Chronic Onset Research Articles

Morbid Obesity and Thyroid Cancer Rate. A Review of Literature.

In the past three decades, several recent studies have analyzed the alarming increase of obesity worldwide, and it has been well established that the risk of many types of malignancies is increased in obese individuals; in the same period, thyroid cancer has become the fastest growing cancer of all malignancies. We investigated the current literature to underline the presence of a connection between excess body weight or Body Mass Index (BMI) and risk of thyroid cancer. Previous studies stated that the contraposition between adipocytes and adipose-resident immune cells enhances immune cell production of multiple pro-inflammatory factors with subsequent induction of hyperlipidemia and vascular injury; these factors are all associated with oxidative stress and cancer development and/or progression. Moreover, recent studies made clear the mitogenic and tumorigenic action of insulin, carried out through the stimulation of mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase/AKT (PI3K/AKT) pathways, which is correlated to the hyperinsulinemia and hyperglycemia found in obese population. Our findings suggest that obesity and excess body weight are related to an increased risk of thyroid cancer and that the mechanisms that combine overweight with this cancer should be searched for in the adipokine pathways and chronic inflammation onset.

Profile of Osteomyelitis Patients Visiting the Orthopedic Clinic of Dr. Hasan Sadikin General Hospital, Indonesia, in 2017–2018

Background: Osteomyelitis is an inflammatory process caused by microorganism infection that leads to bone destruction. Osteomyelitis may affect all bones, particularly long bones, and infects all ages. This disease is hard to diagnose and the treatment is complex due to the disease’s heterogenicity, pathophysiology, clinical presentation, and management. This study aimed to determine the profile of osteomyelitis inpatients and outpatients presented to the Orthopedic Clinic of Dr. Hasan Sadikin General Hospital Bandung, IndonesiaMethods: This was a descriptive cross-sectional study conducted from July to October 2019 using the total sampling method. Data were collected from the medical records of osteomyelitis inpatients and outpatients presented to the Orthopedic Clinic of Dr. Hasan Sadikin General Hospital Bandung, Indonesia from 2017–2018. Data were then analyzed descriptively and the results were presented in frequencies.Result: In total, 90 data were retrieved. Most of data presented male patients (n= 69, 76.7%) with the age range of 20–29 years old (24.4%). The majority of these patients experienced chronic onset of disease (94.4%) located on the tibia (51.1%), which was caused by a post-operative procedure (61.1%). The most common treatment was operative procedure without antibiotic beads (51.1%). Staphylococcus aureus was the common pathogens identified in these patients (22.2%).Conclusion: The majority of osteomyelitis patients are males in productive age with chronic onset of disease located on the tibia caused by a post-operative procedure. Staphylococcus aureus is the common pathogen involved and the most common treatment is an operative procedure without antibiotic beads.

Association between chronic obstructive pulmonary disease, smoking, and interstitial lung disease onset in rheumatoid arthritis.

In rheumatoid arthritis (RA), respiratory manifestations include chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). We assessed whether baseline COPD and smoking were associated with RA-ILD onset. We identified new-onset ILD in incident RA subjects within the MarketScan Commercial Claims database, using physician and/or hospitalisation diagnostic codes. Smoking data (current, past, never) were available for a subset via a health questionnaire. Kaplan-Meier analyses assessed time to ILD onset, stratified by prior COPD and smoking. Multivariate Cox regression models were adjusted for age, sex, and (in the subset) smoking. Sensitivity analyses adjusted for past RA drugs. Among 373,940 new RA subjects, 6343 (1.7%) developed ILD (8.1 events per 1000 person-year, 95% CI 7.9, 8.3). ILD was more common among subjects with baseline COPD. Adjusting for age and sex, the hazard ratio (HR) between baseline COPD and incident ILD was 2.15, 95% CI 1.93, 2.39. We could not establish a clear relationship between current smoking and ILD; in the subset with smoking data, the HR point estimate for COPD was similar but the 95% CI was wider (due to fewer subjects) and included the null value. Adjusting for baseline RA drugs did not change results. Pre-existing COPD in incident RA subjects was associated with higher risk of future ILD. While a trend persisted after adjusting for smoking, we were limited by reduced sample size. Our study highlights the importance of ongoing assessments of potentially complicated relationships between smoking, COPD, and other factors in RA-associated ILD.

