A Chinese adaptation of the Patient Health Questionnaire for Adolescents (PHQ-A): factor structure and psychometric properties.

BACKGROUND: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD). METHODS: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve. RESULTS: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively. CONCLUSION: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission.

The mediating effect of distress tolerance on the relationship between stressful life events and suicide risk in patients with major depressive disorder.

BACKGROUND: Despite widespread acknowledgment of the impact of stressful life events on suicide risk, the understanding of the psychological mechanisms underlying the relationship between stressful life events and suicide risk in major depressive disorder (MDD) remain unclear. This study aim to examine whether the distress tolerance mediates the relationship between the stressful life events and suicide risk in patients with MDD. METHODS: A cross-sectional study was carried out among 125 Chinese patients with MDD, mean age was 27.05 (SD=0.68) and 68.8% were females. The 17-item Hamilton Depression Rating scale (HAMD-17), the validated Chinese version of the Mini International Neuropsychiatric Interview (MINI) suicide module, Life Events Scale (LES) and Distress Tolerance Scale (DTS) were utilized to evaluate depressive symptoms, stressful life events, levels of distress tolerance, and suicide risk, respectively. Mediation analyses was used to test the mediation effect of distress tolerance on the relationship between stressful life events and suicide risk. RESULTS: The ratio of suicide risk in patients with MDD was 75.2%. Pearson correlation analysis showed that stressful life events were positively correlated with suicide risk(r=0.182, p<0.05). Stressful life events(r=-0.323, p<0.01) and suicide risk(r=-0.354, p<0.01) were negatively correlated with distress tolerance. Mediation analyses showed that the direct path from stressful life events to suicide risk was not significant (B= 0.012, 95% confidence interval (CI) [-0.017, 0.042]). Stressful life events affected suicide risk indirectly through distress tolerance (B= 0.018, 95% CI [0.007, 0.031]), and the mediating effect accounted for 60.0% of the total effect. CONCLUSION: Distress tolerance completely played a mediating role between stressful life events and suicide risk. Further suicide prevention and intervention strategies should focus on increasing levels of distress tolerance in patients with MDD.

Utility of Ultra-Wide-Field Imaging for Screening of AIDS-Related Cytomegalovirus Retinitis.

PURPOSE: To explore the potential use of ultra-wide-field (UWF) imaging for screening of cytomegalovirus retinitis (CMVR) in AIDS patients. METHODS: Ninety-four patients whose CD4 count was below 200 cells/µL were enrolled in a prospective study. Each patient underwent UWF imaging and indirect ophthalmoscopy. The main outcome measures were the concordance and detection rates of these 2 approaches and the sensitivity and specificity of UWF imaging. RESULTS: Twenty-seven eyes in 18 patients were diagnosed with CMVR by the indirect ophthalmoscopy. UWF imaging missed the diagnosis in 1 eye because of a zone 3 CMVR lesion. The UWF image showed several CMVR patterns and locations: hemorrhagic necrotizing lesion, granular lesion, frosted branch angiitis, and optic neuropathy lesion. The concordance of the 2 approaches was excellent for the diagnosis of CMVR, classification of CMVR pattern, and location of CMVR. The detection rates of UWF imaging and indirect ophthalmoscopy were 14.0% (26/186; 95% CI 0.089-0.190) and 14.5% (27/186; 95% CI 0.094-0.196), respectively (p = 1.000). The sensitivity and specificity of UWF imaging were 96.3 and 100%, respectively. CONCLUSIONS: UWF imaging is capable of documentation of different CMVR lesions and AIDS-related CMVR screening when examination by an ophthalmologist is not available.

Plasma Cytokine Expression and Immune Reconstitution in Early and Delayed Anti-HIV 96-Weeks Treatment: A Retrospective Study.

HIV is an immunodeficiency disease with emergence of inadequate corresponding reconstruction therapies. Pyroptosis of CD4+T cell is mainly caused by immune activation and inflammation that cannot be reduced by successful antiretroviral therapy (ART) alone. Coinfections because of CD4+T cell reconstitution failure can occur. Anti-inflammatory treatment determines the success of immune reconstitution. In our experiment, only a few cytokines could recover to normal level following a 2-year antiretroviral treatment in early ART initiation, which is consistent with current findings about adjuvant HIV anti-inflammatory therapy. Early infection is often accompanied by a more severe inflammatory response. Innate immunity cytokines like granulocyte macrophage-colony stimulating factor, IFN-γ induced protein 10 kDa, and tumor necrosis factor-α exhibited the most elevated levels among all kinds of inflammatory cytokines. The correlation analysis showed at least eight cytokines contributing to the changes of CD4/CD8 ratio.

