Whipple's disease presenting as weight gain and constipation in a Chinese woman.

BACKGROUND: Whipple's disease is a chronic infection due to Tropheryma whipplei, commonly reported in the Caucasian but not in the Chinese population. CASE PRESENTATION: A 52-year-old female with good past health, was diagnosed with Whipple's disease, presenting with constipation, unintentional weight gain, and fleeting polyarthralgia. Investigations prior to admission showed raised CA125 and computed tomography of the abdomen showed multiple retroperitoneal mesenteric lymphadenopathies. Extensive investigations performed on secondary causes of weight gain were unrevealing. Subsequent PET-CT scan revealed generalized lymphadenopathy involving the left deep cervical, supraclavicular, and retroperitoneal mesenteric area. Excisional biopsy of the left supraclavicular lymph node was performed, with histology showing infiltrations of Periodic acid-Schiff positive foamy macrophages. T. whipplei DNA was detected in her serum, saliva, stool, and lymph node by PCR targeting the 16S ribosomal RNA gene. She was started on intravenous ceftriaxone, and then stepped down to oral antibiotics for a total of 44 months. The recurrence of fever after 12 days of ceftriaxone raised the suspicion of Immune Reconstitution Inflammatory Syndrome (IRIS). Serial imaging showed a gradual reduction in the size of retroperitoneal lymphadenopathies. Literature review on Whipple's disease in the Chinese population identified 13 reports of detectable T. whipplei DNA in clinical specimens. The majority of the cases were pneumonia, followed by culture-negative endocarditis, encephalitis, and skin and soft tissue infection. However, most patients with pneumonia were diagnosed based on next generation sequencing alone, with the resolution of pulmonary infiltrates without adequate duration of antibiotics, suggesting the possibility of colonization instead of infection. The recommendation of long-term doxycycline suppression after treatment may be supported by the slow response of retroperitoneal lymphadenopathies to antibiotics in our patient. CONCLUSIONS: Unintentional weight gain and constipation could be atypical presentations of Whipple's disease. It is a rare disease in the Chinese population despite the advancement of molecular techniques in the diagnosis of infections. A prolonged course of antibiotics may be required due to slow clinical response as documented by serial imaging in our case. The possibility of IRIS should be considered in patients with breakthrough fever during treatment of Whipple's disease.

Cutaneous Mycobacterium szulgai infection in a patient with Cushing's syndrome: a case report and literature review.

BACKGROUND: Opportunistic infection is an under-recognized complication of Cushing's syndrome, with infection due to atypical mycobacterium rarely reported. Mycobacterium szulgai commonly presents as pulmonary infection, with cutaneous infection seldom reported in the literature. CASE PRESENTATION: 48-year-old man with a newly-diagnosed Cushing's syndrome secondary to adrenal adenoma presented with a subcutaneous mass on the dorsum of his right hand, was diagnosed with cutaneous Mycobacterium szulgai infection. The most likely source of the infection was through minor unnoticed trauma and inoculation from a foreign body. The patient's Cushing's syndrome, high serum cortisol levels and secondary immune suppression facilitated mycobacterial replication and infection. The patient was successfully treated with adrenalectomy, surgical debridement of cutaneous lesion, and a combination of rifampicin, levofloxacin, clarithromycin, and ethambutol for 6 months. There were no signs of relapse one year after cessation of anti-mycobacterial treatment. A literature review on cutaneous M. szulgai infection to further characterize the clinical characteristics of this condition, identified 17 cases of cutaneous M. szulgai infection in the English literature. Cutaneous M. szulgai infections with subsequent disease dissemination are commonly reported in immunocompromised hosts (10/17, 58.8%), as well as in immunocompetent patients with a history of breached skin integrity, such as invasive medical procedures or trauma. The right upper extremity is the most commonly involved site. Cutaneous M. szulgai infection is well controlled with a combination of anti-mycobacterial therapy and surgical debridement. Disseminated infections required a longer duration of therapy than localized cutaneous infections. Surgical debridement may shorten the duration of antibiotics. CONCLUSIONS: Cutaneous M. szulgai infection is a rare complication of adrenal Cushing's syndrome. Further studies are needed to provide evidence-based guidelines on the best combination of anti-mycobacterial and surgical therapy for managing this rare infective complication.

Listeriosis in a Metropolitan Hospital: Is Targeted Therapy a Risk Factor for Infection?