A novel method for clinical risk prediction with low-quality data

In real-world data, predictive models for clinical risks (such as adverse drug reactions, hospital readmission, and chronic disease onset) are constantly struggling with low-quality issues, namely redundant and highly correlated features, extreme category imbalances, and most importantly, a large number of missing values. In most existing work, each patient is represented as a value vector with the fixed-length from some feature space, and missing values are forced to be imputed, which introduces much noise for prediction if the data set is highly incomplete. Besides, other challenges are either remaining unresolved or only partially solved when modeling, but without a systematic approach. In this paper, we propose a novel framework to address these low-quality problems, that we first treat patients as bags with the various number of feature-value pairs, called instances, and map them to an embedding space through our proposed feature embedding method to learn from it directly. In this way, predictive models can avoid the negative impact of missing data naturally. A novel multi-instance neural network is then connected, using two computational modules to deal with the problems of correlated and redundant features: multi-head attention and attention-based multi-instance pooling. They are capable of capturing the instance correlations and locating valuable information in each instance or bag. The feature embedding and multi-instance neural network are parameterized and optimized jointly in an end-to-end manner. Moreover, the training process is under both main and auxiliary supervision with focal loss functions to avoid the caveat of a highly imbalanced label set. This proposed framework is named AMI-Net3. We evaluate it on three suitable data sets from real-world settings with different clinical risk prediction tasks: adverse drug reaction of risperidone, schizophrenia relapse, and invasive fungi infection, respectively. The comprehensive experimental results demonstrate the effectiveness and superiority of our proposed method over competitive baselines.

From PNS to CNS: characteristics of anti-neurofascin 186 neuropathy in 16 cases.

Neurofascin (NF) is critical for the formation and maintenance of Ranvier nodes. NF186, the neuronal form of NF, localizes in the initial segment of axon and Ranvier node. NF186 antibody has been detected in demyelinating diseases of both central nervous system (CNS) and peripheral nervous system (PNS). To evaluate the clinical features of patients with anti-NF186 IgG neuropathy. Sixteen patients (16/138) with serum-positive anti-NF186 IgG were included and divided into groups of either CNS or PNS-involved according to their clinical manifestations. Anti-NF186 IgG was detected by cell-based assays. In 7 patients who were confirmed to have CNS involvement, the most frequent symptoms were dizziness (57%) and vision impairment (43%); lesions in centrum semiovale, cerebellum, and meninges were shown by magnetic resonance imaging (MRI). In comparison, limb weakness (78%) and numbness (78%) were the most common symptoms in PNS-involved patients; axonal loss and demyelination were confirmed by nerve conduction examinations. Elevated level of cerebrospinal fluid (CSF) protein was found in 12 cases without statistically significant difference between the CNS and PNS groups. Meanwhile, CSF white blood cell counts were found significantly elevated in CNS-involved patients compared with patients of PNS group. Thirteen patients received immunomodulating treatments, and patients with chronic onset and progressive course showed poor response to the therapies. Patients with anti-NF186 IgG neuropathy showed no specific symptoms or signs. It is worth noting that quite a few patients show CNS-impaired signs only, and cranial MRI is essential for the screening of CNS involvement.

Snowfall reduces the risk of chronic subdural hematoma onset: Analysis of an administrative database in Japan.

