Optimal index for detecting splenic involvement on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in diffuse large B-cell lymphoma.

Accurate clinical staging is important in diffuse large B-cell lymphoma (DLBCL) to adapt to optimal therapy. Splenic involvement of DLBCL has been recently more detectable with the advancement of a diagnostic scan by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Our clinical question is whether splenic involvement was adequately diagnosed by FDG-PET/CT imaging. This retrospective study aimed to determine the optimal index for evaluating splenic involvement in patients with DLBCL. Patients with newly diagnosed DLBCL who were examined with FDG-PET/CT at diagnosis and the end of induction chemotherapy (EOI) was enrolled. The splenic involvement with the splenic FDG uptake value higher than that of the liver at diagnosis or with the decrease of splenic uptake at EOI by visual evaluation was evaluated as positive. The calculative evaluation of splenic involvement, based on the data of standardized uptake value (SUV) of the spleen, used maximum SUV (SUVmax), mean SUV (SUVmean), spleen total lesion glycolysis (spleen TLG), and spleen length. A change in each index following induction chemotherapy was expressed as an index. Receiver operating characteristic analysis was used to set the cutoff value for each index. This study included 52 patients. Spleen TLG (0.904) showed the best accuracy, followed by SUVmax (0.885) and SUVmean (0.885), among the 5 indexes for splenic involvement at diagnosis. Splenic involvement was predicted with a higher accuracy level (0.923) when selecting the cases with values higher than the cutoff level on both spleen TLG and SUVmax. The decision at EOI was more suitable by selecting both positive cases of ∆ TLG and ∆ SUVmax. Obtaining both the positive spleen TLG and SUVmax is recommended at diagnosis to predict splenic involvement. The assessment by ∆ spleen TLG and ∆ SUVmax seems to be optimal.

Chapter 3: Management of kidney injury caused by cancer drug therapy, from clinical practice guidelines for the management of kidney injury during anticancer drug therapy 2022.

Cisplatin should be administered with diuretics and Magnesium supplementation under adequate hydration to avoid renal impairment. Patients should be evaluated for eGFR (estimated glomerular filtration rate) during the treatment with pemetrexed, as kidney injury has been reported. Pemetrexed should be administered with caution in patients with a CCr (creatinine clearance) < 45 mL/min. Mesna is used to prevent hemorrhagic cystitis in patients receiving ifosfamide. Febuxostat is effective in avoiding hyperuricemia induced by TLS (tumor lysis syndrome). Preventative rasburicase is recommended in high-risk cases of TLS. Thrombotic microangiopathy could be triggered by anticancer drugs and there is no evidence of efficacy of plasma exchange therapy. When proteinuria occurs during treatment with anti-angiogenic agents or multi-kinase inhibitors, dose reductions or interruptions based on grading should be considered. Grade 3 proteinuria and renal dysfunction require urgent intervention, including drug interruption or withdrawal, and referral to a nephrologist should be considered. The first-line drugs used for blood pressure elevation due to anti-angiogenic agents are ACE (angiotensin-converting enzyme) inhibitors and ARBs (angiotensin receptor blockers). The protein binding of drugs and their pharmacokinetics are considerably altered in patients with hypoalbuminemia. The clearance of rituximab is increased in patients with proteinuria, and the correlation with urinary IgG suggests similar pharmacokinetic changes when using other antibody drugs. AIN (acute interstitial nephritis) is the most common cause of ICI (immune checkpoint inhibitor)-related kidney injury that is often treated with steroids. The need for renal biopsy in patients with kidney injury that occurs during treatment with ICI remains controversial.

Safety and Accuracy of Professional Continuous Glucose Monitoring in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Hyperglycemia in the early days following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-known risk factor for acute graft-versus-host disease (GVHD) and non-relapse mortality. The FreeStyle Libre Pro, a factory calibrated continuous glucose monitoring (CGM) device, has been used for the retrospective analysis of glucose testing in patients with diabetes. We assessed the safety and accuracy of the device in patients undergoing allo-HSCT. We recruited eight patients who underwent allo-HSCT between August 2017 and March 2020. They wore the FreeStyle Libre Pro on the day before or on the day of transplantation until 28 days after transplantation. Adverse events, especially bleeding and infection, were monitored to assess safety, and blood glucose levels were measured and compared with the device values. None of the eight participants experienced bleeding that was difficult to stop from the sensor site or local infection that required antimicrobial administration. The device value was well correlated with blood glucose (correlation coefficient r=0.795, P<0.01); however, the overall mean absolute relative difference was 32.1%±16.0%. Our study demonstrated the safety of FreeStyle Libre Pro in allo-HSCT patients. However, the sensor results tended to be lower than the blood glucose levels.

