Incidence and co-infection with COVID-19 of dengue during the COVID-19 pandemic.

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.

A rare case of an endobronchial mass due to Neurospora intermedia.

The ascomycete filamentous fungus Neurospora intermedia is commonly used in the food industry and considered nonpathogenic to humans. This study characterizes four N. intermedia isolates recovered from three patients. The first patient had a mediastinal germ cell tumor with multiple metastases. N. intermedia was recovered from his endotracheal aspirate and from the endobronchial mass obtained by bronchoscopic forceps biopsy. Histopathology of the biopsy tissue revealed necrotic tissue mixed with septate fungal hyphae with right-angle branching. An endobronchial mass caused by N. intermedia was thus diagnosed. Another two N. intermedia isolates were recovered from the endotracheal aspirates of two critically ill patients. In vitro, N. intermedia grows rapidly and forms orange, conidiating colonies composed of septate hyphae. Two isolates from the first patient belong to mating type a; the other two isolates belong to mating type A. Coculture of isolates of opposite mating types yielded dark ascomata containing ascospores, supporting that N. intermedia is a heterothallic fungus. N. intermedia isolates cross-reacted with the Aspergillus galactomannan antigen assay and were susceptible to amphotericin B and voriconazole. In conclusion, this report describes the first human infection (endobronchial mass) caused by N. intermedia, highlighting its potential to invade the human respiratory tract.

Sequential multimodal treatments with chemotherapy and surgery for advanced soft tissue sarcoma may be associated with better survival than chemotherapy.

BACKGROUND: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. METHODS: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. RESULTS: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. CONCLUSION: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

Systematic Characterization of the Clinical and Pathological Features of Schwannomas Harboring SH3PXD2A::HTRA1 Fusion.

The understanding of schwannoma tumorigenesis has been reshaped by the recent identification of SH3PXD2A::HTRA1 fusion in 10% of intracranial/spinal schwannomas. Nonetheless, pathologic features of schwannomas harboring this fusion, as well as its prevalence outside intracranial/spinal locations, have not been characterized. We screened 215 consecutive schwannomas for their clinicopathologic characteristics and fusion status using reverse-transcriptase polymerase chain reaction (RT-PCR). Among 29 (13.5%) fusion-positive schwannomas, the most prevalent location was peripheral somatic tissue (30.7%, 19/62), followed by spinal/paraspinal (18.4%, 7/38), body cavity/deep structures (10%, 2/20), intracranial (1.3%, 1/75), and viscera (0/13). All 8 cellular, 4 microcystic/reticular, and 3 epithelioid schwannomas were fusion-negative, as were 41/42 nonschwannomatous peripheral nerve sheath tumors. Remarkably, a distinct 'serpentine' palisading pattern, comprising ovoid/plump cells shorter than usual schwannian cells in a hyalinized stroma, was identified in most fusion-positive cases and the schwannomatous component of the only fusion-positive malignant peripheral nerve sheath tumor. To validate this finding, 60 additional cases were collected, including 36 with (≥10% arbitrarily) and 24 without appreciable serpentine histology, of which 29 (80.6%) and 2 (8.3%) harbored the fusion, respectively. With percentages of 'serpentine' areas scored, 10% was determined as the optimal practical cut-off to predict the fusion status (sensitivity, 0.950; specificity, 0.943). Fusion positivity was significantly associated with serpentine histology, smaller tumors, younger patients, and peripheral somatic tissue, while multivariate logistic linear regression analysis only identified serpentine histology and location as independent fusion-predicting factors. RNA in situ hybridization successfully detected the fusion junction, highly concordant with RT-PCR results. Gene expression profiling on 18 schwannomas demonstrated segregation largely consistent with fusion status. Fusion-positive cases expressed significantly higher HTRA1 mRNA abundance, perhaps exploitable as a biomarker. In summary, we systematically characterize a series of 60 SH3PXD2A::HTRA1 fusion-positive schwannomas, showing their distinctive morphology and location-specific prevalence for the first time.

Clinical impact of the combination of rapid species identification and antifungal stewardship intervention in adults with candidemia.

