Background: Although survival outcomes of multiple myeloma (MM) have improved with the development of new and effective agents, infection remains the major cause of morbidity and mortality. Here, we evaluated the efficacy of levofloxacin prophylaxis (in a real-world setting) during bortezomib, melphalan, and prednisone (VMP) therapy in elderly patients with newly diagnosed MM. Methods: This study retrospectively analyzed the records of patients with newly diagnosed MM treated with the VMP regimen between February 2011 and September 2020 at three institutes of the Republic of Korea. Results: Of a total of 258 patients, 204 (79.1%) received levofloxacin prophylaxis during VMP therapy. The median number of levofloxacin prophylaxis cycles was 4 (range, 1‒9), but 10 patients did not complete the planned prophylaxis because of side effects. Sixty-six patients (25.5%) experienced severe infections during VMP therapy, most of which (74.7%) occurred within the first four cycles of VMP therapy regardless of levofloxacin prophylaxis status. Early severe infection was significantly associated with poor survival.In multivariate analysis, levofloxacin prophylaxis was significantly associated with a lower risk in early severe infection. Conclusion Our findings suggest that levofloxacin prophylaxis should be considered at least during the first four cycles of VMP therapy in elderly patients with newly diagnosed MM.

Background/Aims: South Korean soldiers are exposed to similar environmental factors. In this study, we sought to evaluate the gut microbiome of healthy young male soldiers (HYMS) and to identify the primary factors influencing the microbiome composition. Methods: We prospectively collected stool from 100 HYMS and performed next-generation sequencing of the 16S rRNA genes of fecal bacteria. Clinical data, including data relating to the diet, smoking, drinking, and exercise, were collected. Results: The relative abundances of the bacterial phyla Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria were 72.3%, 14.5%, 8.9%, and 4.0%, respectively. Fifteen species, most of which belonged to Firmicutes (87%), were detected in all examined subjects. Using cluster analysis, we found that the subjects could be divided into the two enterotypes based on the gut microbiome bacterial composition. Compared with enterotype 2 subjects, subjects classified as enterotype 1 tended to be characterized by higher frequencies of potentially harmful lifestyle habits (current smoker: 55.6% vs 36.6%, p=0.222; heavy drinker: 16.7% vs 3.7%, p=0.120; insufficient physical activity: 27.8% vs 14.6%, p=0.318). We identified a significant difference in the microbiome compositions of current and noncurrent smokers (p=0.008); the former differed from the latter mainly in a relatively lower abundance of Bifidobacterium species and a higher abundance of Negativicutes. Conclusions A high abundance of Actinobacteria and low abundance of Bacteroidetes

Background: A healthy microbiome helps maintain the gut barrier and mucosal immune tolerance. Previously, we demonstrated that acute kidney injury (AKI) provoked dysbiosis, gut inflammation, and increased permeability. Here, we investigated the renoprotective effects of the probiotic Bifidobacterium bifidum BGN4 and the underlying mechanisms thereof. Methods: C57BL/6 mice were subjected to bilateral renal ischemia-reperfusion injury (IRI) or sham operation. In the probiotic-treated group, BGN4 was administered by gavage once daily, starting 2 weeks before injury. Results: Administration of BGN4 significantly increased gut microbiome diversity and prevented expansion of the Enterobacteriaceae and Bacteroidetes that were the hallmarks of AKI-induced dysbiosis. Further, BGN4 administration also significantly reduced other IRI-induced changes in the colon microenvironment, including effects on permeability, apoptosis of colon epithelial cells, and neutrophil and proinflammatory macrophage infiltration. Mononuclear cells co-cultured with BGN4 expressed significantly increased proportions of CD103+/CD11c+ and CD4+ CD25+ Treg cells, suggesting a direct immunomodulatory effect. BGN4 induced Treg expansion in colon, mesenteric lymph nodes (MNL), and kidney. BGN4 also reduced CX3CR1intermediateLy6Chigh monocyte infiltration and interleukin (IL)-17A suppression in the small intestine, which may have attenuated AKI severity, kidney IL-6 messenger RNA expression, and AKI-induced liver injury. Conclusion Prior supplementation with BGN4 significantly attenuated the severity of IRI and secondary liver injury. This renoprotective effect was associated with increased Foxp3 and reduced IL-17A expression in the colon, MNL, and kidney, suggesting that BGN4-induced immunomodulation might contribute to its renoprotective effects. Probiotics may therefore be a promising strategy to reduce AKI severity and/or remote organ injury.

