Usefulness of a predictive model to hospitalize patients with low-risk community-acquired pneumonia.

INTRODUCTION: A high proportion of patients with low-risk community-acquired pneumonia (CAP) (classes I-III of the Pneumonia Severity Index) are hospitalized. The purpose of this study was to determine whether validated severity scales are used in clinical practice to make admission decisions, identify the variables that influence this decision, and evaluate the potential predictive value of these variables. MATERIALS AND METHODS: A prospective, observational study of patients ≥ 18 years of age with a diagnosis of low-risk CAP hospitalized or referred from the Emergency Department to outpatient consultations. A multivariate logistic regression predictive model was built to predict the decision to hospitalize a patient. RESULTS: The study population was composed of 1,208 patients (806 inpatients and 402 outpatients). The severity of CAP was estimated in 250 patients (20.7%). The factors that determined hospitalization were "abnormal findings in complementary studies" (643/806: 79.8%; due to respiratory failure in 443 patients) and "signs of clinical deterioration" [64/806 (7.9%): hypotension (16/64, 25%); hemoptoic expectoration (12/64, 18.8%); tachypnea (10/64, 15.6%)]. In total, ambulatory management was not contraindicated in 24.7% of hospitalized patients (199). The predictive model built to decide about hospitalization had a good power of discrimination (AUC 0.876; 95%CI: 0.855-0.897). CONCLUSIONS: Scales are rarely used to estimate the severity of CAP at the emergency department. The decision to hospitalize or not a patient largely depends on the clinical experience of the physician. Our predictive model showed a good power to discriminate the patients who required hospitalization. Further studies are warranted to validate these results.

Advances in inhaled antibiotics for management of respiratory tract infections.

PURPOSE OF REVIEW: The incidence of bacterial respiratory tract infections is growing. In a context of increasing antibiotic resistance and lack of new classes of antibiotics, inhaled antibiotics emerge as a promising therapeutic strategy. Although they are generally used for cystic fibrosis, their use in other conditions is becoming more frequent, including no-cystic fibrosis bronchiectasis, pneumonia and mycobacterial infections. RECENT FINDINGS: Inhaled antibiotics exert beneficial microbiological effects in bronchiectasis and chronic bronchial infection. In nosocomial and ventilator-associated pneumonia, aerosolized antibiotics improve cure rates and bacterial eradication. In refractory Mycobacterium avium complex infections, amikacin liposome inhalation suspension is more effective in achieving long-lasting sputum conversion. In relation to biological inhaled antibiotics (antimicrobial peptides, interfering RNA and bacteriophages), currently in development, there is no still enough evidence that support their use in clinical practice. SUMMARY: The effective antimicrobiological activity of inhaled antibiotics, added to their potential to overcoming resistances to systemic antibiotics, make inhaled antibiotics a plausible alternative.

First evidence of multiple paternity in the blue shark (Prionace glauca).

Multiple paternity (MP) is defined as the behaviour in which females successfully mate with multiple males leading to offspring from different sires within the same litter. MP seems to be frequent and an evolutionary advantage in elasmobranchs. Here the authors report for the first time the occurrence of MP in the cosmopolitan blue shark Prionace glauca L. The evidence, gathered via microsatellite genotyping of pregnant females and their embryos, suggests that MP is very frequent in this species. Knowledge of MP in P. glauca should help describe more precisely its reproductive biology and contribute to the management of its populations.

Effect of high versus low dose of dexamethasone on clinical worsening in patients hospitalised with moderate or severe COVID-19 pneumonia: an open-label, randomised clinical trial.

BACKGROUND: Low-dose dexamethasone demonstrated clinical improvement in patients with coronavirus disease 2019 (COVID-19) needing oxygen therapy; however, evidence on the efficacy of high-dose dexamethasone is limited. METHODS: We performed a randomised, open-label, controlled trial involving hospitalised patients with confirmed COVID-19 pneumonia needing oxygen therapy. Patients were randomly assigned in a 1:1 ratio to receive low-dose dexamethasone (6 mg once daily for 10 days) or high-dose dexamethasone (20 mg once daily for 5 days, followed by 10 mg once daily for an additional 5 days). The primary outcome was clinical worsening within 11 days since randomisation. Secondary outcomes included 28-day mortality, time to recovery and clinical status at day 5, 11, 14 and 28 on an ordinal scale ranging from 1 (discharged) to 7 (death). RESULTS: A total of 200 patients (mean±sd age 64±14 years; 62% male) were enrolled. 32 (31.4%) out of 102 patients enrolled in the low-dose group and 16 (16.3%) out of 98 in the high-dose group showed clinical worsening within 11 days since randomisation (rate ratio 0.427, 95% CI 0.216-0.842; p=0.014). The 28-day mortality was 5.9% in the low-dose group and 6.1% in the high-dose group (p=0.844). There was no significant difference in time to recovery, and in the seven-point ordinal scale at days 5, 11, 14 and 28. CONCLUSIONS: Among hospitalised COVID-19 patients needing oxygen therapy, high dose of dexamethasone reduced clinical worsening within 11 days after randomisation, compared with low dose.