Reintubation in COVID-19 patients: a multicenter observational study in Japan (J-RECOVER study).

BACKGROUND: Reintubation is not an uncommon occurrence following extubation and discontinuation of mechanical ventilation. In COVID-19 patients, the proportion of reintubation may be higher than that of non-COVID-19 patients. Furthermore, COVID-19 patients may have a higher risk for developing laryngotracheal stenosis, along with a higher proportion of reintubation than in non-COVID-19 patients. Our understanding of the proportion of reintubation in COVID-19 patients is limited in Japan. Additionally, the reasons for reintubation have not been adequately examined in previous studies outside of Japan. Thus, the present study aimed to describe the proportion and causes of reintubation among COVID-19 patients in Japan. METHODS: This was a multicenter observational study that included 64 participating centers across Japan. This study included mechanically ventilated COVID-19 patients who were discharged between April 1, 2020 and September 30, 2020. The outcomes examined were the proportion and causes of reintubation. RESULTS: A total of 373 patients were eligible for inclusion in the current analysis. The median age of patients was 64 years and 80.4% were male. Reintubation was required for 35 patients (9.4%) and the most common causes for reintubation were respiratory failure (71.4%; n = 25) and laryngotracheal stenosis (8.6%; n = 3). CONCLUSIONS: The proportion of reintubation among COVID-19 patients in Japan was relatively low. Respiratory failure was the most common cause for reintubation. Reintubation due to laryngotracheal stenosis accounted for only a small fraction of all reintubated COVID-19 patients in Japan.

Unexpected appearance of KMT2A::MLLT10 fusion transcript in acute myeloid leukemia with t(5;11)(q31;q23.3).

As an uncommon but nonrandom translocation in acute myeloid leukemia (AML) t(5;11)(q31;q23) results in fusion between KMT2A at 11q23 and ARHGAP26 at 5q31. The 5q31 region has another KMT2A partner, AFF4, which was identified in acute lymphoblastic leukemia harboring ins(5;11)(q31;q13q23). We report here a 65-year-old woman with AML M5b. G-banding and spectral karyotyping demonstrated 46,XX,t(5;11)(q31;q23.3). Fluorescence in situ hybridization revealed not only separated 5' and 3' KMT2A signals but a faint 5' KMT2A signal. Reverse transcription polymerase chain reaction (RT-PCR), using a KMT2A sense primer and ARHGAP26 antisense primer, detected no band whereas RT-PCR with a AFF4 antisense primer revealed an amplified band. However, sequence analysis unexpectedly disclosed that KMT2A exon 6 was connected with MLLT10 exons 15 to 18. This may be due to cross-hybridization between MLLT10 exon 18 and AFF4 antisense primer derived from AFF4 exon 10 since both exons had eight identical bases (AAGCAGCT). The MLLT10 gene is located at 10p12.31; a faint 5' KMT2A signal was probably present at this locus. These findings indicate that in AML the 5' KMT2A fragment containing exons 1 to 6 may be cryptically inserted into MLLT10 intron 14 when a reciprocal translocation t(5;11)(q31;q23.3) involving KMT2A occurred.

Efficacy and Safety of Synbiotics in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Randomized, Double-blinded, Placebo-controlled Pilot Study.

