A Case of Pyometra Caused by Achromobacter xylosoxidans and γ-Streptococcus in an Elderly Frail Woman.

Pyometra is an easily overlooked disease with nonspecific symptoms; however, a delayed diagnosis can lead to severe complications. An 80-year-old frail woman presented to our hospital with a chief complaint of persistent fever for 10 days. Her blood tests showed an elevated inflammatory response, and computed tomography showed a 10-cm cystic lesion in the pelvic floor compressing the bladder. A catheter was inserted from the vagina into the uterine cavity, resulting in pus drainage and pyometra diagnosis. A pus culture was subsequently performed, which detected Achromobacter xylosoxidans, a common cause of respiratory tract infections in cystic fibrosis and bloodstream infections, andγ-streptococcus. To the best of our knowledge, this is the first report of pyometra caused by Achromobacter xylosoxidans. The patient was treated with drainage and piperacillin-tazobactam administration. Pyometra is especially prevalent in older women with impaired activities of daily living and dementia. Although fever, lower abdominal pain, and increased discharge may occur, symptoms are often nonspecific, and half of such cases are asymptomatic. Furthermore, delayed diagnosis can lead to perforation of the uterus and consequent pan-peritonitis. Thus, the diagnosis of pyometra should be considered in older women presenting with unknown fever, and imaging studies and gynecological consultation should be requested promptly.

Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose.

Among lifestyle-related diseases, fatty liver is the most common liver disease. To date, mammalian models have been used to develop methods for inhibiting fatty liver progression; however, new, more efficient models are expected. This study investigated the creation of a new model to produce fatty liver more efficiently than the high-fat diet medaka model that has been used to date. We compared the GAN (Gubra-Amylin nonalcoholic steatohepatitis) diet, which has been used in recent years to induce fatty liver in mice, and the high-fat diet (HFD). Following administration of the diets for three months, enlarged livers and pronounced fat accumulation was noted. The GAN group had large fat vacuoles and lesions, including ballooning, compared to the HFD group. The GAN group had a higher incidence of lesions. When fenofibrate was administered to the fatty liver model created via GAN administration and liver steatosis was assessed, a reduction in liver fat deposition was observed, and this model was shown to be useful in drug evaluations involving fatty liver. The medaka fatty liver model administered with GAN will be useful in future fatty liver research.

Past infections are associated with low levels of anti-citrullinated protein autoantibodies in rheumatoid arthritis.

Background : Rheumatoid arthritis (RA), an autoimmune disease of unknown etiology, is believed to occur as the result of actions of genetic and environmental factors. In this study, we examined the relation of past histories about infectious diseases with the levels anti-citrullinated protein autoantibodies (ACPA) in RA. Methods : Results of a questionnaire about histories of infectious diseases were obtained from 85 patients with RA, and were analyzed. Results : Significantly lower level of ACPA was detected in patients with the history of tonsillitis, otitis media or urinary cystitis than in those without it. There was no difference in the level of ACPA in RA patients between with and without cold / influenza, rubella, chickenpox, herpes labialis or herpes zoster. When RA patients were divided into two groups, high-level and low-level ACPA, multiple logistic regression analysis revealed that the history of otitis media was a significantly independent factor for the low level of ACPA. There was no significant relation between the level of rheumatoid factor and histories of infectious diseases. Conclusion : This study clarified that the past history of otitis media is associated with the low level of ACPA in RA. J. Med. Invest. 67 : 182-188, February, 2020.

Refractory hypotension due to Nivolumab-induced adrenal insufficiency.

Nivolumab, a new immune checkpoint inhibitor that has been found to improve outcomes for patients with some advanced cancers, is being increasingly used. Immune checkpoint inhibitors can cause immune-related adverse events, including dermatitis, enterocolitis, hepatitis and hypophysitis, but adrenal insufficiency rarely occurs. We present a case of Nivolumab-induced adrenal insufficiency in a man who complained of refractory hypotension. A 52-year-old man with non-small cell lung cancer visited our emergency department complaining of fatigue and diarrhea. He had received Nivolumab every 2 weeks as third-line therapy for a total of 10 times. On arrival, his vital signs revealed shock: blood pressure, 68/48 mmHg; heart rate, 141 beats per minutes. Laboratory examination showed severe hemoconcentration with a hemoglobin level of 19.9 g/dL, normal electrolyte levels and hyperglycemia. We started intravenous infusion of 4.5 L of extracellular fluid, but his vital signs remained unstable. After admission, endocrine examination revealed abnormally low values of serum cortisol (4.86 µg/dL) and ACTH (<1.0 pg/mL), which had been normal at 2 months before admission (21.14 µg/dL and 20.1 pg/mL, respectively). We therefore made a diagnosis of adrenal insufficiency induced by Nivolumab and administered 100 mg hydrocortisone succinate sodium intravenously. He recovered soon after hydrocortisone replacement therapy. Nivolumab is a new immune checkpoint inhibitor and general physicians are not familiar with it. However, adverse events caused by Nivolumab, especially adrenal insufficiency, can lead to serious adverse outcomes if overlooked. We should recognize Nivolumab-induced adrenal insufficiency and administer a glucocorticoid immediately in cancer patients treated with immune checkpoint inhibitors.

Trousseau's syndrome: cancer-associated thrombosis.

Trousseau's syndrome (cancer-associated thrombosis) is the second leading cause of death in cancer patients, after death from cancer itself. The risk of a venous thromboembolism is 4- to 7-fold higher in patients with cancer than in those without cancer. The causes of this impaired coagulation are associated with general patient-related risk factors, and other factors that are specific to the particular cancer or treatment. It is important to assess the risk of thrombotic events in cancer patients and administer effective prophylaxis and treatment. Effective prophylaxis and treatment of venous thromboembolism reduces morbidity and mortality, and improves patients' quality of life. Low molecular weight heparin is the first-line treatment for venous thromboembolism, as an effective and safe means for prophylaxis and treatment, according to guidelines released by international scientific societies. Oral anticoagulation therapy with warfarin is preferable to no therapy. However, warfarin has low efficacy and is associated with high rates of recurrence. If low molecular weight heparin is unavailable, some guidelines recommend the use of vitamin K antagonists that have a target international normalized ratio in the range of 2-3, as acceptable alternatives. Novel oral anticoagulants that directly inhibit factor Xa or thrombin are promising for the prophylaxis of high-risk cancer patients and in the long-term treatment of venous thromboembolism. However, to date, there is insufficient evidence to support the use of these new anticoagulants.

Transformation to small-cell lung cancer as a mechanism of acquired resistance to crizotinib and alectinib.

A 56-year-old woman, a never-smoker, had postoperative recurrence of anaplastic lymphoma kinase rearranged lung cancer. She achieved a partial response to treatment with an anaplastic lymphoma kinase tyrosine kinase inhibitor, crizotinib. After the tumor regrowth, crizotinib was switched to alectinib; once again a partial response was observed. At the second recurrence, transbronchial needle aspiration of the right paratracheal node was performed, which revealed cytological findings of small-cell carcinoma. While treatment with cisplatin-irinotecan chemotherapy made reduction of some tumor shadows, including the biopsied mediastinal lymph nodes, new, small, nodular shadows, highly suggestive of pulmonary metastases, were detected in both lung fields. This case may show proof of the transformation to small-cell lung cancer as a mechanism of resistance to anaplastic lymphoma kinase tyrosine kinase inhibitors in anaplastic lymphoma kinase rearranged tumor. However, this transformation may also be only one part of the resistance mechanism of the heterogeneous tumor.