Multifocal Tuberculosis Verrucosa Cutis: Case Report and Review of the Literature.

Cutaneous tuberculosis (TB) is still a major public health problem worldwide. Tuberculosis verrucosa cutis (TBVC) is a cutaneous form of exogenous TB caused by exogenous reinfection in previously sensitized individuals. TBVC typically presents as a unifocal condition. Multifocal cutaneous lesions without any other tubercular foci are extremely rare in exogenous TB and few cases are reported in the literature. We describe the first case of multifocal TBVC in an 81-year-old Greek man. In total, 14 cases of multifocal TBVC have been reported in the literature (8 males and 6 females), with mean age 47.64 years (SD = 20.75) and mean time to diagnosis of 9.69 years (SD = 15.31). Most cases (11/12) responded rapidly to treatment, implying the accuracy of diagnosis, while no one was reported to be immunocompromised. Finally, in 10 cases (71.4%), history of skin microtrauma was reported (related either to daily life habits or to professional praxis), confirming it as the main risk factor. The tuberculin skin test was positive in 10 cases and tissue culture for mycobacteria was negative in all cases. TBVC can present with multiple lesions, even in countries where TB prevalence is not high, especially in patients with history of skin abrasions. Prompt specialist assessment can expedite the establishment of diagnosis.

Isolation and identification of nontuberculous mycobacteria from hospitalized patients and drinking water samples--examination of their correlation by chemometrics.

Nontuberculous mycobacteria (NTM) have been found to be widely dispersed in the environment and are being considered potentially pathogenic for humans and animals, while reports of their human to human transmission are absent. Water and aerosols are potential transmission modes of NTM to humans. Hospitalized patients with NTM infections were studied together with drinking water samples from their respective residence areas during 2003-2013. Cluster analysis and factor analysis were used to analyze the data matrix. A total of 367 hospitalized patients living in 30 localities in the Prefecture of Larissa were tested positive for NTM. The most frequently isolated NTM species of the 383 NTM isolates from the clinical specimens were Mycobacterium fortuitum (n = 118, 30.8 %), M. gordonae (n = 87, 22.7 %), M. peregrinum (n = 46, 12.0 %), M. chelonae (n = 11, 2.9 %), M. avium (n = 8, 2.1 %), and M. intracellulare (n = 7, 1.8 %), while 88 (23.0 %) of these isolates were not identified. It is noted that in 8 patients, M. tuberculosis was isolated simultaneously with one NTM, in 15 patients, together with two types of NTM, while in 1 patient, it was found at the same time as three different NTM. In addition, 3360 drinking water samples were collected from 30 localities and analyzed during 2010 to 2013; they were found 11.2 % NTM positive. Cluster analysis and factor analysis results confirm that NTM strains are correlated to each other in both isolated samples from patients and drinking water, while the strength of their correlation varied from weak to moderate (e.g., factor loadings ranged from 0.69 to 0.74 when all data are considered). These results provide indications that drinking water could be linked with NTM cases in humans.

Risk assessment of tuberculosis in immunocompromised patients. A TBNET study.

RATIONALE: In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. METHODS: Immunocompromised patients with HIV infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy control subjects were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA), and T-SPOT.TB test (enzyme-linked immunospot) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. MEASUREMENTS AND MAIN RESULTS: Frequencies of positive test results varied from 8.7 to 15.9% in HIV infection (n = 768), 25.3 to 30.6% in chronic renal failure (n = 270), 25.0% to 37.2% in rheumatoid arthritis (n = 199), 9.0 to 20.0% in solid-organ transplant recipients (n = 197), 0% to 5.8% in stem-cell transplant recipients (n = 103), and 11.2 to 15.2% in immunocompetent control subjects (n = 211). Eleven patients (10 with HIV infection and one solid-organ transplant recipient) developed tuberculosis during a median follow-up of 1.8 (interquartile range, 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases per 100 person-years) than with a positive ELISA (1.31 cases per 100 person-years) or enzyme-linked immunospot result (1.78 cases per 100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. CONCLUSIONS: Among immunocompromised patients evaluated in this study, progression toward tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs. Clinical trial registered with www.clinicaltrials.gov (NCT 00707317).