Next-generation sequencing, isolation and characterization of 14 microsatellite loci of Canthon cyanellus (Coleoptera: Scarabaeidae).

BACKGROUND: We used Illumina paired-end sequencing to isolate and characterize microsatellites of Canthon cyanellus, a Neotropical roller dung beetle, encompassing several lineages within its distribution range. METHODS AND RESULTS: We examined C. cyanellus specimens collected at eight different localities in Mexico (two or three specimens per locality). We initially performed amplification tests with 16 loci, but two of which were unsuccessful. The 14 remaining microsatellites were polymorphic, with 2-16 alleles each. The expected and observed heterozygosity ranged from 0.11 to 0.76 and from 0.20 to 0.78, respectively. CONCLUSIONS: These microsatellites will help to assess structure at the population and lineage levels, identify zones of potential hybridization between lineages, and draw a more precise geographic delimitation of C. cyanellus lineages.

Novel thiosemicarbazones induce high toxicity in estrogen-receptor-positive breast cancer cells (MCF7) and exacerbate cisplatin effectiveness in triple-negative breast (MDA-MB231) and lung adenocarcinoma (A549) cells.

Cis-diamminedichloroplatinum(II) (CDDP), known as cisplatin, has been extensively used against breast cancer, which is the most frequent cancer among women, and lung cancer, the leading cancer that causes death worldwide. Novel compounds such as thiazole derivatives have exhibited antiproliferative activity, suggesting they could be useful against cancer treatment. Herein, we synthesized two novel thiosemicarbazones and an aldehyde to combine with CDDP to enhance efficacy against ER-positive breast MCF7 cancer cells, triple-negative/basal-B mammary carcinoma cells (MDA-MB231) and lung adenocarcinoma (A549) human cells. We synthesized 2,3,5,6-tetrafluoro-4-(2-mercaptoetanothiolyl)benzaldehyde (ALD), 5-[(2,3,5,6-tetrafluoro-4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC1) and 5-[(4-(trifluoromethyl)phenyl)thio]-2-furaldehyde thiosemicarbazone (TSC2) and used them alone or in combination with subtoxic CDDP concentrations to evaluate cytotoxicity, cytoskeleton integrity and mitochondrial function. We found that none of the synthesized compounds improved CDDP activity against MCF7 cell cultures; however, TSC2 was effective in enhancing the cytotoxicity of CDDP against MDA-MB231 and A549 cancer cell cultures. We demonstrated that the cytotoxic effect is related to the TSC2 capacity to induce disruption in the cytoskeleton network and to decrease mitochondrial function.

Relevance of Dementia in Atrial Fibrillation Patients within a Specific European Health Care Area.

INTRODUCTION: Atrial fibrillation might increase the risk of dementia. We aim to test the hypothesis that dementia could reclassify the actual risk of stroke and death predicted by the CHA2DS2-VASc in patients with atrial fibrillation (AF). METHODS: A prospective study performed in a specific health care area. RESULTS: From our health care area (n = 348,985), throughout 2013, AF was codified in 7,990 (2.08%). Mean age was 76.83 ± 10.5, mean CHA2DS2-VASc = 3.5, 4,056 (50.8%) were females and 287 (3.6%) were diagnosed to have dementia. Patients with dementia were older and presented a higher rate of all the components of the CHA2DS2-VASc-expect vasculopathy. Differences in overall mortality were observed but not in stroke and haemorrhagic events. After propensity score matched analysis, dementia was independently associated with all-cause mortality. Addition of dementia to CHA2DS2-VASc reclassified 7.7 and 16.6% of the cohort with regard to thromboembolic events and death risk respectively. CONCLUSIONS: Patients with dementia presented a more adverse risk profile, with significant differences in all-cause mortality.

The association between paracetamol and asthma is still under debate.

