Treatment outcome of continuation of intravenous amikacin for Mycobacterium abscessus pulmonary disease with a persistent culture positivity after the treatment initiation

IntroductionWhether prolonged intravenous amikacin treatment would lead to better treatment results in patients with Mycobacterium abscessus subspecies abscessus (M. abscessus) pulmonary disease (PD) is unknown. We investigated the efficacy of continued amikacin treatment for the microbiological outcome of M. abscessus PD patients with persistent culture positivity after treatment initiation.MethodsWe retrospectively evaluated 62 patients with M. abscessus PD who were treated with intravenous amikacin and beta-lactams along with a macrolide-based regimen at 3 tertiary referral centers in South Korea. The intravenous antibiotic treatment duration was determined by the attending physician.ResultsThe median treatment durations with amikacin and beta-lactam in the 62 patients were 25.1 and 8.2 weeks, respectively. The overall microbiological cure rate was 29.0%. Among the 62 patients, 44 showed persistent culture positivity at 8 weeks after treatment with an amikacin-containing multidrug regimen. The median parenteral amikacin treatment duration after 8 weeks in these patients was 18.0 weeks. The conditional probability of microbiological cure with continuation of the amikacin-containing regimen in these patients was 18.2% (95% confidence interval 8.2–32.7). Additionally, the conditional probability of microbiological cure in the 34 patients with persistent culture positivity at 12 weeks was 8.8% (95% confidence interval 1.9–23.7). After 16 weeks, the conditional probability of microbiological cure decreased further, reaching 0% at 28 weeks after treatment initiation.ConclusionThe continuation of intravenous amikacin therapy was usually not followed by culture conversion in M. abscessus PD patients with persistent sputum culture positivity after treatment initiation.     

A case of primary multidrug-resistant pulmonary tuberculosis with high minimum inhibitory concentration value for bedaquiline

Bedaquiline is a new ATP synthesis inhibitor developed as an anti-tuberculosis agent. It has resistance-associated variants (RAV), regardless of preceding bedaquiline exposure. Herein, we describe the case of a patient with multidrug-resistant tuberculosis (MDR-TB) who had no history of bedaquiline therapy but presented a relatively high minimum inhibitory concentration (MIC) of bedaquiline (1 μg/mL). Whole genome sequencing revealed a mutation in the resistance-associated gene Rv0678. The patient was first treated with a five-drug regimen (bedaquiline, delamanid, levofloxacin, cycloserine, and amikacin), which induced negative sputum culture conversion. Despite the successful treatment outcome, several questions remain regarding the efficacy of bedaquiline in this patient. Bedaquiline is an indispensable drug for MDR-TB treatment, but its clinical efficiency in the presence of Rv0678 mutations remains unclear. Therefore, evaluating the MIC of bedaquiline even in patients without a history of bedaquiline use is important for therapeutic regimen selection and may emphasize the importance of therapeutic drug monitoring in cases of bedaquiline RAV.     

Nebulized colistin as the adjunctive treatment for ventilator-associated pneumonia: A systematic review and meta-analysis

PurposeNebulized colistin (NC) is a potential therapy for ventilator-associated pneumonia (VAP); however, the clinical efficacy and safety of NC remain unclear. This study investigated whether NC is an effective therapy for patients with VAP.Materials and methodsWe performed a search in Web of Science, PubMed, Embase, and the Cochrane Library to retrieve randomized controlled trials (RCTs) and observational studies published at any time until February 6, 2023. The primary outcome was clinical response. Secondary outcomes included microbiological eradication, overall mortality, length of mechanical ventilation (MV), length of intensive care unit stay (ICU-LOS), nephrotoxicity, neurotoxicity, and bronchospasm.ResultsSeven observational studies and three RCTs were included. Despite exhibiting a higher microbiological eradication rate (OR,2.21; 95%CI, 1.25–3.92) and the same nephrotoxicity risk (OR,0.86; 95%CI, 0.60–1.23), NC was not significantly different in clinical response (OR,1.39; 95%CI, 0.87–2.20), overall mortality (OR,0.74; 95%CI, 0.50–1.12), MV length (mean difference (MD),-2.5; 95%CI, −5.20–0.19), and the ICU-LOS (MD,-1.91; 95%CI, −6.66–2.84) than by the intravenous antibiotic. Besides, the risk of bronchospasm raised significantly (OR, 5.19; 95%CI, 1.05–25.52) among NC.ConclusionNC was associated with better microbiological outcomes but did not result in any remarkable changes in the prognosis of patients with VAP.     