BACKGROUND: Candidemia is associated with a high mortality rate. This study aimed to evaluate the clinical impact of a diagnostic intervention and antifungal stewardship in adults with candidemia, including effectiveness in facilitating appropriate antifungals and improving patient outcomes. METHODS: A pre-post quasi-experimental study was conducted to analyze the impact of the integrated workflow of rapid species identification and antifungal stewardship intervention provided by infectious disease specialists for adults with candidemia at a medical center in southern Taiwan from March 1st, 2014 to February 29th, 2016. The primary endpoint was 30-day crude mortality, and secondary outcomes included the time to species identification, time to initial antifungal modification, and length of hospital stay. RESULTS: Total 303 patients with candidemia were included, including 152 adults in the pre-intervention period (Mar. 1st, 2014-Feb. 28th, 2015; control group) and 151 in the intervention period (Mar. 1st, 2015-Feb. 29th, 2016; case group). Demographic and clinical characteristics of patients in two groups were similar. The case group had a shorter time to species identification (72 vs. 96 h, P < 0.001) and earlier receipt of antifungals (47 vs. 59 h, P < 0.001) than the control group. Of note, the 30-day mortality rate (27.2% vs. 39.5%, P = 0.028) was lower and the hospital stay (43.5 vs. 46.0 days, P = 0.006) was shorter in the case group. CONCLUSION: Rapid diagnostic workflow and antifungal stewardship provided by infectious disease specialists can promote early initiation of antifungal therapy and improve outcome for adults with candidemia.

Klotho Overexpression Is Frequently Associated With Upstream Rearrangements in Fusion-Negative Phosphaturic Mesenchymal Tumors of Bone and Sinonasal Tract.

Phosphaturic mesenchymal tumors (PMT) are uncommon neoplasms that cause hypophosphatemia/osteomalacia mainly by secreting fibroblast growth factor 23. We previously identified FN1::FGFR1/FGF1 fusions in nearly half of the PMTs and frequent KL (Klotho or α-Klotho) overexpression in only those with no known fusion. Here, we studied a larger cohort of PMTs for KL expression and alterations. By FN1 break-apart fluorescence in situ hybridization (FISH) and reappraisal of previous RNA sequencing data, 6 tumors previously considered "fusion-negative" (defined by negative results of FISH for FN1::FGFR1 fusion and FGF1 break-apart and/or of RNA sequencing) were reclassified as fusion-positive PMTs, including 1 containing a novel FN1::ZACN fusion. The final cohort of fusion-negative PMTs included 33 tumors from 32 patients, which occurred in the bone (n = 18), soft tissue (n = 10), sinonasal tract (n = 4), and brain (n = 1). In combination with previous work, RNA sequencing, RNA in situ hybridization, and immunohistochemistry showed largely concordant results and demonstrated KL/α-Klotho overexpression in 17 of the 28 fusion-negative and none of the 10 fusion-positive PMTs studied. Prompted by a patient in this cohort harboring germline KL upstream translocation with systemic α-Klotho overexpression and multifocal PMTs, FISH was performed and revealed KL rearrangement in 16 of the 33 fusion-negative PMTs (one also with amplification), including 14 of the 17 cases with KL/α-Klotho overexpression and none of the 11 KL/α-Klotho-low fusion-negative and 11 fusion-positive cases studied. Whole genomic sequencing confirmed translocation and inversion in 2 FISH-positive cases involving the KL upstream region, warranting further investigation into the mechanism whereby these rearrangements may lead to KL upregulation. Methylated DNA immunoprecipitation and sequencing suggested no major role of promoter methylation in KL regulation in PMT. Interestingly, KL-high/-rearranged cases seemed to form a clinicopathologically homogeneous group, showing a predilection for skeletal/sinonasal locations and typically matrix-poor, cellular solitary fibrous tumor-like morphology. Importantly, FGFR1 signaling pathways were upregulated in fusion-negative PMTs regardless of the KL status compared with non-PMT mesenchymal tumors by gene set enrichment analysis, perhaps justifying FGFR1 inhibition in treating this subset of PMTs.

