Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients.

RATIONALE: Whole lung lavage (WLL) is a widely accepted palliative treatment for autoimmune pulmonary alveolar proteinosis (aPAP) but does not correct myeloid cell dysfunction or reverse the pathological accumulation of surfactant. In contrast, inhaled recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a promising pharmacological approach that restores alveolar macrophage functions including surfactant clearance. Here, we evaluate WLL followed by inhaled rGM-CSF (sargramostim) as therapy of aPAP. METHODS: 18 patients with moderate-to-severe aPAP were enrolled, received baseline WLL, were randomised into either the rGM-CSF group (receiving inhaled sargramostim) or control group (no scheduled therapy) and followed for 30 months after the baseline WLL. Outcome measures included additional unscheduled "rescue" WLL for disease progression, assessment of arterial blood gases, pulmonary function, computed tomography, health status, biomarkers and adverse events. Patients requiring rescue WLL were considered to have failed their assigned intervention group. RESULTS: The primary end-point of time to first rescue WLL was longer in rGM-CSF-treated patients than controls (30 versus 18 months, n=9 per group, p=0.0078). Seven control patients (78%) and only one rGM-CSF-treated patient (11%) required rescue WLL, demonstrating a 7-fold increase in relative risk (p=0.015). Compared to controls, rGM-CSF-treated patients also had greater improvement in peripheral arterial oxygen tension, alveolar-arterial oxygen tension difference, diffusing capacity of the lungs for carbon monoxide and aPAP biomarkers. One patient from each group withdrew for personal reasons. No serious adverse events were reported. CONCLUSIONS: This long-term, prospective, randomised trial demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP.

Daptomycin Exposure Prediction With a Limited Sampling Strategy.

BACKGROUND: Daptomycin is a cyclic lipopeptide antibiotic used to treat serious infectious endocarditis caused by Staphylococcus aureus. The pharmacodynamic parameter correlating best with efficacy is the ratio of the estimated area under the concentration (AUC0-24)-time curve to the minimum inhibitory concentration. The aim of the study is to develop a limited sampling strategy to estimate AUC0-24 using a reduced number of samples. METHODS: Sixty-eight daptomycin AUC0-24 values were calculated for 50 White patients who underwent treatment for at least 5 consecutive days. Plasma concentrations were detected using a validated high-performance liquid chromatography-tandem mass spectrometry analytical method, with daptomycin-d5 as an internal standard. Multiple regression was used to evaluate the ability of 2 concentration-time points to predict the AUC0-24 calculated from the entire pharmacokinetic profile. Prediction bias was calculated as the mean prediction error, whereas prediction precision was estimated as the mean absolute prediction error. The development and validation datasets comprised 40 and 10 randomly selected patients, respectively. RESULTS: The AUC0-24 (mg*h/L) was best estimated using the daptomycin trough concentration and plasma concentrations detected 2 hours after dosing. We calculated a mean prediction error of 1.6 (95% confidence interval, -10.7 to 10.9) and a mean absolute prediction error of 11.8 (95% confidence interval, 5.3-18.3), with 73% of prediction errors within ±15%. CONCLUSIONS: An equation was developed to estimate daptomycin exposure (AUC0-24), offering clinical applicability and utility in generating personalized dosing regimens, especially for individuals at high risk of treatment failure or delayed response.

Does Meal or Water Intake Affect Ultrasound Attenuation Coefficient Estimate?

OBJECTIVES: To assess whether meal or water intake may affect the measurement of the ultrasound (US) attenuation coefficient (AC) imaging, a parameter that is directly related to liver fat content. METHODS: The study was performed in two centers (Italy and USA). AC was obtained using the ATI algorithm implemented in the Aplio i-series US systems (Canon Medical Systems, Japan) by one operator at each center. Measurements were performed at baseline and 5, 15, 30, 45 minutes after drinking 500 mL of water (group 1), or 30, 45, 60, 90, 120 minutes after eating a meal of about 600 kcal (group 2). Multilevel generalized estimating equations for repeated measures were used for the statistical analysis to consider the clustered nature of the data. RESULTS: Twenty-six individuals were enrolled: 11 (10 females; age, 43.7 ± 12.5 years) in Italy and 15 (10 females; age, 60.7 ± 6.3 years) in USA. At B-mode US, 10 (38.5%) had liver steatosis. The baseline AC values, in decibel/centimeter/megahertz, were 0.64 (0.12) in group 1 and 0.66 (0.13) in group 2. There was not any significant difference in AC values at every time-point after water or meal intake either in group 1 or group 2. This result did not change including sex, age, and skin-to-liver capsule into the models. CONCLUSIONS: The measurement of the AC, which is a biomarker of liver steatosis, does not require a fasting state and drinking water does not affect the result.

