SARS-CoV-2 nucleocapsid protein, rather than spike protein, triggers a cytokine storm originating from lung epithelial cells in patients with COVID-19.

PURPOSE: The aim of this study was to elucidate the factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may initiate cytokine cascades and correlate the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with their serum cytokine profiles. METHODS: Recombinant baculoviruses displaying SARS-CoV-2 spike or nucleocapsid protein were constructed and transfected into A549 cells and THP-1-derived macrophages, to determine which protein initiate cytokine release. SARS-CoV-2-specific antibody titers and cytokine profiles of patients with COVID-19 were determined, and the results were associated with their clinical characteristics, such as development of pneumonia or length of hospital stay. RESULTS: The SARS-CoV-2 nucleocapsid protein, rather than the spike protein, triggers lung epithelial A549 cells to express IP-10, RANTES, IL-16, MIP-1α, basic FGF, eotaxin, IL-15, PDGF-BB, TRAIL, VEGF-A, and IL-5. Additionally, serum CTACK, basic FGF, GRO-α, IL-1α, IL-1RA, IL-2Rα, IL-9, IL-15, IL-16, IL-18, IP-10, M-CSF, MIF, MIG, RANTES, SCGF-ß, SDF-1α, TNF-α, TNF-ß, VEGF, PDGF-BB, TRAIL, ß-NGF, eotaxin, GM-CSF, IFN-α2, INF-γ, and MCP-1 levels were considerably increased in patients with COVID-19. Among them, patients with pneumonia had higher serum IP-10 and M-CSF levels than patients without. Patients requiring less than 3 weeks to show negative COVID-19 tests after contracting COVID-19 had higher serum IP-10 levels than the remaining patients. CONCLUSION: Our study revealed that nucleocapsid protein, lung epithelial cells, and IP-10 may be potential targets for the development of new strategies to prevent, or control, severe COVID-19.

Immune Reconstitution Inflammatory Syndrome Induced by Mycobacterium avium Complex Infection Presenting as Chronic Inflammatory Demyelinating Polyneuropathy in a Young AIDS Patient.

Antiretroviral therapy (ART) can restore protective immune responses against opportunistic infections (OIs) and reduce mortality in patients with human immunodeficiency virus (HIV) infections. Some patients treated with ART may develop immune reconstitution inflammatory syndrome (IRIS). Mycobacterium avium complex (MAC)-related IRIS most commonly presents as lymphadenitis, soft-tissue abscesses, and deteriorating lung infiltrates. However, neurological presentations of IRIS induced by MAC have been rarely described. We report the case of a 31-year-old man with an HIV infection. He developed productive cough and chronic inflammatory demyelinating polyneuropathy (CIDP) three months after the initiation of ART. He experienced an excellent virological and immunological response. Sputum culture grew MAC. The patient was diagnosed with MAC-related IRIS presenting as CIDP, based on his history and laboratory, radiologic, and electrophysiological findings. Results: Neurological symptoms improved after plasmapheresis and intravenous immunoglobulin (IVIG) treatment. To our knowledge, this is the first reported case of CIDP due to MAC-related IRIS. Clinicians should consider MAC-related IRIS in the differential diagnosis of CIDP in patients with HIV infections following the initiation of ART.

Early Seroreversion After 2 Doses of Hepatitis A Vaccination in Human Immunodeficiency Virus-Positive Patients: Incidence and Associated Factors.

Serological responses (Seroresponse) and durability of hepatitis A virus (HAV) vaccination are reduced among human immunodeficiency virus (HIV)-positive patients. Incidence of and associated factors with early seroreversion (loss of seroresponse) among HIV-positive patients who have achieved seroresponses after two doses of HAV vaccination remain unclear. In this multicenter study, we followed HIV-positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis A between 2015 and 2017, a 1:4 case-control study was conducted to identify factors associated with seroreversion. Case patients were those with seroreversion, and controls were those with similar follow-up durations who were able to maintain seroresponses. During the study period, 49 of the 1,256 patients (3.9%) seroreverted after a median follow-up of 611 days. In a case-control study, seroreversion was more likely to occur in patients with a higher weight (adjusted odds ratio [aOR], 1.703; 95% confidence interval [CI], 1.292-2.323, per 10-kg increment) and HIV viremia at the time of vaccination (aOR, 2.922; 95% CI, 1.067-7.924), whereas positive seroresponse at 6 months of HAV vaccination and higher CD4 lymphocyte counts at vaccination were inversely associated with early seroreversion with an aOR of 0.059 (95% CI, 0.020-0.154) and 0.837 (95% CI, 0.704-0.979, per 100-cell/mm3 increment), respectively, in multivariable analyses. Conclusion: During an outbreak setting, early seroreversion following two-dose HAV vaccination occurred in 3.9% of HIV-positive patients. Lower and delayed seroresponses to HAV vaccination, a higher weight, and HIV viremia and lower CD4 lymphocyte counts at the time of HAV vaccination were associated with early seroreversion. Regular monitoring of seroresponse and booster vaccination might be warranted, especially in HIV-positive adults with predictors of early seroreversion.

