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Background: Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management. Objectives: Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection. Sources: We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals. Content: Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes thirdgeneration cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression. Implications: We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions.

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Objective During the last decade, obesity has become an epidemic. As obesity is now considered a state of low-grade inflammation, the purpose of this study was to assess the prevalence of four common elements of inflammation, in individuals with increased BMI. These findings were compared to those of subjects with normal BMI. The effect of gender was also noted. Methods Data were collected from medical records of individuals examined at a screening center in Israel between the years 2000–2014. Cross-sectional analysis was carried out on 7526 men and 3219 women. White blood cell count (WBC); platelet (PLT) count; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed in four BMI categories: normal, overweight, obese and morbidly obese. Results Mean (SD) age of the study sample was 47.5 (9.7) and 46.7 (9.8) years for men and women, respectively. The prevalence of each inflammatory marker increased significantly when comparing abnormal to normal BMI (p<0.0001). The odds ratio (OR) of the prevalence of increased inflammatory markers was compared between subjects with overweight, obese and morbid obesity and subjects with normal BMI. This study showed that the higher the BMI, the higher the OR. For those in the morbid obesity group, the OR for the different inflammatory markers adjusting for age, diabetes mellitus hypertension and kidney function were as follows: WBC levels, 5.1 (2.9–8.7) and 4.7 (2.4–9.1) for men and women, respectively; PLT levels, 1.7 (0.3–8.5) and 2.0 (0.6–7.2) for men and women, respectively; ESR levels, 4.2 (3.2–5.4) and 4.6 (3.2–6.6) for men and women, respectively, and CRP levels, 13.4 (10.0–18.2) and 19.2 (12.9–28.6) for men and women, respectively. Conclusion Inflammatory markers are significantly higher in subjects with abnormal compared to normal BMI. This difference was found to be greater in women than in men.

Nocardia is an opportunistic pathogen that most frequently affects the lungs. Evidence is limited regarding the risk factors for nocardiosis. The current study assessed clinical correlates of nocardiosis. A retrospective study was conducted based on medical records of consecutive adult patients (N = 60) with nocardiosis hospitalized during 2007-2018 at a tertiary hospital in central Israel. A matched comparison group of 120 patients was randomly selected among hospitalized patients with community-acquired pneumonia. Multivariable conditional logistic regression models were fitted. Immunosuppressive pharmacotherapy was positively associated with nocardiosis (matched odds ratio [OR] 4.40, 95% confidence interval [CI] 2.25-8.62, p < 0.001), particularly corticosteroid therapy (matched OR 4.69, 95% CI 2.45-8.99, p < 0.001). Systemic corticosteroid therapy was strongly associated with pulmonary nocardiosis (matched OR 5.90, 95% CI 2.75-12.66, p < 0.001). The positive association between solid organ transplantation and nocardiosis was attenuated following adjustment for systemic corticosteroids in a multivariable model. The association between corticosteroid therapy and nocardiosis appeared stronger in patients with chronic pulmonary disease (OR 5.74, 95% CI 2.75-12.66, p < 0.001) than in the pooled analysis of all nocardiosis cases. In conclusion, corticosteroid therapy was strongly correlated with nocardiosis, particularly among individuals with chronic pulmonary disease and in pulmonary nocardiosis. Nocardiosis is an opportunistic infection that typically occurs in individuals with a history of solid organ transplantation (SOT) 1 , malignancy 2 , human immunodeficiency virus infection 3 or chronic pulmonary diseases 4. Evidence on the independent contribution of each of these conditions to nocardiosis risk remains limited, since most studies were case-series and lacked a comparison group. It is also unclear if the likelihood of nocardiosis is related to the underlying disease itself or to the immunosuppression therapy administered against it. Corticosteroid therapy is prevalent amongst individuals diagnosed with nocardiosis 5,6. A European multicenter case-control study conducted among SOT recipients (SOTR) showed that corticosteroid dosage was related to the risk of nocardiosis (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.03-1.22 for each milligram increase in corticosteroid dose), and a strong positive association was found between high calcineurin inhibitor and nocardiosis (OR 6.11, 95% CI 2.58-14.51) 1. As corticosteroid therapy is the standard of care for many conditions that might be also associated with nocardiosis, such as SOT, chronic pulmonary diseases and cancer, the independent role of each factor, warrant further investigation. As Nocardia is mostly transmitted by inhalation or aspiration 7 , the lungs are the primary site of infection in more than two-thirds of the nocardiosis cases 3. However, evidence on the risk factors for nocardiosis, beyond the general propensity to develop bacterial pne...

Background Fatigue is the most prevalent and debilitating long COVID symptom, however risk factors and pathophysiology of this condition remain unknown. We assessed risk factors for long COVID fatigue and explored its possible pathophysiology. Methods Nested case-control study in a COVID recovery clinic. Individuals with (cases) and without (controls) significant fatigue were included. We performed a multidimensional assessment evaluating various parameters, including pulmonary function tests and cardiopulmonary exercise testing, and implemented multivariable logistic regression to assess risk factors for significant long COVID fatigue. Results Total of 141 individuals were included. Mean age was 47 (SD 13) years; 115 (82%) were recovering from mild COVID-19. Mean time for evaluation was 8 months following COVID-19. Sixty-six (47%) individuals were classified with significant long COVID fatigue. They had significantly higher number of children, lower proportion of hypothyroidism, higher proportion of sore throat during acute illness and long COVID symptoms, and of physical limitation in daily activities. Individuals with fatigue had poorer sleep quality and higher degree of depression. They had significantly lower heart rate [153.52 (22.64) vs 163.52 (18.53), p=0.038] and oxygen consumption per Kg [27.69 (7.52) vs 30.71 (7.52), p=0.036] at peak exercise. The two independent risk factors for fatigue identified in multivariable analysis were peak exercise heart rate (odds ratio [OR] 0.79 per 10 beats/minute, 95% confidence interval [CI] 0.65-0.96, p=0.019); and long COVID memory impairment (OR 3.76, 95% CI 1.57-9.01, p=0.003). Conclusions Long COVID fatigue may be related to autonomic dysfunction, impaired cognition and decreased mood. This may suggest a limbic-vagal pathophysiology. Clinical Trial registration: NCT04851561

Background: Vitamin B12 deficiency is associated with hematological, neurological, and cardiovascular consequences. Epidemiologic data on these related illnesses indicate gender differences. Methods: A cross-sectional study was designed to examine gender differences in vitamin B12 deficiency among a healthy population. Data from healthy individuals aged 18–65, who were provided with a routine medical evaluation during 2000–2014, were retrieved from the medical charts. Individuals with background illnesses and those who had used medications or nutritional supplements were excluded. Vitamin B12 deficiency was defined by 2 cutoff values (206 and 140 pmol/L). The multivariate analysis was adjusted for age, body mass index, estimated glomerular filtration rate, hyperhomocysteinemia, folate deficiency, albumin, and transferrin saturation. Sensitivity analyses were implemented by excluding individuals with anemia, hyperhomocysteinemia, or folate deficiency and by age stratification. Results: In all, 7,963 individuals met the inclusion criteria. Serum vitamin B12 mean levels were 312.36 and 284.31 pmol/L for women and men respectively (p < 0.001). Deficiency prevalence was greater for men (25.5%) in comparison with women (18.9%; p < 0.001). Men were strongly associated with severe deficiency (adjusted OR 2.26; 95% CI 1.43–3.56). Conclusions: Among the healthy population, men are susceptible to vitamin B12 deficiency. This can be explained by neither diet habits nor estrogen effects. Genetic variations are therefore hypothesized to play a role.