Related factors, increased mortality and causes of death in patients with rheumatoid arthritis-associated interstitial lung disease.

Objectives: Interstitial lung disease (ILD) is a life-threatening extra-articular manifestation of rheumatoid arthritis (RA). We aimed to clarify the relationship between chronic ILD with a pattern of usual interstitial pneumonia (UIP) or non-UIP and mortality in RA patients.Methods: We retrospectively surveyed information of consecutive RA patients who visited our hospital from 2009 to 2014. The relationship between their mortality and chronic ILD (UIP or non-UIP) detected by high-resolution computed tomography was examined.Results: Of 2702 patients enrolled, 261 (9.7%) had chronic ILD and among these 120 had a UIP pattern. At the onset of RA, the prevalence of chronic ILD was 6%. Patients with chronic ILD had a higher mortality than those without. The most frequent cause of death was pneumonia including acute exacerbation (AE) of chronic ILD. Lung cancer death was frequently identified in deceased patients with chronic ILD with a UIP pattern compared with the other decedents (p=.062). The estimated mortality of lung cancer in patients with chronic ILD with a UIP pattern was five times higher than the general population.Conclusion: RA patients with ILD with a UIP pattern have a high mortality rate and are prone to die of AE or lung cancer.

Efficacy and Tolerability of High-Flow Nasal Cannula Oxygen Therapy for Hypoxemic Respiratory Failure in Patients with Interstitial Lung Disease with Do-Not-Intubate Orders: A Retrospective Single-Center Study.

BACKGROUND: High-flow nasal cannula (HFNC) oxygen therapy may provide effective respiratory management of hypoxemic respiratory failure in patients with interstitial lung disease (ILD) with a do-not-intubate (DNI) order. OBJECTIVES: The aim was to assess the efficacy and tolerability of HFNC for these patients. METHODS: We retrospectively reviewed the records of patients requesting a DNI order for hypoxemic respiratory failure associated with ILD, comparing treatment with HFNC and noninvasive positive pressure ventilation (NPPV). Outcomes measured were 30-day survival, in-hospital mortality, temporary interruption and discontinuation of the treatment at the patient's request, adverse events, oral intake, and communication ability at the end of life. RESULTS: A total of 84 patients (HFNC, n = 54; NPPV, n = 30) were analyzed. Neither 30-day survival (HFNC 31.5% vs. NPPV 30.0%; p = 0.86) nor in-hospital mortality (HFNC 79.6% vs. NPPV 83.3%; p = 0.78) differed significantly. The temporary interruption and discontinuation rates were significantly lower in the HFNC group than in the NPPV group (3.7 vs. 23.3%; p = 0.009 and 0 vs. 10%; p = 0.043, respectively), and that group had significantly fewer adverse events. Among patients who died in the hospital, those treated with HFNC had significantly better oral intake and ability to converse until just before death. CONCLUSION: HFNC had a survival rate equivalent to that of NPPV and was better tolerated by patients with hypoxemic respiratory failure associated with ILD who had a DNI order. HFNC allowed patients to eat and converse until just before death, suggesting that HFNC in these patients is a reasonable palliative treatment.

A Contemporaneous Onset of Eosinophilic Granulomatosis with Polyangiitis and Myasthenia Gravis: A Case Report.

Autoimmune neuromuscular disorders in patients with eosinophilic granulomatosis with polyangiitis (EGPA) are relatively uncommon. Although two cases of myasthenia gravis (MG) comorbid with EGPA have been reported, both patients developed EGPA several years after starting immunosuppressive treatment for MG. We herein report a 75-year-old man with a rare co-occurrence of EGPA and MG that developed simultaneously and was successfully treated with immunosuppressive therapy. Distinguishing the neurological symptoms of EGPA from complications of other neurological autoimmune diseases, such as MG, is crucial, especially in patients with eosinophilia.

Myasthenia gravis with inclusion body myositis: A case report.

