REVIEW describes an evidence-based approach for managing SSc-ILD in the current treatment era. This review also highlights emerging SSc-ILD treatment strategies and discusses unresolved issues regarding treatment initiation, treatment response monitoring, and the use and duration of maintenance therapy in SSc-ILD. Current treatment approaches Cyclophosphamide The findings of both RCTs (5, 6) and uncontrolled studies (7, 8) have provided evidence that treatment with CYC is effective for stabilizing SSc-ILD progression. The recently updated EULAR recommendations for the treatment of SSc suggest using CYC as first-line therapy in SSc-ILD (9). In SLS I (n = 158) (6), patients receiving daily oral CYC administered over 12 months experienced an improvement in lung function (forced vital capacity [FVC]%-predicted) relative to patients receiving placebo who had the same extent of radiographic fibrosis, especially when the extent of fibrosis exceeded 50% in the zone of maximal involvement, which roughly corresponded to 25% in the whole lung (10). Moreover, treatment with CYC was associated with an improvement in the extent of both visually assessed and computer-assisted quantitative lung fibrosis compared with placebo (10, 11). A smaller RCT (n = 45) (5) found that 6 months of intravenous (IV) CYC followed by

Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by mononuclear cells (principally lymphocytes) infiltrating exocrine glands (e.g., salivary and lacrimal glands), leading to destruction of exocrine epithelial cells and dryness of mucosal surfaces. Cardinal symptoms are dry eyes (xerophthalmia) and dry mouth (xerostomia). Extraglandular sites are affected in 30 to 40% of cases of SS (particularly neurological, kidneys, skin, and lungs). B cell hyperactivity, autoantibody production, and hypergammaglobulinemia are cardinal features of SS. Primary SS is not associated with other autoimmune diseases. However, SS can complicate diverse autoimmune disorders (particularly systemic lupus erythematosus, rheumatoid arthritis, and scleroderma); this form is termed “secondary SS.” Pulmonary involvement is usually not a dominant feature of SS, but may be severe in some cases. In this review, we discuss specific tracheal, bronchiolar, and pulmonary complications of SS including xerotrachea, bronchiolitis, bronchiectasis, interstitial lung disease, nonspecific interstitial pneumonia, usual interstitial pneumonia, lymphoid interstitial pneumonia, organizing pneumonia, acute fibrinous and organizing pneumonia, pulmonary cysts, pleural effusions, pulmonary amyloidosis, and bronchus- or lung-associated lymphomas.

We hypothesize that isoflurane and ketamine impact ventilatory pattern variability (VPV) differently. Adult Sprague-Dawley rats were recorded in a whole-body plethysmograph before, during and after deep anesthesia. VPV was quantified from 60-s epochs using a complementary set of analytic techniques that included constructing surrogate data sets that preserved the linear structure but disrupted nonlinear deterministic properties of the original data. Even though isoflurane decreased and ketamine increased respiratory rate, VPV as quantified by the coefficient of variation decreased for both anesthetics. Further, mutual information increased and sample entropy decreased and the nonlinear complexity index (NLCI) increased during anesthesia despite qualitative differences in the shape and period of the waveform. Surprisingly mutual information and sample entropy did not change in the surrogate sets constructed from isoflurane data, but in those constructed from ketamine data, mutual information increased and sample entropy decreased significantly in the surrogate segments constructed from anesthetized relative to unanesthetized epochs. These data suggest that separate mechanisms modulate linear and nonlinear variability of breathing.

Interleukin-6 blockade (IL-6) has become a focus of therapeutic investigation for the coronavirus-2019 (COVID-19). We report a case of a 34 year-old with COVID-19 pneumonia receiving an IL-6 receptor antagonist (IL-6Ra) who developed spontaneous colonic perforation. This perforation occurred despite a benign abdominal exam and in the absence of other known risk factors associated with colonic perforation. Examination of the colon by electron microscopy revealed numerous intact SARS-CoV-2 virions abutting the microvilli of the colonic mucosa. Multiplex immunofluorescent staining revealed the presence of the SARS-CoV-2 spike protein on the brush borders of colonic enterocytes which expressed angiotensin-converting enzyme 2. However, no viral particles were observed within the enterocytes to suggest direct viral injury as the cause of colonic perforation. These data and absence of known risk factors for spontaneous colonic perforation implicate IL-6Ra therapy as the potential mediator of colonic injury in this case. Furthermore, this report provides the first in situ visual evidence of the virus in the colon of a patient presenting with colonic perforation adding to growing evidence that intact infectious virus can be present in the stool.

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