Objective High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) is an effective treatment option for relapsed and refractory aggressive malignant lymphoma. However, patients frequently experience treatment-induced gastrointestinal symptoms. Synbiotics, including live microorganisms and nondigestible food ingredients, reportedly ameliorate chemotherapy-induced mucosal damage. In this study, we assessed the efficacy and safety of synbiotics in patients undergoing auto-HSCT. Methods This randomized, double-blinded study included patients with malignant lymphoma eligible for auto-HSCT. The patients were randomly assigned to either a synbiotic group receiving Bifidobacterium longum (BB536) and guar gum or a placebo group receiving a placebo containing dextrin. The supplements were administered twice daily from the start of conditioning chemotherapy up to 28 days after auto-HSCT. The primary endpoint was the duration of total parenteral nutrition (TPN). Results In total, 12 patients were included and randomized. The median duration of TPN was 15 (range, 12-33) days in the synbiotic group and 17.5 (range, 0-32) days in the placebo group. The median duration of grade ≥3 diarrhea was shorter in the synbiotic group than in then placebo group (2.5 vs. 6.5 days), as was the duration of hospital stay (31.5 vs. 43 days). The oral intake and quality of life regarding diarrhea and anorexia improved in the synbiotic group after engraftment. Synbiotic infections, including bacteremia, were not observed. Conclusion Synbiotics may reduce gastrointestinal toxicity, thereby reducing nutritional problems and improving the quality of life of patients undergoing auto-HSCT, without severe adverse events.

GSK3 inhibitor enhances gemtuzumab ozogamicin-induced apoptosis in primary human leukemia cells by overcoming multiple mechanisms of resistance.

In acute myeloid leukemia (AML), the heterogeneity of genetic and epigenetic characteristics makes treatment difficult. The prognosis for AML is therefore poor, and there is an urgent need for new treatments for this condition. Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), targets the CD33 antigen expressed in over 90% of AML cases. GO therefore has the potential to counter the heterogeneity of AML patients. However, a major clinical problem is that drug resistance to GO diminishes its effect over time. Here, we report that the inhibition of glycogen synthase kinase 3 (GSK3) alone overcomes several forms of GO resistance at concentrations without antileukemic effects. The GSK3 inhibitors tested significantly enhanced the cytotoxic effect of GO in AML cell lines. We elucidated four mechanisms of enhancement: (1) increased expression of CD33, the target antigen of GO; (2) activation of a lysosomal function essential for hydrolysis of the GO linker; (3) reduced expression of MDR1 that eliminates calicheamicin, the payload of GO; and (4) reduced expression of the anti-apoptotic factor Bcl-2. A similar combination effect was observed against patient-derived primary AML cells. Combining GO with GSK3 inhibitors may be efficacious in treating heterogeneous AML.

A Pathogenic NRAS c.38G>A (p.G13D) Mutation in RARA Translocation-negative Acute Promyelocytic-like Leukemia with Concomitant Myelodysplastic Syndrome.

An acute promyelocytic leukemia (APL) patient not demonstrating the retinoic acid receptor α (RARA) translocation is rare. A 76-year-old man was diagnosed with myelodysplastic syndrome (MDS). After a year, abnormal promyelocytes were detected with pancytopenia and disseminated intravascular coagulopathy. Morphologically, the patient was diagnosed with APL; however, a genetic examination failed to detect RARA translocation. Thereafter, whole-genome sequencing revealed an NRAS missense mutation [c.38G>A (p.G13D)]. This mutation was not detected in posttreatment bone marrow aspirate, despite residual MDS. Few reports are available on similar cases. Furthermore, the NRAS c.38G>A mutation may be a novel pathogenic variant exacerbating RARA translocation-negative acute promyelocytic-like leukemia.

Breath-by-breath P0.1 measured on quasi-occlusion via Hamilton C6 may result in underestimation of respiratory drive and inspiratory effort.

We aimed to identify the threshold for P0.1 in a breath-by-breath manner measured by the Hamilton C6 on quasi-occlusion for high respiratory drive and inspiratory effort. In this prospective observational study, we analyzed the relationships between airway P0.1 on quasi-occlusion and esophageal pressure (esophageal P0.1 and esophageal pressure swing). We also conducted a linear regression analysis and derived the threshold of airway P0.1 on quasi-occlusion for high respiratory drive and inspiratory effort. We found that airway P0.1 measured on quasi-occlusion had a strong positive correlation with esophageal P0.1 measured on quasi-occlusion and esophageal pressure swing, respectively. Additionally, the P0.1 threshold for high respiratory drive and inspiratory effort were calculated at approximately 1.0 cmH2O from the regression equations. Our calculations suggest a lower threshold of airway P0.1 measured by the Hamilton C6 on quasi-occlusion than that which has been previously reported.