Extraskeletal Myxoid Chondrosarcomas: The Uncommon Clinicopathologic Manifestations and Significance of TAF15::NR4A3 Fusion.

Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare sarcoma typically exhibiting myxoid/reticular histology and NR4A3 translocation. However, morphologic variants and the relevance of non-EWSR1::NR4A3 fusions remain underexplored. Three challenging pan-Trk-expressing cases, featuring cellular to solid histology, were subjected to RNA exome sequencing (RES), unveiling different NR4A3-associated fusions. Alongside RES-analyzed cases, fluorescence in situ hybridization was performed to confirm 58 EMCs, with 48 available for pan-Trk immunostaining and KIT sequencing. Except for 1 (2%) NR4A3-rearranged EMC without identifiable partners, 46 (79%), 9 (16%), and 2 (3%) cases harbored EWSR1::NR4A3, TAF15::NR4A3, and TCF12::NR4A3 fusions, respectively. Five EWSR1::NR4A3-positive EMCs occurred in the subcutis (3) and bone (2). Besides 43 classical cases, there were 8 cellular, 4 rhabdoid/anaplastic, 2 solid, and 1 mixed tumor-like variants. Tumor cells were oval/spindle to pleomorphic and formed loose myxoid/reticular to compact sheet-like or fascicular patterns, imparting broad diagnostic considerations. RES showed upregulation of NTRK2/3, KIT, and INSM1. Moderate-to-strong immunoreactivities of pan-Trk, CD117, and INSM1 were present in 35.4%, 52.6%, and 54.6% of EMCs, respectively. KIT p. E554K mutation was detected in 2/48 cases. TAF15::NR4A3 was significantly associated with size >10 cm (78%, P = .025). Size >10 cm, moderate-to-severe nuclear pleomorphism, metastasis at presentation, TAF15::NR4A3 fusion, and the administration of chemotherapy portended shorter univariate disease-specific survival, whereas only size >10 cm (P = .004) and metastasis at presentation (P = .032) remained prognostically independent. Conclusively, EMC may manifest superficial or osseous lesions harboring EWSR1::NR4A3, underrecognized solid or anaplastic histology, and pan-Trk expression, posing tremendous challenges. Most TAF15::NR4A3-positive cases were >10 cm in size, ie, a crucial independent prognosticator, whereas pathogenic KIT mutation rarely occurred.

Identification of COL1A1/2 Mutations and Fusions With Noncoding RNA Genes in Bizarre Parosteal Osteochondromatous Proliferation (Nora Lesion).

Bizarre parosteal osteochondromatous proliferation (BPOP) (Nora lesion) is a benign bone surface lesion, which most commonly occurs in the digits of young patients and has a high rate of recurrence. Histologically, it is composed of a mixture of disorganized bone, cartilage, and spindle cells in variable proportions and characterized by amorphous "blue bone" mineralization. Recurrent chromosomal abnormalities, including t(1;17)(q32-42;q21-23) and inv(7)(q21.1-22q31.3-32), have been reported in BPOP. However, the exact genes involved in the rearrangements remain unknown. In this study, we analyzed 8 BPOP cases affecting the fingers, toe, ulna, radius, and fibula of 5 female and 3 male patients, aged 5 to 68 years. RNA sequencing of 5 cases identified genetic fusions between COL1A2 and LINC-PINT in 3 cases and COL1A1::MIR29B2CHG fusion in 1, both validated using fluorescence in situ hybridization and reverse transcription (RT)-PCR. The remaining fusion-negative case harbored 3 COL1A1 mutations as revealed by whole-exome sequencing and confirmed using Sanger sequencing. All these genetic alterations were predicted to cause frameshift and/or truncation of COL1A1/2. The chromosomal locations of COL1A2 (7q21.3), LINC-PINT (7q32.3), COL1A1 (17q21.33), and MIR29B2CHG (1q32.2) were consistent with the breakpoints identified in the previous cytogenetic studies. Subsequent screening of 3 BPOPs using fluorescence in situ hybridization identified 1 additional case each with COL1A1 or COL1A2 rearrangement. Our findings are consistent with reported chromosomal abnormalities and implicate the disruption of type I collagen, and perhaps of either noncoding RNA gene as a tumor suppressor, in the tumorigenesis of BPOP. The prevalence and tumorigenic mechanisms of these COL1A1/2 alterations in BPOP require further investigation.