Rasch analysis of the Chinese version of the clinically useful depression outcome scale in patients with major depressive disorder.

OBJECTIVE: To examine the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale (CUDOS) in the Chinese patients with major depressive disorder (MDD) using Rasch analysis. METHODS: The sample consisted of 283 patients with MDD (69% females). The Rasch model was applied to examine the overall fit of the Chinese version of CUDOS and the fit of the 18 items. Dimensionality, item-model fit, differential item functioning (DIF), reliability, ordering of response category and targeting were tested to examine the psychometric properties of the Chinese version of CUDOS. RESULTS: Rasch analysis demonstrated the unidimensionality of the Chinese version of CUDOS. Of the 18 items, three items (item 4, item 5, item 6) showed misfit in the model. After merging item 4 into item 3 and item 6 into item 5, the overall model fit improved. The person separation index (PSI) was 3.0 and the person reliability coefficient was 0.90. No evidence of significant DIF was found when associated with gender and age. No disordered category and threshold of the rating response were observed, which meant the response category setting was reasonable. The mean ability of person was - 0.53. CONCLUSION: The results suggested that the Chinese version of CUDOS has acceptable psychometric properties. In order to improve the quality and applicability of the Chinese version of CUDOS, the merging of item 4 into item 3 and item 6 into item 5 are suggested.

The default mode network is affected in the early stage of simian immunodeficiency virus infection: a longitudinal study.

Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network. Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy. Specifically, when brain imaging data at only one time point are analyzed, determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome. However, because infection times and other factors are often uncertain, longitudinal studies cannot be conducted directly in the clinic. Therefore, in this study, we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection. We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation. Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field (FEF). L, area 8/FEF.L and caudal temporal parietal occipital area (TPOC).R, and area 31/V6.R and TPOC.L. ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent. These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.

Immune checkpoint inhibitor-associated arthritis in advanced pulmonary adenocarcinoma: A case report.

BACKGROUND: With the wide application of immune checkpoint inhibitors (ICIs) in cancer treatment, immune-related adverse events occur frequently, involving almost all organs and systems. The incidence of ICI-associated arthritis (IA) is unknown. In most cases, IA is not serious and non-lethal. Higher checkpoint inhibitor arthritis disease activity may be associated with cancer progression. Here, we report a severe case of IA with high arthritis disease activity in advanced pulmonary adenocarcinoma, causing permanent withdrawal of pembrolizumab, but the patient remained in complete remission (CR) 20 mo after the development of IA. CASE SUMMARY: An 81-year-old smoking man was admitted to our hospital because of left chest pain for 9 mo. He was finally diagnosed with advanced pulmonary adenocarcinoma, with programmed cell death 1 ligand 1 expression of 70%. The patient responded to pembrolizumab treatment and achieved CR, but IA occurred after the 5th cycle of pembrolizumab administration. Although non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs were prescribed, arthralgia and joint swelling occurred. The symptoms of arthritis were further aggravated when immunotherapy was given again after short-term withdrawal. Clinical Disease Activity Index (CDAI) score, a traditional measure of arthritis activity, was 43. Intravenous methylprednisolone was prescribed at 20 mg/d and then tapered over the subsequent 4 wk. The symptoms of arthritis steadily improved and completely resolved 4 mo after withdrawal of pembrolizumab. A recent follow-up in June 2022 revealed satisfactory clinical recovery of arthritis and the patient remained in CR. CONCLUSION: This case report highlights that early recognition of IA and appropriate treatment are critical to improving the outcome of both ICI-arthritis and lung cancer.

Equating the PHQ-9 and GAD-7 to the HADS depression and anxiety subscales in patients with major depressive disorder.

