Vaccination, regular exercise, and prevention of chronic lung disease reduce exacerbation of COVID-19 severity in northern Okinawa, Japan: A cross-sectional study.

BACKGROUND: As at June 14, 2023, the coronavirus disease 2019 (COVID-19) pandemic had affected more than 767 million people and caused more than 6.9 million deaths worldwide. This study aimed to clarify the lifestyle factors that influence the exacerbation of COVID-19 severity. METHODS: This was a cross-sectional study of patients with COVID-19 whose severity classification of "moderate or severe" (COVID-19 exacerbation) was defined as an objective variable. The 1,353 participants were selected from 4,899 patients with COVID-19 between August 10, 2020 and December 10, 2022. Participants who underwent a specific health checkup before the date for a COVID-19 consultation were included. Using binominal logistic regression analysis, we evaluated the odds ratios (ORs) for COVID-19 exacerbation according to lifestyle-related factors. Limitations were discussed using a target trial emulation framework which clarifies problems in observational studies. RESULTS: The explanatory variables extracted as factors that exacerbated COVID-19 severity were gender (OR [man vs. woman]: 2.533, 95% confidence interval [CI] 1.484-4.322); age (OR [50s vs. 10s, 20s, or 30s]: 4.858, 95% CI 2.319-10.177; OR [60s]: 9.738, 95% CI 4.355-21.777; OR [70s + 80s + 90s]: 8.327, 95% CI 3.224-21.507); and comorbid chronic lung disease (OR ['yes' vs. 'no']: 2.892, 95% CI 1.227-6.818). The explanatory variables extracted as factors that reduce the severity of COVID-19 were hospital consultation year (OR [2022, predominantly Omicron variant prevalent vs. 2020, predominantly Alpha variant prevalent]: 0.180, 95% CI 0.058-0.559); number of vaccinations (OR [2 doses vs. 0 or one doses]: 0.223, 95% CI 0.114-0.436; OR [≥3 doses vs. 0 or one doses]: 0.090, 95% CI 0.035-0.229); regular exercise (exercising ≥2 days/week ≥30 minutes each at an intensity that causes a slight sweat for ≥1 year) (OR ['yes' vs. 'no']: 0.458, 95% CI 0.242-0.866). CONCLUSIONS: These results suggest the importance of vaccination, regular exercise, and prevention of chronic lung disease as measures against exacerbation of COVID-19 severity.

Human immunodeficiency virus-associated pulmonary sarcoidosis in a Japanese man as a manifestation of immune reconstitution inflammatory syndrome.

Asymptomatic pulmonary sarcoidosis can develop after starting antiretroviral therapy. The decision on whether to treat sarcoidosis with corticosteroids should be based on the disease severity.

Comparison of two screening tests for HIV-Associated Neurocognitive Disorder suspected Japanese patients with respect to cART usage.

In this study, we demonstrated the pervasiveness of HIV-associated neurocognitive disorders (HAND) among a selection of Japanese patients as well as evaluated and compared the Mini Mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) for use as a screening tool among combination anti-retroviral therapy (cART)-naïve and cART experienced patients. The MMSE and the IHDS have both been used as HAND screening tests around the world with variable success. It has been reported the increased usage of cART the utility of these screening tests may have been diminished due to the decreased severity of impairment and the altered pattern of neurocognitive impairments in cART era HAND patients. It is therefore possible the MMSE and the IHDS may still be useful among cART-naïve patients even in the cART era. However, only one study has investigated and compared the screening results of the IHDS among cART-naïve and cART experienced patients. All HIV positive patients who visited, or were admitted, to the Ryukyu University Hospital between January 2009 and March 2014 were evaluated for inclusion. Selected patients (n = 49) had data without omission for all tests. The overall prevalence of HAND in our cohort was 44%. The area under the curve (AUC), for all subjects using the MMSE and the IHDS, were 0.60 and 0.69, respectively. However, the AUC among cART-naïve patients were 0.58 and 0.76 for the MMSE and the IHDS, respectively. Whereas, cART experienced patients had an AUC of 0.60 and 0.61, respectively. Overall, the MMSE demonstrated a poor screening ability for HAND, regardless of cART usage (the cut-off value of 27 had a Youden's J-Index of 0.1, in all groups). Alternatively, the IHDS was moderately useful for HAND screening among cART-naïve patients (the cut-off value of 11 had a Youden's J-Index of 0.4), but performed poorly as a screening test among cART experienced patients (the cut-off value of 11 had a Youden's J-Index of 0.1).

Evaluation of the Lipid Concentrations after Switching from Antiretroviral Drug Tenofovir Disoproxil Fumarate/Emtricitabine to Abacavir Sulfate/Lamivudine in Virologically-suppressed Human Immunodeficiency Virus-infected Patients.