The role of neutrophil-lymphocytes ratio (NLR) in the prognosis of CIN2+ 2 recurrence after excisional treatment.

OBJECTIVES: The main risk factor involved in CIN2+ recurrence after treatment is the HPV persistent infection. The dysregulation of the immune system permits only HR-HPVs to become persistent infections, to promote cancer development and to increase the risk of recurrence after treatment. Therefore, there is a shift to a Th2-type cytokine pattern during the carcinogenesis pathway; for this reason, the neutrophil-lymphocytes ratio (NLR) could be a marker of this immunological change. The study aims to analyse the predictive role of NLR in the recurrence of High-grade CIN (CIN2+) after excisional treatment in a real-world life setting of patients treated for CIN2+ Design: cross-sectional study Participants/Materials, Setting, Methods: We examined a retrospective database of 444 patients, who attended the Colposcopy Service of our Department from 2011 to 2020 due to an abnormal screening pap smear and we compared the clinical characteristics to NLR performed at the time of diagnosis. All analysed patients were treated according to an established protocol (colposcopy every 6 months for the first two years, and every year for the over three years,) and HPV-DNA test and cervical biopsy were performed at entry and the end of follow-up. All patients underwent a blood sample examination, including complete white blood cell counts and collecting neutrophil and lymphocyte values expressed as 103/ml. Results The sensitivity (SE) and specificity (SP) of the NLR cut-off point of 1.34 for the diagnosis of CIN2+ recurrence were 0.76 and 0.67, respectively. We found that CIN2+ recurrences were significantly higher in patients with NLR < 1.34 (3.7% vs. 0.6%, p = 0.033) and the 5-year recurrence-free survival was higher in patients with NLR ≥ 1.34 (97% vs. 93%, p=0.030). Limitations First, the retrospective analysis and low incidence of recurrence may limit the conclusions. Second, for the retrospective design of the study, we did not take into consideration the patient's comorbidities and habits (smoking), that may influence the NLR. On the other hand, the median duration of follow-up in our study was 26 months (IQR 22-31), which fully reflects the incidence of recurrences. Conclusions It is well known that CIN2+ lesions are sustained by deregulation of the immune system caused by persistent HPV infection, which may lead to cervical cancer. Among the actors underlying dysregulation of immunity, lymphocytes are involved in the permission of persistent infection and for this reason, NRL could be a reliable and cost-effective biomarker in predicting the risk of recurrence, especially for high-grade cervical lesions.

Retrospective Investigation of Human Papillomavirus Cervical Infection and Lymphoma Incidence: A Clinical and Pathological Evaluation.

OBJECTIVE: Human papillomavirus (HPV) persistence is considered the main risk factor for neoplastic progression, and evidence suggests that regulatory T cells play an important role in the failure of viral elimination. Regulatory T cells may be involved in maintaining a microenvironment favourable for viral persistence and neoplasticity, through a deregulation of the local immune response. The association between altered immune function and the development of chronic infections, cancer (solid and haematological), and autoimmune diseases is documented in the literature. The purpose of this retrospective analysis was to evaluate the possible correlation between HPV cervical infection and lymphoma incidence in women attending colposcopy due to an abnormal Pap smear during a period of 15 years. DESIGN: This is a cross-sectional study. PARTICIPANTS: We investigated retrospectively the incidence of haematological diseases in women aged 21-84 with an abnormal Pap smear who referred to our centre between 2004 and 2019. SETTING: This study was conducted at the university hospital. METHODS: In our analysis, we included women with diagnoses of HL and NHL after the detection of abnormal Pap smears and HPV infections. We excluded patients with a diagnosis of lymphoma preceding the date of the abnormal Pap smear and HPV test. RESULTS: We divided the patients into two groups in order to analyse the standard incidence ratio (SIR): HL patients (19/7,064, 0.26%) and NHL patients (22/7,064, 0.31%). In our sample, we reported a significant risk of developing lymphoma compared to the general population, both for HL and NHL disease, at age <45 years. Regarding HL, the SIR of disease in women <45 years was 4.886 (95% CI 2.775-9.6029) and in women between 45 and 59 years was 2.612 (95% CI 0.96-7.108804). On the other hand, for NHL in women <45 years, we reported an SIR of about 3.007 (95%, CI 1.273-7.101575), in women aged 45-59 years, the SIR was 4.291 (95% CI 2.444-7.534399), and in women aged 60-74 years, the SIR was 3.283 (95% CI 1.054-10.22303). LIMITATIONS: This retrospective analysis was conducted in a single centre in Northern Italy and did not consider all interregional differences existing in the country in terms of HPV genotypes, ethnicity, and population characteristics. Regarding the analysis of SIR for HL and NHL, we did not divide the disease into subtypes because of the small sample of cases. Finally, we considered in our analysis only women with an abnormal Pap smear and not the general population. CONCLUSIONS: Women with chronic and persistent HPV infections may have a higher relative risk of developing lymphoma. This possible association may be caused by the deregulation of the immune system response against HPV and the failure of viral clearance, especially in younger women.