OBJECTIVE: To analyse the relationship between paracetamol and asthma. DATA SOURCES: An English literature search using electronic search engines (PubMed and EMBASE) was conducted. STUDY SELECTIONS: Articles published in peer-review journals, from 1990 to December 2015 were included. To perform the search for the most suitable and representative articles, keywords were selected ("asthma," "paracetamol" and "acetaminophen"). The evidence level was rated according to the criteria of the Oxford Centre For Evidence-Based Medicine. RESULTS: The exposure to paracetamol during pregnancy was analysed in several cohort studies, showing an association between the prenatal exposure to paracetamol with suffering from asthma or presence of wheezing in childhood, especially for persistent wheezing. Nevertheless, a recent study concluded that the relationship between asthma and paracetamol is explained, at least in part, by confounding factors. Several works have also associated the exposure to paracetamol in the first years of life or in adults with the development of childhood asthma. Several pathophysiological mechanisms are known that could explain this relationship, such as the glutathione pathway, the decrease in the release of Th1 cytokines that are normally produced during febrile episodes, which would then lead to a predominance of Th2 cytokines, the cytotoxic effect of paracetamol for pneumocytes, a modulator effect on the activity of myeloperoxidase, as well as the possible antigenic effect of paracetamol, mediated by IgE. CONCLUSIONS: There are many arguments that suggest a relationship between the use of paracetamol with the appearance of asthmatic symptoms, however the evidence is inconclusive.

A Review of the Bayesian Occupancy Filter.

Autonomous vehicle systems are currently the object of intense research within scientific and industrial communities; however, many problems remain to be solved. One of the most critical aspects addressed in both autonomous driving and robotics is environment perception, since it consists of the ability to understand the surroundings of the vehicle to estimate risks and make decisions on future movements. In recent years, the Bayesian Occupancy Filter (BOF) method has been developed to evaluate occupancy by tessellation of the environment. A review of the BOF and its variants is presented in this paper. Moreover, we propose a detailed taxonomy where the BOF is decomposed into five progressive layers, from the level closest to the sensor to the highest abstractlevelofriskassessment. Inaddition,wepresentastudyofimplementedusecasestoprovide a practical understanding on the main uses of the BOF and its taxonomy.

Poly(ADP-ribose) polymerase-1 silences retroviruses independently of viral DNA integration or heterochromatin formation.

PARP-1 silences retrotransposons in Drosophila, through heterochromatin maintenance, and integrated retroviruses in chicken. Here, we determined the role of viral DNA integration and cellular heterochromatin in PARP-1-mediated retroviral silencing using HIV-1-derived lentiviral vectors and Rous-associated virus type 1 (RAV-1) as models. Analysis of the infection of PARP-1 knockout and control cells with HIV-1 harbouring WT integrase, in the presence or absence of an integrase inhibitor, or catalytic-dead mutant integrase indicated that silencing does not require viral DNA integration. The mechanism involves the catalytic activity of histone deacetylases but not that of PARP-1. In contrast to Drosophila, lack of PARP-1 in avian cells did not affect chromatin compaction globally or at the RAV-1 provirus, or the cellular levels of histone H3 N-terminal acetylated or Lys27 trimethylated, as indicated by micrococcal nuclease accessibility and immunoblot assays. Therefore, PARP-1 represses retroviruses prior to viral DNA integration by mechanisms involving histone deacetylases but not heterochromatin formation.

Characteristics of Patients with Lymphangioleiomyomatosis and Pleural Effusion: A Systematic Review.

The characteristics of patients with lymphangioleiomyomatosis (LAM) are poorly defined, as they may present with or without pleural effusion (PE). We performed a systematic review across four electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of LAM. Case descriptions and retrospective studies were included, unrestricted by year of publication. The review consisted of 94 studies (199 patients) spanning a period of nearly 55 years. The median age was 38 years (range: 1 month to 69 years), and 79.7% were between 21 and 50 years old. All cases had dyspnea, 95% had a cough, and 87.5% had chest pain. PE was exudative chylothorax, usually unilateral (76%) and right-sided, predominantly lymphocytic, and with proportionately higher levels of proteins than lactate dehydrogenase. Sirolimus was effective in all cases, completely in 87%, and partially in 13%, although the number of patients receiving sirolimus was small. The present study confirmed that LAM and PE mainly occur in women of childbearing age (third to fifth decade of life). PE was usually unilateral and presented as a lymphocyte-predominant chylous exudate. The most effective treatment for PE seems to be sirolimus, although studies with larger series are needed to confirm this.

Poly(ADP-ribose) polymerase 1 promotes transcriptional repression of integrated retroviruses.