Positive correlation between voriconazole trough concentrations and C-reactive protein levels in patients with chronic pulmonary aspergillosis: A retrospective cohort study

BackgroundVoriconazole (VRCZ) is the first-line treatment for chronic pulmonary aspergillosis (CPA). VRCZ trough concentration monitoring is recommended for adequate therapy because VRCZ concentrations vary widely. However, factors associated with variations in VRCZ concentrations, especially in the same patient at different time points, have not been identified. The objective of this study was to identify factors influencing VRCZ trough concentrations.Patients and methodsThis single-center retrospective study conducted at our institute between April 2014 and August 2016 included patients with CPA who received VRCZ. Patient trough concentrations were measured more than twice while the patients received the same dose using the same administration route (defined as one series). A step-wise method and multiple regression analysis were used to test the effects of patient characteristics on VRCZ trough concentrations.ResultsSixty-nine series in 49 patients were analyzed. VRCZ was administered orally in 59 series, intravenously in 7 series, and by dry syrup in 3 series. The median VRCZ trough concentration and the median variation in VRCZ concentrations were 1.68 and 0.99 μg/ml, respectively. In the simple regression analysis, creatinine, alkaline phosphatase, C-reactive protein (CRP), and creatinine clearance significantly correlated with VRCZ concentrations. Multiple regression analysis demonstrated a significant positive correlation between CRP and VRCZ concentration (P < 0.0001).ConclusionIn patients with CPA, VRCZ concentration correlated with CRP levels in the same patients receiving the same dose of VRCZ at different time points.     

Effect of renal clearance on vancomycin area under the concentration–time curve deviations in critically ill patients

IntroductionAugmented renal clearance (ARC) increases vancomycin (VCM) clearance. Therefore, higher VCM doses are recommended in patients with ARC; however, impacts of ARC on the area under the concentration–time curve (AUC) discrepancies between initial dosing design and therapeutic drug monitoring (TDM) period remains unclear.MethodsWe retrospectively collected data from critically ill patients treated with VCM. The primary endpoint was the association between ARC and AUC_24–48h deviations. ARC and AUC deviation were defined as a serum creatinine clearance (CCr) ≥130 mL/min/1.73 m² and an AUC at TDM 30% or more higher than the AUC at the initial dosing design, respectively. The pharmacokinetic profiles of VCM were analyzed with the trough levels or peak/trough levels using the Bayesian estimation software Practical AUC-guided TDM (PAT).ResultsAmong 141 patients (median [IQR]; 66 [58–74] years old; 30% women), 35 (25%) had ARC. AUC deviations were significantly more frequent in the ARC group than in the non-ARC group (20/35 [57.1%] and 17/106 [16.0%] patients, respectively, p < 0.001). Age- and sex-adjusted multivariate analyses revealed that the number of VCM doses before TDM ≥5 (odds ratio, 2.56; 95% confidence interval [CI]: 1.01–6.44, p = 0.047) and CCr ≥130 mL/min/1.73 m² were significantly associated with AUC deviations (odds ratio, 7.86; 95%CI: 2.91–21.19, p < 0.001).ConclusionOur study clarifies that the AUC of VCM in patients with ARC is higher at the time of TDM than at the time of dosage design.     

Determination of reactivation rate and risk factors for Hepatitis B virus reactivation in low-positive cases: A retrospective cohort study

IntroductionIn quantitative assays for hepatitis B virus (HBV) DNA, although the amplification reaction signal is detected for low-positive cases, quantification remains challenging. HBV reactivation has been reported in many studies, but only a few have focused on HBV low-positive cases. This study aimed to determine the reactivation rate and risk factors for HBV reactivation in low-positive cases.MethodsIn this retrospective cohort study, we analyzed 7498 patients who had their HBV DNA measured at Sapporo Medical University Hospital between April 2008 and November 2020. Patient selection criteria were defined as follows: hepatitis B surface antigen was negative; HBV DNA was detectable but not quantifiable at least once. HBV DNA was monitored according to the guidelines for HBV reactivation.ResultsIn total, 49,086 HBV DNA quantitative tests were performed. HBV DNA levels of 2578 tests were detectable but not quantifiable. Eighty patients met the criteria in this study. The median observation period was 497 days, and the 2-year reactivation rate was 15%. Ten patients had low HBV DNA positivity at baseline. Malignant lymphoma was observed in 15 patients; chemotherapy was used to treat other solid tumors in 35 patients, and immunosuppressive therapy was used in 30 patients. Multivariate analysis revealed that HBV DNA detected below the quantification level at baseline was an independent risk factor for HBV reactivation (adjusted hazard ratio 5.82; P = 0.010).ConclusionsPatients with low HBV DNA positivity, especially at baseline, are at high risk for HBV reactivation and therefore require closer monitoring.     