Targeted therapies are widely used for treatment of autoimmune diseases as well as solid organ and hematological malignancies. Various opportunistic infections have been described in patients on targeted therapies. Although case reports or a few case series of listeriosis have been reported to be associated with targeted therapy, most of the cases were related to anti-tumor necrosis factor-α monoclonal antibody. In this study, we describe the epidemiological and clinical profiles of listeriosis in a tertiary hospital in Shenzhen, a Southern Chinese metropolitan city in China. During the 9-year-and-6-month study period, a total of five cases of listeriosis were recorded and all of them had Listeria monocytogenes bacteremia. All five patients had predisposing factors, including corticosteroid (n = 3), targeted therapy (n = 2), pregnancy (n = 2) and anti-interferon gamma autoantibody (n = 1). The two patients who had targeted therapy during their course of cancer treatment received inhibitors of the epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) pathway. The first one was a 52-year-old woman with metastatic adenocarcinoma of the lung. She was given gefitinib (EGFR tyrosine kinase inhibitor), osimertinib (third-generation EGFR tyrosine kinase inhibitor) and afatinib (tyrosine kinase inhibitor that can bind to EGFR, HER2 and HER4). The second one was a 40-year-old woman with carcinoma of the breast with brain metastasis. She was given trastuzumab (anti-HER2 monoclonal antibody) and lapatinib (dual tyrosine kinase inhibitor of the EGFR/HER2 pathway). These two patients represent the second and third reports of listeria infections associated with EGFR/HER2 pathway inhibitors in the literature. Targeted therapy is an important predisposing factor for listeriosis. Listeria infection is an important differential diagnosis in patients on targeted therapy who present with sepsis and/or central nervous system infection, and the use of antibiotic regimens that cover listeria is crucial for empirical treatment. Avoidance of high-risk food items in these patients is important for the prevention of listeriosis.

Rapid Diagnosis of Mycobacterium marinum Infection by Next-Generation Sequencing: A Case Report.

We present the first report of histology- and culture-proven Mycobacterium marinum infection diagnosed by next-generation sequencing (NGS). It took <2 days to make a microbiological diagnosis using the Oxford Nanopore Technologies' MinION device, compared to 20 days for the mycobacterium to be isolated from the tissue biopsy. NGS is particularly useful for culture-negative and slow-growing microorganism infections, such as mycobacterial, fungal and partially treated pyogenic bacterial infections. Due to its low equipment cost, short turn-around-time and portable size, the Oxford Nanopore Technologies' MinION device is a useful platform for NGS in routine clinical microbiology laboratories.

Dirofilaria hongkongensis infection presenting as recurrent shoulder mass.

In 2012, a novel canine Dirofilaria species, D. hongkongensis was identified in Hong Kong that caused human diseases and subsequently reported in an Austrian traveller returning from the Indian subcontinent. Here we present a case of human infection by D. hongkongensis manifested as recurrent shoulder mass. Diagnosis was achieved by cox1 gene sequencing of the excised specimen. The case illustrated that parasitic infection represents an important differential diagnosis for musculoskeletal lesions.

Fatal pancytopenia due to albendazole treatment for strongyloidiasis.

We report 7 cases of strongyloidiasis that had occurred from 2016 through 2017 in a tertiary hospital of southern China. Three of the 7 patients (age 66-77) with farming exposure many years ago developed symptomatic infection while receiving immunosuppressant for underlying medical conditions. The majority of them were treated with albendazole due to unavailability of ivermectin in mainland China. One of the 7 patients, with underlying IgG4 sclerosing cholangitis and secondary biliary cirrhosis was on immunosuppressives and developed severe pancytopenia 15 days after albendazole treatment. He ultimately died of polymicrobial sepsis. This was the second fatal case being reported in the literature as a consequence of albendazole-induced myelosuppression. We have undertaken a review of the literature regarding the use of albendazole for strongyloidiasis and its adverse effect with a focus on myelosuppression as a rare but potentially serious event.

MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in vivo and in vitro by directly targeting SOX9.

