Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls. Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively. No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease. Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection. Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism. Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS.

Response to a massive SARS-CoV-2 infection in a nursing home transformed into a caring center.

BACKGROUND: The best policy to follow when nursing homes are massively hit by SARS-CoV2 is unclear. AIM: To describe COVID-19 containment in a nursing home transformed into a caring center. METHODS: Physicians and nurses were recruited. The facility was reorganized and connected with the laboratory of the reference hospital. Ultrasound was used to diagnose pneumonia. Patients needing intensive care were transferred to the reference hospital. Hydroxychloroquine/azithromycin/enoxaparin were used initially, while amiodarone/enoxaparin were used at a later phase. Under both regimens, methylprednisolone was added for severe cases. Prophylaxis was done with hydroxychloroquine initially and then with amiodarone. PERIOD COVERED: March 22-July 31, 2020. RESULTS: The facility was reorganized in two days. Ninety-two guests of the 121 (76%) and 25 personnel of 118 (21.1%) became swab test positive. Seven swab test negative patients who developed symptoms were considered to have COVID-19. Twenty-seven patients died, 23 swab test positive, 5 of whom after full recovery. Four patients needing intensive care were transferred (3 died). Mortality, peaking in April 2020, was correlated with symptoms, comorbidities, dyspnea, fatigue, stupor/coma, high neutrophil to lymphocyte ratio, C-reactive protein, interleukin-6, pro-calcitonin, and high oxygen need (p ≤ 0.001 for all). Among swab-positive staff, 3 had pneumonia and recovered. Although no comparison could be made between different treatment and prophylaxis strategies, potentially useful suggestions emerged. Mortality compared well with that of nursing homes of the same area not transformed into care centers. CONCLUSION: Nursing homes massively hit by SARS-CoV-2 can become caring centers for patients not needing intensive care.

Approach to patients with COVID-19 disease: the procedure in Udine.

Coronavirus disease 2019 poses a serious threat to public health. The protocol developed at the Azienda Sanitaria Universitaria Friuli Centrale (Italy) is based on clinical data, laboratory tests, chest echography and HRCT. Several therapeutic options are considered, since patients vary in disease severity, evolution and co-morbidities and because so far there are no clear indications about therapeutic strategy based on randomized clinical trial. In this protocol chest echography has a central role in categorizing patient status, follow-up and decision-making.

Isoniazid-induced Takayasu arteritis remission.

A 75-year-old man was admitted because of fever, unproductive cough, neck pain and upper limb claudication. The patient was febrile and hypotensive, and a cardiac systolic ejection murmur was heard. Blood tests showed normochromic anemia, elevated erythrocyte sedimentation rate, C-reactive protein, fibrinogen, and alpha-2 and beta-2 globulins. In order to investigate neck pain, an ultrasound examination of the carotid arteries was performed which showed a carotid intima-media thickness reaching the maximum value of 2.3 mm in both carotid arteries. Ultrasound examination of the temporal artery and its rami demonstrated wall thickening, both in the common superficial temporal artery and its frontal and parietal rami. A temporal artery biopsy was performed and was consistent with Takayasu arteritis. A positive interferon-γ release assay revealed latent tuberculosis infection and isoniazid 300 mg every 24 hours was commenced. Neither corticosteroids nor other drugs were prescribed at that time. Two weeks later, ultrasound examination showed a significant reduction in the thickening of all investigated arteries. To our knowledge, this is the first case of isoniazid-induced Takayasu arteritis remission. We believe that isoniazid deserves further investigation regarding its potential immunomodulatory properties.

Chest ultrasound findings in pulmonary tuberculosis.

In resource-limited countries, the diagnosis of pulmonary tuberculosis (TB) is based on clinical findings, chest radiography and the demonstration of acid-fast bacilli in sputum. Few data are available on the use of ultrasound (US) to diagnose pulmonary TB. Chest US was performed in patients with lung TB from a rural African setting, to look for signs of the disease and to clarify the role US may have in the diagnosis of pulmonary TB. Sixty adult patients diagnosed with lung TB underwent chest US. All patients had abnormal findings. The most frequent was a subpleural nodule (SUN), which was mostly multiple and also found in radiologically normal areas. Other findings were lung consolidations, cavitations, miliary patterns made of miniature SUNs, and pleural and pericardial effusions. Chest US is a complementary tool in evaluating patients with suspected lung TB in resource-limited settings where the disease has high prevalence.

Overcoming a "probable" diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature.

Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as "probable" cases. The diagnostic role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of new laboratory tools for AMA and PBC-specific ANA in a large series of PBC sera that were AMA-negative at IIF. We will also provide a discussion of the history and current status of AMA detection methods. We included IIF AMA-negative PBC sera (n=100) and sera from patients with other chronic liver diseases (n=104) that had been independently tested for IIF AMA and ANA; sera were blindly tested with an ELISA PBC screening test including two ANA (gp210, sp100) and a triple (pMIT3) AMA recombinant antigens. Among IIF AMA-negative sera, 43/100 (43%) manifested reactivity using the PBC screening test. The same test was positive for 6/104 (5.8%) control sera. IIF AMA-negative/PBC screen-positive sera reacted against pMIT3 (11/43), gp210 (8/43), Sp100 (17/43), both pMIT3 and gp210 (1/43), or both pMIT3 and Sp100 (6/43). Concordance rates between the ANA pattern on HEp-2 cells and specific Sp100 and gp210 ELISA results in AMA-negative subjects were 92% for nuclear dots and Sp100 and 99% for nuclear rim and gp210. Our data confirm the hypothesis that a substantial part of IIF AMA-negative (formerly coined "probable") PBC cases manifest disease-specific autoantibodies when tested using newly available tools and thus overcome the previously suggested diagnostic classification. As suggested by the recent literature, we are convinced that the proportion of AMA-negative PBC cases will be significantly minimized by the use of new laboratory methods and recombinant antigens.