Background: Chronic subdural hematoma (CSDH) is a frequently observed disease in neurosurgical practice. Although first snowfall has been considered to increase the onset of CSDH, few reports have assessed the relationship between snowfall and CSDH. In this study, we aimed to investigate the relationship between CSDH onset and first snowfall events.Methods: This retrospective study was based on the Japanese Diagnosis Procedure Combination inpatient database from July 1, 2010, to March 31, 2016, and on the global observation of snowfall events in Japan obtained from the Japan Meteorological Agency. We used a binomial approximation to evaluate the average number of CSDH patients after first snowfall events compared with that before first snowfall events. We calculated the odds ratio of CSDH onset on the first snowfall.Results: We identified 8526 CSDH patients from the database. A total of 5573 (65.4%) were observed before first snowfall events, and 2953 (34.6%) after first snowfall events. The first snowfall of winter was significantly associated with a reduction in the occurrence of CSDH (odds ratio, 0.53; 95% confidence interval; 0.51–0.55). In subgroup analysis, only the first snowfall in October was not associated with reduction in the occurrence of CSDH.Conclusion: First snowfall events did not affect the onset of CSDH in Japan.

The JANUS of chronic inflammatory and autoimmune diseases onset during COVID-19 - A systematic review of the literature.

The diverse clinical manifestations of COVID-19 is emerging as a hallmark of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. While the initial target of SARS-CoV-2 is the respiratory tract, it is becoming increasingly clear that there is a complex interaction between the virus and the immune system ranging from mild to controlling responses to exuberant and dysfunctional multi-tissue directed autoimmune responses. The immune system plays a dual role in COVID-19, being implicated in both the anti-viral response and in the acute progression of the disease, with a dysregulated response represented by the marked cytokine release syndrome, macrophage activation, and systemic hyperinflammation. It has been speculated that these immunological changes may induce the loss of tolerance and/or trigger chronic inflammation. In particular, molecular mimicry, bystander activation and epitope spreading are well-established proposed mechanisms to explain this correlation with the likely contribution of HLA alleles. We performed a systematic literature review to evaluate the COVID-19-related autoimmune/rheumatic disorders reported between January and September 2020. In particular, we investigated the cases of incident hematological autoimmune manifestations, connective tissue diseases, antiphospholipid syndrome/antibodies, vasculitis, Kawasaki-like syndromes, acute arthritis, autoimmune-like skin lesions, and neurologic autoimmune conditions such as Guillain–Barré syndrome. We screened 6263 articles and report herein the findings of 382 select reports which allow us to conclude that there are 2 faces of the immune response against SARS-CoV-2, that include a benign virus controlling immune response and a many faceted range of dysregulated multi-tissue and organ directed autoimmune responses that provides a major challenge in the management of this viral disease. The number of cases for each disease varied significantly while there were no reported cases of adult onset Still disease, systemic sclerosis, or inflammatory myositis.

Recent updates on the management of autoimmune hepatitis.

Autoimmune hepatitis (AIH) is an immunoinflammatory chronic liver disease with dynamic and rather heterogeneous disease manifestations. A trend of increasing prevalence of AIH has been observed worldwide, along with a relative increase in the percentage of male patients. AIH is characterized and diagnosed based on serum biochemistry and liver histology: elevated aminotransferases and serum immunoglobulin G (IgG), the presence of serum anti-nuclear antibody or anti-smooth muscle antibody, and interface lympho-plasmacytic hepatitis. Clinical manifestations differ among disease subtypes with distinct time-frames, i.e., AIH with a chronic insidious onset, and acute-onset AIH (the diagnosis of which is often challenging due to the lack of typical serum findings). The absence of disease-specific biomarkers or histological findings may expand the disease phenotype into drug-induced AIH-like liver injury. Corticosteroids and azathioprine are recommended first-line treatments for AIH. The complete normalization of aminotransferases and serum IgG is an essential treatment response to ensure long-term overall survival. An incomplete response or intolerance to these drugs is considered an indication for second-line treatment, especially with mycophenolate mofetil. Life-long maintenance treatment is required for the majority of patients, but the few who achieve prolonged and stringent biochemical remission with lower alanine aminotransferase and IgG within the normal range may be able to discontinue the medications. In the future, the quality of life of AIH patients should be managed by personalized medicine, including the appropriate selection and dosing of first-line therapy and perhaps alternating with potential therapeutics, and the prediction of the success of treatment withdrawal.

