Clinicomicrobiological risk factors for infective endocarditis in viridans group streptococci bacteraemia.

BACKGROUND: When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. OBJECTIVES: We aimed to identify independent risk factors for IE in patients with VGS BSI. METHODS: This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. RESULTS: Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001). CONCLUSIONS: Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.

Risk factors for resistant gram-positive bacteremia in febrile neutropenic patients with cancer.

BACKGROUND: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. METHODS: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. RESULTS: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. CONCLUSIONS: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer.

Impact of T-Cell Engagers on COVID-19-Related Mortality in B-Cell Lymphoma Patients Receiving B-Cell Depleting Therapy.

PURPOSE: B-cell depleting therapies, including T-cell engager (TCE), are increasingly used for patients with hematologic malignancies, including during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the relationship between TCE therapy and COVID-19-related outcomes among patients with COVID-19 and B-cell lymphomas receiving B-cell depleting therapy. MATERIALS AND METHODS: This retrospective cohort study included patients with B-cell lymphoma, who were admitted to Seoul Natio-nal University Hospital with COVID-19 between September 2021 and February 2023, and received B-cell depleting therapy before COVID-19 diagnosis. Multivariable logistic regression was used to identify factors associated with severe to critical COVID-19 and COVID-19-related mortality. RESULTS: Of 54 patients with B-cell lymphomas and COVID-19 who received B-cell depleting therapy, 14 were treated with TCE (TCE group) and 40 with rituximab (RTX group). COVID-19-related mortality was higher in the TCE group than in the RTX group (57.1% vs. 12.5%, p=0.002). In multivariable analyses, TCE therapy (adjusted odds ratio [aOR], 7.08; 95% confidence interval [CI], 1.29 to 38.76; p=0.024) and older age (aOR, 1.06; 95% CI, 1.00 to 1.13; p=0.035) were associated with severe to critical COVID-19. TCE therapy (aOR, 8.98; 95% CI, 1.48 to 54.40; p=0.017), older age (aOR, 1.13; 95% CI, 1.02 to 1.26; p=0.022), and prior bendamustine therapy (aOR, 7.78; 95% CI, 1.17 to 51.65; p=0.034) were independent risk factors for COVID-19-related mortality. CONCLUSION: B-cell lymphoma patients treated with TCE had significantly worse outcomes from COVID-19 than those treated with RTX. TCE therapy should be used with caution in B-cell lymphoma patients during the COVID-19 epidemic.

Empirical vs pre-emptive broad-spectrum antifungal therapy for acute myelogenous leukaemia in the era of antimould prophylaxis.

INTRODUCTION: This study compared clinical outcomes in patients with acute myelogenous leukaemia (AML) who developed prolonged (≥4 days) febrile neutropenia (FN) and received either empirical or pre-emptive antimould prophylaxis in order to evaluate the need for routine empirical antifungal therapy. METHODS: This retrospective study reviewed adult patients (aged ≥18 years) with AML who developed prolonged FN and received antimould prophylaxis during induction or re-induction chemotherapy at a single centre between September 2016 and December 2020. Patients were categorized into pre-emptive or empirical groups based on whether or not there was clinical evidence of invasive fungal infection (IFI) at the start of antifungal treatment, respectively. Clinical outcomes were compared between the two groups after propensity score matching (PSM). RESULTS: In total, 229 chemotherapy episodes (36 and 193 in the empirical and pre-emptive groups, respectively) were analysed. In the pre-emptive group, broad-spectrum antifungal therapy was administered in 45 (23.3%) episodes. After 1:3 PSM, there were no significant differences between the empirical and pre-emptive groups in terms of the incidence of proven or probable IFI [0/36 (0%) vs 5/97 (5.2%); P=0.323], all-cause mortality [3/36 (8.3%) vs 4/97 (4.1%); P=0.388] and IFI-related mortality [0/36 (0.0%) vs 1/45 (2.2%); P=0.556]. CONCLUSION: The differences in clinical outcomes between empirical and pre-emptive antifungal therapy in patients with AML who received antimould prophylaxis were not significant. Therefore, broad-spectrum antifungal therapy in patients receiving antimould prophylaxis may be delayed until there is clear evidence of IFI.