We present the case of a 75-year-old man diagnosed with myasthenia gravis (MG) based on lower leg weakness and ptosis for the past 2 months before admission to our hospital. The patient was anti-acetylcholine receptor antibody-positive at admission. He was treated with pyridostigmine bromide and prednisolone, which improved the ptosis, but the lower leg muscle weakness remained. An additional lower leg magnetic resonance imaging examination suggested myositis. Inclusion body myositis (IBM) was diagnosed after a subsequent muscle biopsy. Although MG is often associated with inflammatory myopathy, IBM is rare. There is no effective treatment for IBM, but various treatment possibilities have recently been proposed. This case emphasises that myositis complications, including IBM, should be considered when elevated creatine kinase levels are observed and conventional treatments do not address chronic muscle weakness.

A case of severe bilateral empyema due to Streptococcus pyogenes.

Bilateral empyema is a rare and severe condition and deciding on a treatment is quite difficult. Additionally, infections caused by group A Streptococcus (GAS [Streptococcus pyogenes]) are known to be invasive. We successfully treated without surgery a previously healthy 59-year-old woman with bilateral empyema due to GAS, with repeated drainages, antibiotics, and fibrinolytic therapy. To our knowledge, there have not been any published reports on cases of bilateral empyema due to GAS infection. In rare, severe cases of bilateral empyema caused by organisms such as GAS, physicians managing the condition should consider the overall condition of the patient.

Treatment-resistant idiopathic multicentric Castleman disease with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly managed with Janus kinase inhibitors: A case report.

RATIONALE: Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome are nonmalignant but life-threatening systemic inflammatory disorders. However, many patients are refractory to treatment, resulting in significant morbidity and mortality. Additionally, established treatment options are unavailable. Therefore, we present 2 cases of adults with the iMCD-TAFRO syndrome refractory to initial treatment but responded to Janus kinase (JAK) inhibitors with ruxolitinib. The report reveals that these rare adult cases of the refractory and treatment-resistant iMCD-TAFRO syndrome can be treated using JAK inhibitors. PATIENT CONCERNS: Case 1 is a 36-year-old previously healthy male patient who presented with fever and general fatigue for 2 weeks. Case 2 is a 42-year-old previously healthy female patient who presented with fever and general fatigue. DIAGNOSIS: The diagnosis met the 2015 criteria for TAFRO syndrome, as determined by All Japan TAFRO Syndrome Research Group in the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW) Japan. INTERVENTIONS: Treatment with tocilizumab and several immunosuppressants were ineffective. So, we performed ruxolitinib. OUTCOMES: Each patient received ruxolitinib, the general condition improved, and CRP levels decreased. LESSONS: These cases showed that ruxolitinib was effective for treatment-resistant/ refractory TAFRO syndrome. Further prospective studies are needed on using ruxolitinib with a small number of cases.

Impact of early inflammatory cytokine elevation after commencement of PD-1 inhibitors to predict efficacy in patients with non-small cell lung cancer.

Early elevation of inflammatory cytokines, such as IL-6 or TNF-α, or CRP, which is a surrogate marker for IL-6, following commencement of PD-1/L1 inhibitors (PD1-I) may represent early activation of immune-cells. Serum IL-6 and TNF-α were measured in 10 non-small cell lung cancer patients who were evaluable within the 7 days before and after commencement of PD1-I. For CRP, medical records were reviewed and 34 patients with measured CRP within the 7 days before and after the treatment were evaluated. In the 10 patients analyzed for IL-6/TNF-α, the serum levels of IL-6/TNF-α were not significantly different between pre- and post-initial PD1-I [IL-6 20.3 (2.6-49.9) and 22.9 (3.6-96.1) pg/mL, p = 0.453; TNF-α 1.6 (0.7-6.3) and 3.3 (0.7-9.6) pg/mL, p = 0.329]; however, all four responses were observed among the 7 IL-6-elevated cases, resulting in a response rate of 57%. In the 34 patients analyzed for CRP, CRP was significantly increased after initial PD1-I [1.8 (0.1-17.8) mg/dL, 2.4 (0.0-27.8), p = 0.001]. Notably, in the 31 evaluable cases, all responses were again observed in either the IL-6 or CRP elevated groups and the response rate was 46% (11 of 24). The median overall survival time was not reached in the elevated group and was 112 days in the non-elevated group (p = 0.069). The early increase in inflammatory cytokines with PD1-I was indicated to be predictive for the efficacy in patients with non-small cell lung cancer.