The association of high Vancomycin trough concentration with acute kidney injury during combination therapy of Piperacillin/Tazobactam and Vancomycin.

BACKGROUND: Co-administration of Piperacillin/Tazobactam (PIPC/TAZ) and Vancomycin (VCM) as an antibiotic therapy for severe infectious diseases increases the risk of nephrotoxicity. We retrospectively investigated the utility of monitoring VCM trough concentration in early stage of developing acute kidney injury (AKI) on this combination therapy. METHODS: We enrolled all infectious disease patients who were managed with concurrent PIPC/TAZ and VCM. The record of dosage and the administration interval of each antibiotic and its clinical parameters, as well as the VCM trough concentrations, blood culture for bacteria, and serum creatinine values, were collected. VCM trough concentration was measured during the initial 48-72 h of VCM administration. Nephrotoxicity was evaluated as the degree of AKI. RESULTS: A total of 47 patients fulfilling the criteria were registered, and AKI developed in 10 patients. There was no statistical difference between the AKI and non-AKI groups with regard to age, height, weight, basal creatinine level, body surface area, body mass index, PIPC/TAZ dose, VCM dose, gender, artificial management, and death within around 30 days. The VCM trough level was increased significantly in the AKI group (mean [standard deviation {SD}]: 25.9 [7.8] µg/mL) compared to that in the non-AKI group (mean [SD]: 15.7 [6.9] µg/mL) (p = 0.003). During the clinical course, renal function returned to normal levels in three out of four AKI stage 2 patients, whereas only partial recovery was achieved in all AKI stage 3 patients. CONCLUSIONS: A high VCM trough concentration may have an influence on the occurrence of AKI during combination therapy of PIPC/TAZ and VCM. Careful monitoring of VCM trough concentration will be required to prevent AKI progression.

On-site placement of resuscitative endovascular balloon occlusion of the aorta (REBOA) in a hemorrhagic shock patient: A successful endeavor involving long-distance air transport.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is primarily utilized in traumatic non-compressible torso hemorrhage. We present a 49-year-old male with hemorrhagic shock necessitating on-site REBOA placement on an island 986 km away from the nearest critical care center. The patient experienced sudden pain in the right costal margin and visited the local clinic where computed tomography revealed a massive intra-abdominal hemorrhage and a renal artery aneurysm. An emergency care physician was deployed via fixed-wing aircraft who positioned the REBOA on-site in the thoracic aorta. Partial balloon inflation (partial REBOA) and intermittent inflation/deflation (intermittent REBOA) was repeated throughout the 5-h return flight. Despite prolonged REBOA placement, no safety issues or ischemic complications were documented and parent artery occlusion was subsequently performed via interventional radiology at our facility. The patient was later discharged home in a good state of health. On-site REBOA placement is not only applicable to trauma but also internal hemorrhaging due to non-traumatic causes. Partial and intermittent REBOA successfully stabilized circulation, prevented organ ischemia and facilitated long-distance patient transport in the present case.

Association between adjunct clindamycin and in-hospital mortality in patients with necrotizing soft tissue infection due to group A Streptococcus: a nationwide cohort study.

Necrotizing soft tissue infection (NSTI) due to group A Streptococcus (GAS) is a severe life-threatening microbial infection. The administration of adjunct clindamycin has been recommended in the treatment of NSTIs due to GAS. However, robust evidence regarding the clinical benefits of adjunct clindamycin in NSTI patients remains controversial. We aimed to investigate the association between early administration of adjunct clindamycin and in-hospital mortality in patients with NSTI attributed to GAS. The present study was a nationwide retrospective cohort study, using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. Data was extracted on patients diagnosed with NSTI due to GAS. We compared patients who were administered clindamycin on the day of admission (clindamycin group) with those who were not (control group). A propensity score overlap weighting method was adopted to adjust the unbalanced backgrounds. The primary endpoint was in-hospital mortality and survival at 90 days after admission. We identified 404 eligible patients during the study period. After adjustment, patients in the clindamycin group were not significantly associated with reduced in-hospital mortality (19.2% vs. 17.5%; odds ratio, 1.11; 95% confidence interval, 0.59-2.09; p = 0.74) or improved survival at 90 days after admission (hazard ratio, 0.92; 95% confidence interval, 0.51-1.68; p = 0.80). In this retrospective study, early adjunct clindamycin does not appear to improve survival. Therefore, the present study questions the benefits of clindamycin as an adjunct to broad spectrum antibiotics in patients with NSTI due to GAS.