Midterm Results of Total Hip Arthroplasty for Osteonecrosis of the Femoral Head in Human Immunodeficiency Virus-Infected Patients in South Korea.

Background: Studies have reported that osteonecrosis of the femoral head (ONFH) is more prevalent in patients with human immunodeficiency virus (HIV). Total hip arthroplasty (THA) is considered reasonable management of ONFH. However, only scarce data exist on the outcomes of THA for HIV-infected patients in South Korea. The purpose of this study was to evaluate the midterm results of HIV-positive patients who underwent THA for ONFH. Methods: We performed a retrospective review of HIV-infected patients with ONFH who underwent THA in our institution from 2005 to 2021. Twenty-two hips in 15 patients underwent THAs with cementless implants. The clinical and radiographic evaluation was performed at each follow-up, and any complication was recorded. Results: The mean follow-up period was 5.2 years (range, 1.0-16.0 years). The mean age of the HIV infected patients with osteonecrosis at the time of surgery was 44.7 ± 11.6 years. ONFH occurred 9.8 ± 3.7 years after the initial diagnosis of HIV infection. The average modified Harris hip score improved from 58.3 ± 14.8 to 95.2 ± 11.3 at the latest follow-up. Surgical complications such as infection, nerve injury, or dislocation were not present. The radiographic evidence of stable fixation by bone ingrowth without migration was seen in all implants. Conclusions: Our data suggest that THA is a safe and valid option of treatment for ONFH in well-controlled HIV-infected patients in Korea. Further large-scale nationwide studies are warranted.

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19.

Introduction: Tocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response. Methods: We prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively. Results: A total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group. Conclusion: There were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19.

Prospective longitudinal analysis of antibody response after standard and booster doses of SARS-COV2 vaccination in patients with early breast cancer.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants brought waves of pandemics with breakthrough infections in vaccinated individuals. We analyzed the antibody responses after primary and booster vaccination in healthy controls (HC) and patients with early breast cancer (BC). Methods: In this prospective longitudinal cohort study, the binding activity of serum antibody level against spike proteins and antigens of SARS-CoV-2 variants was measured within 21 days after each vaccination in the BC group and HC group. Results: All participants, 40 in the BC and 20 in the HC group, had increased antibody response after vaccination. BC group, however, had weaker humoral responses than the HC group (IgG: 1.5, 2.3, 2.5-folds in BC vs. 1.9, 3.6, 4.0-folds in HC after each dose; IgA: 2.1, 3.0, 3.6-folds in BC vs. 4.2, 10.4, 5.2-folds in HC after each dose, respectively). Those under concurrent cytotoxic chemotherapy had weaker antibody response than the non-cytotoxic treatment group and HC. Adjunct use of steroids and age were not significant risk factors. The levels of binding antibody against the Delta and the Omicron (BA1) variants were lower than the wild-type, especially in BC. Conclusion: In the waves of new sub-variants, our study suggests that an additional dose of vaccinations should be recommended according to the anti-cancer treatment modality in patients with BC who had received booster vaccination.

Laboratory Perspective of Concurrent Acute Myeloid Leukemia and COVID-19: a Case Report and Review of Literature.

BACKGROUND: Whether the diagnosis and treatment of coronavirus disease 2019 (COVID-19) affect the clinical course of patients with hematologic malignancies has been of interest during the COVID-19 pandemic. METHODS: We describe a 47-year-old female who was concurrently diagnosed with COVID-19 and acute myeloid leukemia (AML). RESULTS: She developed COVID-19 pneumonia which required treatment with remdesivir and dexamethasone, and induction therapy for t-AML was delayed. After her COVID-19 was resolved and isolation ended, follow-up bone marrow examination showed decreased leukemic burden. CONCLUSIONS: This case describes possible effects of COVID-19 treatment on the clinical course of patients with AML from a laboratory perspective.