Clinical and Electrophysiological Features of Chronic Motor Axonal Neuropathy.

To determine the clinical and electrophysiological characteristics of chronic motor axonal neuropathy (CMAN) and identify the associated similarities and differences between CMAN, acute motor axonal neuropathy (AMAN), and motor neuropathy secondary to amyotrophic lateral sclerosis. The study described clinical and electrophysiological features of five patients with CMAN and compared with 20 AMAN patients, 42 amyotrophic lateral sclerosis patients and 41 healthy controls. To compare the distribution of different nerve involvement in the same limb, split ratio was introduced. Split ratio of upper limb = amplitude of compound muscle action potential abductor pollicis brevis (APB)/amplitude of compound muscle action potential abductor digiti minimi, and split ratio of lower limb = amplitude of compound muscle action potential extensor digitorum brevis/amplitude of compound muscle action potential abductor hallucis. Chronic motor axonal neuropathy patients manifested lower motor neuron syndrome with positive IgG anti-monosialoganglioside antibodies and good outcome. The CMAN patients shared similar clinical manifestation with AMAN patients except for disease course and higher Medical Research Council scores. Compared with healthy controls, the split ratio of lower limb was higher in both CMAN and AMAN, despite comparable split ratio of upper limb. There was significant difference between CMAN group and amyotrophic lateral sclerosis group in nerve involvement presented as split hand and split leg signs in amyotrophic lateral sclerosis and reverse split leg sign in CMAN. Chronic motor axonal neuropathy associated with monosialoganglioside might be a "mild" AMAN with chronic onset by similar clinical and electrophysiological features. There was a unique pattern of nerve involvement presenting as reverse split leg sign in both CMAN and AMAN.

Clinical reasoning in feline vestibular syndrome: which presenting features are the most important?

The aim of this study was to evaluate whether clinical variables from the history, clinical presentation, and physical and neurological examinations of cats with vestibular syndrome were statistically predictive of the underlying diagnosis. In total, 174 cats presenting with vestibular syndrome between January 2010 and May 2019 were investigated. Univariate statistical analysis of clinical variables was performed and those statistically associated with a diagnosis were retained for multivariable binary logistic regression modelling. The seven most prevalent diagnoses represented 95% of vestibular presentations, which included: otitis media/interna (n = 48), idiopathic vestibular syndrome (n = 39), intracranial neoplasia (n = 24), middle ear polyp (n = 17), feline infectious peritonitis (n = 13), thiamine deficiency (n = 13) and intracranial empyema (n = 11). Idiopathic vestibular syndrome was commonly associated with non-purebred cats and had 17.8 times the odds of an improving clinical progression (95% confidence interval [CI] 1.3-250.0; P = 0.03). Intracranial neoplasia was associated with older age and chronic onset of clinical signs, and was significantly more likely to have a central vestibular neuroanatomical localisation (95% CI 8.5-344,349,142.0; P = 0.015) with postural deficits on neurological examination. Thiamine deficiency was more common in female cats, with 52.6 times the odds of a waxing and waning clinical progression (95% CI 1.2-1000; P = 0.038) and 6.8 times the odds of presenting with bilateral vestibular signs (95% CI 1.0-45.7; P = 0.047) and wide excursions of the head (95% CI 1.0-45.7; P = 0.047). Middle ear polyps were associated with 8.8 times the odds of presenting with Horner syndrome (95% CI 1.5-50.0; P = 0.015). Although it may be difficult to identify the underlying diagnosis in cats with vestibular syndrome from the presenting features alone, there are instances in which discrete clinical features may help to guide clinical reasoning when evaluating cats with vestibular presentations.

The Context Matters: A Retrospective Analysis of Life Stage at Chronic Pain Onset in Relation to Pain Characteristics and Psychosocial Outcomes.