This study was performed to evaluate the effect of cyclic precalcification treatment on the improvement of bioactivity of Ti-6Al-4V mini-screws. The cutted plate-shaped specimens of 10 mm × 10 mm dimensions, and a mini-screw with a diameter of 1.6 mm × 6.0 mm in length were used. Anodic oxidation treatment was carried out in a glycerol electrolyte solution containing 20 wt% H2O and 1.5 wt% NH 4F. Voltage of 20 V with current density of 20 mA/cm2 was applied for 1 hour to form a nanotube TiO2 layer. Afterwards, to improve the bioactivity, specimens were immersed in 0.5 vol% silica aqueous solution at 37 ℃ for 5 minutes, and then cyclic precalcification treatment with 0.05 M NH 4H2PO4and 0.01 M Ca(OH)2 solution at 90 ℃ was repeated with 20 times. Based on surface treatment the experimental groups were divided into three groups, namely untreated group (UT), anodized and heat-treated group (AH), and anodized, silica-treated, cyclic precalcified and heat-treated group (ASPH). There were TiO2 nanotubes completely self-aligned and formed in a dense structure on the surface after anodic oxidation treatment. A fine granular cluster layer of hydroxyapatite and octacalcium phosphate were formed on the surface after the cyclic precalcification treatment. As a result of immersion test in the simulated body fluid (SBF), bioactivity was confirmed to be improved by the precipitation of protrusions appearing at the initial stage of formation of hydroxyapatite.

Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.

BACKGROUND: FcRgamma-deficient natural killer (NK) cells (g-NK cells) have been associated with cytomegalovirus (CMV) infection. However, the frequency of g-NK cells in a CMV-endemic area (i.e., Korea) has not yet been studied. We examined the frequency of g-NK cells and expression of CD57 on NK cells in cord blood (CB) and adult blood (AB). METHODS: Of the 24 AB samples collected, 95.8% (23/24) were CMV IgG+/IgM-, while 100% of the 13 healthy CB samples were CMV IgG+/IgM-. We performed whole-blood flow cytometry assays to analyze intracellular FcRgamma and CD3zeta expression of CD3-/CD56dim NK cells from 13 CB and 24 AB samples, and surface CD57 expression on CD3-/CD56dim/CD16+ NK cells from 13 CB and 19 AB samples. RESULTS: All CMV seropositive AB samples contained g-NK cells (23/23), and the median proportion of g-NK cells in the CD3-/CD56dim NK cell pool was 35.0% (range: 11-77%). CD57+ NK cells in the CD3-/CD56dim/CD16+ NK cell population were detected in all 19 AB samples tested, but not in any CB samples. CONCLUSIONS: Our data suggest that g-NK cells and CD57+ NK cells are present at a very high frequency in CMV-seropositive AB, but rare in CMV-naive CB.
Adult* ; Cytomegalovirus ; Fetal Blood* ; Flow Cytometry ; Humans ; Killer Cells, Natural*

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

Clinical presentations associated with acute human immunodeficiency virus (HIV) infection are various and nonspecific. Neurologic manifestations may accompany acute HIV infection. Aseptic meningitis has been described in several reports; however, acute encephalitis during acute HIV infection is rare. Some studies have suggested that antiretroviral therapy for treatment of symptomatic acute HIV infection could be beneficial, especially in severe cases. Encephalitis is life-threatening; therefore, early diagnosis and antiretroviral therapy may be needed. We report on a case of encephalitis associated with acute HIV infection. The patient received early antiretroviral therapy and recovered from encephalitis without neurological sequelae.
Early Diagnosis ; Encephalitis ; HIV ; HIV Infections ; Humans ; Meningitis, Aseptic ; Neurologic Manifestations

There is no consensus for the surgical indications, as well as the surgical technique, for the treatment of inferior vena cava (IVC) invasion by pancreas head cancer. The authors experienced a case of pancreas head cancer invading the anterior wall of the IVC. We performed en bloc excision of the anterior wall of the IVC combined with pancreatoduodenectomy in this case under the assumption that only a margin-negative surgical resection could offer a chance for cure. Technically, the sequence of dissection and addressing the IVC at the end of dissection are considered to be important to secure the operative field surrounding the IVC and to achieve a margin-negative resection. There has been no recurrence up to now, 8 months after the extensive radical operation.
Consensus ; Head and Neck Neoplasms ; Pancreas ; Pancreatic Neoplasms ; Pancreaticoduodenectomy ; Recurrence ; Vena Cava, Inferior

There is no consensus for the surgical indications, as well as the surgical technique, for the treatment of inferior vena cava (IVC) invasion by pancreas head cancer. The authors experienced a case of pancreas head cancer invading the anterior wall of the IVC. We performed en bloc excision of the anterior wall of the IVC combined with pancreatoduodenectomy in this case under the assumption that only a margin-negative surgical resection could offer a chance for cure. Technically, the sequence of dissection and addressing the IVC at the end of dissection are considered to be important to secure the operative field surrounding the IVC and to achieve a margin-negative resection. There has been no recurrence up to now, 8 months after the extensive radical operation.
Consensus ; Head and Neck Neoplasms ; Pancreas ; Pancreatic Neoplasms ; Pancreaticoduodenectomy ; Recurrence ; Vena Cava, Inferior