Association of Single Nucleotide Polymorphisms in Nucleotide-Binding Domain Leucine-Rich Repeat Protein 1 with Clostridioides difficile Colonization or Infection.

Introduction: Nucleotide-binding domain leucine-rich repeat protein (NLRP) is critical in the inflammasome-activation pathway, which is important for host survival and the clearance of Clostridioides difficile. Therefore, the influence of NLRP1 polymorphisms on C. difficile colonization (CdC) or infection (CDI) was analyzed. Materials and Methods: A prospective cohort study consisted of hospitalized adults was conducted from January 2011 to January 2013. Single nucleotide polymorphisms (SNPs) of NLRP1, including rs12150220, rs2670660, rs6502867, rs878329, rs8182352, rs3744717, and rs11078571, were incorporating in analyses. The episodes of CdC and CDI were the primary and secondary outcome, respectively. Results: Of the total of 509 eligible patients, 376 (73.9%) had neither CdC nor CDI, 104 (21.8%) had CdC without developing CDI, and 29 (4.3%) developed CDI during the study period. Through multivariate analyses, comorbid diabetes mellitus (adjusted odds ratio [AOR] 1.59, P=0.04) and CC genotype in NLRP1 rs3744717 (AOR 1.70, P=0.02) were recognized as the risk factor of CdC. After adjusting the independent predictors of CDI, in terms of comorbid diabetes mellitus (AOR 3.18, P=0.005) and prior exposure to ceftazidime/ceftriaxone (AOR 2.87, P=0.04) or proton pump inhibitors (AOR 3.86, P=0.001), patients with CC+GC genotype in NLRP1, rs878329 (AOR 2.39, P=0.03) remained a higher risk of CDI. Conclusion: For hospitalized adults, the association of CC genotype in NLRP1 rs3744717 and CdC as well as the CC+GC genotype in NLRP1 rs878329 and CDI was respectively evidenced. We believed the prompt identification of patients having specific genotype in NLRP1 would prevent and improve the quality of care in CDI.

Outcomes and clinicopathologic characteristics associated with disseminated tumor cells in bone marrow after neoadjuvant chemotherapy in high-risk early stage breast cancer: the I-SPY SURMOUNT study.

PURPOSE: Disseminated tumor cells (DTCs) expressing epithelial markers in the bone marrow are associated with recurrence and death, but little is known about risk factors predicting their occurrence. We detected EPCAM+/CD45- cells in bone marrow from early stage breast cancer patients after neoadjuvant chemotherapy (NAC) in the I-SPY 2 Trial and examined clinicopathologic factors and outcomes. METHODS: Patients who signed consent for SURMOUNT, a sub-study of the I-SPY 2 Trial (NCT01042379), had bone marrow collected after NAC at the time of surgery. EPCAM+CD45- cells in 4 mLs of bone marrow aspirate were enumerated using immunomagnetic enrichment/flow cytometry (IE/FC). Patients with > 4.16 EPCAM+CD45- cells per mL of bone marrow were classified as DTC-positive. Tumor response was assessed using the residual cancer burden (RCB), a standardized approach to quantitate the extent of residual invasive cancer present in the breast and the axillary lymph nodes after NAC. Association of DTC-positivity with clinicopathologic variables and survival was examined. RESULTS: A total of 73 patients were enrolled, 51 of whom had successful EPCAM+CD45- cell enumeration. Twenty-four of 51 (47.1%) were DTC-positive. The DTC-positivity rate was similar across receptor subtypes, but DTC-positive patients were significantly younger (p = 0.0239) and had larger pretreatment tumors compared to DTC-negative patients (p = 0.0319). Twenty of 51 (39.2%) achieved a pathologic complete response (pCR). While DTC-positivity was not associated with achieving pCR, it was significantly associated with higher RCB class (RCB-II/III, 62.5% vs. RCB-0/I; 33.3%; Chi-squared p = 0.0373). No significant correlation was observed between DTC-positivity and distant recurrence-free survival (p = 0.38, median follow-up = 3.2 years). CONCLUSION: DTC-positivity at surgery after NAC was higher in younger patients, those with larger tumors, and those with residual disease at surgery.

