ChatGPT as a tool to improve access to knowledge on sexually transmitted infections.

OBJECTIVES: Specific to sexual health, individuals in need of information may be adolescents who have limited ability to formally access healthcare. These digital natives may turn to ChatGPT to address their concerns on sexually transmitted infections (STI). We sought to evaluate the veracity of ChatGPT's responses to commonly asked questions on STIs. METHODS: We instructed ChatGPT (GPT 3.5) to answer STI questions from three domains, namely, (1) general risk factors for STIs, (2) access to care and diagnosis of STIs and (3) management of STIs and postexposure prophylaxis. The responses were recorded and checked against the US Centers for Disease Control and Prevention STI Treatment Guidelines 2021. RESULTS: Overall, the responses were concise and accurate. In terms of prevention, ChatGPT could also recommend measures like safe sex practices and human papillomavirus vaccination. However, it failed to recommend HIV pre-exposure prophylaxis. When an individual expressed a symptom that could potentially represent STI (eg, dyspareunia) ChatGPT appropriately provided reassurance that other possibilities exist, but advocated for testing. In terms of treatment, ChatGPT consistently communicated the importance of partner testing and follow-up testing, but at times, failed to highlight the importance of testing for other STIs. Overall, the advice given was not tailored to the specific individual's circumstances. CONCLUSIONS: ChatGPT can provide helpful information regarding STIs, but the advice lacks specificity and requires a human physician to fine-tune. Its ubiquity may make it a useful adjunct to sexual health clinics, to improve knowledge and access to care.

Acquisition of regulator on virulence plasmid of hypervirulent Klebsiella allows bacterial lifestyle switch in response to iron.

Hypervirulent Klebsiella pneumoniae causes liver abscess and potentially devastating metastatic complications. The majority of Klebsiella-induced liver abscess are caused by the CG23-I sublineage of hypervirulent Klebsiella pneumoniae. This and some other lineages possess a >200-kb virulence plasmid. We discovered a novel protein IroP nestled in the virulence plasmid-encoded salmochelin operon that cross-regulates and suppresses the promoter activity of chromosomal type 3 fimbriae (T3F) gene transcription. IroP is itself repressed by iron through the ferric uptake regulator. Iron-rich conditions increase T3F and suppress capsule mucoviscosity, leading to biofilm formation and cell adhesion. Conversely, iron-poor conditions cause a transcriptional switch to hypermucoid capsule production and T3F repression. The likely acquisition of iroP on mobile genetic elements and successful adaptive integration into the genetic circuitry of a major lineage of hypervirulent K. pneumoniae reveal a powerful example of plasmid chromosomal cross talk that confers an evolutionary advantage. Our discovery also addresses the conundrum of how the hypermucoid capsule that impedes adhesion could be regulated to facilitate biofilm formation and colonization. The acquired ability of the bacteria to alternate between a state favoring dissemination and one that favors colonization in response to iron availability through transcriptional regulation offers novel insights into the evolutionary success of this pathogen. IMPORTANCE Hypervirulent Klebsiella pneumoniae contributes to the majority of monomicrobial-induced liver abscess infections that can lead to several other metastatic complications. The large virulence plasmid is highly stable in major lineages, suggesting that it provides survival benefits. We discovered a protein IroP encoded on the virulence plasmid that suppresses expression of the type 3 fimbriae. IroP itself is regulated by iron, and we showed that iron regulates hypermucoid capsule production while inversely regulating type 3 fimbriae expression through IroP. The acquisition and integration of this inverse transcriptional switch between fimbriae and capsule mucoviscosity shows an evolved sophisticated plasmid-chromosomal cross talk that changes the behavior of hypervirulent K. pneumoniae in response to a key nutrient that could contribute to the evolutionary success of this pathogen.

Risk Factors of Septic Metastatic Infection among Patients with Klebsiella pneumoniae Liver Abscess in Singapore: A Case-Control Study.