OBJECTIVE: The present study aimed to equate the 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7) to the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscales (HADS-D,HADS-A) respectively in patients with major depressive disorder (MDD) and generate crosswalks of raw scores. METHODS: As it is a single group design that adopts common-person equating method, a total of 460 patients with MDD completed the PHQ-9, GAD-7 and HADS at the same time. Rasch analysis was used to filter out invalid participants, investigate the psychometric properties of test items and participants, link the PHQ-9 and HADS-D as well as GAD-7 and HADS-A, and produce conversion tables respectively. The differences between original scores and converted scores were analyzed to validate the crosswalks. RESULT: 401 samples of depression part and 396 samples of anxiety part were left for final samples. Both the PHQ-9 / HADS-D and GAD-7 / HADS-A combined analysis adequately fit the unidimensional Rasch model, demonstrated acceptable reliability and item-person targeting and showed no disordering category. Slight differential item functioning across gender was found in item PHQ9 and item GAD6. The crosswalks were generated and verified to be validity. LIMITATIONS: The results might be restricted to patients with MDD recruited in a single mental health center. CONCLUSION: The PHQ-9, GAD-7 and HADS depression and anxiety subscales were successfully linked, producing conversion tables that could be used for directly converting raw score from one instrument to the other.

Macular Changes Observed on Optical Coherence Tomography Angiography in Patients Infected With Human Immunodeficiency Virus Without Infectious Retinopathy.

Purpose: As the human immunodeficiency virus (HIV) pandemic is far from over, whether there are subclinical macular changes in HIV-positive patients is something that should not be overlooked. We aimed to apply optical coherence tomography angiography (OCTA) to assess the macular structure and microvasculature changes in patients with HIV without infectious retinopathy. Methods: HIV-positive and -negative participants were included and classified into three groups: HIV-negative, HIV-positive, and HIV-positive with microvasculopathy. OCTA parameters regarding macular structure and microvasculature were analyzed. Results: Compared with the HIV-negative group, the superficial retinal vessel density (VD) in the parafovea sectors and the whole Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and the choroidal vascularity index (CVI) in the whole ETDRS grid were significantly decreased in the HIV-positive and HIV-positive with microvasculopathy groups (p < 0.05). No differences were found in OCTA parameters between the HIV-positive and HIV-positive with microvasculopathy groups. Retinal, retinal nerve fiber layer-ganglion cell layer-inner plexiform layer (RNFL-GCL-IPL), RNFL, GCL-IPL, and INL thickness showed a negative association with the duration of HIV diagnosis or antiretroviral therapy (ART) (all p < 0.05). All OCTA microvasculature parameters showed no association with HIV-related clinical variables (all p > 0.05). Conclusions: Subclinical macular changes existed in HIV-infected patients without clinical infectious retinopathy. Substructures from inner retinal layers might be associated with HIV infection or ART duration.

A Chinese adaptation of six items, self-report Hamilton Depression Scale: Factor structure and psychometric properties.

OBJECTIVES: The objective of this research was to verify the psychometric characteristics of the Chinese Adaptation of self-report HAMD-6. METHODS: Outpatients and inpatients who met the DSM-5 criterion for major depressive disorder (MDD) were evaluated by the Chinese self-report HAMD-6, seventeen items of Hamilton Depression Rating Scale (HAMD-17), Patient Health Questionnaire Depression Scale (PHQ-9) and Improved Clinical Global Impression Scale (iCGI-S). The internal consistency reliability, retest reliability, criterion validity and construct validity of the Chinese self-report HAMD-6 were tested. Pearson correlation coefficient was used to assess the correlativity between the total score and the item scores. By drawing the Receiver Operating Characteristics (ROC) curve, the best cut-off value, sensitivity and specificity of Chinese Adaptation self-report HAMD-6 were obtained. RESULTS: Cronbach's alpha coefficient of the Chinese self-report HAMD-6 was 0.91, and the intra-group correlation coefficient (ICC) of retest reliability was 0.81(P < 0.01). The Spearman correlation coefficients of the Chinese self-report HAMD-6, Chinese clinician version of HAMD-6, PHQ-9 and HAMD-17 were 0.86, 0.81 and 0.86, respectively (all P < 0.01). Results of the confirmatory factor analysis (CFA) supported a unidimensional construct. In addition, HAMD-17 ≤ 7 and iCGI-S= 1 were taken as the remission criteria for depression disorder, and the ROC curves of the Chinese self-report HAMD-6 were plotted with a cut-off value of 3/4, the specificity and sensitivity were 0.85/0.92 and 0.96/0.93 respectively. CONCLUSION: These results suggested that the abbreviated Chinese self-report HAMD-6 has good reliability and validity among the Chinese population. This study suggested that the remission cut-off value of the scale is 3/4.