A Case of Paroxysmal Cold Hemoglobinuria Possessing Moderate Paroxysmal Nocturnal Hemoglobinuria-Type Erythrocytes.

BACKGROUND Paroxysmal cold hemoglobinuria (PCH) is an autoimmune hemolytic disease caused by the Donath-Landsteiner (DL) antibody. Paroxysmal nocturnal hemoglobinuria (PNH) is a non-autoimmune hemolytic disease that is caused by a dysfunction in the synthesis of the glycosyl phosphatidylinositol anchor protein, resulting in the deregulation of the complement cascade and hypersensitivity for a hemolytic attack against erythrocytes. The mechanisms of these 2 hemolytic diseases are distinct. If PCH and PNH coexist in a patient, it is difficult to perform a differential diagnosis. We introduce a case of PCH that had DL antibodies and large PNH-type clones. CASE REPORT An 82-year-old female patient was referred to our hospital because of anemia. Initial workup revealed a negative antiglobulin test and a positive DL test. For the differential diagnosis, we surveyed the population of cells that had PNH-type clones, which revealed erythrocyte PNH clones (19.6%) and granulocyte PNH clones (73.3%). During the patient's clinical course, mild hemolysis persisted without any attack. The percentage of the PNH-type erythrocytes was not obviously changed, and the DL antibody was detected 8 months after the initial admission. We determined that the persistent mild anemia was caused by concomitant diseases of PCH and PNH, although determining which of the 2 hemolytic systems was primarily responsible for the anemia was difficult. CONCLUSIONS When considering the differential diagnosis for hemolytic diseases, an adequate combination of laboratory tests for hemolysis is required.

Prevalence of COVID-19 Mimics in the Emergency Department.

Objective Due to the lack of specific clinical manifestations and symptoms, it is difficult to distinguish COVID-19 from mimics. A common pitfall is to rush to make a diagnosis when encountering a patient with COVID-19-like symptoms. The present study describes a series of COVID-19 mimics using an outpatient database collected from a designated COVID-19 healthcare facility in Tokyo, Japan. Methods We established an emergency room (ER) tailored specifically for patients with suspected or confirmed COVID-19 called the "COVID-ER." In this single-center retrospective cohort study, we enrolled patients who visited the COVID-ER from February 1 to September 5, 2020. The outcomes included the prevalence of COVID-19, admission, potentially fatal diseases and final diagnosis. Results We identified 2,555 eligible patients. The median age was 38 (interquartile range, 26-57) years old. During the study period, the prevalence of COVID-19 was 17.9% (457/2,555). Non-COVID-19 diagnoses accounted for 82.1% of all cases. The common cold had the highest prevalence and accounted for 33.0% of all final diagnoses, followed by gastroenteritis (9.4%), urinary tract infections (3.8%), tonsillitis (2.9%), heat stroke (2.6%) and bacterial pneumonia (2.1%). The prevalence of potentially fatal diseases was 14.2% (298/2,098) among non-COVID-19 patients. Conclusion Several potentially fatal diseases remain masked among the wave of COVID-19 mimics. It is imperative that a thorough differential diagnostic panel be considered prior to the rendering of a COVID-19 diagnosis.

Exploratory Analysis to Predict Optimal Tumor Burden for Starting Lenvatinib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer.

BACKGROUND: We previously reported that a high tumor burden is a prognostic factor based on an analysis of 26 patients with radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) who were treated with lenvatinib. However, the optimal tumor burden for starting lenvatinib still remains to be defined. The aim of this retrospective study was to further explore in the same patient cohort the optimal timing for the start of lenvatinib by focusing on the pre- and post-treatment tumor burden. METHODS: The 26 patients were treated with lenvatinib from 2012 to 2017. We explored the optimal timing for the start of lenvatinib by comparing the characteristics of long-term responders who were defined as patients with progression-free survival ≥ 30 months and non-long-term responders. RESULTS: Long-term responders had a smaller post-treatment tumor burden at maximum shrinkage than non-long-term responders. Further, post-treatment tumor burden had a strong linear correlation with baseline tumor burden. We created an estimation formula for baseline tumor burden related to prognosis, using these regression lines. Patients with a sum of diameters of target lesions < 60 mm or maximum tumor diameter < 34 mm at baseline were estimated to have significantly better survival outcomes. CONCLUSIONS: We found a strong linear correlation between pre- and post-treatment tumor burden. Our results suggested a cut-off value for baseline tumor burden for long-term prognosis among patients treated with lenvatinib.