Accurate Diagnosis of COVID-19 from Self-Collectable Biospecimens Using Synthetic Apolipoprotein H Peptide-Coated Nanoparticle Assay.

A high-throughput, accurate screening is crucial for the prevention and control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current methods, which involve sampling from the nasopharyngeal (NP) area by medical staffs, constitute a fundamental bottleneck in expanding the testing capacity. To meet the scales required for population-level surveillance, self-collectable specimens can be used; however, its low viral load has hindered its clinical adoption. Here, we describe a magnetic nanoparticle functionalized with synthetic apolipoprotein H (ApoH) peptides to capture, concentrate, and purify viruses. The ApoH assay demonstrates a viral enrichment efficiency of >90% for both SARS-CoV-2 and its variants, leading to an order of magnitude improvement in analytical sensitivity. For validation, we apply the assay to a total of 84 clinical specimens including nasal, oral, and mouth gargles obtained from COVID-19 patients. As a result, a 100% positivity rate is achieved from the patient-collected nasal and gargle samples, which exceeds that of the traditional NP swab method. The simple 12 min pre-enrichment assay enabling the use of self-collectable samples will be a practical solution to overcome the overwhelming diagnostic capacity. Furthermore, the methodology can easily be built on various clinical protocols, allowing its broad applicability to various disease diagnoses.

Evaluation of Seropositivity After Standard Doses of Vaccination Against SARS-CoV-2 in Patients With Early Breast Cancer Receiving Adjuvant Treatment.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic affected millions of individuals, and patients with cancer are known to be more susceptible. Vaccines against SARS-CoV-2 have been developed and used for patients with cancer, but scarce data are available on their efficacy in patients under active anti-cancer therapies. MATERIALS AND METHODS: In this study, we semi-quantitatively measured the titers of the immunoglobulin G against the anti-spike protein subunit 1 of SARS-CoV-2 after vaccination of patients with early breast cancer undergoing concurrent chemotherapy, endocrinal or targeted non-cytotoxic treatments, and no treatments. RESULTS: Standard doses of COVID-19 vaccines provided sufficient immune responses in patients with early breast cancer, regardless of the type of anticancer therapies. However, the post-vaccination serum anti-spike antibody titers were significantly lower in the patients under cytotoxic chemotherapy. CONCLUSION: Our study emphasizes the importance of the personalized risk stratification and consideration for booster doses in more vulnerable populations.

Positivity rates of mycobacterial culture in patients with tuberculous spondylitis according to methods and sites of biopsies: An analysis of 206 cases.

OBJECTIVES: We aimed to evaluate the mycobacterial culture positivity rates according to biopsy methods and sites in patients with tuberculous spondylitis (TS) and identify which tissues are the best sites for the diagnosis of TS. METHODS: We retrospectively identified and reviewed medical records of all patients with TS in three university-affiliated hospitals in the Republic of Korea from January 2003 to December 2020. TS was diagnosed by culture or histopathologic examination of vertebral bodies or paraspinal tissues and characteristic clinical and radiologic features. Patients with TS who received a needle biopsy or underwent surgical biopsy were investigated. The sites of needle biopsy were classified as vertebral bodies or paraspinal tissues. RESULTS: During the study period, 206 tissues from 200 patients with TS were included in the analysis. The culture positivity rates of vertebral bodies obtained by needle biopsy, paraspinal tissues obtained by needle biopsy, and tissues obtained by surgery were 69.0%, 85.3%, and 83.2%, respectively. Multivariate logistic regression identified that paraspinal tissues as biopsy sites were independently associated with mycobacterial culture positivity in TS undergoing needle biopsy (adjusted odds ratio, 3.68; 95% confidence interval: 1.13-11.99, P = 0.030). CONCLUSIONS: We demonstrated that the positivity rates of mycobacterial culture in TS were 69.0-85.3%. Paraspinal tissues as biopsy sites were significantly associated with culture positivity in needle biopsy, suggesting that targeting paraspinal tissues during needle biopsy may be the best method for diagnosing TS.