Identifying the Relationship Between Economic Prosperity and Quality of Life in Chronic Obstructive Pulmonary Disease Patients.

Background Chronic obstructive pulmonary disease (COPD) places a significant economic burden on national healthcare systems, and the economic effects of diseases have long been known. The study aimed to evaluate the association of parental family financial wealth with current economic prosperity and the combined effect of both on health-related quality of life (HRQOL) in a sample of patients with COPD. The moderating effect of birth order is further investigated. Methods The results of the study are based on a purposive sample of 105 COPD patients at the Larisa University Hospital pulmonology clinic (94 males and 11 females), with an average age of 68.9 (SD = 9.2). The data collection was carried out in the spring and summer of 2020. Participants completed the 36-item Short Form Survey (SF-36) and a sociodemographic questionnaire with self-reported parental and current wealth items. A mediation model with the moderation of the indirect effect of parental wealth on current wealth and the direct effect of parental wealth on HRQOL was applied to test the research hypotheses among the variables studied. Results Parental wealth was found to affect current wealth significantly, and both were involved considerably in HRQOL. Birth order had a significant moderating effect on the relationship between parental wealth and HRQOL. Among parental families with lower financial status, patients who grew up as third or later children had significantly lower HRQOL than the first or second children of these families. Neither age nor COPD duration was related to current wealth or HRQOL. Conclusions An intergenerational transmission of poverty was found in our sample. In addition, a birth order effect can provide further insight into the harsher environment that the later children of a low-income family are exposed to and the long-term implications for their HRQOL.

Are younger COPD patients adequately vaccinated for influenza and pneumococcus?

Influenza and pneumococcal pneumonia are major causes of increased morbidity and mortality among elderly and COPD patients. Vaccines against influenza and pneumococcus are recommended for COPD patients according to GOLD 2020 guidelines to prevent serious illnesses. Despite their high morbidity and mortality burden, the vaccination coverage rates remain far below the WHO's recommended targets. In Greece, there are insufficient data on influenza and pneumococcal immunization rates among younger COPD patients. This study investigated whether COPD patients under the age of 65 are adequately vaccinated against influenza and pneumococcus and the factors that influence vaccination rates. 1100 individuals at 22 Primary Health Centers in Central Greece participated in a two-year spirometry monitoring program. Face-to-face interviews were used to collect information regarding demographics, smoking status, comorbidities, respiratory illnesses in the previous two years, and influenza and pneumococcal vaccination coverage from all COPD patients. 117 patients aged 40-65 years old were diagnosed with COPD and 80.3% were males. Only 40.2% of them had received influenza and 32.5% pneumococcus vaccinations. Age, advanced stage of COPD, years on COPD diagnosis, respiratory infection within the previous two years, comorbidity, and smoking cessation are all positively connected with influenza and pneumococcus vaccine coverage in younger COPD patients. Gender, education level, and marital status did not affect influenza and pneumococcus vaccination rates. These vaccination rates among younger COPD patients demonstrate the need for increased awareness and knowledge about the advantages of immunizations in lowering morbidity and mortality.

SARS-Cov-2 Infection in Severe Asthma Patients Treated With Biologics.