BackgroundDevelopmental life stage at chronic pain onset differs among chronic pain patients. Although pain affects multiple life domains, it is unknown whether the timing of chronic pain onset relates to pain characteristics and psychosocial outcomes. The purpose of this retrospective study was to investigate differences in pain characteristics and psychosocial outcomes in patients at different developmental life stages at chronic pain onset.MethodsCross-sectional baseline data from the Swedish Quality Registry for Pain Rehabilitation (2009 to 2016) were used, selecting the middle-aged patients (45–65 years, n=6225) reporting chronic nonmalignant pain. Patients were categorized into three groups, depending on their developmental life stage at chronic pain onset: early onset (age ≤30 years), intermediate onset (age 31–45 years), and late onset (age ≥46 years). Pain characteristics and psychosocial outcomes were assessed with validated self-reported measures.ResultsOne-way MANCOVA indicated differences in number of pain locations and psychosocial outcomes among the groups. Post hoc analysis showed differences in the trends for how groups differed on outcome domains. Overall, patients with earlier chronic pain onset showed significantly poorer psychosocial outcomes and more spreading of pain.ConclusionDevelopmental life stage at chronic pain onset is associated with different pain outcomes. Pain onset early in life is linked to worse outcomes in multiple domains, pointing to a need for identifying these patients early.

Aspergillosis infection over 20\u2009years: a case report of probable vascular invasion in central nervous system

BackgroundAspergillosis infection of central nervous system (CNS) is rare and fatal. Diagnosis of invasive aspergillosis remains difficult. Aspergillosis of CNS can be an acute, subacute, or chronic onset, and the longest course of the disease was currently reported to be 4 years. Here, we report a case with recurrent headache over 20 years.Case presentationA 54-year-old man was admitted to our neurological disease ward due to intermittent throbbing headache lasting for more than 20 years that had grown notably worse over the past week. The headache was localized to the side of his head blown by a cold wind. He also experienced nausea and vomiting when the headache became severe. The headache usually lasted for 3–4 h after he was blown by the cold wind, though he had no fever. The neurological examination was normal. Magnetic resonance imaging (MRI) of the brain was negative for parenchymal and meningeal lesions. However, the case had increased intracranial pressure (ICP), and elevated protein level in the cerebrospinal fluid (CSF). Aspergillus fumigatus was found in CSF by nanopore targeted sequencing (NTS) and in blood by enzyme-linked immunosorbent assay (ELISA). Aspergillus fumigatus-specific antibody IgG was 104.62 AU/mL, aspergillus galactomannan (GM) antigen was 3.27 μg/L, D-dimer was 3.25 mg/L and fibrinogen degradation product was 11.50 mg/L, which were markedly higher than the normal levels. The patient was prescribed by voriconazole. After the treatment of 14 days, the ICP, CSF protein level, Aspergillus fumigatus-specific antibody IgG, GM antigen, D-dimer and fibrinogen degradation product returned normal. Aspergillus was disappeared by NTS test of CSF. His headache has never occurred again after blowing by a cold wind.ConclusionsThis report reveals that aspergillosis infection of CNS can last for more than 20 years and the major symptom is only intermittent throbbing headache in an immunocompetent patient. Vascular invasion is probably the mechanism of headache in our case with CNS aspergillosis infection. Performing high-throughput gene sequencing technology in CSF is important when the pathogen is not determined for the patients with suspected CNS infection.

Hypertrophic Pachymeningitis in Chinese Patients: Presentation, Radiological Findings, and Clinical Course.