Outbreak of COVID-19 among children and young adults in a cancer centre daycare unit.

Nosocomial transmission of COVID-19 among immunocompromised hosts can have a serious impact on COVID-19 severity, underlying disease progression and SARS-CoV-2 transmission to other patients and healthcare workers within hospitals. We experienced a nosocomial outbreak of COVID-19 in the setting of a daycare unit for paediatric and young adult cancer patients. Between 9 and 18 November 2020, 473 individuals (181 patients, 247 caregivers/siblings and 45 staff members) were exposed to the index case, who was a nursing staff. Among them, three patients and four caregivers were infected. Two 5-year-old cancer patients with COVID-19 were not severely ill, but a 25-year-old cancer patient showed prolonged shedding of SARS-CoV-2 RNA for at least 12 weeks, which probably infected his mother at home approximately 7-8 weeks after the initial diagnosis. Except for this case, no secondary transmission was observed from the confirmed cases in either the hospital or the community. To conclude, in the day care setting of immunocompromised children and young adults, the rate of in-hospital transmission of SARS-CoV-2 was 1.6% when applying the stringent policy of infection prevention and control, including universal mask application and rapid and extensive contact investigation. Severely immunocompromised children/young adults with COVID-19 would have to be carefully managed after the mandatory isolation period while keeping the possibility of prolonged shedding of live virus in mind.

Successful treatment of angioinvasive aspergillosis causing diaphragmatic rupture with bowel perforation and cerebral aspergillosis in a patient with FLT3-mutated acute myeloid leukemia: A case report.

RATIONALE: Throughout the clinical course of acute myeloid leukemia (AML), aspergillosis infection remains a significant determinant of treatment outcomes and survival. To emphasize the importance of early diagnosis and appropriate application of integrated therapeutic approaches, we present a case of AML patient who survived through angioinvasive aspergillosis infection causing diaphragmatic rupture with bowel perforation and cerebral aspergillosis during active AML treatment. PATIENT CONCERNS: A 39-year old male with FLT3-mutated AML was transferred to our hospital due to persistent fever after induction therapy. DIAGNOSIS AND INTERVENTIONS: During voriconazole treatment for his invasive pulmonary aspergillosis, the patient was diagnosed with colon perforation at splenic flexure and suspected perforation of left diaphragm with communication with left pleural space. Although pancytopenic, emergency laparotomy was performed with granulocyte transfusion. Also, dual antifungal therapy with voriconazole and micafungin was applied. With supportive care, he was able to successfully complete 3 cycles of consolidation using tyrosine kinase inhibitor. However, 80 days after the last chemotherapy, the patient experienced seizure caused by a single 1.5 cm sized enhancing mass in the right occipital lobe. Diagnostic and therapeutic mass removal was carried out, and pathology-confirmed cerebral aspergillosis was diagnosed. OUTCOMES: The patient's neurologic symptoms are resolved and he is leukemia free, but remains on voriconazole for his cerebral aspergillosis till this day. CONCLUSIONS: Our case highlights the importance of timely integrated intervention and adequate underlying disease control in treatment of invasive aspergillosis in immunocompromised patients. Such rigorous efforts can save even the most seemingly dismal case.

Exploration for the effect of renal function and renal replacement therapy on pharmacokinetics of remdesivir and GS-441524 in patients with COVID-19: A limited case series.

