Diabetes and tuberculosis: An emerging dual threat to healthcare.

Tuberculosis (TB) remains a huge global healthcare challenge even in the 21st century though the prevalence has dropped in developed countries in recent decades. Diabetes mellitus (DM) is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with DM. The coexistence of both diseases in the same individual also aggravates disease severity, complications, and chance of treatment failure because of gross immune alterations posed by DM as well as TB. Various complex cellular and humoral immunological factors are involved in the dangerous interaction between TB and DM, some of which remain unknown even today. It is highly important to identify the risk factors for TB in patients with DM, and vice versa, to ensure early diagnosis and management to prevent complications from this ominous coexistence. In their research study published in the recent issue of the World Journal of Diabetes, Shi et al elaborate on the factors associated with the development of TB in a large cohort of DM patients from China. More such research output from different regions of the world is expected to improve our knowledge to fight the health devastation posed by TB in patients with diabetes.

Erythema Migrans in Patients with Post-Traumatic Splenectomy.

Information on asplenic Lyme borreliosis (LB) patients with erythema migrans (EM) is lacking. We compared the course and outcome of 26 EM episodes in 24 post-trauma splenectomized patients (median age 51 years) diagnosed at a single clinical center in Slovenia during 1994-2023 with those of 52 age- and sex-matched patients with EM but with no history of splenectomy. All patients were followed for one year. A comparison of pre-treatment characteristics revealed that EM in splenectomized patients was of shorter duration before diagnosis (4 vs. 8 days, p = 0.034) with a smaller EM diameter (10.5 vs. 14 cm, p = 0.046), and more frequently fulfilled criteria for disseminated LB (3/26, 11.5% vs. 0%, p = 0.034). Treatment failure occurred in 5/26 (19.2%) EM episodes in splenectomized patients versus 0/52 in non-splenectomized patients (p = 0.003). The five treatment failure cases were retreated with antibiotic regimens used to treat EM and had complete resolution of all symptoms/signs. In conclusion, our study showed that splenectomized adult patients with EM differ somewhat in presentation and more often have treatment failure compared with non-splenectomized patients with EM.

Impact of glycemic control on residual kidney function and technique failure associated with volume overload in diabetic patients on peritoneal dialysis.

Background: It is unclear whether poor glycemic control contributes to residual kidney function (RKF) decline and consequent volume overload in diabetic patients on peritoneal dialysis (PD). Methods: This retrospective analysis included 80 diabetic patients who started PD at a single center. The first 2 years of patient data were collected to investigate the impact of glycemic control on RKF and volume overload in the early stages of PD. We used the time-averaged glycated hemoglobin (HbA1c) levels to estimate glycemic control. RKF loss was measured as the slope of RKF decline and time to anuria. To assess the association between glycemic control and volume overload, we examined technique failure (TF) associated with volume overload (TFVO), defined as TF due to excessive fluid accumulation. Multivariable linear regression and Cox regression analysis were performed to assess how glycemic control affects RKF and TFVO. Results: Over the first 2 years, the mean rate of RKF decline was -3.25 ± 3.94 mL/min/1.73 m2 per year. Multivariable linear regression showed that higher time-averaged HbA1c was associated with a rapid RKF decline (ß = -0.95; 95% confidence interval [CI], -1.66 to -0.24; p = 0.01). In the adjusted Cox regression analysis, higher time-averaged HbA1c increased the risk of progression to anuria (adjusted hazard ratio [HR], 1.97; 95% CI, 1.29-3.00; p = 0.002) and TFVO (adjusted HR, 2.88; 95% CI, 1.41-5.89; p = 0.004). Conclusion: Poor glycemic control is associated with rapid RKF decline and leads to volume overload in diabetic patients on PD.

Resistance to protease inhibitors among persons living with HIV in Ghana: a case for viral load and drug resistance monitoring.