Metastatic infection resulting from Klebsiella pneumoniae liver abscess (KPLA) results in high mortality and morbidity. This study aimed to determine the risk factors associated with metastatic infection among patients with KPLA in Singapore. A retrospective case-control analysis among adult patients admitted to the National University Hospital with KPLA between 2013 and 2017 was conducted. Univariate and multivariate regression analysis was conducted. Of the 116 KPLA patients, 38.8% had pulmonary metastatic infection. Length of hospital stay (P = 0.001) and intensive care unit admissions (P = 0.044) were significantly longer and greater, respectively, among the patients with metastatic infection. Sepsis-induced hypotension (adjusted odds ratio [AOR], 4.88; 95% CI, 1.1-21.69), breathlessness (AOR, 5.10; 95% CI, 1.42-18.27), and abscess size (AOR, 1.02; 95% CI, 1.01-1.03) were associated independently with septic metastatic infection. Patients with KPLA who had breathlessness and larger abscess size are at a greater risk of septic metastatic infection.

A blood RNA transcriptome signature for COVID-19.

BACKGROUND: COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has not been fully characterised. Analysis of whole-blood RNA expression may provide valuable information on disease pathogenesis. METHODS: We studied 45 patients with confirmed COVID-19 infection within 10 days from onset of illness and a control group of 19 asymptomatic healthy volunteers with no known exposure to COVID-19 in the previous 14 days. Relevant demographic and clinical information was collected and a blood sample was drawn from all participants for whole-blood RNA sequencing. We evaluated differentially-expressed genes in COVID-19 patients (log2 fold change ≥ 1 versus healthy controls; false-discovery rate < 0.05) and associated protein pathways and compared these to published whole-blood signatures for respiratory syncytial virus (RSV) and influenza. We developed a disease score reflecting the overall magnitude of expression of internally-validated genes and assessed the relationship between the disease score and clinical disease parameters. RESULTS: We found 135 differentially-expressed genes in the patients with COVID-19 (median age 35 years; 82% male; 36% Chinese, 53% South Asian ethnicity). Of the 117 induced genes, 14 were found in datasets from RSV and 40 from influenza; 95 genes were unique to COVID-19. Protein pathways were mostly generic responses to viral infections, including apoptosis by P53-associated pathway, but also included some unique pathways such as viral carcinogenesis. There were no major qualitative differences in pathways between ethnic groups. The composite gene-expression score was correlated with the time from onset of symptoms and nasal swab qPCR CT values (both p < 0.01) but was not related to participant age, gender, ethnicity or the presence or absence of chest X-ray abnormalities (all p > 0.05). CONCLUSIONS: The whole-blood transcriptome of COVID-19 has overall similarity with other respiratory infections but there are some unique pathways that merit further exploration to determine clinical relevance. The approach to a disease score may be of value, but needs further validation in a population with a greater range of disease severity.

High specificity of OraQuick® rapid HIV-1/2 antibody testing during dengue infection.

BACKGROUND: OraQuick® is a rapid test with high specificity demonstrated in non-dengue endemic settings. However, reports of false positive OraQuick® results suggest poor specificity in the context of dengue fever. OBJECTIVES: To assess the specificity of OraQuick® for HIV-1/2 in patients with dengue fever. STUDY DESIGN: In a study performed across two Singapore hospitals, adult participants meeting WHO 2009 criteria for probable dengue (fever >37.5 °C plus two other clinical or haematological criteria) were identified at hospital outpatient clinics from April 2012 to July 2013. Eligible participants were asked for informed consent to complete a questionnaire on HIV risk factors, as well as HIV testing by OraQuick®, fourth-generation EIA and NAAT. Dengue testing was by Dengue Duo NS1Ag + Ab Combo kits. Confirmed dengue was defined as NS1-positive and probable dengue as IgM-positive. RESULTS: Of 152 eligible patients, 82 consented to inclusion in the study. Fifty-two of these had dengue; 43 confirmed and 9 probable cases. All patients with dengue had a negative OraQuick® result, negative EIA and undetectable HIV-1 RNA, corresponding to a specificity of 100 %. CONCLUSIONS: OraQuick® has high specificity in the context of dengue infection. It can be used to diagnose HIV-associated illness as a cause of fever in dengue endemic settings.

Oral vs Intravenous Antibiotics for Patients With Klebsiella pneumoniae Liver Abscess: A Randomized, Controlled Noninferiority Study.