Poly(ADP-ribose) polymerase 1 (PARP-1) is a cellular enzyme with a fundamental role in DNA repair and the regulation of chromatin structure, processes involved in the cellular response to retroviral DNA integration. However, the function of PARP-1 in retroviral DNA integration is controversial, probably due to the functional redundancy of the PARP family in mammalian cells. We evaluated the function of PARP-1 in retroviral infection using the chicken B lymphoblastoid cell line DT40. These cells lack significant PARP-1 functional redundancy and efficiently support the postentry early events of the mammalian-retrovirus replication cycle. We observed that DT40 PARP-1(-/-) cells were 9- and 6-fold more susceptible to infection by human immunodeficiency virus type 1 (HIV-1)- and murine leukemia virus (MLV)-derived viral vectors, respectively, than cells expressing PARP-1. Production of avian Rous-associated virus type 1 was also impaired by PARP-1. However, the susceptibilities of these cell lines to infection by the nonretrovirus vesicular stomatitis virus were indistinguishable. Real-time PCR analysis of the HIV-1 life cycle demonstrated that PARP-1 did not impair reverse transcription, nuclear import of the preintegration complex, or viral DNA integration, suggesting that PARP-1 regulates a postintegration step. In support of this hypothesis, pharmacological inhibition of the epigenetic mechanism of transcriptional silencing increased retroviral expression in PARP-1-expressing cells, suppressing the differences observed. Further analysis of the implicated molecular mechanism indicated that PARP-1-mediated retroviral silencing requires the C-terminal region, but not the enzymatic activity, of the protein. In sum, our data indicate a novel role of PARP-1 in the transcriptional repression of integrated retroviruses.

Characteristics of patients with yellow nail syndrome and pleural effusion.

Yellow nail syndrome (YNS) can be associated with a pleural effusion (PE) but the characteristics of these patients are not well defined. We performed a systematic review across four electronic databases for studies reporting clinical findings, PE characteristics, and most effective treatment of YNS. Case descriptions and retrospective studies were included, unrestricted by year of publication. We reviewed 112 studies (150 patients), spanning a period of nearly 50 years. The male/female ratio was 1.2/1. The median age was 60 years (range: 0-88). Seventy-eight percent were between 41-80 years old. All cases had lymphoedema and 85.6% had yellow nails. PEs were bilateral in 68.3%. The appearance of the fluid was serous in 75.3%, milky in 22.3% and purulent in 3.5%. The PE was an exudate in 94.7% with lymphocytic predominance in 96% with a low count of nucleated cells. In 61 of 66 (92.4%) of patients, pleural fluid protein values were >3 g/dL, and typically higher than pleural fluid LDH. Pleurodesis and decortication/pleurectomy were effective in 81.8% and 88.9% of cases, respectively, in the treatment of symptomatic PEs. The development of YNS and PE occurs between the fifth to eighth decade of life and is associated with lymphoedema. The PE is usually bilateral and behaves as a lymphocyte-predominant exudate. The most effective treatments appear to be pleurodesis and decortication/pleurectomy.

[Diabetes and obstructive sleep apnoea: A case-control study]. / Diabetes y apnea obstructiva del sueño. Un estudio de casos y controles.

INTRODUCTION: Obstructive sleep apnoea (OSA) and diabetes mellitus (DM) are very prevalent diseases frequently associated. Their coexistence is independently associated with an increased prevalence of cardiovascular comorbidities. As this association is underdiagnosed, it is necessary to optimise clinical suspicion by studying independent predictors of DM or prediabetes (preDM) in patients with OSA. METHOD: A simple randomised case-control study, matched for sex, body mass index (BMI) and age, aimed to study the association of OSA with DM and preDM and to identify independent predictors for both diseases in people with OSA. RESULTS: We included 208 cases with OSA and 208 controls without OSA. In the former, 18.8% had DM compared to only 10.1% in the latter (P=.00). Prevalence of preDM was 41.8% vs. 10.6%, respectively (P=.00). One hundred and twenty-four cases (59.6%) reported excessive daytime sleepiness (EDS) (Epworth scale, 10.5±3.1) vs. 24.5% of the control group (Epworth scale, 6.6±2.9). Apnoea-hypopnoea index (AHI) and O2 desaturation indices (IDO, CT90 and CT80) were significantly higher in the case group. The risk of MD was related to age, nocturnal hypoxaemia and EDS. The risk of pre-MD was related to BMI and AHI. CONCLUSIONS: OSA is associated with DM and preDM. Age, nocturnal hypoxaemia and EDS are predictors of DM. BMI and AHI are predictors of pre-MD.

Hypersensitivity pneumonitis: application of a new diagnostic algorithm to a time series of the disease.