What are the risk factors for recurrent UTI with repeated ESBL-producing Enterobacteriaceae? A retrospective cohort study

IntroductionA previous study has shown that two-thirds of patients with urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae experience recurrence with the same bacteria on subsequent UTI episodes. However, little is known about which patients suffer from UTI due to ESBL-producing Enterobacteriaceae repeatedly. This study aimed to investigate the risk factors for recurrent UTI due to repeated ESBL-producing organism infections.MethodsThis retrospective, single-center, observational cohort study screened all patients with UTI caused by ESBL-producing strains between January 2012 and April 2019. Among the patients who were followed up, patients who experienced UTI recurrence were enrolled and divided into two groups: ESBL recurrence group and non-ESBL recurrence group. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between patient characteristics and the development of recurrent UTI caused by ESBL-producing Enterobacteriaceae.ResultsA total of 330 patients were followed up after the diagnosis of UTI caused by ESBL-producing organisms. Among the patients, 115 (34.8%) experienced UTI recurrence, and 71 (61.7%) of them experienced subsequent recurrent UTI due to ESBL-producing organisms. Patient's age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00–1.04; P = 0.046) and recurrent UTI history (HR, 1.69; 95% CI, 1.05–2.72; P = 0.031) were significantly associated with an increased risk of recurrence with ESBL-producing Enterobacteriaceae.ConclusionThese findings showed that a history of previous frequent UTI recurrence is the risk factor for recurrence of UTI due to repeated ESBL producing Enterobacteriaceae infections.     

Skin Cancer in Solid Organ Transplant Recipients: A Review for the Nondermatologist

Solid organ transplant recipients (SOTRs) are at increased risk for the development of skin cancer compared with the general population, which requires consistent monitoring and management from a multidisciplinary team. The aim of this review is to provide a comprehensive overview for nondermatologist clinicians, outlining skin cancer diagnosis, treatment pearls, and skin cancer prevention strategies as they relate to SOTRs. A comprehensive search of the literature was conducted through the MEDLINE database with search terms including organ transplantation, transplant recipient, skin cancer, cutaneous neoplasms, management, and therapies. The search was limited to the English language and dates ranging from January 1, 2011, to December 28, 2021. All studies were reviewed for inclusion. Skin cancer will develop in more than half of SOTRs at some point in their life, most often nonmelanoma skin cancer such as basal cell carcinoma or squamous cell carcinoma. Melanoma and rarer cutaneous malignant neoplasms, such as Merkel cell carcinoma and Kaposi sarcoma, are also more frequent among SOTRs. A multidisciplinary effort at skin cancer screening and patient education is invaluable to prevent skin cancer–related morbidity and mortality in this population of patients. Reduction in immunosuppressive medications and surgical intervention are effective therapeutic approaches, and more novel systemic therapies including G protein–coupled receptor inhibitors and immune checkpoint inhibitors are possible options when traditional treatment approaches are not feasible. Checkpoint inhibitor therapy, however, comes with the risk of allograft rejection. With a growing and aging SOTR population, it is essential that SOTRs have support from dermatologists and nondermatologists alike in skin cancer prevention and treatment.     

A systematic review and meta-analysis of myelosuppression in pediatric patients treated with linezolid for Gram-positive bacterial infections

BackgroundThe incidence of linezolid-induced myelosuppression in pediatric patients was reported at large difference among prospective studies, with a range of 0–24%. Additionally, there is little study which evaluated the impact of linezolid administration period on myelosuppression in pediatric patients, while it is one of the most frequent reason that linezolid therapy has to be discontinued in adult patients. Here, we performed a systematic review and meta-analysis to reveal the incidence of linezolid-induced thrombocytopenia and anemia, and impact of the administration period of linezolid on myelosuppression based on individual data analysis of pediatric patients.MethodsWe systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed, and CINAHL until April 2020. We investigated the incidence of linezolid-induced thrombocytopenia and anemia using pooled analysis, and evaluated the impact of linezolid administration period on myelosuppression using meta-analysis.ResultsThirteen studies with 969 pediatric patients were identified. The pooled incidences of thrombocytopenia and anemia were 9% (95% confidence interval (CI), 3–18%) and 4% (95% CI, 0–12%), respectively. Our meta-analysis showed the extension of linezolid administration period (more than 14 days) resulted in higher incidence of thrombocytopenia (OR 4.86, 95% CI 1.10–21.55) and anemia (OR 4.57, 95% CI 0.13–160.49).ConclusionsThe incidence of linezolid-induced myelosuppression in pediatric patients was less than 10%. However, our meta-analysis revealed linezolid administration period for more than 14 days was one of risk factors associated with linezolid-induced myelosuppression. Therefore, especially for pediatric patients treated with linezolid for more than 14 days, careful monitoring of myelosuppression is required.     