Background Hypertrophic pachymeningitis (HP) is generally regarded as a rare inflammatory disease, which results in a diffuse thickening of the dura mater. We retrospectively collected data from patients with HP. Methods A total of 16 patients with HP were included in our study. The clinical features, laboratory evaluation, imaging findings, treatment, and outcome were reviewed. Results Of the 16 cases, half were male, with a mean age of 52.6 ± 13.2 years. The mean duration from onset to diagnosis was 8.6 months. The most frequent presenting symptoms in HP cases were a recurrently chronic headache (81.3%) and multiple cranial nerve injury (50%). Antineutrophil cytoplasmic antibody- (ANCA-) related HP was found in 5 cases and IgG4-related HP in 1 case. The intracranial pressure was elevated in 4 cases. The cerebrospinal fluid (CSF) had lymphocytosis in 5 cases and increased protein in 12 cases. Immunoglobulins (IgG, IgA, and IgM) and protein showed linear relationships in the CSF. On magnetic resonance imaging (MRI), localized or diffuse dura maters were thickened in all cases. HP combined with subacute subdural hemorrhage or hypertrophic spinal pachymeningitis was also observed in individual cases. Biopsy of the dura mater in one case showed amounts of inflammatory cells infiltrating, with an increased percentage of IgG4-positive plasma cells. Of all cases referring to glucocorticoid treatment, the symptoms have improved significantly in 10 cases. In other 6 cases, mycophenolate mofetil or azathioprine was added. All patients showed clinical improvement at the follow-up visits. Conclusion The clinical characters of HP are chronic onset, recurrently chronic headache, and multiple cranial nerves paralysis. Inflammatory changes in CSF caused by intrathecal synthesis of immunoglobulin, characteristic dural enhancement on MRI, and pathologic biopsy are all helpful for diagnosis. The addition of immunosuppressant, especially mycophenolate mofetil, is a good choice for steroid-resistance HP.

NEUROGENIC PULMONARY EDEMA: KOMPLIKASI YANG MENGANCAM JIWA AKIBAT KERUSAKAN BERAT SISTEM SARAF PUSAT

ABSTRACT
 Neurogenic Pulmonary Edema (NPE) is one of the complications due to severe damage of the central nervous system (CNS). The incidence is about 2-8% in the world and still rarely reported. Neurogenic pulmonary edema (NPE) commonly found in cases of intracranial hemorrhage such as SDH, SAH, and ICH, in conditions of uncontrolled epilepsy and recurrent seizures, and in some cases of spinal cord trauma. The pathogenesis of Neurogenic Pulmonary Edema (NPE) cannot be fully understood, but there are 2 theories of the occurrence of Neurogenic Pulmonary Edema (NPE), the first namely as theory of hemodynamic changes and the second is NPE trigger zones involving the central control of the brain's autonomic and cardiovascular system. Neurogenic Pulmonary Edema (NPE) has an acute and chronic onset, which is characterized by ARDS-like symptoms such as dyspnea, tachypnea, tachycardia, reddish sputum, crackles in auscultation, and radiological features in the form of diffuse alveolar infiltrat bilateral. Early recognition of signs and symptoms of Neurogenic Pulmonary Edema (NPE) can improve the patient's outcome. Initial treatment of this condition uses two management principles, first overcoming the underlying disease condition and second is supportive therapy, such as mechanical ventilator, ECMO, and transpulmonary thermodilution, the use of diuretics, and controlling fluid therapy.

Chronic Manganese Administration with Longer Intervals Between Injections Produced Neurotoxicity and Hepatotoxicity in Rats.

Subacute exposure to manganese (Mn) produced Parkinson’s disease-like syndrome called Manganism. Chronic onset and progression are characteristics of Manganism, therefore, this study aimed to examine Mn toxicity following chronic exposures. Male Sprague-Dawley rats were injected Mn2+ 1 and 5 mg/kg, every 10 days for 150 days (15 injections). Animal body weight and behavioral activities were recorded. At the end of experiments, the brain and liver were collected for morphological and molecular analysis. Chronic Mn exposure did not affect animal body weight gain, but the high dose of Mn treatment caused 20% mortality after 140 days of administration. Motor activity deficits were observed in a dose-dependent manner at 148 days of Mn administration. Immunofluorescence double staining of substantia nigra pars compacta (SNpc) revealed the activation of microglia and loss of dopaminergic neurons. The chronic neuroinflammation mediators TNFα, inflammasome Nlrp3, Fc fragment of IgG receptor IIb, and formyl peptide receptor-1 were increased, implicating chronic Mn-induced neuroinflammation. Chronic Mn exposure also produced liver injury, as evidenced by hepatocyte degeneration with pink, condensed nuclei, indicative of apoptotic lesions. The inflammatory cytokines TNFα, IL-1β, and IL-6 were increased, alone with stress-related genes heme oxygenase-1, NAD(P)H:quinone oxidoreductase-1 and metallothionein. Hepatic transporters, such as multidrug resistant proteins (Abcc1, Abcc2, and Abcc3) and solute carrier family proteins (Slc30a1, Slc39a8 and Slc39a14) were increased in attempt to eliminate Mn from the liver. In summary, chronic Mn exposure produced neuroinflammation and dopaminergic neuron loss in the brain, but also produced inflammation to the liver, with upregulation of hepatic transporters.Graphic