Demographic differences in people living with HIV according to recruitment sources: comparison between health-care systems and social media networks.

With the improvement of internet technology in health applications, the utilization of internet and social media as new survey methodologies and recruitment source for research participants have been encouraged, yet evidence of the feasibility in people living with HIV (PLHIV) study is still lacking. We conducted a cross-sectional survey to determine whether there are differences among PLHIV recruited from social media networks and health-care systems using an HIV stigma and discrimination questionnaire. The result revealed that PLHIV recruited from social media networks were younger, more sexually active, and had higher educational status and awareness of the country's HIV rights protection laws than those recruited from hospitals. By contrast, participants recruited from hospitals were more diverse regarding key population compositions, had lived with HIV for a longer duration, had a higher prevalence of concomitant physical disabilities than those recruited from social media networks, and fit Taiwan PLHIV characteristics described by 2016 census from Taiwan Centres for Disease Control. We conclude that sampling bias exists when utilizing social media networks for PLHIV studies.

Positive Anti-SSA/Ro Antibody in a Woman with SARS-CoV-2 Infection Using Immunophenotyping: A Case Report.

The clinical spectrum of novel coronavirus infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia, with respiratory failure and even death. Autoantibodies, especially antiphospholipid antibodies, can occur in severe infections. Other autoantibodies are seldom reported. Here, a 60-year-old female patient without dry-mouth symptoms detected positive for anti-60 kDa SSA/Ro antibodies on day 43 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To investigate this unique clinical case of SARS-CoV-2 infection, immunological characteristics of this case were detected by using flow cytometry and were compared to the other three groups of patients-health subjects, 2019 novel coronavirus disease (COVID-19) recovery patients, and Sjögren's syndrome (SS) patients. Monitoring the autoantibody level and the development of subsequently related autoimmune diseases are warranted after SARS-CoV-2 infection.

Anti-inflammatory and anti-osteoarthritis effects of Cm-02 and Ck-02.

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive deterioration of articular cartilage. There have been reports that small molecule inhibitors have anti-osteoarthritis effects; however, the effects of 3-(4-chloro-2-fluorophenyl)-6-(2,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Cm-02) and 6-(2,4-difluorophenyl)-3-(3,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Ck-02), small molecule inhibitors which share many structural similarities with quercetin (a potent anti-inflammatory flavonoid), remain unclear. In this study, TNF-α-stimulated porcine and human chondrocyte models were used to investigate the inhibitory effects of Cm-02 and Ck-02 on the molecular mechanisms underlying the anti-OA effects. TNF-α was used to stimulate porcine and human chondrocytes to mimic immunomodulatory potency in-vitro. Anti-osteoarthritic effects were characterized in terms of protein and mRNA levels associated with the pathogenesis of OA. We also examined (1) the inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system in cultured chondrocytes, (2) matrix metalloproteinases (MMPs) in cultured chondrocytes, and (3) aggrecan degradation in cartilage explants. Finally, we tested the activation of nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), and activate the protein-1 (AP-1), and we tested the signal transduction and activation of transcription-3 (STAT-3). Our results indicate that, in chondrocytes, Cm-02 and Ck-02 inhibit TNF-α induced NO production, iNOS, MMP, the expression of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the enzyme activity of MMP-13. Furthermore, both Cm-02 and Ck-02 were found to stimulate TNF-α, which has been shown to suppress the activation of several transcription factors, including NF-κB, STAT-3, and IRF-1 in porcine and human chondrocytes. Cm-02 and Ck-02 were also found to help prevent the release of proteoglycans from cartilage explants. Our findings demonstrate that both Cm-02 and Ck-02 have potent anti-inflammatory activities and the ability to protect cartilage in an OA cell model. These findings indicate that Cm-02 and Ck-02 have the potential to be further developed for the therapeutic treatment of OA.

Association between pneumococcal pneumonia and venous thromboembolism in hospitalized patients: A nationwide population-based study.