OBJECTIVE: Routine viral load and drug resistance testing are well supported in most resource-rich settings and provide valuable benefits in the clinical care of PLWH in these communities. Undoubtedly, there exist financial and political constraints for the scale-up of viral load and drug resistance testing in Sub-Saharan Africa. To achieve the global UNAIDS 95/95/95 targets, there is the need to bridge this inequity in patient care and allow for a universal approach that leaves no community behind. METHODS: Venous blood from 96 PLWH on second-line ART from Korle-Bu Teaching Hospital were collected and processed into plasma for CD4+ T- cell and viral load assessments. Ribonucleic acid (RNA) was extracted from stored plasma and the protease gene amplified, sequenced and analyzed for subtype and drug resistance mutations using the Stanford HIV drug resistance database. RESULTS: Out of the 96 PLWH, 37 experienced virological failure with 8 patients' samples successfully sequenced. The predominant HIV-1 subtype identified was CRF02_AG (6/8, 75.0%) with 12.5% (1/8) each of CFR06_cpx infection and one case unable to subtype. The major PI resistance mutations identified were; M46I, I54V, V82A, I47V, I84V and L90M. CONCLUSIONS: Persons living with HIV who had experienced virologic failure in this study harboured drug resistance mutations to PI, thus compromise the effectiveness of the drugs in the second line. Resistance testing is strongly recommended prior to switching to a new regimen. This will help to inform the choice of drug and to achieve optimum therapeutic outcome among PLWH in Ghana.

Antimicrobial Susceptibility of Various MRSA Clinical Isolates and the Impact of Glycopeptide MICs on Clinical and Microbiological Outcomes.

Objective: While vancomycin has remained the mainstay of the treatment for methicillin-resistant Staphylococcus aureus (MRSA) infections, there is growing evidence of the clinical impact of increased glycopeptide minimum inhibitory concentrations (MICs) in MRSA isolates. This study aimed to determine the susceptibility of various MRSA isolates to different antibiotics with antistaphylococcal activity and the impact of glycopeptide MICs on clinical and microbiological outcomes. Materials and Methods: This retrospective cohort study, conducted between 2013 and 2017, evaluated the susceptibility of MRSA strains isolated from various clinical samples to antistaphylococcal antibiotics using the gradient strip method. The clinical and laboratory features of patients infected with MRSA isolates with elevated glycopeptide MICs (>1 mg/L) and with isolates that had low glycopeptide MICs (≤1 mg/L) were compared. Results: A total of 104 patients infected with MRSA strains were included in this study. Male sex (odds ratio [OR]=2.48, 95% confidence interval [CI]=1.01-6.10, p=0.048), two or more comorbidities (OR=2.48, 95% CI=1.03-6.50, p=0.044), history of MRSA infection (OR=4.91, 95% CI=1.70-14.28, p=0.003) and a longer hospital stay prior to MRSA infection (OR=2.32, 95% CI=1.05-7.85, p=0.040) were independent risk factors for high glycopeptide MICs. In MRSA infections with a teicoplanin MIC of >0.75mg/L, the microbiological and treatment failures were 46.2% (p=0.044) and 60.6% (p=0.042), respectively. Conclusion: This study showed that the critical MIC value, which suggested treatment failure as well as microbiological failure in the teicoplanin-treated MRSA infections, was >0.75 mg/L rather than >1 mg/L in our study cohort. The identification of high-risk patients;for treatment failures and mortality considering gradient strip method MIC values is crucial for the effective management of MRSA infections.

HIV1 drug resistance among patients experiencing first-line treatment failure in Ethiopia: protocol for a systematic review and meta-analysis.

BACKGROUND: The emergence of HIV drug resistance presents a substantial challenge. Current antiretroviral treatments, along with current classes, face the danger of becoming partially or entirely inactive. As a result, alternative treatment regimens are limited, and treatment choices are complicated. According to the recommendation of the WHO, nations should consider changing their first-line ART regimen if HIV drug resistance exceeds 10%. In spite of the fact that a number of primary studies have been performed on HIV drug resistance in Ethiopia, their pooled prevalence rate has not been determined in a systematic review and meta-analysis, which may provide stronger evidence. Therefore, the objective of this systematic review and meta-analysis will be to estimate the pooled prevalence rate of HIV1 drug resistance in patients with first-line treatment failure in Ethiopia. METHODS: Primary studies will be identified from PubMed/MEDLINE, Scopus, Embase, Web of Science Core Collection, and Google Scholar. The period of search will be from 01 April to 30 June 2024. Studies identified through the search strategies will first be screened by titles and abstracts. Included studies meeting established criteria will be evaluated for risk of bias using the JBI checklist. Data will be extracted, and the pooled prevalence rate of HIV drug resistance will be computed using STATA 14 software. Random effect models will be used when heterogeneity is suspected. The I2 statistic and its corresponding P value will be checked to distinguish heterogeneity. Additionally, publication bias and heterogeneity will be checked using visual funnel plots, Egger's test, trim-and-fill tests, meta-regression, and subgroup analysis. To present and synthesize the results, narrative synthesis will be performed to describe study characteristics and findings, and forest plots will be used to visually represent effect sizes and confidence intervals from individual studies. DISCUSSION: Estimating the pooled prevalence rate of HIV drug resistance through a systematic review and meta-analysis improves the reliability of the evidence, the availability of effective HIV treatment options, and the ability to assist in making decisions for both clinical practice and public health policy in Ethiopia. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42024533975.