Clinical characteristics in the misdiagnosis of cytomegalovirus retinitis: A retrospective analysis of eight patients.

Purpose: To highlight characteristics in the misdiagnosis of cytomegalovirus retinitis (CMVR). Methods: Misdiagnosed cases related to CMVR were analyzed retrospectively at the Department of Ophthalmology, Beijing Youan Hospital, from July 2017 to October 2019. The medical records were reviewed by two independent senior ophthalmologists and the patients' clinical characteristics were analyzed. Results: Eight patients (16 eyes) were identified with misdiagnoses related to CMVR. Six of the patients with CMVR were previously unaware of their human immunodeficiency virus (HIV) infection; one patient with CMVR concealed their history of HIV infection. The cases were initially misdiagnosed as diabetic retinopathy (1/7, 14.3%), branch retinal vein occlusion (1/7, 14.3%), ischemic optic neuropathy (1/7, 14.3%), Behçet's disease (1/7, 14.3%), iridocyclitis (2/7, 28.6%), and progressive outer retinal necrosis (1/7, 14.3%). One patient with binocular renal retinopathy and chronic renal insufficiency was misdiagnosed with CMVR. Four eyes (4/16, 25%) presented with pan-retinal involvement. Fourteen eyes (14/16, 87.5%) had optic disc or macular area involvement. At the final diagnosis, one patient was blind, and two patients had low vision. Seven AIDS patients showed an extremely low level of CD4+ T lymphocytes (median of 5 cells/µl; range 1-9 cells/µl). Conclusion: CMVR may be misdiagnosed in the absence of known immune suppression. CMVR and HIV screening cannot be overlooked if a young male patient presents with yellowish-white retinal lesions. These misdiagnosed patients had severe retinitis associated with poor vision.

High Blood Cytomegalovirus Load Suggests Cytomegalovirus Retinitis in HIV/AIDS Patients: A Cross-Sectional Study.

PURPOSE: To clarify the cut off value of blood CMV load to indicate CMV retinitis and its relationships with ocular features. METHODS: Patients were divided into non-CMV and CMV retinitis groups. A logistic regression model was applied to estimate the association of each variable with CMV retinitis. Spearman correlation was used to estimate the correlation between the blood and aqueous CMV load. RESULTS: Blood CMV load higher than 4log10 (OR, 6.897; CI: 2.813-16.910; P < .001) was the major predictor of CMV retinitis. Blood CMV load wasn't different between the initial and early stage (P = .066). No correlation was observed between the blood and aqueous CMV load (P = .083, r = 0.228). CONCLUSIONS: Blood CMV load higher than 4log10 is an important predictor for CMV retinitis in HIV/AIDS patients, but it couldn't indicate the ocular features. Ophthalmologic screening is still necessary.Abbreviations: CMV: Cytomegalovirus; CMVR: Cytomegalovirus retinitis; HIV: Human Immunodeficiency Virus; AIDS: Acquired Immune Deficiency Syndrome; ART: Antiretroviral therapy; EOD: End-organ diseases; PCR: Polymerase Chain Reaction; OR: Odds Ratio; CI: 95% Confidence Interval; IQR: Interquartile range.

5'-AMP-activated protein kinase (AMPK) regulates progesterone receptor transcriptional activity in breast cancer cells.

The steroid hormone progesterone is an essential regulator of the cellular processes that are required for the development and maintenance of reproductive function. The diverse effects of progesterone are mediated by the progesterone receptor (PR). The functions of the PR are regulated not only by ligands but also by modulators of various cell signaling pathways. However, it is not clear which energy state regulates PR activity. AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, is a key modulator of energy homeostasis. Once activated by an increasing cellular AMP:ATP ratio, AMPK switches off ATP-consuming processes and switches on ATP-producing processes. We found that both 5-aminoimidazole-4-carboxamide 1-ß-d-ribofuranoside (AICAR) and metformin, traditional pharmacological activators of AMPK, inhibited the PR pathway, as evidenced by progesterone response element (PRE)-driven luciferase activity and PR target gene expression. Compound C, an inhibitor of AMPK, partly but significantly reversed the anti-PR effects of AICAR and metformin. The downregulation of endogenous AMPK by small interfering RNAs (siRNAs) stimulated PR activity. AMPK activation by AICAR decreased the progesterone-induced phosphorylation of PR at serine 294 and inhibited the recruitment of PR to an endogenous PRE. Taken together, our data suggest that AMPK, an energy sensor, is involved in the regulation of PR signaling.

