MiRNAs and Microbiota in Non-Small Cell Lung Cancer (NSCLC): Implications in Pathogenesis and Potential Role in Predicting Response to ICI Treatment.

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown.

TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.

Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies.

OBJECTIVE: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). DESIGN: Umbrella review. DATA SOURCES: PubMed, PsychInfo, Embase, up to 9 February 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. RESULTS: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). CONCLUSIONS: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events. STUDY REGISTRATION: PROSPERO CRD42018093045. FUNDING: None.

Inhibition of Fatty Acid Amide Hydrolase (FAAH) Regulates NF-kb Pathways Reducing Bleomycin-Induced Chronic Lung Inflammation and Pulmonary Fibrosis.

The deadly interstitial lung condition known as idiopathic pulmonary fibrosis (IPF) worsens over time and for no apparent reason. The traditional therapy approaches for IPF, which include corticosteroids and immunomodulatory drugs, are often ineffective and can have noticeable side effects. The endocannabinoids are hydrolyzed by a membrane protein called fatty acid amide hydrolase (FAAH). Increasing endogenous levels of endocannabinoid by pharmacologically inhibiting FAAH results in numerous analgesic advantages in a variety of experimental models for pre-clinical pain and inflammation. In our study, we mimicked IPF by administering intratracheal bleomycin, and we administered oral URB878 at a dose of 5 mg/kg. The histological changes, cell infiltration, pro-inflammatory cytokine production, inflammation, and nitrosative stress caused by bleomycin were all reduced by URB878. Our data clearly demonstrate for the first time that the inhibition of FAAH activity was able to counteract not only the histological alteration bleomycin-induced but also the cascade of related inflammatory events.

RNA-Binding Proteins as a Molecular Link between COPD and Lung Cancer.

Chronic obstructive pulmonary disease (COPD) represents an independent risk factor for lung cancer development. Accelerated cell senescence, induced by oxidative stress and inflammation, is a common pathogenic determinant of both COPD and lung cancer. The post transcriptional regulation of genes involved in these processes is finely regulated by RNA-binding proteins (RBPs), which regulate mRNA turnover, subcellular localization, splicing and translation. Multiple pro-inflammatory mediators (including cytokines, chemokines, proteins, growth factors and others), responsible of lung microenvironment alteration, are regulated by RBPs. Several mouse models have shown the implication of RBPs in multiple mechanisms that sustain chronic inflammation and neoplastic transformation. However, further studies are required to clarify the role of RBPs in the pathogenic mechanisms shared by lung cancer and COPD, in order to identify novel biomarkers and therapeutic targets. This review will therefore focus on the studies collectively indicating the role of RBPs in oxidative stress and chronic inflammation as common pathogenic mechanisms shared by lung cancer and COPD.

Postoperative Quality of Life After Full-sternotomy and Ministernotomy Aortic Valve Replacement.

BACKGROUND: Few longitudinal data exist comparing quality of life (QoL) after full sternotomy (fs) aortic valve replacement (AVR) (fsAVR) with ministernotomy AVR (msAVR). METHODS: A total of 1844 consecutive patients undergoing AVR who were prospectively enrolled in a European multicenter registry were dichotomized according to surgical access. Nonparsimonious propensity score matching selected 187 pairs of patients who underwent fsAVR or msAVR with comparable baseline characteristics. Hospital outcome was compared in the 2 groups. QoL was assessed with the Short Form-36, further detailed in its Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. QoL was investigated at hospital admission, at discharge, and at 1 month, 6 months, and 1 year thereafter. RESULTS: There were 1654 patients undergoing fsAVR and 190 undergoing msAVR in the entire population. The fsAVR group showed a worse preoperative risk profile, a longer intensive care unit length of stay (59.7 hours vs 38.8 hours; p = .002), and a higher rate of life-threatening or disabling bleeding (4.1% vs 0%; P = .011); the msAVR group had a higher rate of early reintervention for failed index intervention (2.1% vs 0.5%; P = .001). QoL investigations showed better PCS and MCS at 1 month after fsAVR, but no temporal trend differences (PCS group-time P = .202; MCS group-time P = .141). Propensity-matched pairs showed comparable baseline characteristics and hospital outcomes (P = not significant for all end points) and comparable improvements of PCS and MCS over time, but no between-group differences over time (PCS group time P = .834; MCS group time P = .737). CONCLUSIONS: Patients with similar baseline profiles report comparable hospital outcomes and comparable improvements of physical and mental health, up to 1 year after surgery, with both fsAVR and msAVR. As for QoL, ministernotomy does not seem to offer any advantage compared with the traditional approach.

Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Atrazine Inhalation Worsen Pulmonary Fibrosis Regulating the Nuclear Factor-Erythroid 2-Related Factor (Nrf2) Pathways Inducing Brain Comorbidities.

BACKGROUND/AIMS: Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis. METHODS: Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior. RESULTS: Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR. CONCLUSION: Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain.

Epigallocatechin-3-Gallate Modulates Postoperative Pain by Regulating Biochemical and Molecular Pathways.

Treating postoperative (PO) pain is a clinical challenge. Inadequate PO pain management can lead to worse outcomes, for example chronic post-surgical pain. Therefore, acquiring new information on the PO pain mechanism would increase the therapeutic options available. In this paper, we evaluated the role of a natural substance, epigallocatechin-3-gallate (EGCG), on pain and neuroinflammation induced by a surgical procedure in an animal model of PO pain. We performed an incision of the hind paw and EGCG was administered for five days. Mechanical allodynia, thermal hyperalgesia, and motor dysfunction were assessed 24 h, and three and five days after surgery. At the same time points, animals were sacrificed, and sera and lumbar spinal cord tissues were harvested for molecular analysis. EGCG administration significantly alleviated hyperalgesia and allodynia, and reduced motor disfunction. From the molecular point of view, EGCG reduced the activation of the WNT pathway, reducing WNT3a, cysteine-rich domain frizzled (FZ)1 and FZ8 expressions, and both cytosolic and nuclear ß-catenin expression, and the noncanonical ß-catenin-independent signaling pathways, reducing the activation of the NMDA receptor subtype NR2B (pNR2B), pPKC and cAMP response element-binding protein (pCREB) expressions at all time points. Additionally, EGCG reduced spinal astrocytes and microglia activation, cytokines overexpression and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway, downregulating inducible nitric oxide synthase (iNOS) activation, cyclooxygenase 2 (COX-2) expression, and prostaglandin E2 (PGE2) levels. Thus, EGCG administration managing the WNT/ß-catenin signaling pathways modulates PO pain related neurochemical and inflammatory alterations.

Simultaneous pneumothorax and pneumoperitoneum as a late consequence of traumatic injury of the diaphragm: Multimodality imaging approach with surgical correlation and treatment.

Simultaneous occurrence of pneumothorax and pneumoperitoneum is a rare event, usually related to traumas or surgical procedures involving the diaphragm. However, clinicians should be aware of the possible onset of these two clinical conditions even in patients without a recent clinical history that can clearly explain them. Cross-sectional imaging techniques are of great importance, providing crucial information about the patient's clinical status and guiding the following patient management. This work describes a unique case of a sudden occurrence of simultaneous pneumothorax and pneumoperitoneum in a previous asymptomatic man with a solely clinical history of minor trauma during childhood, evaluated through a multimodality imaging approach and treated with video-assisted thoracoscopy surgery.

Nodular fasciitis of the anterior chest wall mimicking myxofibrosarcoma: A case report and literature review.

Nodular fasciitis is a benign tumor of soft tissues originating from the proliferation of fibroblasts and myofibroblasts, generally developing between the subcutaneous tissue and the underlying muscular layer. Nodular fasciitis predominantly localizes in the upper extremities, trunk, head and neck. Biomolecular and immunohistochemical analyses result essential to demonstrate the benign origin of the process, also confirmed by very low recurrence rate after complete excision, which represents the gold standard for treatment. We report the case of a 36 years-old man who developed a nodular protuberance clinically evident in the upper-left side of the thorax. We further, highlight the main characteristics of this rare neoplasm trough a thorough review of the literature.