BACKGROUND AND OBJECTIVES: This was a nationwide population-based retrospective cohort study to investigate the risk of developing deep-vein thrombosis (DVT) and pulmonary embolism (PE) in patients with a pneumococcal pneumonia. METHODS: We analysed data from 1998 to 2010 from the Taiwan National Health Insurance Database. The follow-up period was extended to the end of 2011. We identified patients with pneumococcal pneumonia and selected a comparison cohort matched for age, sex and diagnosis year at a ratio of one pneumococcal pneumonia patient to four control patients. We analysed the risks of DVT and PE by using Cox proportional hazards regression models, including gender, age and comorbidities. RESULTS: In total, 18,928 pneumococcal pneumonia patients and 75,712 controls were included in the study. The risks of developing DVT and PE were 1.78-fold (95% CI: 1.39-2.28) and 1.97-fold (95% CI: 1.43-2.72), respectively, in patients with pneumococcal pneumonia compared to the control cohort after adjusting for age, gender and comorbidities. The increased risks of DVT and PE were significant in patients who exhibited any comorbidity. The incidences of DVT and PE were highest in the first 4 weeks after pneumonia and remained slightly elevated from 13 weeks to 2 years after acute infection. CONCLUSION: Pneumococcal pneumonia should be considered a risk factor for DVT and PE, even after the patient has recovered from the acute infection.

Increased lung cancer risk among patients with pneumococcal pneumonia: a nationwide population-based cohort study.

BACKGROUND: The possible effects of pneumonia on subsequent lung cancer have been reported, but no relevant publications have focused on the association between pneumococcal pneumonia and lung cancer. The purpose of this study was to perform a nationwide population-based cohort study to investigate the risk of lung cancer after pneumococcus infection. METHODS: This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database. In total, 22,034 pneumococcal pneumonia patients and 88,136 controls, matched for age and sex, were recruited for the study from 1997 to 2010. RESULTS: The incidence rate of lung cancer (28.2 per 1,000 person-years) was significantly higher in pneumococcal pneumonia patients than in controls (8.7 per 1,000 person-years; incidence rate ratio, 3.25; 95 % confidence interval, 3.09-3.42; p < 0.001). Cox proportional hazards regression analysis showed a hazard ratio of 4.24 (95 % confidence interval, 3.96-4.55) for the pneumococcal pneumonia cohort after adjustment for age, gender, and comorbidities. CONCLUSIONS: Pneumococcal pneumonia is associated with an increased risk of lung cancer. Thus, physicians should remain aware of this association when assessing patients with pneumococcal pneumonia.

Anti-Jo-1 myositis and the antiphospholipid syndrome showing right ventricular thrombus: a novel overlap syndrome with atypical presentation.

It has long been recognized that patients with myositis and positive anti-Jo1 antibody tend to be associated with interstitial lung disease. Recent studies revealed that such patients may also have fever, Raynaud's phenomenon, mechanic's hand, polyarthralgia, or usually mild, self-limiting, non-erosive or erosive polyarthritis known as antisynthetase syndrome. The hallmark of this disorder is the presence of the autoantibodies that recognize the aminoacyl-tRNA synthetases, which play a critical role in protein synthesis. The most well recognized of the autoantibodies is anti-histidyl (Jo-1). Antisynthetase syndrome cases associated with other autoimmune diseases are rarely reported. We here present a case of antisynthetase syndrome presented with right ventricle thrombus and deep vein thrombosis in the lower limbs. Secondary antiphospholipid syndrome was then diagnosed after a series of examinations. The patient was successfully treated with anticoagulant alone without surgical thrombectomy. Our case revealed that clinical physicians should watch for thrombotic complications when facing patients with antisynthetase syndrome. Medical therapy with anticoagulants alone may be an alternative treatment option in patients with right ventricle thrombus who cannot tolerate surgical thrombectomy.

A randomized, phase I, 3-way crossover study to examine the effects of food on the pharmacokinetics of single doses of 400 mg posaconazole oral suspension in healthy male Taiwanese subjects.