Clinical analysis of skin lesions in 796 Chinese HIV- positive patients.

Skin lesions are often associated with human immunodeficiency virus (HIV) infection, reflecting the immunocompromised status of the individual. We investigated the relationship between skin lesions and immune function in a retrospective study of 796 Chinese HIV patients with and without highly active antiretroviral therapy (HAART). Of the 651 patients who had not received HAART, we found that 531 (81.6%) had apparent skin lesions. The incidence of infectious skin diseases (fungi, viruses, bacteria, spirochetes and parasites) and non-infectious skin diseases (excluding skin cancer) was 68.8% and 34.9%, respectively. Mean CD4(+) T-cell counts and CD4(+)/CD8(+) ratios were lower in patients with skin lesions than in patients without lesions (178 ± 96/µl vs. 306 ± 189/µl (p < 0.05) and 0.22 vs. 0.34 (p < 0.01), respectively). Candidiasis (25.8%), eczema (19.2%), nodular prurigo (13.8%), dermatophyte infections (10.6%) and herpes zoster (9.4%) were most common in Chinese patients with HIV. Among the 145 patients who had started HAART, there was a significantly lower prevalence of skin diseases (29.0%), although drug eruptions (12.4%) were more commonly observed. These findings indicate that HAART often reduces the incidence of infectious and non-infectious skin lesions in patients with HIV, but can itself be the cause of drug eruptions.

Psychometric Properties of the Chinese Version of the Clinically Useful Depression Outcome Scale for Patients with Major Depressive Disorder.

OBJECTIVE: This study aimed to evaluate the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale (CUDOS). METHODS: One hundred ninety patients with major depressive disorder (MDD) according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria were recruited to the study. The English version of the CUDOS was translated into Chinese using a forward and backward translation method, which was according to the guidelines of adaptation and validation of instruments in cross-cultural health care research. The Chinese version of the CUDOS, the 17-item Hamilton Rating Scale for Depression (HRSD) and the improved Clinical Global Impression-Severity Scale (iCGI-S) were used to evaluate depressive symptoms in one hundred ninety patients with MDD. One week after the first evaluation, sixteen patients were selected randomly for a second assessment. Reliability and validity tests and receiver operating characteristic curves were performed. RESULTS: The internal consistency of the CUDOS was 0.95, and the split-half reliability coefficient of the CUDOS was 0.92. The correlation coefficient of the retest in sixteen patients was 0.77 (P < 0.01). There was a significant difference in the total score of the Chinese version of the CUDOS between the different levels of depression severity groups (P < 0.01). The ability of the CUDOS to identify patients in remission was high (area under ROC curve= 0.97). A cut-off score of 14/15 yielded 90.20% sensitivity and 93.60% specificity when iCGI-S=1. CONCLUSION: The Chinese version of the CUDOS is valuable as a brief and reliable instrument to assess depressive symptoms and clinical outcome. The findings suggest that the optimal cut-off score to identify patients in remission was 14/15.

Macular Structure and Microvasculature Changes in AIDS-Related Cytomegalovirus Retinitis Using Optical Coherence Tomography Angiography.