Agar and agarose used for Staphylococcus aureus biofilm cultivation impact fluoroquinolone tolerance.

AIMS: Staphylococcus aureus is an opportunistic pathogen whose treatment is further complicated by its ability to form biofilms. In this study, we examine the impact of growing S. aureus biofilms on different polymerizing surfaces, specifically agar and agarose, on the pathogen's tolerance to fluoroquinolones. METHODS AND RESULTS: Biofilms of two methicillin-resistant strains of S. aureus were grown on agar or agarose in the presence of the same added nutrients, and their antibiotic susceptibility to two fluoroquinolones, moxifloxacin (MXF) and delafloxacin (DLX), were measured. We also compared the metabolism and extracellular polymeric substances (EPS) production of biofilms that were grown on agar and agarose. CONCLUSIONS: Biofilms that were grown on agarose were consistently more susceptible to antibiotics than those grown on agar. We found that in biofilms that were grown on agar, extracellular protein composition was higher, and adding EPS to agarose-grown biofilms increased their tolerance to DLX to levels that were comparable to agar-grown biofilms.

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

OBJECTIVE: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. DESIGN: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. RESULTS: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. CONCLUSION: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

OBJECTIF: Identifier les indicateurs d'alerte précoce au niveau individuel de l'échec virologique chez les patients séropositifs recevant un traitement antirétroviral (TAR) en Afrique du Sud. MÉTHODE: Une étude cas-témoins appariée de personnes avec et sans échec virologique (FV, pour l'anglais « virologic failure ¼) (>5 mois sous ART et charge virale plasmatique du VIH-1 >1 000 copies/ml) a été menée entre juin 2014 et juin 2018. Sur les 1 000 participants inscrits dans la cohorte parente, 96 ont présenté une FV et 199 témoins supplémentaires ont été identifiés dans la cohorte parentale et appariés 1:2 (certains appariés 1:3) pour le sexe, l'âge, la durée du TAR et le site. Les participants ont été interrogés pendant que des données cliniques, de renouvellement de pharmacie, de laboratoire et pharmacologiques objectives ont été obtenues. Des modèles de régression logistique conditionnelle multivariée ont été construits à l'aide d'une sélection de modèles pour identifier les facteurs associés à la FV. Les déterminants significatifs de la FV ont été identifiés à l'aide d'un niveau alpha de 0,05. RÉSULTATS: Dans un modèle conditionnel complet, une observance cumulative plus élevée du TAR, quantifiée à l'aide des concentrations de ténofovir-diphosphate dans les gouttes de sang séché (OR 0,26) et du ratio de possession de médicaments (OR 0,98) protégeait contre la FV, tandis qu'une augmentation du score de dépression totale (OR 1,20) était prédictive de la FV. CONCLUSION: Cette analyse démontre l'importance de la dépression en tant qu'indicateur précoce clé au niveau individuel de la FV. Les efforts visant à résoudre les problèmes de santé mentale chez les personnes vivant avec le VIH pourraient améliorer la suppression virologique.

Emergence of heteroresistance to carbapenems in Gram-negative clinical isolates from two Egyptian hospitals.

