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Background Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%–5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings. Methods A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens. Results E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure. Conclusions The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q. [ABSTRACT FROM AUTHOR]

Serum KL-6 can distinguish between different phenotypes of severe COVID-19 We read the article by D'Alessandro et al with great interest and appreciate their efforts to evaluate the role of serum Krebs von den Lungen-6 (KL-6) as a prognostic biomarker of severe coronavirus disease 2019 (COVID-19).1 KL-6 is a mucin-like high-molecular-weight glycoprotein expressed in type II pneumocytes and respiratory bronchiolar epithelial cells in the healthy lung.2 Elevated serum levels can predict the prognosis of various interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF),3 and D'Alessandro et al1 observed a significant increase in serum KL-6 in critically ill patients with COVID-19 who required mechanical ventilation or intensive care. Here, we report different serum KL-6 kinetics in two patients with severe COVID-19. [Extracted from the article]

Introduction: Late diagnosis of the human immunodeficiency virus (HIV) is a major concern epidemiologically, socially and for national healthcare systems. Although the association of certain demographics with late HIV diagnosis has been reported in several studies, the association of other factors, including clinical and phylogenetic factors, remains unclear. In the present study, we conducted a nationwide analysis to explore the association of demographics, clinical factors, HIV-1 subtypes/circulating recombinant form (CRFs) and genetic clustering with late HIV diagnosis in Japan, where new infections mainly occur among young men who have sex with men (MSM) in urban areas., Methods: Anonymized data on demographics, clinical factors and HIV genetic sequences from 39.8% of people newly diagnosed with HIV in Japan were collected by the Japanese Drug Resistance HIV-1 Surveillance Network from 2003 to 2019. Factors associated with late HIV diagnosis (defined as HIV diagnosis with a CD4 count <350 cells/μl) were identified using logistic regression. Clusters were identified by HIV-TRACE with a genetic distance threshold of 1.5%., Results: Of the 9422 people newly diagnosed with HIV enrolled in the surveillance network between 2003 and 2019, 7752 individuals with available CD4 count at diagnosis were included. Late HIV diagnosis was observed in 5522 (71.2%) participants. The overall median CD4 count at diagnosis was 221 (IQR: 62-373) cells/μl. Variables independently associated with late HIV diagnosis included age (adjusted odds ratio [aOR] 2.21, 95% CI 1.88-2.59, ≥45 vs. ≤29 years), heterosexual transmission (aOR 1.34, 95% CI 1.11-1.62, vs. MSM), living outside of Tokyo (aOR 1.18, 95% CI 1.05-1.32), hepatitis C virus (HCV) co-infection (aOR 1.42, 95% CI 1.01-1.98) and not belonging to a cluster (aOR 1.30, 95% CI 1.12-1.51). CRF07&#95;BC (aOR 0.34, 95% CI 0.18-0.65, vs. subtype B) was negatively associated with late HIV diagnosis., Conclusions: In addition to demographic factors, HCV co-infection, HIV-1 subtypes/CRFs and not belonging to a cluster were independently associated with late HIV diagnosis in Japan. These results imply the need for public health programmes aimed at the general population, including but not limited to key populations, to encourage HIV testing., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Diabetes mellitus (DM) is a risk factor of tuberculosis (TB). We studied the clinical presentation of pulmonary TB among patients with DM in comparison with patients without DM who were admitted into the hospital of the University of the Ryukyus from 2006 to 2010. The clinical data were collected from medical records retrospectively. Ten cases (25%) of hospitalized patients with pulmonary TB had DM. The DM group showed lower Body Mass Index and higher incidence of chronic heart failure and chronic renal failure. The DM group also were more likely to have cavitary lesion, had longer period of hospitalization, and higher mortality. Their causes of deaths were mainly the co-morbidities and associated complications. Further studies are warranted in order to fully elucidate the relationships between pulmonary TB and DM.

Background: The A-DROP is a predicting pneumonia severity index which is adopted in the Japanese Respiratory Society (JRS) guidelines. For community-acquired pneumonia, we made a modified A-DROP, adding two new index items to the current A-DROP. Then, we retrospectively compared the modified A-DROP with the current A-DROP regarding 30-day mortality., Methods and Results: We analyzed consecutive 227 patients hospitalized with community-acquired pneumonia (mean age 79.0 years). The added index items were respiratory rate > or = 30/min and the presence or absence of underlying diseases. There were 16 fatalities (7.0%). In the extremely severe group, the sensitivities of the 30-day death and odds ratios were 19.9% and 9.5 in the current A-DROP, but 75.0% and 14.1 for the modified A-DROP, respectively. In addition, regarding the receiver-operating characteristic (ROC) area under the curve for the 30-day death ratio, the current A-DROP and modified A-DROP were 0.807 and 0.840, respectively., Conclusions: The modified A-DROP improved the ability to predict outcomes compared with the current A-DROP.