BACKGROUND: At the beginning of the pandemic, there have been considerable concerns regarding coronavirus disease 2019 (COVID-19) severity and outcomes in patients with severe asthma treated with biologics. OBJECTIVE: To prospectively observe a cohort of severe asthmatics treated with biologics for the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and disease severity during the COVID-19 pandemic. METHODS: Physicians from centers treating patients with severe asthma all over Greece provided demographic and medical data regarding their patients treated with biologics. Physicians were also asked to follow up patients during the pandemic and to perform a polymerase chain reaction test in case of a suspected SARS-Cov-2 infection. RESULTS: Among the 591 severe asthmatics (63.5% female) included in the study, 219 (37.1%) were treated with omalizumab, 358 (60.6%) with mepolizumab, and 14 (2.4%) with benralizumab. In total, 26 patients (4.4%) had a confirmed SARS-CoV-2 infection, 9 (34.6%) of whom were admitted to the hospital because of severe COVID-19, and 1 required mechanical ventilation and died 19 days after admission. Of the 26 infected patients, 5 (19.2%) experienced asthma control deterioration, characterized as exacerbation that required treatment with systemic corticosteroids. The scheduled administration of the biological therapy was performed timely in all patients with the exception of 2, in whom it was postponed for 1 week according to their doctors' suggestion. CONCLUSION: Our study confirms that despite the initial concerns, SARS-CoV-2 infection is not more common in asthmatics treated with biologics compared with the general population, whereas the use of biologic treatments for severe asthma during the COVID-19 pandemic does not seem to be related to adverse outcomes from severe COVID-19.

Underestimation of respiratory symptoms by smokers: a thorn in chronic obstructive pulmonary disease diagnosis.

Primary care centers are ideal positions to identify chronic obstructive pulmonary disease (COPD). We determined the COPD prevalence among ever-smokers aged 40-65 years attending a 2-year program conducted in 22 Greek primary healthcare centers and made comparisons between genders, patients less than or greater than 55 years, and newly or previously diagnosed COPD patients. A total of 117 persons, after studying 1100 people, were diagnosed with previously unknown or known COPD, providing a COPD prevalence of 10.6% among the study population. In all, 7.5% of the participants were newly diagnosed with COPD. Women with COPD reported smoking less but experienced worse respiratory and depressive symptoms than men. A total of 19% of the COPD population below 55 years experienced wheezing and exacerbations more frequently than older patients. Newly diagnosed COPD patients were significantly younger, reported a significant burden of symptoms without seeking medical help. Primary health care has a crucial role in the early detection of COPD among unsuspecting smokers.

2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth.

BACKGROUND/AIM: Malignant pleural mesothelioma (MPM) is a therapy-resistant neoplasm of the pleura. Standard chemotherapy consists of a combination of cisplatin (CPDD) and pemetrexed (PEM). The aim of this study was to assess whether inhibition of aerobic glycolysis by 2-deoxy-glucose (2DG) would enhance the effects of standard chemotherapy. MATERIALS AND METHODS: MeT-5A, M14K, MSTO and ZL34 cell lines were used. Cell viability with 2DG and cell proliferation and spheroid formation with CPDD+PEM alone and with 2-DG were tested. RESULTS: Viability with 2-DG was dose-dependent. Cell proliferation with CPDD+PEM on 2D surface was reduced in all cell types, 2-DG inclusion demonstrated a synergistic effect in MSTO and ZL34 cells. Spheroid growth in 3D with CPDD+PEM or CPDD+PEM+2-DG lowered spheroid growth in all cell types. CONCLUSION: 2-DG synergizes with CPDD+PEM in lowering MPM cell proliferation in 2D to <20%. In 3D MPM spheroid growth 2-DG synergism with CPDD+PEM treatment is not maintained.

Whole-blood interferon-gamma assay for the diagnosis of tuberculosis infection in an unselected Greek population.

BACKGROUND AND OBJECTIVE: Although QuantiFERON-TB Gold (QFT-G) has been approved for the diagnosis of latent tuberculosis infection (LTBI), there are limited data regarding its performance in routine clinical practice. The aim of this study was to compare QFT-G 'In Tube' results, based on stimulation with Mycobacterium tuberculosis-specific antigens, with tuberculin skin test (TST) results in an unselected hospital-based Greek population. METHODS: This was a prospective study of inpatients and outpatients in the University Hospital of Larissa, Greece. Demographic, clinical and microbiological data were collected and correlated to the QFT-G 'In Tube' results. Agreement was tested using the Q-test; kappa coefficient and confounding factors were adjusted for by univariate and multivariable logistic regression. RESULTS: Among the 191 patients with valid results for both tests, the concordance between the TST and the QFT-G was 68.5%, with a kappa value of 0.38 (95% CI 0.2-0.5). In 27 (14.1%) patients with active tuberculosis, QFT-G 'In Tube' yielded 85.1% positive results compared with 74% for the TST (P = 0.45). CONCLUSIONS: Overall agreement between the QFT-G 'In Tube' assay and the TST in this unselected hospital population was low, mainly due to discordant TST-positive/QFT-negative results.