PURPOSE: The pharmacokinetic parameters of a single 400-mg oral dose of posaconazole suspension, administered under fasting and fed conditions, were compared in healthy male Taiwanese volunteers. METHODS: After an overnight fast, 16 subjects received a single oral dose of posaconazole suspension (400 mg) under fasting conditions or immediately after a normal-fat (700-800 calories, 30% fat) or high-fat breakfast meal (800-1000 calories, 50% fat). The treatments were administered as per the 3 × 6 Williams square design, with a 1-week washout phase between treatments. Blood samples were drawn at predetermined time points (0, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours). All plasma concentrations of posaconazole were measured by high-performance liquid chromatography. The observed maximum plasma concentration (C max), area under the plasma concentration-time curve (AUC 0-t and AUC 0-∞), time to reach C max (t max), and plasma half-life (t 1/2) were assessed. RESULTS: Fourteen subjects completed the study; 2 subjects withdrew because of adverse events. Thirteen subjects were included in the pharmacokinetic analysis. Sixteen subjects were included in the safety analysis. The mean posaconazole C max, AUC 0-t, and AUC 0-∞ values were significantly lower under fasting conditions than after a normal- or a high-fat meal. The mean C max values under fasting, normal-fat, and high-fat conditions were 279.00 ± 123.32 ng/mL, 662.46 ± 251.02 ng/mL, and 608.38 ± 183.22 ng/mL, respectively (P < 0.0001); the mean AUC 0-t values under each condition were 6828.56 ± 3349.12 ng · mL(-1) · h(-1), 20,629.84 ± 8346.45 ng · mL(-1) · h(-1), and 20,741.09 ± 7681.02 ng · mL(-1) · h(-1), respectively (P < 0.0001); and the mean AUC 0-∞ values under each condition were 7304.72 ± 3444.54 ng · mL(-1) · h(-1), 21,326.65 ± 8495.01 ng · mL(-1) · h(-1), and 21,626.08 ± 8193.31 ng · mL · h(-1), respectively (P < 0.0001). The mean t max value was significantly shorter at 3.15 hours under fasting conditions than at 4.88 hours after normal- or high-fat meals (P = 0.0176). The mean t 1/2 values were 22.0, 20.8, and 22.0 hours, respectively. CONCLUSIONS: The posaconazole AUC increased by approximately 3-fold, C max by 2.2-fold, and t max by 1.5-fold when healthy Taiwanese subjects were administered the drug with food compared with under fasting conditions. These parameters were similar when the drug was administered with either a normal- or high-fat meal.

Association of protein disulfide isomerase family A, member 4, and inflammation in people living with HIV.

OBJECTIVES: Protein disulfide isomerase (PDI) family members are specific endoplasmic reticulum proteins associated with inflammation, obesity, and cancer. In HIV infection, the role of PDI family A, member 4 (PDIA4), is unclear. This study aimed to clarify the association between plasma PDIA4 levels and inflammation in people living with HIV (PLWH). METHODS: In this study, 287 PLWH and 74 healthy participants were enrolled. The plasma PDIA4 values, demographic data, laboratory data, and other inflammatory markers were recorded. The association between PDIA4 level and inflammatory extent was analyzed using logistic regression and Spearman rank-order correlations. Other results were analyzed using Student's t-test or chi-square test. RESULTS: In PLWH, the PDIA4 levels were positively associated with the inflammatory markers, interleukin 6 (r = 0.209, p = 0.001), and tumor necrosis factor-α (r = 0.162, p = 0.01) levels, but not with high-sensitivity C-reactive protein levels. Moreover, the plasma PDIA4 level of PLWH decreased after anti-viral treatment (p = 0.0001). CONCLUSION: Plasma PDIA4 levels are closely associated with inflammation in PLWH and have a positive correlation with the viral load during anti-viral therapy.

Hidden diagnosis of Tuberculous pleurisy masked by concomitant Pseudomonas oryzihabitans bacteremia.

The clinical presentations of tuberculous pleurisy are usually nonspecific and have an insidious course, thus resulting in diagnostic challenges. Pseudomonas oryzihabitans is a nonfermenting, oxidase-negative, catalase-positive, Gram-negative bacillus that has rarely been encountered as a human pathogen. We present the case of a 30-year-old male patient who exhibited intermittent fever despite antibiotic treatment for Pseudomonas oryzihabitans bacteremia for 6 days. Tuberculous pleurisy was finally diagnosed by histopathologic and microbiologic studies. He recovered after a 2-week antibiotic course and 6-month antituberculosis treatment.

[Fulminant lobulated lung empyema caused by Pseudomonas aeruginosa]. / Absceso pulmonar y empiema fulminante por Pseudomonas aeruginosa.

