Fusobacterium necrophorum pelvic peritonitis and bacteremia mimicking intestinal necrosis.

Fusobacterium necrophorum infection is known to cause Lemierre's syndrome, not pelvic peritonitis. Herein, we report a case of Fusobacterium necrophorum pelvic peritonitis and bacteremia, without Lemierre's syndrome, mimicking intestinal necrosis. A 28-year-old woman with peritoneal irritation and shock was suspected of having intestinal necrosis due to the presence of hepatoportal venous gas and pneumatosis intestinalis. Intestinal necrosis was ruled out by emergency laparotomy. However, massive opaque ascites and inflammatory changes in the uterus and fallopian tubes were observed. Fusobacterium necrophorum and Gardnerella vaginalis were found in ascetic fluid cultures. Moreover, Fusobacterium necrophorum was also found in blood culture. Systemic management of septic shock and antibiotic treatment improved the patient's general condition and abnormal gas on imaging. The patient had untreated bacterial vaginosis prior to admission. Pelvic peritonitis caused by Fusobacterium necrophorum is extremely rare. However, it must be recognized to avoid its rapid development into severe onset mimicking intestinal necrosis.

A case of insulinoma effectively treated with low-dose diazoxide.

Diazoxide is a benzothiadiazine that can be effective in managing hypoglycemia in frail patients with surgical risk. We report here a case of insulinoma effectively treated with diazoxide, as our report will be helpful for similar cases.

Usefulness of next-generation DNA sequencing for the diagnosis of urinary tract infection.

Acute urinary tract infection (UTI) is a highly common clinical condition. Although bacterial culture is the gold standard diagnostic test, false negative results may be possible, leading to the pathogen being unidentified. In recent years, bacterial DNA sequencing analysis has garnered much attention, but clinical studies are rare in Japan. In this study, we assessed the usefulness of next-generation DNA sequencing (NGS) analysis for acute UTI patients. We thus performed an observational, retrospective case series study. Urine and blood samples were collected from ten acute UTI patients, of whom four had also been diagnosed with urosepsis. Seven variable regions of bacterial 16S rRNA genes were amplified by PCR and then sequenced by IonPGM. The identified bacterial species were compared with those identified using the culture tests and the clinical parameters were analyzed. As a result, the NGS method effectively identified predominant culture-positive bacteria in urine samples. The urine NGS also detected several culture-negative species, which have been reported to be potentially pathogenic. Out of four urosepsis cases, three were pathogen-positive in blood NGS results, while two were pathogen-negative in blood culture. In one sepsis case, although blood culture was negative for Escherichia coli, this species was detected by blood NGS. For non-sepsis cases, however, blood NGS, as well as blood culture, was less effective in detecting bacterial signals. In conclusion, NGS is potentially useful for identifying pathogenic bacteria in urine from acute UTI patients but is less applicable in patients who do not meet clinical criteria for sepsis.

Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model.

ACTH-independent Cushing's syndrome (CS) is mainly caused by cortisol-secreting adrenocortical tumours. It is well known that secondary adrenal insufficiency occurs after surgical resection of these tumours. In this regard, impaired adrenocortical function is likely induced by atrophy of the residual adrenal tissue as a result of chronic suppression by the low ACTH levels of the hypercortisolism state. Therefore, we considered the prevention of adrenal atrophy as a method for preventing postoperative adrenal insufficiency. On the basis of these findings, we hypothesized that the use of a glucocorticoid receptor (GR) antagonist before surgery in ACTH-independent CS would rapidly activate the hypothalamic-pituitary-adrenal (HPA) axis and residual adrenal function. We thus examined adrenal function in a dexamethasone- (DEX-) induced CS rat model with or without mifepristone (MIF). In this study, MIF-treated rats had elevated plasma ACTH levels and increased adrenal weights. In addition, we confirmed that there were fewer atrophic changes, as measured by the pathological findings and mRNA expression levels of corticosterone synthase CYP11B1 in the adrenal glands, in MIF-treated rats. These results indicate that MIF treatment prevents the suppression of the HPA axis and the atrophy of the residual adrenal tissue. Therefore, our study suggests that preoperative GR antagonist administration may improve residual adrenal function and prevent postoperative adrenal insufficiency in ACTH-independent CS.

Helicobacter pylori-negative Advanced Gastric Cancer with Massive Eosinophilia.