BACKGROUND: Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. METHODS: This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein <20 mg/L, and reduction in abscess size. A noninferiority margin of 12% was used. RESULTS: Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, -4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. CONCLUSIONS: Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. CLINICAL TRIALS REGISTRATION: NCT01723150.

Population genomics of hypervirulent Klebsiella pneumoniae clonal-group 23 reveals early emergence and rapid global dissemination.

Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICEKp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23's evolutionary history, showing several deep-branching sublineages associated with distinct ICEKp acquisitions. Over 80% of liver abscess isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition of ICEKp10 (encoding yersiniabactin and colibactin), and then disseminated globally within the human population. CG23-I's distinguishing feature is the colibactin synthesis locus, which reportedly promotes gut colonisation and metastatic infection in murine models. These data show circulation of CG23 K. pneumoniae decades before the liver abscess epidemic was first recognised, and provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To support such studies we present an open access, completely sequenced CG23-I human liver abscess isolate, SGH10.

Characterization and Perceptions of Surgical Clinician Educators: An International Survey.

OBJECTIVE: Surgeons worldwide face unique time and practice pressures differentiating them from other types of physicians, specifically as clinician educators (CEs). The purpose of this study is to identify and describe academic surgical clinician educators (SCEs) in international graduate medical education systems, characterize their perceptions of roles, preparedness, and factors affecting job satisfaction and retention, as compared to nonsurgical international CEs. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional survey of CEs was conducted June 2013-June 2014 at academic medical centers in Singapore, Qatar, and the United Arab Emirates that adopted competency-based graduate medical education and received accreditation by the Accreditation Council for Graduate Medical Education-International. RESULTS: Two hundred seventy-six (76.3%) of 359 eligible physicians responded; 64 (23.2%) were SCEs. SCEs were predominantly male (80%), less than 50 years of age (83%), with 64% having been in their current position less than 5 years. Overall, SCEs were significantly less confident, as compared to nonsurgical CEs, in aspects of educational programs, including curriculum development, assessment, and mentorship. SCEs spent significantly more time engaged in patient care activities, as compared to nonsurgeon colleagues. There were no significant differences between SCEs and nonsurgical CEs in terms of work-life balance and satisfaction with responsibilities, position, or potential promotion, with most SCEs intending to stay in academic medicine. CONCLUSIONS: Academic SCEs working in the international programs reported overall job satisfaction with a desire to remain in academic medicine. However, SCEs have several faculty development needs. International surgical training programs can develop and expand offerings in teaching and education to improve skills and maintain SCE satisfaction and retention, necessary to successfully train the next generation of surgeons.

Comparison of Diabetic and Non-diabetic Human Leukocytic Responses to Different Capsule Types of Klebsiella pneumoniae Responsible for Causing Pyogenic Liver Abscess.

The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups. Clinical hvKP isolates universally stimulated KLA patient neutrophils to produce NETs ex vivo, regardless of host diabetic status. Ability of representative capsule types (K1, K2, and non-K1/K2 strains) to survive intra- and extra-cellular killing by type 2 DM and healthy neutrophils was subsequently examined. Key findings were: (1) type 2 DM and healthy neutrophils exhibited comparable total, phagocytic, and NETs killing against hvKP, (2) phagocytic and NETs killing were equally effective against hvKP, and (3) hypermucoviscous K1 and K2 strains were more resistant to total, phagocytic, and NETs killing compared to the non-mucoviscous, non-K1/K2 strain. The cytokine response and intracellular killing ability of type 2 DM as well as healthy PBMCs upon encounter with the different capsule types was also examined. Notably, the IL-12-IFNγ axis and its downstream chemokines MIG, IP-10, and RANTES were produced at slightly lower levels by type 2 DM PBMCs than healthy PBMCs in response to representative K1 and non-K1/K2 strains. Furthermore, type 2 DM PBMCs have a mild defect in its ability to control hvKP replication relative to healthy PBMCs. In summary, our work demonstrates that type 2 DM does not overtly impact neutrophil intra- and extra-cellular killing of hvKP, but may influence cytokine/chemokine production and intracellular killing by PBMCs.