Preexisting Interstitial Lung Disease and Lung Injury Associated with Irinotecan in Patients with Neoplasms.

BACKGROUND/AIM: The aim of this study was to reveal risk factors for lung injury following irinotecan administration for the treatment of neoplasms. PATIENTS AND METHODS: This study included 204 patients who received irinotecan from October 2005 to November 2014 and had evaluable chest CT images before initiation of irinotecan. RESULTS: Six (2.9%) patients developed lung injury and, of these, 2 had preexisting interstitial lung disease (pre-ILD). The frequency of lung injury in patients with pre-ILD was 11% (2 of 19) while that in patients without pre-ILD was 2.2%. Risk factor analysis for the lung injury showed pre-ILD was the most predictable factor [odds ratio (OR) 5.00, p=0.07]. Combination with other agents, origin of neoplasms (lung or not), initial dose or minimum interval were not observed to be related to risk. CONCLUSION: The risk of lung injury with irinotecan was high when pre-ILD was present and the risk was comparable with previously reported other agents.

Clinical impact of minocycline on afatinib-related rash in patients with non-small cell lung cancer harboring epidermal growth factor receptor mutations.

BACKGROUND: The management of skin toxicity is crucial for efficient afatinib treatment, but the role of tetracycline class antibiotics (TCs) in managing these rashes is relatively unknown. METHODS: We reviewed the clinical records of patients who were administered afatinib for the treatment of non-small cell lung cancer harboring epidermal growth factor receptor mutations between October 2014 and November 2016. Twenty-five patients, who received TCs for the management of afatinib-related skin disorders, were enrolled. RESULTS: Minocycline was administered orally to participants. Afatinib-related toxic effects, such as rash, diarrhea, and paronychia, were observed in 92%, 92%, and 40% of cases, respectively. Although 24% of diarrhea and 4% of paronychia cases were rated grade 3 or higher, no severe cases of rash were observed during afatinib treatment. Of the 18 afatinib dose reductions, 14 (78%), three (17%), and one (6%) resulted from diarrhea, paronychia, and stomatitis, respectively; no patients required a dose reduction because of rash. When minocycline treatment started, 21 patients (84%) had a rash of grade 1 or less, and three patients had a grade 2 rash. A response to afatinib was observed in 18 patients (72%) and the median duration of afatinib administration was 501 days. An adverse event related to minocycline (grade 1 nausea) was observed in one patient. CONCLUSIONS: A large proportion of the study patients started minocycline before grade 2 rash development and the severity of afatinib-related rash was lower than that previously reported. Oral TCs may be beneficial, especially if started early.

Pasteurella multocida Infective Endocarditis: A Possible Link with Primary Upper Respiratory Tract Infection.

A 50-year-old Japanese man presented with fever and upper respiratory tract symptoms that required urgent inpatient admission. A physical examination revealed conjunctival hemorrhages and peripheral embolic phenomena. Blood cultures grew Pasteurella multocida, and an echocardiography revealed a mitral valve vegetation suggestive of infective endocarditis (IE), which was confirmed using the Modified Duke Criteria. After several antibiotic regimens proved ineffective, valve replacement was performed, with a good eventual outcome. P. multocida IE is rare and may sometimes have no preceding risk factors. P. multocida infections of the upper respiratory tract are unusual but may be an inciting event for IE. It is essential to check blood cultures and to repeat the performance of physical examinations to appreciate the developing features of IE.

Transient hemiparesis and hemianesthesia in an atypical case of adult-onset clinically mild encephalitis/ encephalopathy with a reversible splenial lesion associated with adenovirus infection.

We herein report the case of a previously healthy 24-year-old Japanese woman who developed adult-onset clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) presenting with hemiparesis and hemianesthesia secondary to adenovirus infection. The patient's neurological symptoms and the lesion in the splenium resolved within 17 days without therapy. The radiographic features and clinical course observed in this case were consistent with a diagnosis of MERS; however, the only neurological symptoms were hemiparesis and hemianesthesia. This is the first reported case of MERS involving only hemiparesis and hemianesthesia at onset. This case suggests that a diagnosis of MERS should be suspected in patients with hemiparesis and hemianesthesia, especially when these conditions are preceded by infection.