The incidence of Helicobacter pylori-negative gastric cancer is very low. A 60-year-old man was referred to Tokai University Hospital from a local clinic because of eosinophilia. The laboratory data revealed prominent eosinophilia, with a white blood cell count of 7,900 /µL and increased eosinophil granulocyte level of 1,659 /µL. After an examination for secondary eosinophilia, esophagogastroduodenoscopy showed an enlarged gastric fold in the corpus, suggesting type 4 gastric cancer. Repeated esophagogastroduodenoscopy (EGD) and a re-biopsy demonstrated poorly differentiated adenocarcinoma and signet ring cell carcinoma. The patient was negative for Helicobacter pylori infection according to the serum anti-Helicobacter pylori antibody, culture and histopathological findings.

Clinical Course of Eosinophilic Cellulitis.

The patient was a previously healthy 23-year-old woman who made an outpatient visit to our hospital's Department of General Internal Medicine after developing pain and edema of the lower legs a week earlier. The patient was diagnosed with eosinophilic cellulitis (EC) based on an increased eosinophil count of 5,418/mm3 and the results of a skin biopsy of the lower leg that showed eosinophilic infiltration of the dermal tissue. Her condition improved after oral prednisone therapy. EC presents clinically as edema and eosinophilia. Therefore, in many cases, patients make an outpatient visit to the internal medicine department. In the present study, the clinical course of nine patients diagnosed with EC as outpatients at our Department of General Internal Medicine over the past 10 years was examined.

A Case of Eosinophilic Myocarditis Associated with Cardiogenic Shock.

The patient was a 32-year-old man with a previous history of bronchial asthma. He was admitted with chief complaints of dyspnea and skin rash associated with itching of the palms and soles of the feet, which began 2 weeks earlier. Because of the presence of cardiac failure and increase in the peripheral blood eosinophil count, eosinophilic myocarditis (EM) was suspected. His blood pressure gradually decreased and the patient went into cardiogenic shock. Therefore, endomyocardial biopsy was performed and was immediately followed by corticosteroid therapy and intra-aortic balloon pump (IABP) placement. With the findings of eosinophil infiltration associated with myocardial interstitial edema on endomyocardial biopsy, EM was diagnosed. In this case, early therapeutic intervention led to resolution of shock resolved and improvement of the peripheral blood eosinophilia and cardiac function; the patient was discharged 33 days after the onset of symptoms. EM is a rare cardiomyopathy in which myocardial eosinophil infiltration is seen. Although it has been perceived as having a mild clinical course, this report described a severe case of EM associated with cardiogenic shock, which improved as a result of early diagnosis and therapeutic intervention.

Irreversible metronidazole encephalopathy in an elderly woman with primary biliary cholangitis.

An 82-year-old woman with primary biliary cholangitis was diagnosed with an irreversible neurological disorder, caused by metronidazole (MNZ)-induced encephalopathy. Although the disorder is a reversible pathological condition, in rare cases, it can cause serious sequelae or could even be fatal. Therefore, medications should be administered carefully, particularly in patients who require long-term administration of large doses or those with liver dysfunction.

Secondary Adrenal Insufficiency Following Nivolumab Therapy in a Patient with Metastatic Renal Cell Carcinoma.

Currently, nivolumab (an anti-programmed cell death-1 receptor monoclonal antibody) is available for many types of advanced cancers in Japan. However, there have been few detailed case reports about endocrine-related adverse events of this therapy. Here, we report a patient with metastatic renal cell carcinoma who presented with secondary adrenal insufficiency following nivolumab therapy. Endocrinological assessment by rapid adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) tests revealed that the patient's disorder was a secondary adrenal insufficiency due to pituitary dysfunction. Moreover, the results of the thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LH-RH) and growth hormone-releasing peptide-2 (GHRP-2) tests showed that only the ACTH function was destroyed (isolated ACTH deficiency). The magnetic resonance imaging (MRI) findings of hypophysitis, which is the major cause of isolated ACTH deficiency, usually demonstrate enlargement of the pituitary gland. However, the MRI findings of our case showed no abnormalities of the pituitary gland and stalk. Therefore, not only oncologists, but also other specialists, including doctors in emergency units, should have knowledge of this specific feature. Our clinical observation could be useful to avoid a delay in diagnosis and to treat life-threatening adverse effects of nivolumab therapy, such as secondary adrenal insufficiency.

A Case of Overwhelming Postsplenectomy Infection Caused by Streptococcus pneumoniae with Fulminant Purpura.

Severe infection in patients who have lost splenic function is called overwhelming postsplenectomy infection (OPSI). Untimely treatment of patients with OPSI results in critical conditions with mortality rates as high as 50 %-70 %. For patients who undergo a splenectomy, vaccination is recommended for the prevention of OPSI. However, in Japan, the vaccination utilization rates are low. Herein, we report a case of OPSI caused by Streptococcus pneumoniae with a fulminant purpura resulting in multi-organ failure, which could be reversed by intensive care.