Background: Cytomegalovirus retinitis (CMVR) is a crucial blind-causing disease of AIDS-related ocular opportunistic infection. The CMVR lesions produced retinal necrosis. It is not entirely clear whether CMVR eyes without macular-involved necrotic lesions may have subtle macular damage. In this study, we conducted a cross-sectional study using optical coherence tomography angiography (OCTA) to evaluate macular microvasculature and structure in eyes with AIDS-related CMVR. Methods: Acquired immune deficiency syndrome (AIDS)-related CMVR patients (active and inactive CMVR) and healthy controls treated in the Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University between August 25, 2019, and October 18, 2019, were recruited. All OCTA parameters, including the foveal avascular zone (FAZ), retinal vessel density (VD), choroidal vascularity index (CVI), retinal thickness, and choroidal thickness, were compared between groups after the signal strength was corrected. Results: Signal strength in the 3 × 3 and 6 × 6 mm scan patterns was significantly weaker in the inactive CMVR group than in the control group (both p < 0.001). After adjusting for signal strength, heterogeneity in the central fovea and parafoveal quadrants was present with a shift toward lower macular chorioretinal vasculature, decreased full choroidal thickness, and thicker retinal thickness in the active and inactive CMVR groups. The retinal nerve fiber layer (RNFL) and inner nuclear layer (INL) were significantly thicker in the active and inactive CMVR groups than in the control group (all p < 0.05). For photoreceptor-retinal pigment epithelium (PR-RPE) thickness, no significant differences were found in any quadrant between groups. Foveal avascular zone areas were not significantly different among the three groups (p = 0.053). Conclusions: Subtle macular structure and microvasculature damage still existed in CMVR eyes without macular-involved necrotic lesions. The results of our study are helpful for a deep understanding of the damage caused by CMVR.

Switching from efavirenz to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide reduces central nervous system symptoms in people living with HIV.

BACKGROUND: Central nervous system (CNS) symptoms after efavirenz (EFV) treatment in people living with human immunodeficiency virus (HIV) could persist and impact their quality of life. We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF), which is considered an alternative option for subjects who do not tolerate EFV. Most specifically, we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants' neuropsychiatric toxicity symptoms in a real-life setting. METHODS: A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity ≥ grade 2. The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks. The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire, as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index. The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12, 24, and 48. Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch. RESULTS: One hundred ninety-six participants (96.9% men, median age: 37.5 years, median: 3.7 years on prior EFV-containing regimens) were included in the study. Significant improvements in anxiety and sleep disturbance symptoms were observed at 12, 24, and 48 weeks after switching to E/C/F/TAF (P < 0.05). No significant change in depression symptom scores was observed. At 48 weeks after switch, HIV viral load <50 copies/mL was maintained in all of the participants, median fasting lipid levels were moderately increased (total cholesterol [TC]: 8.2 mg/dL, low-density lipoprotein cholesterol [LDL-C]: 8.5 mg/dL, high-density lipoprotein cholesterol [HDL-C]: 2.9 mg/dL, and triglyceride (TG): 1.6 mg/dL, and the TC:HDL-C ratio remained stable. CONCLUSIONS: The single-pill combination regimens E/C/F/TAF is safe and well tolerated. This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.

Histopathological features of multiorgan percutaneous tissue core biopsy in patients with COVID-19.

AIMS: The global outbreak of COVID-19 has resulted in an increased mortality. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs is still unclear. In this study, postmortem percutaneous biopsies of multiple organs from deceased patients were performed to understand the histopathological changes caused by COVID-19. METHODS: Biopsy specimens of pulmonary, cardiac, hepatic and lymphoid tissues were obtained from three patients, who died due to COVID-19 pneumonia. H&E stain, Masson trichrome stain, immunohistochemistry stain and in-situ hybridisation were used. RESULTS: Pulmonary damages caused by SARS-CoV-2 infection was diffuse alveolar damage (DAD). In the early phase, the histological findings were mainly those of exudative features of DAD. The later phase was characterised by organisation of DAD combined with bacterial pneumonia. No serious damage was found in the bronchiolar epithelium and submucosal glands. The hepatic tissue revealed features of ischaemic necrosis, but findings suggestive of mild lobular hepatitis were also observed. The lymphoid tissue revealed features of non-specific acute lymphadenitis. The cardiac tissue revealed changes of underlying disease. SARS-CoV-2 RNAs were not detected in hepatocytes, cholangiocytes and lymphocytes of lymph nodes. CONCLUSIONS: COVID-19 predominantly involves the pulmonary tissue, causes DAD and aggravates the cardiovascular disease. However, other extrapulmonary tissues did not reveal any virus-specific findings, but were affected by multiple factors. The findings in this report caution the pathologists that they should not mistakenly attribute all the histological features to CoV infection. Moreover, the clinicians should pay attention to the potentially injurious and correctable causes.