Asymptomatic lymphangioleiomyomatosis: Large cyst mimicking a hydropneumothorax in a healthy patient.

Lymphangioleiomyomatosis (LAM) is a rare, idiopathic, cystic disease that affects lungs of young women at childbearing age. Usually, LAM clinical manifestations are pneumothorax, progressive dyspnea and chylous pleural effusions. In many cases, due to unusual and nonspecific symptoms, LAM is mis-recognized and patients, who are affected by such disease, receive delayed diagnosis. This case report focuses on a 45-year-old woman patient with asymptomatic lymphangioleiomyomatosis who presented a big cyst which makes it looks like hydropneumothorax condition. Although chest radiograph and following CT scan has given an incidental diagnosis of right hydropneumothorax, treatment with drainages and video-assisted thorascopic surgery, instead, has allowed us to formulate correct diagnosis of cysts in LAM.

Longitudinal Course of Depressive, Anxiety, and Posttraumatic Stress Disorder Symptoms After Heart Surgery: A Meta-Analysis of 94 Studies.

OBJECTIVE: This study aimed to analyze the longitudinal course of depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms in patients with cardiac disease after heart surgery (HS). METHODS: We conducted a systematic review and random-effects meta-analysis of cohort studies in patients undergoing HS, measuring anxiety, depressive, and PTSD symptoms before and at least 30 days thereafter. Subgroup and meta-regression analyses, investigation of publication bias, and quality assessment were undertaken. RESULTS: We included 94 studies relating to 15,561 patients. HS included coronary artery bypass graft surgery, valve replacement, implantable cardioverter-defibrillator placement, left ventricular assist device placement, heart transplantation, and other types of HS. Across studies, symptoms of depression (g = 0.32; 95% confidence interval [CI] = 0.25 to 0.39; p < .001) and anxiety improved after HS (g = 0.52; 95% CI = 0.43 to 0.62; p < .001), whereas PTSD symptoms worsened (g = -0.42; 95% CI = -0.80 to -0.04; p = .032). The reduction of depression and anxiety levels was more pronounced for patients with underlying coronary artery disease and heart failure and persisted for 1 year after HS, whereas the increase in PTSD symptoms returned to baseline after 6 months. Depression improvement was inversely associated with older age, diabetes, hypertension, and dyslipidemia and positively with baseline heart failure. No additional clinical or demographic variables were associated with the course of anxiety symptoms. Quality of included studies was low overall. Publication bias was nonsignificant. CONCLUSIONS: Depressive and anxiety symptoms improve for 1 year after HS, whereas PTSD symptoms might worsen. Older patients and those with metabolic comorbidities, valve disease, or ventricular arrhythmias are at higher risk for continued depressive and anxiety symptoms and should be monitored closely.

Catastrophic descending necrotizing mediastinitis of the anterior and posterior compartments: A case report.

Descending necrotizing mediastinitis (DNM) is a medical emergency with a high associated morbidity and mortality. DNM may arise secondary to primary odontogenic or neck infection in susceptible patients and it may spread contiguously via the "danger" space to the mediastinum. This case report is focused on complications following an odontogenic infection in a healthy 48-year-old male that led to a massive inflammation associated an extensive empyema. After chest and neck computed tomographic scan a diagnosis of cervical necrotizing fasciitis with DNM was made. A multidisciplinary approach with an urgent surgical intervention and the finding of the right antibiotic therapy resulted to be successful. After 2 weeks the patient was dismissed in better health condition.

Phenotypical and molecular assessment of the virulence potential of KPC-3-producing Klebsiella pneumoniae ST392 clinical isolates.