Primary Effusion Lymphoma-like Lymphoma in a Patient with Neurofibromatosis Type 1.

To date, there are only 15 case reports of lymphoma in patients with neurofibromatosis type 1 (NF1), a common autosomal dominant tumor predisposition syndrome. Here, we present the first report of a primary effusion lymphoma (PEL)-like lymphoma (PEL-L), which is a human herpes virus 8/Kaposi sarcoma herpes virus-unrelated PEL, in a 73-year-old woman with NF1. The woman presented with pleural effusion following surgery for a small intestinal gastrointestinal stromal tumor and a malignant peripheral nerve sheath tumor. We prepared cellblocks to accurately differentiate between PEL, PEL-L, and pyothorax-associated lymphoma, for establishing a starting point for treatment and for prolonging survival. Attention should be paid to malignant neoplasms in NF1 patients. Diffuse large B-cell lymphoma may not be a rare complication in these patients, although how NF1 promotes its development remains to be determined. PEL-L should be suspected when body cavity effusion is observed in elderly patients. If feasible, it should be treated via rituximab-containing chemotherapy, which according to the literature, results in longer survival times than does drainage or regimens consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone.

Salmonella Enterica Serotype Enteritidis Vertebral Osteomyelitis and Epidural Abscess Complicated with Meningitis.

Infection with non-typhoidal Salmonella often results in a self-limited acute gastroenteritis. Extra-intestinal Salmonella infection is relatively rare and occurs predominantly in infants and adults with significant underlying conditions. We describe a 54-year-old Japanese man with a history of heavy alcohol consumption and daily contact with a dog, who developed bacteremia complicated by vertebral osteomyelitis, spinal epidural abscess, and meningitis, due to Salmonella enterica serotype Enteritidis. This case suggests that Salmonella should be considered as an etiologic pathogen in adult patients with perivertebral infection or meningitis.

Clinical Characteristics of Legionella Pneumonia Diagnosed with Legionella Urinary Antigen Test.

OBJECTIVE: The aim of our study was to describe the clinical characteristics of Legionella pneumonia diagnosed with a positive urinary antigen test, and factors associated with severe Legionella pneumonia were investigated. METHODS: We retrospectively investigated the clinical characteristics of patients with Legionella pneumonia diagnosed at Tokai University Hospital between February 2006 and June 2012. The clinical characteristics of ICU cases and non-ICU cases were compared. RESULTS: Twenty-six patients with Legionella pneumonia were identified (mean age 66.7 ± 19.3). Twenty patients were men (76.9 %). Impaired consciousness was observed in 12 patients (46.2 %), followed by gastrointestinal symptoms (38.5 %). Ten patients had severe pneumonia which required ICU admission. A case-controlled study comparing non-ICU cases and ICU cases demonstrated that cases with diabetes (OR 10.1, 95 % CI 1.1-90.5) and tachycardia (OR 10.1, 95 % CI 1.1-90.5) were significantly associated with ICU admission. CONCLUSIONS: Legionella pneumonia did not always present as severe pneumonia. Extrapulmonary manifestations may be useful clues for diagnosis. Diabetic patients have not only a risk of contracting Legionella pneumonia, but also a risk of progression. Legionella pneumonia should be included in the differential diagnosis even in cases of mild to moderate pneumonia when presenting with extrapulmonary symptoms, especially in diabetic patients.

A Rare Case of Subclinical Primary Aldosteronism and Subclinical Cushing's Syndrome without Cardiovascular Complications.

We report a rare case of subclinical primary aldosteronism (PA) and subclinical Cushing's syndrome (CS). A 49-year-old woman was referred to our hospital for the evaluation of an adrenal incidentaloma. The patient had no previous medical history and no family history of notable illness. Her blood pressure was 103/60 mmHg. She had no Cushingoid features. Routine laboratory examinations were within the normal ranges including normokalemia. Based on the endocrinological results and imaging findings, we finally made a diagnosis of subclinical PA caused by both adrenal glands and subclinical CS caused by bilateral adrenal tumors. Interestingly, this patient had no risk factors for cardiovascular disease. In addition, the optimal management of patients with subclinical CS and subclinical PA has not been established. Therefore, we are observing her without medical therapy. Four years after diagnosis, no cardiovascular complications have been detected, including cerebral infarction, chronic kidney disease, cardiomegaly on echocardiography, and atherosclerosis on carotid ultrasonography. One important question is why the excessive hormone secretion did not affect the cardiovascular status of this patient. In this regard, we discuss several possible mechanisms including mineralocorticoid resistance and glucocorticoid sensitivity.