Remdesivir, an antiviral agent for the treatment of coronavirus disease 2019 (COVID-19), is metabolized intracellularly, with these metabolites eliminated predominantly in urine. Because of a lack of safety and pharmacokinetic (PK) data, remdesivir is not currently recommended for patients with estimated glomerular filtration rate less than 30 ml/min/1.73 m2 and those on hemodialysis. This study evaluated the PKs of remdesivir and its metabolite, GS-441524, in patients with COVID-19 who were and were not receiving renal replacement therapy (RRT). This study enrolled two patients with normal renal function, two with impaired renal function not receiving RRT, two receiving continuous RRT (CRRT), and three undergoing intermittent hemodialysis (IHD). Patients were administered 200 mg remdesivir on the first day, followed by 100 mg/day for 5-10 days. Serial blood samples were collected for PK analysis, and PK parameters were assessed by a noncompartmental method. Systemic exposure to remdesivir was higher in patients with impaired renal function and those receiving CRRT than in patients with normal renal function, but was similar in patients undergoing IHD and those with normal renal function. By contrast, systemic exposure to GS-441524 was highest in patients undergoing IHD, followed by patients with impaired renal function and those receiving CRRT, and lowest in patients with normal renal function. The PK profiles of remdesivir and GS-441524 varied according to renal function and RRT. The impact of PK changes of remdesivir and its metabolite on safety and efficacy should be considered when administering remdesivir to patients with COVID-19 with renal impairment.

Incidence of invasive fungal infection in acute lymphoblastic and acute myelogenous leukemia in the era of antimold prophylaxis.

The incidence of invasive fungal infection (IFI) in patients with acute myeloid leukemia (AML) has decreased with the introduction of antimold prophylaxis. Although acute lymphoblastic leukemia (ALL) has a lower risk of IFI than does AML, the incidences of IFI in both AML and ALL in the era of antimold prophylaxis should be re-evaluated. We analyzed adults with AML or ALL who had undergone induction, re-induction, or consolidation chemotherapy from January 2017 to December 2019 at Seoul National University Hospital. Their clinical characteristics during each chemotherapy episode were reviewed, and cases with proven or probable diagnoses were regarded as positive for IFI. Of 552 episodes (393 in AML and 159 in ALL), 40 (7.2%) were IFI events. Of the IFI episodes, 8.1% (12/148) and 5.9% (13/220) (P = 0.856) occurred in cases of ALL without antimold prophylaxis and AML with antimold prophylaxis, respectively. After adjusting for clinical factors, a lack of antimold prophylaxis (adjusted odds ratio [aOR], 3.52; 95% confidence interval [CI], 1.35-9.22; P = 0.010) and a longer duration of neutropenia (per one day, aOR, 1.02; 95% CI, 1.01-1.04; P = 0.001) were independently associated with IFI. In conclusion, the incidence of IFI in ALL without antimold prophylaxis was not lower than that in AML. A lack of antimold prophylaxis and prolonged neutropenia were independent risk factors for IFI. Clinicians should be on guard for detecting IFI in patients with ALL, especially those with risk factors.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10-3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10-3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

Microbiologic Diagnosis of Pyogenic Spondylitis.

Pyogenic spondylitis requires long-term antibiotics treatment and identification of the etiologic microorganism is essential. The first test in the microbiologic diagnosis of pyogenic spondylitis is a blood culture. Any microorganisms that grow in blood culture are highly likely to be the etiological microorganisms of pyogenic spondylitis. If the microbial etiology cannot be defined by the blood culture, a needle biopsy is performed on the inflamed tissues. Here, it is recommended that paraspinal tissues, rather than spinal tissues, are collected to increase the positive rate in tissue culture. If the microbial etiology cannot be defined by the first needle biopsy, another needle biopsy may be performed. The collected tissue sample is used in culture tests on bacteria and mycobacteria as well as pathological tests. If tuberculous spondylitis is suspected, polymerase chain reaction is carried out to detect Mycobacterium tuberculosis. In the case that the etiological microorganisms cannot be identified, the data of the patient regarding age, sex, vertebrae involved, history of spinal surgery or procedure, previous or concurrent urinary tract or intra-abdominal infection are analyzed. Based on this the most probable microbial etiology is determined to select the antibiotics to be used in the empiric treatment.

Immunogenicity and safety of a live herpes zoster vaccine in hematopoietic stem cell transplant recipients.