Integration of antimicrobial stewardship intervention with rapid organism identification improve outcomes in adult patients with bloodstream infections.

BACKGROUND: Integration of antimicrobial stewardship intervention (ASI) with rapid organism identification has the potential for early customization of antimicrobial therapy and improved clinical outcomes. We aimed to evaluate the impact of this combined approach on antimicrobial therapy-related outcomes in patients with bloodstream infections (BSIs). MATERIALS AND METHODS: A pre-post quasi-experimental study was conducted to analyze the impact of ASI with organism identification via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) among patients with BSIs. Outcomes were compared to a historic pre-intervention group. The 30-day mortality was the primary endpoint. Secondary outcomes included time to first antibiotic modification, length of hospital stay. RESULTS: A total of 1004 adult patients with BSIs were included in the final analysis, 519 patients classified into the intervention group and 485 patients in the preintervention group. The patients in the intervention group were younger (66 vs. 70 years, P = 0.02). The 30-day crude mortality (14.6% vs. 29.9%, P < 0.001) was lower, the time to organism identification (72.25 vs. 83.6 h, P < 0.001) and length of hospital stay (12 days vs. 14 days, P < 0.001) were shorter in the intervention group. Acceptance of an ASI was associated with a trend toward a reduced 30-day mortality on multivariable analysis (odds ratio 0.33; 95% CI: 0.24-0.47; P < 0.001). CONCLUSION: The ASI combined with MALDI-TOF-MS approach decreased time to organism identification and time to appropriate antimicrobial therapy would achieve a better clinical outcome in the patients with BSIs.

Maintenance therapy of low-dose nivolumab, S-1, and leucovorin in metastatic pancreatic adenocarcinoma with a germline mutation of MSH6: A case report.

Immune checkpoint inhibitors (ICIs) provide substantial benefits to a small subset of patients with advanced cancer with mismatch repair deficiency (MMRD) or microsatellite instability (MSI), including patients with pancreatic ductal adenocarcinoma (PDAC). However, the long duration of ICI treatment presents a considerable financial burden. We present the case of a 63-year-old woman with metastatic PDAC refractory to conventional chemotherapy. Genetic analyses identified an MSH6 germline mutation and a high tumor mutation burden (TMB). Complete response (CR) was achieved after a short course of low-dose nivolumab (20 mg once every 2 weeks) with chemotherapy. CR was maintained for over 1 year with low-dose nivolumab and de-escalated chemotherapy without any immune-related adverse events. This case supports the further exploration of low-dose, affordable ICI-containing regimens in patients with advanced MSI-high/TMB-high cancer.

Risk Factors and Clinical Impact of Carbapenem-Resistant Enterobacterales Coinfections Among Hospitalized Patients with Clostridioides difficile Infection.

Introduction: The risk factors and clinical impact of carbapenem-resistant Enterobacterales (CRE) coinfection among hospitalized patients with Clostridioides difficile infection (CDI) were analyzed in this study. Materials and Methods: A clinical study was performed at the medical wards of Tainan Hospital, Ministry of Health and Welfare in southern Taiwan. Patients with CDI between January 2013 and April 2020 were included. Results: Among 238 patients included for analysis, 22 (9.2%) patients developed CRE coinfections within 14 days before or after the onset of CDI. CDI patients with CRE coinfection had longer hospitalization stays (103.0 ± 97.0 days vs 42.5 ± 109.6 days, P = 0.01) than those without CRE coinfection. In the multivariate analysis, age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.10, P = 0.02) was independently associated with CRE coinfection. In contrast, underlying old stroke (OR 0.15, 95% CI 0.03-0.70, P = 0.02) was negatively linked to CRE coinfection. Conclusion: Among patients with CDI, CRE coinfections were associated with prolonged hospitalization for CDI. Age was an independent risk factor for CRE coinfection among patients with CDI.