BACKGROUND: Antimicrobial resistance is a global concern, linking bacterial genotype and phenotype. However, variability in antibiotic susceptibility within bacterial populations can lead to misclassification. Heteroresistance exemplifies this, where isolates have subpopulations less susceptible than the main population. This study explores heteroresistance in Gram-negative bacteria, distinguishing between carbapenem-sensitive isolates and stable heteroresistant isolates (SHIs). METHODS: A total of 151 Gram-negative clinical isolates including Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii and Proteus mirabilis from various sources were included. Heteroresistant isolates and their stability were detected by disc-diffusion technique while genotypic analysis was carried out by PCR and efflux activity was assessed by ethidium bromide (EtBr)-agar cartwheel method. RESULTS: A total of 51 heteroresistant subpopulations were detected, producing 16 SHIs upon stability-detection. Amplified resistance genes and EtBr-agar cartwheel method showed a significant difference between resistant subpopulations and their corresponding-sensitive main populations. CONCLUSION: Genotypic analysis confirmed that genetic mutation can lead to resistance development although the main populations were sensitive, thereby leading to treatment failure. This is a neglected issue which should be highly considered for better treatment outcomes.

The effect of supportive counseling on self-esteem of infertile women after in vitro fertilization (IVF) failure: a randomized controlled trial study.

BACKGROUND: The unsuccessful treatment of infertility can lead to heightened levels of negative emotions, which are often associated with various psychological consequences. These consequences may include a decrease in self-confidence, feelings of loneliness, reduced self-esteem, and even discontinuation of treatment. Therefore, it is crucial to implement interventions that can help improve these consequences for women who have experienced IVF failure. The present study aimed to examine the effect of supportive counseling on self-esteem of infertile women after IVF failure. METHODS: this randomized clinical trial study was conducted on 63 infertile women after IVF failure, referred to Milad Infertility Center in Mashhad in 2021. In the intervention group, the researcher provided individual supportive counseling sessions. These sessions took place over a span of four weeks, with each session lasting 60 min (One session every week). Data collection was conducted both before and one month after the study using Eysenck self-esteem Questionnaire. Data were analyzed using SPSS25, as well as statistical tests such as chi-square, independent t-test, Paired t-test and Mann-Whitney tests. A significance level of less than 5% was considered. RESULTS: The study found no significant difference in mean scores of self-esteem between the two groups before the study (p = 0.823). However, after one month, the intervention group had significantly higher self-esteem scores (24.3 ± 18.55) compared to the control group (21.74 ± 5.62) (p = 0.043) Moreover, Based on the Within-group comparison, there was a 2.43 ± 3.24 point increase in self-esteem scores of the intervention group after one month, while the control group showed a -0.33 ± 3.72 point decrease. CONCLUSION: Supportive counseling was found to be effective in improving self-esteem following IVF failure. As a result, it can be recommended as an effective, affordable, and low-risk counseling approach for women who have experienced IVF failure. By offering supportive counseling, it is possible to help prevent and alleviate the psychological consequences associated with IVF failure. TRIAL REGISTRATION: This research project was registered at the Iranian Registry of Clinical Trials with code IRCT20210407050883N1- Date of registration 2021-05-25.

Elevated Serum Levels of YKL-40, YKL-39, and SI-CLP in Patients with Treatment Failure to DMARDs in Patients with Rheumatoid Arthritis.

Around 30-60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case-control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs' utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: p < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, p < 0.001) and SI-CLP (rho = 0.23, p = 0.011) and YKL-39 with SI-CLP (rho = 0.34, p < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) p < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models.

Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure.

Background and aims: Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure. Methods: This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab). Results: A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16-0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27-0.8; p=0.005). Conclusion: CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure.

Outcomes of venetoclax-based therapy in patients with t(11;14) light chain amyloidosis after failure of daratumumab-based therapy.

BACKGROUND: Daratumumab's incorporation in the upfront treatment of light chain (AL) amyloidosis has led to daratumumab (dara) refractoriness early in disease course. Patients who experience relapse or have suboptimal response to dara-based-therapy, have limited options. OBJECTIVE: This study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara. METHODS: Thirty-one patients with AL were included in this bi-institutional retrospective analysis. RESULTS: Dara failure was due to inadequate response in 20 (65%) patients, haematologic relapse in 7 (22%), and both haematologic plus organ relapse in 4 (13%). Overall haematologic response rate to venetoclax-based therapy was 97%, with ≥ VGPR being 91%. Of the 19 evaluable patients with cardiac involvement, 14 (74%) achieved organ response. Of the 13 evaluable patients with renal involvement, 6 (46%) achieved organ response. With a median follow-up of 22 months, median time-to-next-treatment (TTNT) and overall survival (OS) were not reached. The 12- and 24-month TTNT rates were 74% and 56%, respectively. At data-cut-off, four patients had died, all from AL-related organ complications. The 12- and 24-month OS rates were 89% and 85%, respectively. Grade ≥3 adverse events occurred in 26% of patients, with 6% due to infections. CONCLUSION: These findings are encouraging for the use of venetoclax as salvage therapy post-dara failure.