Physical Activity and Mortality Across Levels of Adiposity: A Prospective Cohort Study From the UK Biobank

ObjectiveTo examine the combined and stratified associations of physical activity and adiposity measures, modelled as body mass index (BMI), abdominal adiposity (waist circumference), and body fat percentage (BF) with all-cause mortality.Patients and MethodsUsing the UK Biobank cohort, we extracted quintiles of self-reported weekly physical activity. Categories of measured BMI, waist circumference, and BF were generated. Joint associations between physical activity-adiposity categories and mortality were examined using Cox proportional hazards models adjusted for demographic, behavioral, and clinical covariates. Physical activity-mortality associations were also examined within adiposity strata. Participants were followed from baseline (2006 to 2010) through January 31, 2018.ResultsA total of 295,917 participants (median follow-up, 8.9 years, during which 6684 deaths occurred) were included. High physical activity was associated with lower risk of premature mortality in all strata of adiposity except for those with BMI ≥35 kg/m². Highest risk (HR, 1.54; 95% CI; 1.33 to 1.79) was observed in individuals with low physical activity and high BF as compared with the high physical activity–low BF referent. High physical activity attenuated the risk of high adiposity when using BF (HR, 1.24; 95% CI; 1.04 to 1.49), but the association was weaker with BMI (HR, 1.45; 95% CI; 1.21 to 1.73). Physical activity also attenuated the association between mortality and high waist circumference.ConclusionLow physical activity and adiposity were both associated with a higher risk of premature mortality, but high physical activity attenuated the increased risk with adiposity irrespective of adiposity metric, except in those with a BMI ≥35 kg/m².     

A Target Antigen–Based Approach to the Classification of Membranous Nephropathy

ObjectiveTo describe the clinical and pathological phenotype of membranous nephropathy (MN) associated with M-type-phospholipase–A₂-receptor (PLA₂R), thrombospondin-type-1-domain-containing-7A (THSD7A), semaphorin 3B (SEMA3B), neural-epidermal-growth-factor-like-1-protein (NELL-1), protocadherin 7 (PCDH7), exostosin 1/exostosin 2 (EXT1/EXT2) and neural cell adhesion molecule 1 (NCAM-1) as target antigens.MethodsA retrospective cohort of 270 adult patients with biopsy-proven MN diagnosed between January 2015 and April 2020 was classified as PLA₂R-, THSD7A-, SEMA3B-, NELL-1–, PCDH7-, EXT1/EXT2-, NCAM-1–associated or septuple-negative MN using serologic tests, immunostaining, and/or mass spectrometry. Clinical, biochemical, pathologic, and follow-up data were systematically abstracted from the medical records, including disease activity of conditions traditionally associated with MN and occurring within 5 years of MN diagnosis.ResultsPatients with PLA₂R-associated MN were predominantly middle-aged white men without associated disease. The presence of associated disease did not affect the clinical and pathologic characteristics of PLA₂R-associated MN, suggesting that they were coincidental rather than causally linked. THSD7A-, NELL-1–, PCDH7-, and NCAM-1–associated MN were rare and SEMA3B-associated MN was not discovered in our cohort. EXT1/EXT2-associated MN was primarily diagnosed in younger women with active systemic autoimmunity. A significant proportion of septuple-negative patients had associated malignancy or systemic autoimmunity.ConclusionThe widely used distinction between primary and secondary MN has limitations. We propose a refined terminology that combines the target antigen and associated disease to better classify MN and guide clinical decision making.     