A Longitudinal RCT on the Effectiveness of a Psychological Intervention for Hospital Healthcare Workers During the COVID-19 Pandemic: What We Learned to Date.

The COVID-19 pandemic has led to significant psychological distress among frontline healthcare workers (HCWs), with a particular increase in trauma-related symptoms. This study investigated the longitudinal course of trauma-associated symptoms and behaviors in HCWs and the effectiveness of a brief dialectical behavior therapy (DBT)-informed intervention in mitigating these symptoms over 12 months. The trial included 225 HCWs randomly assigned to one of three groups: no intervention (control), in-person DBT-informed intervention, or online DBT-informed intervention. Over time, a natural decrease in PTSD symptoms was observed in all groups. Contrary to expectations, no difference was found between the control and intervention groups. However, for participants with severe PTSD symptoms, the intervention significantly mitigated their distress. No differences emerged between in-person and online interventions, suggesting equal effectiveness. Females reported higher trauma-related symptoms, while no differences emerged among different professional roles. These findings underscore the importance of targeted interventions for HCWs experiencing severe symptoms and highlight the potential of online modalities. Further research is needed to optimize the deployment of mental health resources within the healthcare setting, particularly during crises.

One year of experience with combined pharmacokinetic/pharmacogenetic monitoring of anti-TNF alpha agents: a retrospective study.

Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (-308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.

Neuropsychological evaluation of phenoconversion risk in REM sleep behaviour disorder: A scoping review.

The objective of this study was to assess the role of cognitive evaluation in the prediction of phenoconversion in polysomnography-confirmed idiopathic or isolated rapid eye movement sleep behaviour disorder, through a scoping review focussing on a longitudinal comprehensive neuropsychological assessment of patients with idiopathic REM sleep behaviour disorder. A literature search (2006-2022) yielded 1034 records, and 20 were selected for analysis. The sample included 899 patients from eight different cohorts and five countries. We extracted data on clinical evolution, mild cognitive impairment diagnosis, neuropsychological tests used, and classification of cognitive domains. Tests, cognitive domains, and mild cognitive impairment definitions were heterogeneous across the studies, precluding a meta-analysis. Ten studies (50%) evaluated the presence of mild cognitive impairment; 14 studies (70%) grouped neuropsychological tests into between three (6 studies, 21.4%) and seven (1 study, 7.1%) cognitive domains. The most frequently used tests were semantic fluency, Stroop colour word test, trail making test A and B, digit span, Rey auditory verbal learning test, and Rey-Osterrieth figure. All except digit span showed a role in predicting phenoconversion. The authors did not consistently assign tests to specific cognitive domains. In conclusion, we discuss methodological differences between the studies and highlight the need for a standardised framework for neuropsychological data acquisition and presentation, based on a multilevel approach covering test selection, domain assignment, and mild cognitive impairment diagnostic criteria.

PEG 400 Ion Suppression in Busulfan Detection by High-Performance Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Busulfan (Bu), an alkylating agent commonly used in chemotherapy and transplantation, exhibits high intraindividual pharmacokinetic variability and possible time-dependent variations in clearance, which complicate therapeutic drug monitoring. Numerous analytical methods have been developed to reduce analysis time and facilitate timely decision-making regarding treatment changes; however, the validation procedures rarely involve analysis of potentially interfering excipients. Macrogol 400 (PEG 400) should be considered as a possible interfering agent in the detection of plasma Bu levels, especially as an ionization suppressor. METHODS: Six intravenous formulations of Bu were compared with identify at least 1 common excipient (PEG 400). During the 176 therapeutic drug monitoring analyses of Bu, one of the PEG 400 specific mass-to-charge ratio transitions was determined using an instrumental method. After coelution with Bu and its internal standard (Bu-d8) was confirmed, all analyses were repeated using a different experimental setup free of ion suppression induced by PEG. The concentration-time profile of PEG 400 was also analyzed. RESULTS: The area under the curve obtained from the 2 data sets was compared and analyzed using Lin concordance correlation coefficient and Bland-Altman plot analysis. The results from the 2 analytical methods were comparable: PEG 400 negatively affected the Bu-d8 coefficient of variation but not the Bu/Bu-d8 ratio. CONCLUSIONS: The possible interference of PEG 400 should be thoroughly investigated, especially with respect to analytical methods that cannot be supported by correction of the stable isotopically labeled internal standard analog.