Immune reconstitution inflammatory syndrome (IRIS) caused by mycobacterium in patients with AIDS is often experienced in clinical practice. There is, however, a paucity of data documenting the histopathological findings and the pathogenesis. We determined the immunopathological characteristics of IRIS associated with Mycobacterium parascrofulaceum infection in an AIDS patient. A patient presented with pulmonary lymphadenitis and involvement of the pulmonary lingular segment. Portions of the involved lymph nodes and lung were excised, and the immunological properties were analyzed by immunohistochemical assays. The histological characteristics of lymph nodes showed a caseous necrosis. Histopathologically, the pulmonary lesion was composed of exudative and proliferative lesions. CD4(+), CD8(+), CD57(+), and CD25(+)/FoxP3(+) cells were observed in both types of lesions. Clusters of CD20(+) cells and GATA3(+) cells were predominantly observed in exudative lesions, while T-bet(+) cells were dominant in proliferative lesions. ROR-γ(+) cells were also observed in exudative lesions. These results indicate that the cellular immunity to mycobacteria was recovering in the lung tissue. In M. parascrofulaceum pulmonary infection, the exudative lesion had characteristics of Th2 and Th17-type immunities. In contrast, the proliferative lesion had characteristics of Th-1 type immunity. Our data provide the first evidence to reveal the status of the axis of distinctive immunity in the process of granuloma formation caused by a mycobacterium-related infection., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

Purpose: This study was designed to evaluate the mechanism of Mycobacterium avium extension in lung infection., Study Design: Retrospective study., Participants: A 42-year-old man with acquired immune deficiency syndrome and immune reconstitution inflammatory syndrome. The patient developed mediastinal lymphadenopathy and a peripheral lesion in the right upper lobe within 2 weeks of starting highly active antiretroviral therapy., Methods: Pulmonary tissue and lymph nodes were dissected under thoracoscopy and evaluated pathologically and immunohistochemically., Results: Pulmonary pathologic examination revealed extensive granuloma formation throughout the acini. Mycobacterial antigens were found in the macrophages in the alveoli and in the alveolar septa. Some macrophages including mycobacterial antigens were surrounded by lymphatic endothelial cells in the interstitium. In addition, a proliferative granulomatous lesion was found under the intact epithelial layer of a bronchiole. Pathological examination of the lymph nodes revealed aggregated proliferative granulomas with few mycobacteria. Genetically closely related M. avium strains were isolated from both tissues., Conclusions: This study showed the mechanism involved in the progression of pulmonary M. avium infection from the pulmonary focus to the regional lymph nodes via the lymphatic vessels.

A 28-year-old woman was admitted to our hospital complaining of a 7-day chilly sensation with fever. She was given a diagnosis of pneumococcal pneumonia because of infiltration on chest radiography, sputum gram staining and testing positive for a pneumococcal urinary antigen. A 10-day course of antibiotics showed improvements in symptoms and infiltration. However, her X-ray film revealed severe volume loss in the right lung. Organizing pneumonia was diagnosed with lymphocytosis in BALF and Masson bodies upon TBLB examination. Administration of prednisolone obtained rapid improvement of the volume loss. This case was interesting, showing an organizing tendency in the acute-stage pneumococcal pneumonia.

A 56-year-old man, having no particular past history, was admitted to our hospital, with a 9-month history of painful ulcerated lesion of the tongue and a 6-month history of productive cough. A physical examination revealed swelling of his cervical lymph nodes, and a chest roentgenogram on admission showed cavities in the both upper lung fields and nodular shadows over the both lung fields. He was initially suspected of having both cancer of the tongue and pulmonary tuberculosis, but finally diagnosed as secondary tuberculosis of the tongue due to sputum smear-positive pulmonary tuberculosis by biopsy of the tongue and sputum examination. He was treated with isoniazid, rifampicin, ethambutol and pyrazinamide, and his pain and ulcerated lesion of the tongue rapidly improved. Due to our search for recent 16 cases of tuberculosis of the tongue in Japan, we found that the patients of tuberculosis of the tongue were more likely to have concurrently sputum smear-positive pulmonary tuberculosis. In some cases, the delay in diagnosis was seen. These cases suggest that refractory ulcerated cases of the tongue should be subjected to the biopsy and examination for acid fast bacilli of the tongue with suspicion of tuberculosis of the tongue, and then a chest roentgenogram with suspicion of pulmonary tuberculosis.