Adrenal Venous Sampling Is Useful for a Definitive Diagnosis in Cushing's Syndrome with Bilateral Adrenal Tumors.

We report three cases of Cushing's syndrome (CS) with bilateral adrenal tumors. When bilateral adrenal tumors are encountered, a differential diagnosis is difficult to make, especially in the case of functioning bilateral adrenocortical adenoma. Adrenal scintigraphy has become a standard technique to determine the laterality of excessive hormone secretion; however, this examination results in bilateral adrenal activity in the functioning bilateral adrenocortical adenoma. Our three patients were diagnosed with adrenocorticotropic hormone (ACTH)-independent CS based on biochemical testing, and an abdominal computed tomography (CT) scan detected bilateral adrenal tumors. Adrenal scintigraphy showed bilateral adrenal activity in all cases. However, adrenal venous sampling (AVS) demonstrated three different hormone-excess patterns (case 1: bilateral cortisol-excess secretions; case 2: unilateral cortisol-excess secretion and bilateral aldosterone-excess secretions; and case 3: bilateral cortisol-excess secretions and bilateral aldosterone-excess secretions). Based on these findings, we could select optimal treatment for each case. Therefore, AVS is useful to obtain a definitive diagnosis and adequate therapy for CS with bilateral adrenal tumors.

A Case of a TSH-secreting Pituitary Adenoma Associated with Evans' Syndrome.

We present a case of a TSH-secreting pituitary adenoma (TSHoma) associated with Evans' syndrome. A 30-year-old woman was referred to our hospital due to purpura and ecchymoses on her limb and body and epistaxis. Evans' syndrome was diagnosed based on idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. She had a history of malocclusion and thyroid gland enlargement 4 years prior to admission. Endocrinological tests and magnetic resonance imaging also revealed that this patient had hyperthyroidism due to the TSHoma and that this adenoma concomitantly secreted GH. Recently, several cases of Evans' syndrome were associated with hyperthyroidism caused by autoimmune thyroid disease, such as Graves' disease, suggesting that these 2 conditions may have a common immunological basis. To the best of our knowledge, there is no case report of Evans' syndrome associated with hyperthyroidism due to TSHoma. Our report suggests that the excess of thyroid hormone itself promotes autoimmunity in Evans' syndrome. Thus, early treatment for hyperthyroidism is necessary in TSHomas because of the possibility that thyroid hormone normalization may prevent the development of Evans' syndrome.

A case of quadruple malaria infection imported from Mozambique to Japan.

A 35-year-old Japanese man had an intermittent fever and mild headache for eight weeks after he returned to Japan from working in Mozambique. He had taken antimalarial prophylaxis (doxycycline) for 25 weeks, and stopped taking this drug two weeks after his return. Microscopic examination of a peripheral blood smear showed a mixed infection with Plasmodium vivax, P. falciparum, and P. ovale. In addition, a nested polymerase chain reaction and subsequent sequencing detected specific DNA sequences of four species of Plasmodium, including P. malariae. The patient was successfully treated with artemether-lumefantrine and primaquine phosphate. The present case is a rare instance of a mixed infection with four species of Plasmodium. Nonimmune persons in malaria-endemic areas may have a risk of mixed infection. All four species must be identified by using sensitive and specific tests, such as a nested polymerase chain reaction, in addition to conventional morphologic identification.

Disseminated mucormycosis infection after the first course of dose-modified R-EPOCH for advanced-stage lymphoma.

We report the case of a 63-year-old man who presented at our hospital after experiencing fever and dyspnea for more than 1 month. Because his general condition was deteriorating, he was referred to our intensive care unit. He needed critical care and was treated with vasopressors, artificial ventilation, and continuous hemodialysis. Considering his systemic condition, hematological malignancy was suspected. Bone marrow and skin biopsies were performed, and the condition was diagnosed as diffuse large B-cell lymphoma. On the 15th day, suspecting infectious lung disease, we performed bronchoscopy, which showed Rhizopus infection. Thus, the patient was administered high- dose liposomal amphotericin B (10 mg/kg) therapy. On the 54th day, he died of a massive pulmonary hemorrhage. Autopsy revealed mucormycosis infection in multiple organs, including the lungs and liver. Vigilance regarding possible mucormycosis infection is required, even after initial chemotherapy in patients whose bone marrow is significantly affected by lymphoma cells and leukemic changes.