We report the case of a 27-year-old man with a history of diabetes mellitus who presented with conscious disturbance, fever, and stiff neck after upper respiratory tract infection. Following diagnosis of meningoencephalitis, antibiotic therapy and deamethasone was initiated. He received endotracheal tube intervention under mechanical ventilation in the intensive care unit, and underwent successful weaning on day 4. One week later, he was diagnosed with pneumonia and a rapidly progressing lung empyema with abscess formation was noted. Microbiological culture of the pleural fluid revealed the presence of Pseudomonas aeruginosa. Nosocomial pneumonia is often caused by Staphylococcus aureus and P. aeruginosa; however, the latter often causes bronchopneumonia rather than fulminant empyema or lung abscess formation. The underlying diabetes mellitus and the history of steroid therapy may explain the present condition of this patient. The possibility of P. aeruginosa being the causative agent should be considered during differential diagnosis in patients presenting with fulminant lung empyema, especially in immunocompromised patients.

Clinical Characteristics of COVID-19 Patients and Application to an Artificial Intelligence System for Disease Surveillance.

During the coronavirus disease (COVID-19) pandemic, we admitted suspected or confirmed COVID-19 patients to our isolation wards between 2 March 2020 and 4 May 2020, following a well-designed and efficient assessment protocol. We included 217 patients suspected of COVID-19, of which 27 had confirmed COVID-19. The clinical characteristics of these patients were used to train artificial intelligence (AI) models such as support vector machine (SVM), decision tree, random forest, and artificial neural network for diagnosing COVID-19. When analyzing the performance of the models, SVM showed the highest sensitivity (SVM vs. decision tree vs. random forest vs. artificial neural network: 100% vs. 42.86% vs. 28.57% vs. 71.43%), while decision tree and random forest had the highest specificity (SVM vs. decision tree vs. random forest vs. artificial neural network: 88.37% vs. 100% vs. 100% vs. 94.74%) in the diagnosis of COVID-19. With the aid of AI models, physicians may identify COVID-19 patients earlier, even with few baseline data available, and segregate infected patients earlier to avoid hospital cluster infections and to ensure the safety of medical professionals and ordinary patients in the hospital.

Pulmonary cryptococcus infection after mono-chemotherapy with gemcitabine.

Mono-chemotherapy with gemcitabine (difluorodeoxycytidine) is an effective cancer chemotherapy, and is often used instead of a more effective but more toxic combination chemotherapy regimen. Infection associated with gemcitabine is very rare. We present a case of Cryptococcus neoformans pneumonia that developed after 5 courses of gemcitabine for advanced bladder carcinoma. Lung biopsy and antigens demonstrated C. neoformans. The pneumonia resolved after antifungal therapy.

Growth arrest-specific 6 protein in HIV-infected patients: Determination of plasma level and different antiretroviral regimens.

BACKGROUND/PURPOSE: Growth arrest-specific 6 (Gas6) protein is involved in cell proliferation, differentiation, adhesion, migration in response to inflammatory processes. Human immunodeficiency virus (HIV) infection induces a chronic inflammatory condition and combination of antiretroviral therapy improves immune function and decreases the inflammatory state. The aim of this study was to assess the implications of Gas6 in chronic inflammation status of HIV-infected patients undergoing different third regimens of antiretroviral therapy. The Gas6 may be a marker of chronic inflammation of HIV-infected patients. METHODS: A total of 356 adult males, including 258 HIV-infected patients and 98 healthy controls, were recruited. The demographic and clinical characteristics of the patients were collected. Laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), hepatitis B and C viruses, and serum biochemistry. Plasma Gas6 concentrations were determined. RESULTS: The values of Gas6 were lower in HIV patients compared to healthy subjects (14.3 ± 6.4 vs 21.5 ± 15.2, p = 0.01). HIV patients that received antiviral regimen with abacavir had similar Gas6 level than those who received antiviral regimens with tenofovir (14.3 ± 6.5 vs 13.8 ± 5.9, p = 0.99). HIV patients that received antiviral regimen with protease inhibitors (PIs) had lower Gas6 level (13.1 ± 3.5 vs 14.2 ± 6.6 vs 14.6 ± 6.5, p = 0.03) than those who received antiviral regimens with non-nucleoside reverse transcriptase inhibitors (nNRTIs) and integrase inhibitors (INSTIs), respectively. CONCLUSIONS: Decreased plasma Gas6 concentrations were observed in HIV patients. Gas6 levels are associated with different third regimen of highly active antiretroviral therapy. Gas6 may represent a unique marker for assessing the chronic inflammation state difference among cART regimens in HIV patients.

Micafungin Inhibits Dengue Virus Infection through the Disruption of Virus Binding, Entry, and Stability.

Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world's population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of ß-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection.