Evaluation of a HIV voluntary opt-out screening program in a Singapore hospital.

BACKGROUND: Early diagnosis of human immunodeficiency virus (HIV) allows for appropriately timed interventions with improved outcomes, but HIV screening among asymptomatic persons and the general population in Singapore remains low. In 2008, Singapore's Ministry of Health implemented HIV voluntary opt-out screening (VOS) for hospitalised adults. We evaluated the outcome of VOS and surveyed reasons for its low uptake in our institution. METHODS: We assessed the outcomes of the VOS programme from January 2010 to December 2013 at National University Hospital, a 1081-bed tertiary hospital in Singapore. We also examined reasons for opting-in and opting-out using an interviewer-administered structured questionnaire in a representative sample in January 2013. RESULTS: 107,523 patients fulfilled VOS criteria and were offered HIV screening, of which 5215 (4.9%) agreed to testing. 4850 (93.1%) of those who opted-in had an HIV test done. Three (0.06%) tested positive for HIV. 238 patients (14.2%) were surveyed regarding reasons for opting-in or out of VOS. 21 (8.8%) had opted-in. Patients who opted-in were likely to be younger, more educated and reported having more regular sexual partners. Type of housing, number of casual sexual partners, sexual orientation, intravenous drug use, condom use and previous sexually transmitted infection were not associated with deciding to opt-in/out. Patients' most common reasons for opting-out were: belief that they were at low risk (50.2%), belief that they were too old (26.8%), cost (6.9%) and aversion to venepuncture (6.5%). The most common reason for opting-in was desire to know their HIV status (47.6%). CONCLUSION: The success of an HIV-VOS program is largely determined by test uptake. Our study showed that the majority of eligible VOS patients opted-out of HIV screening. Given the considerable cost and low yield of this programme, more needs to be done to better equip patients in self-risk assessment and opting in to testing.

CT appearance of pyogenic liver abscesses caused by Klebsiella pneumoniae.

PURPOSE: To retrospectively compare the computed tomographic (CT) features of liver abscesses caused by Klebsiella pneumoniae with those caused by other bacterial pathogens. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board, with waiver of informed consent. Hospital records of all patients with a diagnosis of liver abscess between July 2003 and July 2010 were retrieved from an electronic hospital database. One hundred and thirty-one consecutive patients with confirmed pyogenic liver abscesses were studied. Data on clinical presentation, comorbid conditions, septic hematogenous complications, hospitalization duration, and abscess-related mortality were obtained. CT characteristics of abscesses including number, distribution, unilocular or multilocular appearance, cystic or solid appearance, gas in cavity, pylephlebitis, thrombophlebitis, and pneumobilia were reviewed. Etiology was established by pus and/or blood culture. Patients were placed into a monomicrobial K pneumoniae liver abscess group and a comparison group. A comparison of the CT features and clinical findings between the two groups was performed. The χ(2) analysis or Fisher exact test was used for categorical variables, and Student t and log-rank tests were used for continuous variables. A P value of less than .05 was considered to indicate a significant difference. RESULTS: Monomicrobial K pneumoniae liver abscesses were present in 92 cases (70.2%). On CT images, characteristics more likely to be associated with monomicrobial K pneumoniae liver abscesses than other pyogenic liver abscesses were a single abscess (79.3% vs 56.4%, P = .01), unilobar involvement (82.6% vs 61.5%, P = .01), solid appearance (57.6% vs 35.9%, P = .03), multilocular (94.6% vs 71.8%, P = .01), association with thrombophlebitis (30.4% vs 5.1%, P < .01), and hematogenous complications (28.3% vs 7.7%, P < .01). Thrombophlebitis was associated with higher incidence of hematogenous septic complications (50.0% vs 13.9%, P < .001). Monomicrobial K pneumoniae liver abscesses were associated with significantly shorter duration of antibiotic treatment (P = .018) and hospital stay (P = .005), but there was no significant difference in incidence of septic shock and abscess-related mortality as compared with other pyogenic liver abscesses. CONCLUSION: Monomicrobial K pneumoniae liver abscesses appear as single, solid, or multiloculated liver abscesses and are associated with thrombophlebitis and septic hematogenous complications.