Clonal Megakaryocyte Dysplasia with Isolated Thrombocytosis Is a Distinct Myeloproliferative Neoplasm Phenotype.

INTRODUCTION: About 15% of people with a myeloproliferative neoplasm (MPN) are identified as MPN, unclassifiable using the 2016 WHO classification. METHODS: We tested whether persons with platelet concentration ≥450 × 10E+9/L, bone marrow megakaryocyte morphology typical of prefibrotic/early myelofibrosis (pre-MF), and no minor criteria of pre-MF should be classified as a distinct MPN subtype, clonal megakaryocyte dysplasia with isolated thrombocytosis (CMD-IT). RESULTS: 139 subjects meet these criteria who we compared with primary myelofibrosis (PMF) including 402 with pre-MF and 521 with overt myelofibrosis. CMD-IT subjects were more likely female and younger. They had lower frequencies of JAK2V617F compared with persons with PMF (55% vs. 70%; p < 0.001) and higher frequencies of CALR mutations (37% vs. 17%; p < 0.001). They also had lower frequency of variations associated with JAK2V617F susceptibility, JAK2 46/1 (35% vs. 47%; p = 0.021), and VEGFA rs3025039 (12% vs. 17%; p = 0.030). Subjects with CMD-IT had lower incidences of thrombotic events compared with those with pre-MF (9.7% vs. 26%; p < 0.001) and longer survival (median, not reached vs. 23 years; HR = 0.34 (0.10, 0.30); p < 0.001). CONCLUSION: Our data indicate CMD-IT is a distinct MPN subtype and should be included in the classification of myeloid neoplasms.

Long-Term Follow-Up of Non-Enhancing Renal Masses on CEUS.

PURPOSE: To determine the natural history and necessity of long-term follow-up of renal masses that do not demonstrate enhancement on contrast-enhanced ultrasound (CEUS). METHODS: This retrospective single-center study was approved by our local IRB and is HIPAA compliant. Exactly 405 patients with 620 non-enhancing renal masses on CEUS from a previously reported study were followed for up to 10 years. Techniques and equipment are described in the original manuscript. Patient charts and imaging studies were reviewed for the change in features. There were 117 (18.6%) patients lost to follow-up leading to 341 patients with 512 lesions. The lesion size, patient age, number of lesions per patient, and Bosniak class assigned at the initial examination was recorded. RESULTS: Mean patient age was 66 ± 12.6 years (range 17-95 years). Average time of follow-up was 58.9 ± 41.7 months (range 1-207 months). There was a mean of 1.5 ± 1.0 lesions per patient (range 1-7 lesions). Lesion size was 24.9 ± 18.2 mm (range 3-161 mm). There were 276 (53.9%) patients with >5-year follow-up and 78 (15.2%) patients with >10-year follow-up. The probability of change within 5 years was 0% (95% CI: 0-0.37 per 100PY) and 10 years 0% (95% CI: 0.0-0.18 per 100PY). Two lesions (0.4%) resolved by 60 months. Five lesions (1.0%) decreased in size. Four lesions (0.8%) increased in size >20% during the follow-up period but remained benign on subsequent imaging. CONCLUSION: Any non-enhancing renal mass on CEUS can be classified as benign.

Liver Fat Quantification With Ultrasound: Depth Dependence of Attenuation Coefficient.