Klebsiella pneumoniae is a Gram-negative bacterium of clinical importance, due to its resistance to several antibiotic classes. We have identified 4 clinical isolates of K. pneumoniae sequence type (ST) 392 KPC-3-producing strains from patients at the Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (IRCCS-ISMETT), a Southern Italian transplantation health facility, during a routine surveillance for carbapenemase-producing Enterobacterales from in-house clinical samples. Since those were among, to the best of our knowledge, the first KPC-producing K. pneumoniae ST392 isolated in Europe, we assessed their virulence potential, to understand if this particular ST can become an endemic clinical threat. ST392 isolates were investigated to assess their virulence potential, namely resistance to human sera, formation of abiotic biofilms, adhesion to biotic surfaces, exopolysaccharide production and in vivo pathogenesis in the wax moth Galleria mellonella animal model. ST392-belonging strains were highly resistant to human sera. These strains also have a high capacity to form abiotic biofilms and high levels of adhesion to the human epithelial colorectal adenocarcinoma HT-29 cell line. An increase of transcriptional levels of genes involved in serum resistance (aroE and traT) and adhesion (pgaA) was observed when compared with the Klebsiella quasipneumoniae subsp. similipneumoniae strain ATCC 700603 reference strain. Infection of G. mellonella larvae with ST392 clinical isolates showed that the latter were not highly pathogenic in this model. Together, our results indicate that ST392 isolates have the potential to become a strain of clinical relevance, especially in health settings where patients are immunosuppressed, e.g., transplant recipients.

Quality of life 10 years after cardiac surgery in adults: a long-term follow-up study.

BACKGROUND: Quality of life (QoL) is a multifactorial concept that assesses physical and mental health. We prospectively studied the quality of life of patients undergoing coronary artery bypass graft (CABG) surgery using the Short-Form 36-item questionnaire (SF-36) up to 10 years after surgery. METHODS: Between January 2000 and December 2002, all patients undergoing elective isolated CABG in the cardiac & thoracic surgery department of a large university hospital in Eastern France underwent initial QoL evaluation with the SF-36. The same questionnaire was mailed to every patient annually (± 2 weeks around the date of surgery) up to 10 years after their operation. We recorded socio-demographic and clinical variables at inclusion. Predictors of impaired QoL at 10 years were identified by logistic regression. RESULTS: A total of 272 patients (213 men, 59 women) were enrolled; mean age at inclusion was 65 ± 10 years. At 10 years post-surgery, 81 patients had died (29.7%). The physical component summary (PCS) score was significantly higher at 5 years after surgery than at baseline (p < 0.01), and significantly lower at 10 years than at 5 years (p < 0.01), although there remained a significant difference between 10-year PCS and baseline score (p = 0.004). The mental component summary (MCS) score was significantly higher at 5 years than at the time of surgery (p < 0.001), and remained significantly higher compared to baseline at 10 years after surgery (p = 0.010). By multivariate analysis, diabetes and dypsnea were both associated with worse PCS at 10 years, while lower age was associated with better 10-year PCS. Only diabetes was associated with impaired MCS at 10 years. CONCLUSIONS: Cardiac surgery appears to durably and positively affect both physical and mental components of quality of life.

Environmental risk factors and nonpharmacological and nonsurgical interventions for obesity: An umbrella review of meta-analyses of cohort studies and randomized controlled trials.

BACKGROUND: Multiple environmental factors have been implicated in obesity, and multiple interventions, besides drugs and surgery, have been assessed in obese patients. Results are scattered across many studies and meta-analyses, and they often mix obese and overweight individuals. MATERIALS AND METHODS: PubMed and Cochrane Database of Systematic Reviews were searched through 21 January 2017 for meta-analyses of cohort studies assessing environmental risk factors for obesity, and randomized controlled trials investigating nonpharmacological and nonsurgical therapeutic interventions for obesity. We excluded data on overweight participants. Evidence from observational studies was graded according to criteria that included the statistical significance of the random-effects summary estimate and of the largest study in a meta-analysis, the number of obesity cases, heterogeneity between studies, 95% prediction intervals, small-study effects and excess significance. The evidence of intervention studies for obesity was assessed with the GRADE framework. RESULTS: Fifty-four articles met eligibility criteria, including 26 meta-analyses of environmental risk factors (166 studies) and 46 meta-analyses of nondrug, nonsurgical interventions (206 trials). In adults, the only risk factor with convincing evidence was depression, and childhood obesity, adolescent obesity, childhood abuse and short sleep duration had highly suggestive evidence. Infancy weight gain during the first year of life, depression and low maternal education had convincing evidence for association with paediatric obesity. All interventions had low or very-low-quality evidence with one exception of moderate-quality evidence for one comparison (no differences in efficacy between brief lifestyle primary care interventions and other interventions for paediatric obesity). Summary effect sizes were mostly small across compared interventions (maximum 5.1 kg in adults and 1.78 kg in children) and even these estimates may be inflated. CONCLUSIONS: Depression, obesity in earlier age groups, short sleep duration, childhood abuse and low maternal education have the strongest support among proposed risk factors for obesity. Furthermore, there is no high-quality evidence to recommend treating obesity with a specific nonpharmacological and nonsurgical intervention among many available, and whatever benefits in terms of magnitude of weight loss appear small.