Objective Recently, tenofovir disoproxil fumatate (TDF)-related side effects, such as renal nephrotoxicity and reduction of bone mineral density, have been reported. Consequently, increased switching from fixed-dose tablet TDF and emtricitabine (TDF/FTC) to abacavir and lamivudine (ABC/3TC) has occurred. Interestingly, while TDF has a lipid-lowering property, one of the ABC-related side effects is hyperlipidemia. Therefore, such switching could cause lipid elevation. To evaluate the change in lipid levels associated with switching from TDF/FTC to ABC/3TC in virologically-suppressed human immunodeficiency virus (HIV)-infected patients. Methods This is a retrospective, single-center study. We included the HIV-infected patients whose therapy included a drug switch from TDF/FTC to ABC/3TC between September 2009 and December 2012 at Ryukyu University Hospital. The exclusion criteria were HIV-RNA >40 copies/mL on the switching day, and a documented therapy change to a lipid-lowering agent or any other antiretroviral agents within 3 months before or after switching. We compared the low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and triglyceride (TG) levels before switching to three months after. Results A total of 18 patients met the inclusion criteria. The LDL, HDL, and TC levels significantly increased three months following the switch (p<0.05), with median (interquartile range) values of 17 (7, 32), 6 (2, 13), and 27 (10, 45) mg/dL, respectively. The TG values did not markedly change. Conclusion Switching from TDF/FTC to ABC/3TC resulted in significantly increased LDL, HDL, and TC levels.

Interleukin-17A in Legionella pneumonia: a retrospective study.

Interleukin (IL)-17A affects the immune system of the lung. Legionella infection can potentially lead to severe pneumonia. The present study aimed to evaluate the role of IL-17A in Legionella pneumonia. Serum IL-17A levels were quantified in both patients with Legionella pneumonia and control subjects; IL-17 was detected in sera from 4 out of 31 patients with Legionella pneumonia but in any controls. There were no differences in peripheral white blood cell counts or other serum biomarkers (C-reactive protein, and lactate dehydrogenase) between IL-17A-positive and IL-17A-negative patients. All IL-17A-positive patients in this cohort survived, where 8 of 27 IL-17A-negative patients did not. IL-17A was detected in available bronchoalveolar (BA) fluid samples from 7 patients with Legionella pneumonia within our cohort. However, the IL-17A and IFN-γ concentrations in BA fluids did not correlate with each other. IL-17A might play a significant role in some cases of Legionella pneumonia.

Pure red cell aplasia induced by lamivudine without the influence of zidovudine in a patient infected with human immunodeficiency virus.

We herein report the case of a patient with human immunodeficiency virus infection and acquired immune deficiency syndrome who was diagnosed with drug-induced pure red cell aplasia consequent to lamivudine treatment. The patient was admitted to our hospital for treatment of increasing shortness of breath following physical effort. Upon admission, routine blood tests revealed a hemoglobin level of 7.6 g/dL and a hematocrit proportion of 21.2%, with normal leukocyte and platelet counts. After stopping the lamivudine treatment, the patient's hemoglobin concentration and hematocrit level returned to normal. A bone marrow examination showed an exclusive reduction in erythrocyte formation. This case indicates that lamivudine can induce severe anemia without the influence of zidovudine.

The prevalence of airway obstruction among Japanese HIV-positive male patients compared with general population; a case-control study of single center analysis.

BACKGROUND AND OBJECTIVE: Previous studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients. METHODS: Case-control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method. RESULTS: Forty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/µL (79-935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infection was an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p = 0.006). None of patient was detected the airway colonization of Pcj. CONCLUSIONS: HIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients.

Are MMSE and HDS-R neuropsychological tests adequate for screening HIV-associated neurocognitive disorders?

HIV-associated neurocognitive disorders (HAND) are one of major comorbidities in patients with HIV-1 infection. There are currently no standardized tests for screening HAND in such patients. The sensitivity of the cognitive function tests routinely used in clinical practice, such as the Mini-Mental State Examination and the Revised Hasegawa's Dementia Scale, is inadequate to rule out HAND, even in patients with clear abnormal behavior. We report a 41-year-old man with HIV-associated dementia, the most severe form of HAND, in whom the simplified methods did not show abnormal results, and a comprehensive battery of neuropsychological tests which covering several cognitive domains was needed to detect cognitive impairment.

Depression of local cell-mediated immunity and histological characteristics of disseminated AIDS-related Mycobacterium avium infection after the initiation of antiretroviral therapy.

OBJECTIVE: The aim of the present study was to examine the immunohistological characteristics of disseminated Mycobacterium avium infection after the initiation of antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS). METHODS: We histologically investigated five autopsied AIDS patients with systemic M. avium infection. RESULTS: The inflammatory cell composition in the affected tissues was assessed using immunohistochemistry. The celiac lymph nodes and intestinal canal were the most commonly involved organs in the AIDS cases. The most common histological feature was unstructured aggregation of histiocytes. Immunohistochemistry revealed depression of CD4(+), CD8(+) and CD57(+) cells in the gut lamina propria and mesenteric lymph nodes. CONCLUSION: These findings suggest that local cell-mediated immunity is depressed in affected tissues and that the primary histological feature is poor organization of granulomas in mycobacterial lesions, despite the administration of adequate ART.