Lung cancer metastatic to the masticator space.

BACKGROUND: Distant metastasis from lung cancer occurs most frequently to the brain, bone, adrenal gland, liver, lymph nodes, and spinal cord. However, masticator space metastasis is rarely found among lung cancer patients. CASE REPORT: We report a case of large cell neuroendocrine carcinoma of the lung with metastasis to the masticator space diagnosed by imaging and histopathological examinations. CONCLUSION: The present case highlights the fact that large cell neuroendocrine carcinoma of the lung can result in an uncommon isolated masticator space metastasis. Clinicians should carefully evaluate cancer patients who report a painful sensation in the cheek. Thorough dental and physical examination, and imaging studies could provide early diagnosis and treatment.

Monitoring early developed low bone mineral density in HIV-infected patients by intact parathyroid hormone and circulating fibroblast growth factor 23.

BACKGROUND/PURPOSE: HIV-infected patients have a high prevalence of low bone mineral density (BMD), but BMD changes remain unclear. This cross-sectional retrospective observational study aimed to characterize the prevalence and associated factors of low BMD in HIV patients. METHODS: Between 1 January 2015 and 31 December 2016, all patients aged 20 years or greater who sought for HIV care were included. BMD was measured by dual-energy X-ray absorptiometry. Multivariable analyses of the association with HIV disease status, treatment and anthropometric parameters were performed. Circulating fibroblast growth factor 23 and intact parathyroid hormone were measured. RESULTS: A total of 137 patients was included; their median age was 39 years old; 97.8% were treated with combination antiretroviral therapy (cART); Body mass index (BMI) was 21.97 kg/m2. Sixty-one patients (44.5%) showed low BMD (osteopenia and osteoporosis) based on the WHO criteria. The median BMD was -0.80 g/cm2 (IQR, -1.5 to -0.2). The prevalence rate of low BMD was 37% in those who were aged 20-29 years, 45.2% in those who were aged 30-39 years, 45.2% in those who were aged 40-49 years, 45.8% in those who were aged 50-59 years, and 53.8% in those who were aged ≧60 years. More than half of patients (50.4%, 69/137) were younger than 40 years. Compared with normal BMD group, the low BMD group has a higher proportion of secondary hyperparathyroidism (18.0% vs 5.3%, p: 0.026) and a lower median C-terminal FGF23 level (48.92 vs 62.61 pg/ml, p: 0.008). Univariate and multivariate analyses of the factors associated with low BMD. We found that only serum intact-parathyroid hormone (iPTH) > 69 pg/ml (OR, 3.86; 95% CI, 1.14-13.09) was statistically significant associated with low BMD in multivariate analysis. CONCLUSIONS: This cohort-based survey showed a high prevalence of low BMD among HIV-infected adults which included young-age patient in an university hospital. Secondary hyperparathyroidism was significantly associated with low BMD. There was no association between FGF23 and low BMD.

Risk of Parkinson disease in Sjögren syndrome administered ineffective immunosuppressant therapies: A nationwide population-based study.

To determine the incidence and risk of Parkinson disease (PD) in patients with Sjögren syndrome (SS) according to a nationwide population-based database.In total, 12,640 patients in the SS cohort and 50,560 in the non-SS cohort were enrolled from Taiwan's National Health Insurance Research Database from 2000 to 2010. We used the Cox multivariable proportional hazards model to determine the risk factors for PD in the SS cohort.We observed an increased incidence of PD in patients with SS, with a crude hazard ratio (HR) of 1.40 and an adjusted HR (aHR) of 1.23. The cumulative incidence of PD was 1.95% higher in the SS cohort than in the non-SS cohort. The SS cohort had an elevated HR under medication use, namely cevimeline and pilocarpine (crude HR, 1.28), hydroxychloroquine (crude HR, 1.43; aHR, 1.46), and methylprednisolone (crude HR, 2.21; aHR, 1.49). Patients receiving other non-hydroxychloroquine immunosuppressant therapies had a lower risk (aHR, 0.86) of PD. Furthermore, patients with SS aged 20 to 49 years had a 1.93-fold higher risk of PD than did those without SS (aHR, 1.93). The risk of PD was higher (aHR, 2.20) in patients with SS without comorbidities than in those with comorbidities. The aHR of PD significantly increased when the follow-up period exceeded 9 years (aHR, 1.93).We determined an increased risk of PD in patients with SS. Further investigation is warranted to determine the possible underlying mechanisms and the potential role of non-hydroxychloroquine immunosuppressants in ameliorating PD.