MK256 is a novel CDK8 inhibitor with potent antitumor activity in AML through downregulation of the STAT pathway.

Acute myeloid leukemia (AML) is the most lethal form of AML due to disease relapse. Cyclin dependent kinase 8 (CDK8) is a serine/threonine kinase that belongs to the family of Cyclin-dependent kinases and is an emerging target for the treatment of AML. MK256, a potent, selective, and orally available CDK8 inhibitor was developed to target AML. We sought to examine the anticancer effect of MK256 on AML. In CD34+/CD38- leukemia stem cells, we found that MK256 induced differentiation and maturation. Treatment of MK256 inhibited proliferation of AML cell lines. Further studies of the inhibitory effect suggested that MK256 not only downregulated phosphorylated STAT1(S727) and STAT5(S726), but also lowered mRNA expressions of MCL-1 and CCL2 in AML cell lines. Efficacy of MK256 was shown in MOLM-14 xenograft models, and the inhibitory effect on phosphorylated STAT1(S727) and STAT5(S726) with treatment of MK256 was observed in vivo. Pharmacologic dynamics study of MK256 in MOLM-14 xenograft models showed dose-dependent inhibition of the STAT pathway. Both in vitro and in vivo studies suggested that MK256 could effectively downregulate the STAT pathway. In vitro ADME, pharmacological kinetics, and toxicity of MK256 were profiled to evaluate the drug properties of MK256. Our results show that MK256 is a novel CDK8 inhibitor with a desirable efficacy and safety profile and has great potential to be a promising drug candidate for AML through regulating the STAT pathway.

A brief on new waves of monkeypox and vaccines and antiviral drugs for monkeypox.

Monkeypox virus (MPXV), genetic closely linked to the notorious variola (smallpox) virus, currently causes several clusters and outbreaks in the areas outside Africa and is noted to be phylogenetically related to the West African clade. To prepare for the upsurge of the cases of monkeypox in the Europe and North America, two vaccines, Jynneos® in the U.S. (Imvamune® in Canada or Imvanex® in the Europe) and ACAM2000® (Acambis, Inc.) initially developed in the smallpox eradication program, can provide protective immunity to monkeypox, and their production and availability are rapidly scaled up in the response to the emerging threat. So far, these two vaccines are recommended for people at a high risk for monkeypox, instead of universal vaccination. Tecovirimat, an inhibitor of extracellular virus formation, and brincidofovir, a lipid conjugate of cidofovir, both are in vitro and in vivo active against MPXV, and are suggested for immunocompromised persons, who are at risk to develop severe diseases. However, current general consensus in the response to the monkeypox outbreak among public health systems is early identification and isolation of infected patients to prevent its spread.

Impacts of Corticosteroid Therapy at Acute Stage of Hospital-Onset Clostridioides difficile Infections.

Introduction: The influence of corticosteroid therapy before or after the onset of Clostridioides difficile infections (CDIs) on the clinical outcomes of adults with hospital-onset CDIs was investigated. Materials and Methods: A clinical study was conducted on the medical wards of a teaching hospital between January 2013 and April 2020. Adults (aged ≥ 20 years) with hospital-onset CDIs (ie, symptom onset at least 48 hours after hospitalization) were included. "Corticosteroid therapy during acute CDIs" was defined as the receipt of a corticosteroid at the prednisolone equivalent (PE) dose of ≥10 mg for at least 48 hours within one week after the CDI diagnosis. "Prior corticosteroid exposure" was defined as the receipt of a corticosteroid at the PE dose of ≥5 mg PE for at least 48 hours within one month before the CDI diagnosis. Results: Of the 243 adults with hospital-onset CDIs, patients (44, 18.1%) who received corticosteroid therapy during acute CDIs were more likely to have prior corticosteroid exposure (86.4% vs 11.9%, P <0.001) and CDI episodes in intensive care units (31.8% vs 10.8%, P =0.001). Of note, a crucial association between corticosteroid therapy during acute CDIs and CDI recurrence was evidenced (13.6% vs 1.5%, P =0.002). Prior corticosteroid exposure was not associated with favorable CDI outcomes in terms of successful treatment (78.3% vs 74.9%, P =0.89), in-hospital crude mortality (17.4% vs 24.0%, P =0.61), or CDI recurrence (4.3% vs 5.3%, P = 1.00). However, for 177 patients without prior corticosteroid exposure, corticosteroid therapy during acute CDIs was linked to a higher proportion of CDI recurrence (33.3% vs 5.3%, P =0.046). Conclusion: Corticosteroid therapy during acute CDIs might impact the recurrence of CDIs, particularly in those with a lack of prior corticosteroid exposure.