Imported malaria cases in Okinawa Prefecture, Japan.

With the increase in global transportation, imported malaria has become a significant public health concern in Japan. In the present study, we retrospectively analyzed all imported malaria cases in Okinawa Prefecture from 1988 to 2012. In that period, 23 patients with imported malaria were admitted to the University of the Ryukyus Hospital. Malaria types observed included Plasmodium falciparum (14 cases), P. vivax (7 cases), combined P. falciparum and P. ovale (1 case), and combined P. vivax and P. malariae (1 case). All cases were resolved by anti-malarial treatment. The clinical data from these patients highlights the importance of collecting patient travel history and ensuring an adequate supply of both diagnostic test and drug treatments in Okinawa.

Acquired immune-deficiency syndrome with focal onset of Mycobacterium avium infection displaying a histological/genetic pattern of disseminated mycobacteria.

A 66-year-old man with human immunodeficiency virus (HIV) infection was admitted for treatment of Pneumocystis pneumonia. Upon admission, a tumor mass adjacent to the thoracic descending aorta was revealed on computed tomography. Histology revealed an exudative granuloma with histiocytes packed with numerous acid-fast bacilli. Mycobacterium avium was isolated from the tissue. A genetic examination of the isolates demonstrated this strain to be located in the cluster consisting of strains that cause systemic infection. The patient's baseline CD4+ cell count was 9/µL and the HIV-RNA viral load was 43,800 copies/mL. This case suggests the possibility of a localized onset of disseminated M. avium infection.

Drug-induced acute interstitial nephritis mimicking acute tubular necrosis after initiation of tenofovir-containing antiretroviral therapy in patient with HIV-1 infection.

We describe a case of 68-year-old Japanese man with HIV-1 infection who developed acute kidney injury with prominent tubular dysfunction immediately after starting tenofovir-containing antiretroviral therapy. Antiretroviral therapy was discontinued in two weeks but renal function, as well as tubular function, did not shown full recovery even at a 3-year follow-up examination. Acute tubular necrosis, a rare but well-known side effect of tenofovir, was suspected, but kidney biopsy confirmed interstitial nephritis. It is important to distinguish drug-induced interstitial nephritis from acute tubular necrosis, because early steroid administration can improve renal dysfunction caused by acute interstitial nephritis.

[Clinical features of diabetic patients with pulmonary tuberculosis admitted to a university hospital].

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.

[Comparison of pneumonia severity indices between modified A-DROP system and current A-DROP system predicting outcomes for patients hospitalized with community-acquired pneumonia].

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.

Immunopathological characteristics of immune reconstitution inflammatory syndrome caused by Mycobacterium parascrofulaceum infection in a patient with AIDS.

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.

Mechanisms involved in the extension of pulmonary Mycobacterium avium infection from the pulmonary focus to the regional lymph nodes.

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.

Pneumocystis jirovecii pneumonia and alveolar hemorrhage in a pregnant woman with human T cell lymphotropic virus type-1 infection.

Acute lung injury during pregnancy results in morbidity and mortality in both the mother and the fetus. Pneumocystis jirovecii pneumonia (PCP) is a rare disease but may occur in pregnant immune-suppressed women. Here, we describe a case of acute lung injury due to PCP and alveolar hemorrhage in a pregnant woman who was a human T lymphotropic virus type-1 (HTLV-1) carrier. PCP should be considered in the differential diagnosis of pulmonary complications during pregnancy in HTLV-1 endemic areas.

Whole-body 18F-fluorodeoxyglucose positron emission tomography/computed tomography images before and after chemotherapy for Kaposi sarcoma and highly active antiretrovirus therapy.

Kaposi sarcoma is an acquired immunodeficiency syndrome-related disease that mainly involves the skin, gastrointestinal gut, and lungs. Whole-body 18F-fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT) scanning is useful for simultaneous detection of multiple lesions of Kaposi sarcoma. We present a 67-year-old man with a history of infection with human immunodeficiency virus who presented with numerous cutaneous lesions. FDG-PET/CT images showed lesions in the skin, lung, and lymph nodes. The gastrointestinal lesions were detected using gastric fiberscopy (GF) and colon fiberscopy (CF). After Kaposi sarcoma therapy, the uptake in the lesions of the skin, lung, and lymph nodes decreased, but new lesions were detected in the pancreas and lumbar spine. He had pancreatitis and Candida spondilitis. Whole-body FDG-PET/CT is useful for detecting lesions and determining the extension to which the disease has spread, adding the gastrointestinal lesions by GF and CF. After therapy, FDG-PET/CT can be used to demonstrate which lesions remain active and to determine the overall response to treatment. In this case, we show how useful FDG-PET/CT is and how difficult it is to treat Kaposi sarcoma.