Abnormal pulmonary function and imaging studies in critical COVID-19 survivors at 100 days after the onset of symptoms.

BACKGROUND: The long-term repercussions of critical COVID-19 on pulmonary function and imaging studies remains unexplored. In this study, we investigated the pulmonary function and computed tomography (CT) findings of critical COVID-19 patients approximately 100 days after symptom onset. METHODS: We retrospectively extracted data on critical COVID-19 patients who received invasive mechanical ventilation during hospitalization from April to December 2020 and evaluated their pulmonary function, residual respiratory symptoms and radiographic abnormalities on CT. RESULTS: We extracted 17 patients whose median age was 63 (interquartile range [IQR], 59-67) years. The median lengths of hospitalization and mechanical ventilation were 23 (IQR, 18-38) and 9 (IQR, 6-13) days, respectively. At 100 days after symptom onset, the following pulmonary function abnormalities were noted in 8 (47%) patients: a diffusion capacity of the lung for carbon monoxide (%DLCO) of <80% for 6 patients (35%); a percent vital capacity (%VC) of <80% for 4 patients (24%); and a forced expiratory volume in one second/forced vital capacity (FEV1%) of <70% for 1 patient (6%) who also presented with %DLCO and %VC abnormalities. Twelve (71%) patients reported residual respiratory symptoms and 16 (94%) showed abnormalities on CT. CONCLUSIONS: Over 90% of the critical COVID-19 patients who underwent invasive mechanical ventilation continued presenting with abnormal imaging studies and 47% of the patients presented with abnormal pulmonary function 100 days after symptom onset. The extent of the residual CT findings might be associated with the degree of abnormal pulmonary function in critical COVID-19 survivors.

Prevalence of thromboembolic events and status of prophylactic anticoagulant therapy in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: One of the most prominent and concerning complications associated with coronavirus disease 2019 (COVID-19) is venous and arterial thromboembolisms. The aim of the present study was to delineate the prevalence of thromboembolic events and the current status of prophylactic anticoagulation therapy in patients with COVID-19 in Japan. METHODS: Between February 1 and August 31, 2020, we performed a dual-center, retrospective cohort study based on data obtained from the medical charts of COVID-19 patients admitted to healthcare facilities in Japan. The primary outcome was any thromboembolic event including pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction, ischemic stroke and other systemic thromboemboli. RESULTS: During the study period, we extracted 628 consecutive patients admitted for COVID-19. Prophylactic anticoagulant therapy was administered in 63 (10%) patients of whom 20 (31.7%) were admitted to the intensive care unit (ICU). Thromboembolic events occurred in 18 (2.9%) patients (14.3% of patients in ICU and 2.2% of patients in the general wards). DVT were detected in 13 (2.1%) patients, PE in 11 (1.8%), and both DVT and PE in 6 (0.96%) patients. An increasing prevalence in thromboembolic events was noted with progressive clinical severity. Overall in-hospital mortality was 4.8%. CONCLUSIONS: Prophylactic anticoagulation therapy was administered in only 10% of all hospitalized COVID-19 patients. The prevalence of any thromboembolic events was 2.9% in COVID-19 patients with most events occurring in severe and critical patients. Therefore, prophylactic anticoagulation therapy may be warranted in severe and critical patients but in asymptomatic to moderate patients the practice remains controversial.

Expression of a novel type of KMT2A/EPS15 fusion transcript in FLT3 mutation-positive B-lymphoblastic leukemia with t(1;11)(p32;q23).