Differential diagnosis in joint and spine damages

The lecture covers main approaches to differential diagnosis in rheumatic diseases. It highlights the key questions that should be answered at the primary examination of the patient. The most important signs that can identify severe, sometimes urgent nonrheumatic diseases are presented. The author describes pain of different patterns and intensity and the most common variants of acute or chronic onset of mono-, oligo-, or polyarthritis. The 2016 European League Against Rheumatism (EULAR) definition of arthralgia suspicious for the development of rheumatoid arthritis is given. The lecture presents the signs indicating the inflammatory nature of back pain in cases of suspected spondyloarthritis (SpA), as well as a two-step diagnostic strategy for axial SpA. Attention is paid to the semiotics of joint damage and extra-articular manifestations in various rheumatic diseases. A brief algorithm for a differential diagnostic search for joint pain is given.

Oral adverse events in cancer patients treated with immune checkpoint inhibitors.

e15106 Background: Immune-checkpoint inhibitors (ICIs) are increasingly used to treat a variety of cancers. Immune-related adverse events (irAEs) have been reported. Oral manifestations of irAEs include stomatitis, oral ulcers, and xerostomia. However, the trajectory and frequency of oral irAEs remain unclear. This study aims to evaluate the prevalence, trajectory and nature of oral irAEs and their association with primary cancer diagnosis and other irAEs. Methods: A retrospective electronic chart review using the Partners Research Patient Data was performed for all patients treated with ICIs at Partners Healthcare hospitals and the Dana-Farber Cancer Institute between 12/2011 and 9/2019. Keywords specific to oral irAE such as oral mucositis, stomatitis or mouth sore were used. We collected data on demographics, cancer features, treatments, and characteristics of oral irAEs. Results: 822 of 4683 patients who received ICIs therapy were identified by keyword filtering. Lung cancer, gastrointestinal cancer, and skin cancer (including melanoma) were the most common types of primary malignancies with a frequency of 35.5%, 12.4 % and 11.7%, respectively. Oral irAEs were identified in 106 patients with the median age of 69 (range: 29-92) years and the female to male ratio of 1:1. 57.5% (n = 61) presented with symptomatic oral mucosal lesions. 47.2% (n = 50) had xerostomia and 17.0% (n = 18) had dysgeusia. The median time from the date of ICIs initiation to the date of oral irAE onset was 105 days (range: 2-631 days) in patients presented with oral mucosal lesions, 103 days (2-860 days) in xerostomia patients, and 156 days (range: 5-836 days) in dysgeusia patients. Melanoma was the most common cancer seen in oral irAE patients (30.2%), followed by lung cancer (26.4%) and oral/oropharyngeal cancer (12.3%). 60, 42, and 12 patients received pembrolizumab, nivolumab, and ipilimumab, respectively. 86.8% of oral irAE patients received only one type of ICIs therapy. Concomitant cutaneous, intestinal, and rheumatological irAEs were commonly reported with a frequency of 19.4%, 15.3%, and 12.2%, respectively in those patients. Conclusions: Oral irAEs can present with both acute and chronic onset in patients with ICIs therapy but are not as common as oral AEs associated with conventional cytotoxic regimens. While data relative to capturing oral irAEs is still preliminary, the current provides insight into their nature and course. Prospective studies focused on assessing the impact of ICI on oral irAEs are likely to provide additional insight into the character, course and impact of these conditions.

