant difference between the baseline characteristics of the 3 groups was observed with the exception of race. There was a lower proportion of Caucasians in the voriconazole only group compared with the itraconazole only and combined itraconazole/voriconazole groups (p=0.02). Out of the 91 patients included in the study, 40 (44.0%) were diagnosed with skin cancer post-transplant, and 5 (12.5%) developed aggressive, metastatic cutaneous squamous cell carcinoma. Follow-up time was similar between patients who developed skin cancer (93.0 ± 45.0 months) and those who did not (62.0 ± 49.0 months, p=0.23). No significant difference was found in incidence of skin cancer or rate of metastatic squamous cell carcinoma between patients in the three groups (p=0.65) Duration of itraconazole was greater in patients who developed skin cancer [median 62.5 months (22.7, 87.5) vs 32.0 (18.0, 64.8), p=0.07] despite similar follow-up time. Absolute exposure (i.e. exposed to itraconazole or not) did not appear to correlate with the development of skin cancer post-transplant. Conclusion Prolonged itraconazole exposure when used as a prophylactic agent in lung transplant recipients appears to correlate with the development of skin cancers but further studies are warranted.

Purpose The objective of this study was to review the reasons lung transplant recipients discontinue antifungal prophylaxis, as documented by treating physicians. Methods We retrospectively reviewed patients who received a single or double lung transplant at Mayo Clinic Rochester from 2002 to 2010 examining the type of antifungal medication and reasons for discontinuation. Lung transplant recipients at our institution receive triazole therapy, voriconazole or itraconazole, for prevention of invasive fungal infections. Results We identified 102 patients who underwent lung transplant at Mayo Clinic from 2002 to 2010; 11 patients died within 6 months of transplant and were excluded. Of the 91 patients who survived longer than 6 months post lung transplant: 86 received itraconazole, 44 received voriconazole, and 37 received both (Table 1). A significantly higher proportion of patients discontinued voriconazole than itraconazole [31 out of 44 (70.5%) versus 41 out of 86 (47.6%), p=0.01]. Side effects (gastrointestinal intolerance, hepatitis, and fluorosis) were the most common reason for discontinuing voriconazole [20/44 (45.5)] compared to one of the least common reasons itraconazole was discontinued [6/86 (8.4), p<0.0001]. Suspected or diagnosed fungal infection was the most common reason itraconazole was discontinued [10/86 (11.6%) vs 2/44 (4.5%) p=0.19]. Itraconazole was the initial antifungal agent in the majority of these patients (8/10), and most patients had therapeutic serum itraconazole levels at the time of suspected fungal infection (6/10). Ultimately 6 patients who received prophylaxis with itraconazole were diagnosed with an invasive fungal infection compared with no patients receiving voriconazole. Conclusion Itraconazole was discontinued prior to the prophylactic end point significantly less often than voriconazole and appeared to be better tolerated; although, several patients were diagnosed with an invasive fungal infection while on itraconazole prophylaxis.

Case presentation: A 40-year-old male subject employed as a grocery store manager presented to a pulmonary clinic with a dry cough and progressive dyspnea of 1 year duration. The patient was previously an avid cyclist and first noted his dyspnea when he was unable to bike as far as before. Bilateral interstitial lung infiltrates were recently noted on chest radiography. At the time of presentation, he could no longer cycle due to dyspnea. The patient's medical history was significant for albinism and severe visual impairment. He had no family history of albinism or pulmonary disorders. He had never smoked, drank alcohol only occasionally, and had no significant environmental exposures.