The t(1;11)(p32;q23) translocation is a rare but recurrent cytogenetic aberration in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL). This translocation was initially shown to form a fusion gene between KMT2A exon 8 at 11q23 and EPS15 exon 2 at 1p32 in AML. Activating mutations of FLT3 are frequently found in AML but are very rare in ALL. Here, we describe a 75-year-old woman who was diagnosed with B-ALL since her bone marrow was made up of 98.2% lymphoblasts. These blasts were positive for CD19, CD22, CD79a, CD13, and CD33 but negative for CD10 and myeloperoxidase. The karyotype by G-banding and spectral karyotyping was 46,XX,t(1;11)(p32;q23). Expression of KMT2A/EPS15 and reciprocal EPS15/KMT2A fusion transcripts were shown: KMT2A exon 8 was in-frame fused to EPS15 exon 12, indicating that this fusion transcript was a novel type. Considering three reported B-ALL cases, EPS15 breakpoints were markedly different between AML (exon 2) and B-ALL (exons 10-12). Furthermore, an uncommon type of FLT3 mutation in the juxtamembrane domain was detected: in-frame 4-bp deletion and 10-bp insertion. Accordingly, our results indicate that the novel type of KMT2A/EPS15 fusion transcript and FLT3 mutation may cooperate in the pathogenesis of adult B-ALL as class II and class I mutations, respectively.

In-hospital mortality among patients with invasive non-group A ß-hemolytic Streptococcus treated with clindamycin combination therapy: a nationwide cohort study.

AIM: Combination treatment with clindamycin is recommended in patients with invasive group A Streptococcus infection; however, whether the same treatment is effective in invasive group B Streptococcus and S. dysgalactiae subspecies equisimilis infections remains unknown. We aimed to investigate whether clindamycin added to standard of care therapy would be effective in patients with invasive non-group A ß-hemolytic Streptococcus infections. METHODS: This was a nationwide retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database focusing on the period between 2010 and 2018. We extracted data on patients diagnosed with sepsis due to non-group A ß-hemolytic Streptococcus. One-to-four propensity score-matching was undertaken to compare patients who were treated with clindamycin within 2 days of admission (clindamycin group) and those who did not (control group). The primary outcome was in-hospital mortality. RESULTS: We identified 3754 eligible patients during the study period. The patients were divided into the clindamycin (n = 296) and control groups (n = 3458). After one-to-four propensity score matching, we compared 289 and 1156 patients with and without clindamycin, respectively. In-hospital mortality did not significantly differ between the two groups (9.7% versus 10.3%; risk difference 0.3%; 95% confidence interval, -3.5% to 4.2%). CONCLUSIONS: This nationwide database study showed that combination therapy involving the use of clindamycin was not associated with lower in-hospital mortality in patients with invasive non-group A ß-hemolytic Streptococcus.

A comparison on the percentage of polymerase chain reaction positivity for SARS-CoV-2 between Public Health Center referrals and direct walk-in patients: A single center retrospective analysis in Tokyo.

INTRODUCTION: The Public Health Center (PHC)-known as hokenjo in Japan-assume a crucial role in disease control. Coronavirus disease 2019 (COVID-19) is one of many designated infectious diseases monitored by the agency. During the present pandemic, patients who suspected COVID-19 were instructed to call the Coronavirus Consultation Center in the PHC prior to visiting the hospital. The aim of this study was to elucidate the differences in polymerase chain reaction (PCR) positivity between PHC referrals and direct walk-in patients. METHODS: The present was a single-center, retrospective cohort study conducted at the Tokyo Metropolitan Hospital from March to September, 2020. Patients who received a PCR test for SARS-CoV-2 were included and categorized into the PHC referral or direct walk-in groups. The outcomes included the total number of patients undergoing PCR tests and the percentage of PCR positivity in each group. RESULTS: We identified 1680 patients (781 PHC referred and 899 direct walk-in groups). The percentage of PCR positivity did not significantly differ between the PHC referral and direct walk-in groups during the first wave (30.5% vs. 29.2%; p = 0.78). PCR positivity was significantly higher in the PHC referral group than the direct walk-in group during the second wave (30.1% vs. 23.1%; p = 0.051) and entire study period (30.2% vs. 24.7%; p = 0.011). CONCLUSIONS: Despite health authority recommendations, the number of direct walk-in patients were higher than PHC referral patients. The percentage of PCR positivity was significantly higher in the PHC referral group than in the direct walk-in group.