BACKGROUND: Herpes zoster (HZ) infection of hematopoietic stem cell transplant (HSCT) patients is of clinical concern. Vaccination could help restore immunity to varicella zoster virus (VZV); however, temporal changes in immunogenicity and safety of live HZ vaccines after HSCT is still unclear. The aim of this study was to elucidate the temporal immunogenicity and safety of the HZ vaccine according to time since HSCT and to determine optimal timing of vaccination. METHODS: Live HZ vaccine was administered to patients 2-5 years or > 5 years post-HSCT. Control groups comprised patients with a hematologic malignancy who received cytotoxic chemotherapy and healthy volunteers. Humoral and cellular immunogenicity were measured using a glycoprotein enzyme-linked immunosorbent assay (gpELISA) and an interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. Vaccine-related adverse events were also monitored. RESULTS: Fifty-six patients with hematologic malignancy (41 in the HSCT group and 15 in the chemotherapy group) along with 30 healthy volunteers were enrolled. The geometric mean fold rises (GMFRs) in humoral immune responses of the 2-5 year and > 5 year HSCT groups, and the healthy volunteer group, were comparable and significantly higher than that of the chemotherapy group (3.15, 95% CI [1.96-5.07] vs 5.05, 95% CI [2.50-10.20] vs 2.97, 95% CI [2.30-3.83] vs 1.42, 95% CI [1.08-1.86]). The GMFR of cellular immune responses was highest in the HSCT 2-5 year group and lowest in the chemotherapy group. No subject suffered clinically significant adverse events or reactivation of VZV within the follow-up period. CONCLUSION: Our findings demonstrate that a live HZ vaccine is immunogenic and safe when administered 2 years post-HSCT.

Effect of Perioperative Subglottic Secretion Drainage on Ventilator-Associated Pneumonia After Cardiac Surgery: A Retrospective, Before-and-After Study.

OBJECTIVES: Although postoperative subglottic secretion drainage prevents ventilator-associated pneumonia (VAP) after cardiac surgery, its role during the perioperative period is unclear. For the present study, the effect of subglottic secretion drainage during and after cardiac surgery on postoperative VAP was investigated. DESIGN: Retrospective, single-center, before-and-after study. SETTING: Perioperative care of cardiac surgical patients in a tertiary university hospital. PARTICIPANTS: Adult patients who underwent cardiac surgery from January 2013-December 2018. INTERVENTIONS: Conventional and subglottic suctioning endotracheal tubes were used in the control and intervention groups before and after a change in institutional policy, respectively. In the intervention group, subglottic secretion drainage was performed continuously during surgery and intermittently after surgery. MEASUREMENTS AND MAIN RESULTS: The risk of postoperative VAP, identified by the National Healthcare Safety Network surveillance definition algorithm, was compared by weighted logistic regression. Logistic regression analyses, with propensity score matching and inverse probability weighting, also were performed. A total of 2,576 patients were analyzed (control [n = 2108]; intervention [n = 468]). Postoperative VAP occurred less frequently in the intervention group (1/468 [0.2%]) compared with the control group (30/2,108 [1.4%]). In the multivariate weighted logistic regression analysis, the risk of VAP after cardiac surgery was significantly lower in the intervention group than in the control group (odds ratio 0.29; 95% confidence interval 0.14-0.58). Similar results were obtained in multivariate analyses after propensity score matching (odds ratio 0.04; 95% confidence interval 0.01-0.14) and inverse probability weighting (odds ratio 0.16; 95% confidence interval 0.05-0.42). CONCLUSIONS: Routine perioperative subglottic secretion drainage using subglottic suctioning endotracheal tubes in patients undergoing cardiac surgery was associated with a reduction in the risk of VAP after surgery.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. 1-4 These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. 2,5,6 A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. 7,8 Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of Clostridium Difficile (HR=2.0, 95% CI: 1.2-3.3, p=6×10 -3 ) and Streptococcus/Enterococcus infections (HR=1.5, 95% CI=1.1-2.1, p=5×10 -3 ). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.