Overview of Lymphedema for Physicians and Other Clinicians: A Review of Fundamental Concepts

Lymphedema has historically been underrated in clinical practice, education, and scholarship to the detriment of many patients with this chronic, debilitating condition. The mechanical insufficiency of the lymphatic system causes the abnormal accumulation of protein-rich fluid in the interstitium, which triggers a cascade of adverse consequences such as fat deposition and fibrosis. As the condition progresses, patients present with extremity heaviness, itchiness, skin infections, and, in later stages, dermal fibrosis, skin papillomas, acanthosis, and other trophic skin changes. Correspondingly, lymphedema results in psychological morbidity, including anxiety, depression, social avoidance, and a decreased quality of life, encompassing emotional, functional, physical, and social domains. For this review, we conducted a literature search using PubMed and EMBASE and herein summarize the evidence related to the fundamental concepts of lymphedema. This article aims to raise awareness of this serious condition and outline and review the fundamental concepts of lymphedema.     

A Road Map of the Axial Spondyloarthritis Continuum

Axial spondyloarthritis (axSpA) is a chronic, immune-mediated inflammatory disease characterized by inflammatory low back pain, inflammation in peripheral joints and entheses, and other extra-articular or systemic manifestations. Although our understanding of the natural history of axSpA has been limited by incomplete knowledge of disease pathogenesis, axSpA is increasingly understood as a spectrum of axial, peripheral, and extra-articular inflammatory conditions that includes nonradiographic axSpA and radiographic axSpA, also known as ankylosing spondylitis. In this narrative review, we present a road map of this axSpA continuum, highlighting genetic risk factors for the development of axSpA, triggers of disease, and reasons for and implications of diagnostic delay. We present a detailed overview of the spectrum of axSpA clinical manifestations and highlight factors known to influence the risk of disease progression. Finally, we provide some expert commentary on the practical use of this road map to assist health care providers in the identification of axSpA in clinical practice.     

In asymptomatic late preterm and term infants,with neonatal hypoglycaemia,is the administration of 40% glucose gel effective in establishing normoglycaemia and reducing neonatal admissions?: A literature review

IntroductionTransient neonatal hypoglycaemia (TNH) is a common condition affecting newborn infants in homeostatic transition from maternal glucose supply to own metabolic adaptation.ObjectivesTo review published research after the cochrane systematic review in 2016 on the use of 40% glucose gel for the treatment of asymptomatic TNH.DesignCritical analysis was undertaken through a literature review and themes amongst the studies were categorised.Databases sourcesGrey literature, trial documents and databases inclusive of CINAHL, Cochrane, Medline and PubMed were searched between April 2017 and February 2018.Findings40% glucose gel may reduce NICU admissions, reduce length of stay in hospital, reduce maternal and infant separation and decrease hospital expenditure for asymptomatic hypoglycaemic infants.ConclusionAlthough with limitations, the studies add to the growing evidence of support for 40% glucose gel as a safe, simple and effective intervention for asymptomatic hypoglycaemic infants. Future large-scale studies may increase the evidence and support the development of a national protocol/guideline.     

The effect of massage therapy on pain after surgery: A comprehensive meta-analysis

BackgroundFindings on the usefulness of massage therapy (MT) in postoperative pain management are often inconsistent among studies.ObjectivesThis study’s aim is to conduct a meta-analysis of randomized controlled trials (RCT) to clarify the effects of massage therapy in the treatment of postoperative pain.MethodsThree databases (PubMed, Embase, and Cochrane Central Register of Controlled Trials) were searched for RCTs published from database inception through January 26, 2021. The primary outcome was pain relief. The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. The random-effect model was used to calculate the effect sizes and standardized mean difference (SMD) with 95 % confidential intervals (CIs) as a summary effect. The heterogeneity test was conducted through I². Subgroup and sensitivity analyses were used to explore the source of heterogeneity. Possible publication bias was assessed using visual inspection of funnel plot asymmetry.ResultsThe analysis included 33 RCTs and showed that MT is effective in reducing postoperative pain (SMD, −1.32; 95 % CI, −2.01 to −0.63; p = 0.0002; I² = 98.67 %). A similar significant effect was found for both short (immediate assessment) and long terms (assessment performed 4–6 weeks after the MT). Remarkably, we found neither the duration per session nor the dose had an impact on the effect of MT and there seemed to be no difference in the effects of different MT types. In addition, MT seemed to be more effective for adults. Furthermore, MT had better analgesic effects on cesarean section and heart surgery than orthopedic surgery.LimitationsPublication bias is possible due to the inclusion of studies in English only. Additionally, the included studies were extremely heterogeneous. Double-blind research on MT is difficult to implement, and none of the included studies is double-blind. There was some heterogeneity and publication bias in the included studies. In addition, there is no uniform evaluation standard for the operation level of massage practitioners, which may lead to research implementation bias.ConclusionsMT is effective in reducing postoperative pain in both short and long terms.