Management of a case of unacknowledged foreign body in the upper airway.

Tracheobronchial foreign body aspiration occurs rarely in adults and may go unrecognized for a long time, but early detection and immediate retrieval of the foreign body are essential to prevent major morbidity. We describe the case of an adult who unusually aspirated part of his dental prosthesis during an attempted strangulation, which was unacknowledged until 6 months later when he was hospitalized with acute respiratory failure and required an emergency surgical tracheotomy. The foreign body was successfully removed via flexible bronchoscopy.

Prevalence of Catatonia and Its Moderators in Clinical Samples: Results from a Meta-analysis and Meta-regression Analysis.

Catatonia is an independent syndrome that co-occurs with several mental and medical conditions. We performed a systematic literature review in PubMed/Scopus until February 2017 and meta-analyzed studies reporting catatonia prevalence. Across 74 studies (cross-sectional = 32, longitudinal = 26, retrospective = 16) providing data collected from 1935 to 2017 across all continents, mean catatonia prevalence was 9.0% (k = 80, n = 110764; 95% CI = 6.9-11.7, I2 = 98%, publication bias P < .01), decreasing to 7.8% (k = 19, n = 7612, 95% CI = 7-8.7, I2 = 38.9%) in a subgroup with low heterogeneity. Catatonia prevalence was 23.9% (k = 8, n = 1168, 95% CI = 10-46.9, I2 = 96%) in patients undergoing ECT/having elevated creatinine phosphokinase. Excluding ECT samples, the catatonia prevalence was 8.1% (k = 72, n = 109606, 95% CI = 6.1-10.5, I2 = 98%, publication bias P < .01), with sensitivity analyses demonstrating that country of study origin (P < .001), treatment setting (P = .003), main underlying condition (P < .001), and sample size (P < .001)moderated catatonia prevalence, being highest in Uganda (48.5%, k = 1) and lowest in Mexico (1.9%, 95% CI = 0.4-8.8, I2 = 67%, k = 2), highest in nonpsychiatric out- or inpatient services (15.8%, 95% CI = 8.1-28.4, I2 = 97%, k = 15)and lowest in psychiatric outpatients services (3.2%, 95% CI = 1.7-6.1, I2 = 50%, k = 3), highest in presence of medical or neurological illness with no comorbid psychiatric condition (20.6%, 95% CI = 11.5-34.2, I2 = 95%, k = 10)and lowest in mixed psychiatric samples (5.7%, 95% CI = 4.2-7.7, I2 =98%, k = 43), highest in studies with sample sizes <100 (20.7%, 95% CI = 12.8-31.6, I2 = 90%, k = 17) and lowest in studies with sample sizes >1000 (2.3%, 95% CI = 1.3-3.9, I2 = 99%, k = 16). Meta-regression showed that smaller sample size (P < .01) and less major depressive disorder (P = .02) moderated higher catatonia prevalence. Year of data collection did not significantly moderate the results. Results from this first meta-analysis of catatonia frequencies across time and disorders suggest that catatonia is an epidemiologically and clinically relevant condition that occurs throughout several mental and medical conditions, whose prevalence has not decreased over time and does not seem to depend on different rating scales/criteria. However, results were highly heterogeneous, calling for a cautious interpretation.