Methods for Bioaerosol Characterization: Limits and Perspectives for Human Health Risk Assessment in Organic Waste Treatment

Bioaerosol characterization represents a major challenge for the risk assessment and management of exposed people. One of the most important bioaerosol sources is the organic waste collection and treatment. This work analyzed and discussed the literature with the purpose of investigating the main techniques used nowadays for bioaerosol monitoring during organic waste treatment. The discussion includes an overview on the most efficient sampling, DNA extraction, and analysis methods, including both the cultural and the bio-molecular approach. Generally, an exhaustive biological risk assessment is not applied due to the organic waste heterogeneity, treatment complexity, and unknown aerosolized emission rate. However, the application of bio-molecular methods allows a better bioaerosol characterization, and it is desirable to be associated with standardized cultural methods. Risk assessment for organic waste workers generally includes the evaluation of the potential exposition to pathogens and opportunistic pathogens or to other microorganisms as biomarkers. In most cases, Saccharopolyspora rectivirgula, Legionella spp., Aspergillus spp., and Mycobacterium spp. are included. Future perspectives are focused on identifying common composting biomarkers, on investigating the causality process between chronic bioaerosol exposure and disease onset, and finally, on defining common exposure limits.

Phenolic Compounds and Bioaccessibility Thereof in Functional Pasta.

Consumption of food products rich in phenolic compounds has been associated to reduced risk of chronic disease onset. Daily consumed cereal-based products, such as bread and pasta, are not carriers of phenolic compounds, since they are produced with refined flour or semolina. Novel formulations of pasta have been thus proposed, in order to obtain functional products contributing to the increase in phenolic compound dietary intake. This paper aims to review the strategies used so far to formulate functional pasta, both gluten-containing and gluten-free, and compare their effect on phenolic compound content, and bioaccessibility and bioavailability thereof. It emerged that whole grain, legume and composite flours are the main substituents of durum wheat semolina in the formulation of functional pasta. Plant by-products from industrial food wastes have been also used as functional ingredients. In addition, pre-processing technologies on raw materials such as sprouting, or the modulation of extrusion/extrusion-cooking conditions, are valuable approaches to increase phenolic content in pasta. Few studies on phenolic compound bioaccessibility and bioavailability in pasta have been performed so far; however, they contribute to evaluating the usefulness of strategies used in the formulation of functional pasta.

Clinical, radiological, and pathological features of anti-asparaginyl tRNA synthetase antibody-related interstitial lung disease.

Myositis and interstitial lung disease (ILD) frequently occur in patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies. Nearly half of ARS-ILD patients have the acute or subacute form of the disease, and one-third of these patients show a deterioration in pulmonary function over the long-term course because of frequent recurrences and refractoriness to therapy. Several reports recently described different characteristics depending on the individual anti-ARS antibodies, and the anti-asparaginyl tRNA synthetase (KS) antibody was strongly linked to ILD rather than to myositis. We therefore hypothesized that KS-ILD may have clinical characteristics that differ from those of other ARS-ILDs. The aim of this study was to clarify the clinical, radiological, and pathological features of KS antibody-positive ILD. We retrospectively analyzed 19 consecutive patients with KS-ILD who underwent initial clinical measurements and high-resolution computed tomography and pathological assessments. We also analyzed disease behavior based on pulmonary function test results during the follow-up period. Our KS-ILD cohort included patients with dermatomyositis (10.5%), primary Sjögren syndrome (5.3%), and idiopathic ILD (84.2%). Most patients presented with chronic onset (89.5%) and a nonspecific pattern of interstitial pneumonia at each radiological and pathological assessment (89.4% and 85.7%, respectively). The pulmonary function test results showed that the mean changes from the initial %forced vital capacity and %diffusing capacity of the lung for carbon monoxide at 3 years were 3.7%±2.9% and 9.35%±3.0%, respectively. Most KS-ILD patients showed a tendency for chronic disease onset and long-term stabilization of pulmonary function.