Assay Interference Causing Persistently Elevated Vancomycin Levels Leading to Treatment Failure and Fatal Outcome.

In patients receiving vancomycin therapy, serum drug levels are routinely monitored to ensure therapeutic dosing and minimize toxicity. In rare cases, vancomycin levels may be falsely or persistently elevated without any apparent cause. In this case report, we explore a rare case of persistently elevated vancomycin levels despite discontinuation of the drug for days.  This is a case of a 69-year-old female admitted for altered mental status secondary to sepsis from leg cellulitis. Antibiotic therapy included vancomycin. To ensure proper dosing, vancomycin trough levels were collected before the fourth dose, and the result showed a high value of 39 ug/ml. Vancomycin doses were adjusted as per the Bayesian dosing software, and the same remained to be in supratherapeutic levels. The patient eventually deteriorated, and due to persistently high vancomycin levels, the antibiotic regimen was switched to a different antibiotic. Despite normal renal functions, the vancomycin levels remained high, between 27 ug/ml and 32 ug/ml, even in the absence of any further doses. Subsequently, vancomycin serum concentration was determined by another method using high-performance liquid chromatography (HPLC). Blood cultures grew both coagulase-negative Staphylococcus aureus and Achromobacter xylosoxidans. Vancomycin levels remained high a week after discontinuation of the drug. Vancomycin by HPLC assay eventually showed that vancomycin was undetectable in the blood, but, unfortunately, the results came at a time when the patient had already expired. In conclusion, clinicians should maintain a high level of suspicion if persistently higher vancomycin levels cannot be accounted for by renal function or other causes. In patients with persistently high vancomycin levels who continue to clinically deteriorate, it is crucial to consider that assay interference can result in inaccurately elevated vancomycin levels.

Risk factors for vancomycin treatment failure in heterogeneous vancomycin-intermediate Staphylococcus aureus bacteremia.

The incidence of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (P < 0.001) and more frequently had solid cancer (P = 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (P < 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (P = 0.01) and Acute Physiology and Chronic Health Evaluation II scores (P < 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.IMPORTANCEIn this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated Staphylococcus aureus (hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.

Empiric antibiotic regimens in adults with non-ventilator-associated hospital-acquired pneumonia: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: The optimal empiric antibiotic regimen for non-ventilator-associated hospital-acquired pneumonia (HAP) is uncertain. OBJECTIVES: To compare the effectiveness and safety of alternative empiric antibiotic regimens in HAP using a network meta-analysis. DATA SOURCES: Medline, EMBASE, Cochrane CENTRAL, Web of Science, and CINAHL from database inception to July 06, 2023. STUDY ELIGIBILITY CRITERIA: RCTs. PARTICIPANTS: Adults with clinical suspicion of HAP. INTERVENTIONS: Any empiric antibiotic regimen vs. another, placebo, or no treatment. ASSESSMENT OF RISK OF BIAS: Paired reviewers independently assessed risk of bias using a modified Cochrane tool for assessing risk of bias in randomized trials. METHODS OF DATA SYNTHESIS: Paired reviewers independently extracted data on trial and patient characteristics, antibiotic regimens, and outcomes of interest. We conducted frequentist random-effects network meta-analyses for treatment failure and all-cause mortality and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Thirty-nine RCTs proved eligible. Thirty RCTs involving 4807 participants found low certainty evidence that piperacillin-tazobactam (RR compared to all cephalosporins: 0.65; 95% CI: 0.42, 1.01) and carbapenems (RR compared to all cephalosporins: 0.77; 95% CI: 0.53, 1.11) might be among the most effective in reducing treatment failure. The findings were robust to the secondary analysis comparing piperacillin-tazobactam vs. antipseudomonal cephalosporins or antipseudomonal carbapenems vs. antipseudomonal cephalosporins. Eleven RCTs involving 2531 participants found low certainty evidence that ceftazidime and linezolid combination may not be convincingly different from cephalosporin alone in reducing all-cause mortality. Evidence on other antibiotic regimens is very uncertain. Data on other patient-important outcomes including adverse events was sparse, and we did not perform network or pairwise meta-analysis. CONCLUSIONS: For empiric antibiotic therapy of adults with HAP, piperacillin-tazobactam might be among the most effective in reducing treatment failure. Empiric methicillin-resistant Staphylococcus aureus coverage may not exert additional benefit in reducing mortality. REGISTRATION: PROSPERO (CRD 42022297224).

Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma receiving first-line combination immunotherapies: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Lymphocytes are closely linked to mechanisms of action of immuno-oncology (IO) agents. We aimed to assess the prognostic significance of absolute lymphocyte count (ALC) in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Using the International mRCC Database Consortium (IMDC), patients receiving first-line IO-based combination therapy were analysed. Baseline patient characteristics, objective response rates (ORRs), time to next treatment (TTNT), and overall survival (OS) were compared. RESULTS: Of 966 patients included, 195 (20%) had lymphopenia at baseline, and they had a lower ORR (37% versus 45%; P < 0.001), shorter TTNT (10.1 months versus 24.3 months; P < 0.001), and shorter OS (30.4 months versus 48.2 months; P < 0.001). Among 125 patients with lymphopenia at baseline, 52 (42%) experienced ALC recovery at 3 months, and they had longer OS (not reached versus 30.4 months; P = 0.012). On multivariable analysis for OS, lymphopenia was an independent adverse prognostic factor (hazard ratio 1.68; P < 0.001). Incorporation of lymphopenia into the IMDC criteria improved OS prediction accuracy (C-index from 0.688 to 0.707). CONCLUSIONS: Lymphopenia was observed in one-fifth of treatment-naive patients with mRCC and may serve as an indicator of unfavourable oncologic outcomes in the contemporary IO era.

Urinary drug metabolite profiling of tuberculosis treatment failure using proton nuclear magnetic resonance.

The underlying cause of tuberculosis (TB) treatment failure is still largely unknown. A 1H NMR approach was applied to identify and quantify a subset of TB drugs and drug metabolites: ethambutol (EMB), acetyl isoniazid (AcINH), isonicotinic acid, pyrazinamide (PZA), pyrazinoic acid and 5-hydroxy-pyrazinoic acid, from the urine of TB patients. Samples were collected before, during (weeks one, two and four) and after standardised TB treatment. The median concentrations of the EMB and PZA metabolites were comparable between the samples from patients with eventually cured and failed treatment outcomes. The INH metabolites showed comparatively elevated concentrations in the treatment failure patients during and after treatment. Variation in INH metabolite concentrations couldn't be associated with the varying acetylator genotypes, and it is therefore suggested that treatment failure is influenced more so by other conditions, such as environmental factors, or individual variation in other INH metabolic pathways.

Adherence to AUA guidelines for the work-up, medical management, surgical evaluation and treatment of BPH: Work from a quality improvement collaborative.

INTRODUCTION: Previous studies noted varied adherence to clinical practice guidelines (CPGs), but studies are yet to quantify adherence to American Urological Association BPH guidelines. We studied guideline adherence in the context of a new quality improvement collaborative (QIC). METHODS: Data were collected as part of a statewide QIC. Medical records for patients undergoing select CPT codes from January 2020 to May 2022 were retrospectively reviewed for adherence to selected BPH guidelines. RESULTS: Most men were treated with transurethral resection of the prostate. Notably, 53.3% of men completed an IPSS and 52.3% had a urinalysis. 4.7% were counseled on behavioral modifications, 15.0% on medical therapy, and 100% on procedural options. For management, 79.4% were taking alpha-blockers and 59.8% were taking a 5-ARI. For evaluation, 57% had a PVR, 63.6% had prostate size measurement, 37.4% had uroflowmetry, and 12.3% were counseled about treatment failure. Postoperatively, 51.6% completed an IPSS, 57% had a PVR, 6.50% had uroflowmetry, 50.6% stopped their alpha-blocker, and 75.0% stopped their 5-ARI. CONCLUSIONS: There was adherence to preoperative testing recommendations, but patient counseling was lacking in the initial work-up and preoperative evaluation. We will convey the data to key stakeholders, expand data collection to other institutions, and devise an improvement implementation plan.