Endobronchial metastasis from prostate cancer.

We report a case of endobronchial metastasis from prostate adenocarcinoma. A patient with a history of prostate cancer under complete androgen blockade presented to the respiratory department complaining of dyspnea and dry coughing. Flexible bronchoscopy showed multiple polypoid lesions in the tracheobronchial tree and the immunohistochemical studies on the biopsy specimen determined the diagnosis. The patient was treated with paclitaxel, estramustine phosphate and carboplatine, and experienced symptoms suppression. To our knowledge, this is the first case of endobronchial metastasis of a patient with androgen refractory prostate cancer without any evidence of extrathoracic metastasis. The current report also emphasises the need for a multidisciplinary approach for cases of endobronchial metastases, with the collaboration of pneumologists, urologists, pathologists and oncologists.

The pharmacological cost of COPD during Greek economic crisis.

INTRODUCTION: The economic crisis in Greece has substantially affected patients with COPD. The reduction of disposable income has its consequences on patients' ability to afford their medication. The aim of the study is to evaluate the cost of treatment for patients with COPD and the influence of the financial crisis to the patients. METHODS: Data were collected from 189 patients (male: 178, mean age: 70.1±8.4) who visited the outpatient department of University Hospital of Larissa in 2014 and 2015. The pharmacological cost of treatment was calculated based on national pharmaceutical formulary prices. RESULTS: COPD patients were classified into four stages according to Global Initiative for Chronic Obstructive Lung Disease (GOLD): 7.4% were in stage I, 43.4% in stage II, 34.4% in stage III, and 14.8% in stage IV. Patients were graded as per GOLD as follows: 18% as grade A, 14.3% as B, 23.3% as C, and 44.4% as D. The annual cost of COPD maintenance treatment per patient was €952.92 (±398.01), of which €239.91 were patients' expenses. The annual treatment cost for stable disease ranged from €615.44 to €1302.03 depending on disease stages (GOLD stages I-IV) and from €715.01 to €1101.05 depending on GOLD grades (grades A-D). The cost of maintenance medication was statistically and significantly higher for patients with advanced disease (GOLD stages III-IV) and for patients at high risk (GOLD grades C-D [P=0.000]). CONCLUSION: The pharmacological cost of treatment for COPD patients seems to be considerably high, in all disease stages. As the average income is decreased, patients face difficulties to afford inhaled medication.

A M. avium complex spondylodiscitis in a middle-aged woman with diabetes.

Spondylodiscitis, the inflammation of the vertebral bodies and the intervertebral disk space, is the reason for low back pain in a minority of cases. This is caused by various pathogens. Mycobacterium tuberculosis is responsible for 17-39% of all the cases of spondylodiscitis. On the contrast, spondylodiscitis from non tuberculous mycobacteria is extremely rare in literature. We describe a 68 -year old diabetic woman which is the first case of bone marrow involvement by M. intracellulare (member of M avium complex)with spondylodiscitis.

Combination of staphylococcal chromosome cassette SCCmec type V and Panton-Valentine leukocidin genes in a methicillin-resistant Staphylococcus aureus that caused necrotizing pneumonia in Greece.

We describe a case of necrotizing pneumonia in Greece caused by a community-acquired methicillin-resistant Staphylococcus aureus (MRSA) producing Panton-Valentine leukocidin (PVL) carrying the staphylococcal chromosome cassette mec (SCCmec) type V. The pulse field gel electrophoresis (PFGE) pattern of this strain differed significantly from the PVL-positive multi-locus sequence typing (MLST)-80 clone of MRSA, which predominates in Greece and in Europe. Further analysis of this strain revealed that it belonged to the agr1 allele type, and its resistance to tobramycin, gentamicin, and kanamycin was associated to the presence of aac-(6')-Ie+aph(2') gene. This is the 1st report that documents the emergence of CA-MRSA with PVL genes in combination with the SCCmec type V in Europe.