Accumulating evidence indicates that dysregulation of miRNAs could contribute to tumor growth and metastasis of chondrosarcoma by infuencing cell proliferation and invasion. In the current study, we are interested to examine the role of miRNAs in the carcinogenesis and progression of chondrosarcoma. Here, using comparative miRNA profiling of tissues and cells of chondrosarcoma and cartilage, we identified miR-494 as a commonly downregulated miRNA in the tissues of patients with chondrosarcoma and chondrosarcoma cancer cell line, and upregulation of miR-494 could inhibit proliferation and invasion of chondrosarcoma cancer cells in vivo and in vitro. Moreover, our data demonstrated that SOX9, the essential regulator of the process of cartilage differentiation, was the direct target and functional mediator of miR-494 in chondrosarcoma cells. And downregulation of SOX9 could also inhibit migration and invasion of chondrosarcoma cells. In the last, we identified low expression of miR-494 was significantly correlated with poor overall survival and prognosis of chondrosarcoma patients. Thus, miR-494 may be a new common therapeutic target and prognosis biomarker for chondrosarcoma.

IL17A gene polymorphisms, serum IL-17A and IgE levels, and hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection.

Interleukin (IL)-17A plays important roles in hepatitis B virus (HBV)-induced liver diseases. This study aims to investigate IL17A single nucleotide polymorphisms (SNPs) and the predispositions to chronic HBV infection and hepatocellular carcinoma (HCC) risk and the correlations to IL-17A and IgE levels. Three hundred ninety-five chronic HBV patients, 75 HBV infection resolvers, and 174 healthy controls were included. IL17A SNPs rs8193036 (C/T) and rs2275913 (A/G) and serum IL-17A and IgE levels were determined. HBV infection resolvers had higher rs8193036 allele T and allele T-containing genotypes than HBV patients or controls. Compared with chronic hepatitis, HCC patients had more frequent rs2275913 genotype GG (odds ratios [OR] 3.317, 95% confidence interval [CI] 1.663-6.617, P = 0.001) and allele G (OR 1.844, 95% CI 1.311-2.595, P < 0.001), and more frequent haplotypes CG (OR 1.868, 95% CI 1.256-2.778, P = 0.002) and TG (OR 1.788, 95% CI 1.031-3.101, P = 0.037) of rs8193036 and rs2275913. Comparison of HCC patients with cirrhosis yielded similar findings. Apart from male gender and older ages, IL-17A level (OR 1.020, 95% CI 1.003-1.036, P = 0.019) and rs2275913 genotypes AG and GG (OR 1.704, 95% CI 1.214-2.390, P = 0.006) were factors significantly associated with HCC risk in multivariate analysis in comparison with HBV patients without HCC. These factors remained significant in multivariate analysis in relation to cirrhosis. IL17A rs2275913 genotype GG was associated with significantly increased IL-17A and IgE levels. IL17A polymorphisms may influence HCC risk in chronic HBV infection via regulating IL-17A production.

CpG oligodeoxynucleotide-adjuvanted fusion peptide derived from HBcAg epitope and HIV-Tat may elicit favorable immune response in PBMCs from patients with chronic HBV infection in the immunotolerant phase.

The absence or insufficiency of specific immune response results in chronic hepatitis B virus (HBV) infection and immunotolerance. Therapeutic fusion peptide containing hepatitis B core antigen (HBcAg)(18-27) CTL epitope and human immunodeficiency virus (HIV)-Tat(49-57) peptide was synthesized and the activity when adjuvanted with CpG oligodeoxynucleotide (CpG ODN) was evaluated in PBMCs from patients with chronic HBV infection in the immunotolerant phase in this study. Results showed that the fusion peptide when adjuvanted with CpG ODN could induce significantly higher levels of IFN-γ and IL-4 in the PBMCs compared with fusion peptide or CpG ODN alone. The magnitude of augmentation to IFN-γ by the fusion peptide plus CpG ODN was much higher than that to IL-4. Cytotoxicity assay showed that the percentage of target cell lysis by effector cells stimulated by fusion peptide plus CpG ODN was higher than that in fusion peptide or CpG ODN alone at most of the E/T ratios tested. The magnitude augmented to IFN-γ by fusion peptide plus CpG ODN was also much higher than that to the percentage of target cell lysis. It is concluded that HBcAg(18-27) and HIV-Tat(49-57) fusion peptide when adjuvanted with CpG ODN may have much higher potency to induce IFN-γ than to induce IL-4 and cytotoxicity, suggesting the favorable immune response towards noncytolytic inactivation of the virus mediated by IFN-γ and the potential to break the tolerant state in chronic HBV infection.