A Single-Arm Phase Ib/II Study of Lenvatinib plus Eribulin in Advanced Liposarcoma and Leiomyosarcoma.

PURPOSE: Satisfactory treatment options for advanced leiomyosarcoma and liposarcoma are limited. The LEADER study (NCT03526679) investigated the safety and efficacy of lenvatinib plus eribulin. METHODS: LEADER is a multicenter phase Ib/II study for advanced leiomyosarcoma or liposarcoma. The phase Ib part enrolled 6 patients to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) with the starting dose of lenvatinib 18 mg/day and eribulin 1.1 mg/m2 D1, D8 every 21 days. The primary endpoint of the phase II part was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors 1.1, with phase Ib patients preplanned to be included in the efficacy analysis. Translational analyses were based on the transcriptomic data obtained from the NanoString nCounter platform. RESULTS: Thirty patients were enrolled (leiomyosarcoma 21, liposarcoma 9); the median age was 59. One patient had to temporarily stop lenvatinib due to grade 2 arthritis in the first cycle, meeting DLT criteria. Four of 6 patients had to decrease the dose of lenvatinib to 14 mg between cycles two and three. RP2D was determined at lenvatinib 14 mg/day and eribulin 1.1 mg/m2. The confirmed ORR was 20%, and the ORR was not significantly different between phase Ib/II cohorts (P = 0.23). The median progression-free survival was 8.56 months (95% confidence interval, 4.40-not reached). Translational studies suggested increased dendritic cells in the tumor microenvironment (TME) after treatment. CONCLUSIONS: Lenvatinib plus eribulin has a manageable safety profile and exhibits promising efficacy for treating advanced leiomyosarcoma and liposarcoma.

Reappraisal of the clinical role of metronidazole therapy for Clostridioides difficile infection in Taiwan: A multicenter prospective study.

BACKGROUND/PURPOSE: Although metronidazole is not recommended to treat Clostridioides difficile infection (CDI) in Western countries, it was still to be recommended for the treatment of non-severe CDI among Taiwanese adults in 2020. This controversy in the clinical role of metronidazole therapy for CDI was examined in a prospective clinical study. METHODS: The study was conducted from January 2015 to December 2016 in three hospitals in Taiwan. Metronidazole treatment failure (MTF) was defined as the persistence of diarrhea after six days of treatment, medication modification (shifting to oral vancomycin), or death after five days of therapy. RESULTS: Overall, 325 patients receiving metronidazole for CDI were included. The overall MTF rate was 48.6% (158 patients). Leukocyte counts of >15,000 cells/mL in peripheral blood (odd ratio [OR] 1.81; P = 0.04) and congestive heart failure (OR 3.26; P = 0.02) were independently associated with MTF. The MTF rate for patients with leukocyte counts of ≤15,000 cells/mL and no congestive heart failure, leukocyte counts of >15,000 cells/mL and no congestive heart failure, leukocyte counts of ≤15,000 cells/mL and congestive heart failure, and leukocyte counts of >15,000 cells/mL and congestive heart failure were 44.2%, 51.8%, 73.3%, and 66.7%, respectively. Of note, patients who experienced MTF had a higher recurrence rate of CDI than those with metronidazole treatment success (13.9% vs. 6.0%, P = 0.02). CONCLUSION: For Taiwanese adults with CDI, the failure rate of metronidazole therapy approached 50%, which suggests the reappraisal of the therapeutic role of metronidazole therapy, especially for patients with leukocytosis or underlying congestive heart failure.