The -938C>A Polymorphism in MYD88 Is Associated with Susceptibility to Tuberculosis: A Pilot Study.

Introduction. Tuberculosis (TB) is a major disease worldwide, caused by Mycobacterium tuberculosis (MTB) infection. The Toll-Like Receptor (TLR) pathway plays a crucial role in the recognition of MTB. Aim. The present study aimed to investigate the involvement of myeloid differentiation primary response protein 88 (MYD88) gene polymorphisms in TB. Materials and Methods. A total of 103 TB cases and 92 control subjects were genotyped for the MYD88 -938C>A (rs4988453) and 1944C>G (rs4988457) polymorphisms. Results. The MYD88 -938CA and -938AA genotypes were associated with an increased risk for tuberculosis with odds ratio (OR) of 5.71 (95% confidence intervals [CIs] 2.89-11.28, p = 0.01). Conclusions. The MYD88 -938C>A genetic polymorphism is associated with increased susceptibility to TB and may serve as a marker to screen individuals who are at risk.

A multicentre evaluation of the accuracy and performance of IP-10 for the diagnosis of infection with M. tuberculosis.

IP-10 has potential as a diagnostic marker for infection with Mycobacterium tuberculosis, with comparable accuracy to QuantiFERON-TB Gold In-Tube test (QFT-IT). The aims were to assess the sensitivity and specificity of IP-10, and to evaluate the impact of co-morbidity on IP-10 and QFT-IT. 168 cases with active TB, 101 healthy controls and 175 non-TB patients were included. IP-10 and IFN-γ were measured in plasma of QFT-IT stimulated whole blood and analyzed using previously determined algorithms. A subgroup of 48 patients and 70 healthy controls was tested in parallel with T-SPOT.TB IP-10 and QFT-IT had comparable accuracy. Sensitivity was 81% and 84% with a specificity of 97% and 100%, respectively. Combining IP-10 and QFT-IT improved sensitivity to 87% (p < 0.0005), with a specificity of 97%. T-SPOT.TB was more sensitive than QFT-IT, but not IP-10. Among non-TB patients IP-10 had a higher rate of positive responders (35% vs 27%, p < 0.02) and for both tests a positive response was associated with relevant risk factors. IFN-γ but not IP-10 responses to mitogen stimulation were reduced in patients with TB and non-TB infection. This study confirms and validates previous findings and adds substance to IP-10 as a novel diagnostic marker for infection with M. tuberculosis. IP-10 appeared less influenced by infections other than TB; further studies are needed to test the clinical impact of these findings.

Tuberculous disseminated lymphadenopathy in an immunocompetent non-HIV patient: a case report.

INTRODUCTION: In cases of patients with disseminated lymphadenopathy, the differential diagnosis has to include both benign and malignant causes, including sarcoidosis, metastatic disease, lymphoma and, although rarely present, tuberculosis. Tuberculosis is still one of the most frequently occurring infectious diseases worldwide. However, disseminated mycobacterial lymphadenitis is rare in immunocompetent patients. CASE PRESENTATION: We present the case of a 56-year-old Caucasian Greek male, who was immunocompetent and HIV negative, with a two-month history of recurring fever, loss of appetite and disseminated lymphadenopathy. The patient was diagnosed with mycobacterial lymphadenopathy. CONCLUSION: This case highlights the need for suspicion in order to identify mycobacterial infection in patients with generalized lymphadenopathy, since misdiagnosis is possible and may lead to fatal complications for the patient.

Direct detection of Clostridium sordellii in pleural fluid of a patient with pneumonic empyema by a broad-range 16S rRNA PCR.

We report the case of a 56-y-old male admitted with a left-sided post-pneumonic empyema. Clostridium sordellii DNA was directly detected in its pleural fluid by a broad-range 16S rRNA PCR, after 24 h of specimen collection. This is the third case of pleural infection caused by C. sordellii in the literature.