BACKGROUND: The diagnostic criteria for Hypersensitivity pneumonitis (HP) have changed over time. Our aim is to apply a recent diagnostic algorithm to a historical series of patients diagnosed with HP to assess its distribution according to current diagnostic criteria and the diagnostic confidence achieved. RESEARCH DESIGN AND METHODS: Application to each patient the algorithm criteria. The diagnosis was HP (≥90%), provisional high (70-89%) or low confidence (51-69%) or non-HP (unlikely) (≤50%); or HP, provisional or non-HP, if they had lung biopsy. RESULTS: 129 patients [mean age 64 ± 12 years; 79 (61.2%) women] were included of which 16 (12.4%) were diagnosed on the basis of high clinical suspicion. After applying the algorithm, 106 patients (82.2%) could be evaluated and 83 (78.3%) had a diagnosis of HP or high confidence. Lung biopsy was able to establish a diagnosis of certainty in another 21 patients and a provisional diagnosis in 9 more [total, 113 (87.6%)]. The 16 patients without strict diagnostic criteria for HP had a low confidence diagnosis. A total of 56 lung biopsies (64.4%) could have been avoided according to the new guidelines. CONCLUSIONS: The application of this algorithm achieves a high diagnostic yield in HP, significantly reducing the number of lung biopsies required.

Non-specific pleuritis: long-term follow-up outcomes.

BACKGROUND: The definitive etiology of nonspecific pleuritis (NSP), the influence of the type of pleural biopsy on clinical results and the minimum duration of follow-up is controversial. RESEARCH DESIGN AND METHODS: A retrospective, observational study of patients ≥ 18 years with NSP confirmed by closed pleural biopsy (CPB), local anesthesia pleuroscopy (LAP), or video-assisted thoracic surgery (VATS). RESULTS: A total of 167 patients were included (mean follow-up, 14.4 months), of which 25 (15%) were diagnosed within one month; [15 (60%) malignant]. Of the remaining 142 pleural effusions (PEf), 69 (48.6%) were idiopathic; 49 (34.5%) not-malignant and 24 (16.9%) malignant (4 mesotheliomas and 20 metastasic). The diagnosis of NSP was established by CPB (7; median time to diagnosis, 9.4 months), LAT (5; 15.8 months), and VATS (8; 13.5 months) (p = 0.606). Sixty-eight patients (40.7%) died during follow-up (mean time, 12 months). CONCLUSIONS: In a substantial percentage of patients diagnosed with NSP, a definitive diagnosis will not be obtained, a relevant number of patients will develop a malignant PEf. The diagnostic procedure used for the diagnosis of NSP does not seem to influence delay in the diagnosis of malignant PEf. The data obtained suggest that follow-up should be maintained for at least 24 months.

[Relationship between obstructive sleep apnea and type 2 diabetes mellitus]. / Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2.

INTRODUCTION: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. METHODS: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. RESULTS: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5-13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. CONCLUSIONS: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk.

Analysis of the quality of e-Consultations in chronic obstructive pulmonary disease.

INTRODUCTION: The quality of e-Consultations in the COPD is unknown. The objectives of this study were (i) to evaluate the quality of referrals; (ii) to define the characteristics of patients referred from Primary Care (PC) to the Unit of Pulmonology; and (iii) to describe differences between accepted and rejected patients. METHODS: A retrospective, observational study of e-Consultations requested by PC for suspected COPD throughout 2022. To quantify the quality of the e-Consultations, an arbitrary scale of 12 variables (score 0-10) was created. RESULTS: In total, 384 e-Consultations were reviewed, of which 167 (43.5 %) resulted in a face-to-face visit, and 217 (56.5 %) were rejected. No differences were observed between the two types of patients, except for confirmations of diagnostic suspicion of COPD [significantly higher in accepted patients (p = 0.042)]; physical examination data of rejected patients (more data provided; p = 0.015); and lung function (significantly better in rejected patients). The mean quality of referrals was acceptable (5.6 ± 2.1 score): 121 (31.3 %) had insufficient quality; 118 (30.5 %) acceptable; 75 (19.4 %) good, and 30 (7.8 %) excellent. Quality was low in half of the variables analyzed (6/12); acceptable in 3, and good in another 3. The capacity of resolution of referrals was good (one e-Consultation) in 199 requests (66.1 %); deficient (two e-Consultations) in 72 (23.9 %), and poor (≥3 e-Consultations) in 30 (10 %). Overdiagnosis was 40.2 % (86/214 e-Consultations). The risk could be classified in 247 patients (64.3 %; 135 low-risk; 90 high-risk). CONCLUSIONS: When adequate information is provided, e-Consultations help identify different levels of severity. However, the quality and capacity of resolution of referrals were suboptimal, with a high percentage of overdiagnoses.