OBJECTIVES: The primary aim was to estimate the influence of various depths on ultrasound attenuation coefficient (AC) of multiple vendors in the liver. The secondary aim was to evaluate the impact of region of interest (ROI) size on AC measurements in a subset of participants. METHODS: This Institutional Review Board (IRB)-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study was carried out in two centers using AC-Canon and AC-Philips algorithms and extracting AC-Siemens values from ultrasound-derived fat fraction algorithm. Measurements were performed positioning ROI upper edge (3 cm size) at 2, 3, 4, 5 cm from the liver capsule with AC-Canon and AC-Philips and at 1.5, 2, 3 cm with Siemens algorithm. In a subset of participants, measurements were obtained with 1 and 3 cm ROI size. Univariate and multivariate linear regression models and Lin's concordance correlation coefficient (CCC) were used for statistical analysis as appropriate. RESULTS: Three different cohorts were studied. Sixty-three participants (34 females; mean age: 51 ± 14 years) were studied with AC-Canon, 60 (46 females; mean age: 57 ± 11 years) with AC-Philips, and 50 (25 females; 61 ± 13 years) with AC-Siemens. There was a decrease in AC values per 1 cm increase in depth in all. In multivariable analysis, the coefficient was -0.049 (-0.060; -0.038 P < .001) with AC-Canon, -0.058 (-0.066; -0.049 P < .001) with AC-Philips and -0.081 (-0.112; -0.050 P < .001) with AC-Siemens. AC values with 1 cm ROI were significantly higher than those obtained with 3 cm ROI at all depths (P < .001) but the agreement between AC values obtained with different ROI size was excellent (CCC 0.82 [0.77-0.88]). CONCLUSIONS: There is depth dependence in AC measurement that affects results. A standardized protocol with fixed ROI's depth and size is needed.

New International Guidelines and Consensus on the Use of Lung Ultrasound.

Following the innovations and new discoveries of the last 10 years in the field of lung ultrasound (LUS), a multidisciplinary panel of international LUS experts from six countries and from different fields (clinical and technical) reviewed and updated the original international consensus for point-of-care LUS, dated 2012. As a result, a total of 20 statements have been produced. Each statement is complemented by guidelines and future developments proposals. The statements are furthermore classified based on their nature as technical (5), clinical (11), educational (3), and safety (1) statements.

Genital perception and vulvar appearance after childbirth: a cohort analysis of genital body image and sexuality.

PURPOSE: The mode of delivery influences the genital image and perception, especially regarding the effects of delivery on sexual life and intercourse. The current literature has not adequately investigated the relationship between delivery and genital appearance. The aim of the study is to determine whether the mode of delivery changes the genital perception of the woman and, in doing so, influences their acceptance. The secondary aim is to analyze the impact of genital appearance on sexuality. METHODS: A prospective survey regarding genital appearance and the impact of delivery mode on vulvar perception was conducted in patients 6 weeks after childbirth. We enrolled 365 women for evaluation, divided into three groups: spontaneous vaginal delivery (SVD 295 women 80.82%), operative vaginal delivery (OVD 36 women 9.86%) and cesarean section (CS 34 women 9.31%). RESULTS: There was a statistically significant difference in the frequency of vulva inspection and in the perception of genital modifications among the groups (p < 0.001 and p < 0.001, respectively). The perception of overall genital modifications was significantly correlated with the frequency of inspection (p = 0.004) and the delivery mode (p = 0.0002). CONCLUSION: Mode of delivery may influence the genital perception and appearance of genitalia without a decrease of sexual life and daily activity in childbirth.

HLA-G as a prognostic marker in stage II/III colorectal cancer: not quite there yet.

Identifying innovative molecules involved in the tumor immune escape process could help refine the survival stratification of colorectal cancer (CRC) patients. HLA-G, a non-classical HLA molecule, physiologically involved in tolerogenic mechanisms, has recently emerged as a relevant prognostic marker in other tumor types, but ambiguous data are reported in the CRC setting. This study aims to evaluate the HLA-G expression and prognostic potential in a series of stage II/III CRCs. HLA-G expression was evaluated in 100 pT3 CRC cases by means of immunohistochemistry using the 4H84 and MEM-G/2 monoclonal antibodies. We observed heterogeneous expression of HLA-G showing different ranges: 4H84 expression ranged from > 1 to 40%-median 7%; MEM-G/2 expression ranged from 20 to 90%-median 50%. HLA-G positivity (any intensity > 1%) varied according to the antibody employed, identifying: 8 4H84 positive, 34 MEM-G/2 positive, 6 double-positive and 52 negative cases. Correlation with clinico-pathologic data showed a significant association with a poor tumor differentiation in stage III right-sided CRC subgroup (p = 0.043), while no other pathologic variable was significantly associated. Survival analysis revealed a reduced disease-free survival rate (HR 4.304613; p = 0.031) in the subgroup of CRC-related death cases, while no correlations were observed considering the whole series and the overall survival. In conclusion, HLA-G is a promising CRC prognostic marker however much work is still required regarding technical aspects and evaluation of expression.

A mini-whole lung lavage to treat autoimmune pulmonary alveolar proteinosis (PAP).

BACKGROUND: PAP is an ultra-rare respiratory syndrome characterized by the accumulation of surfactant within the alveoli. Whole lung lavage (WLL) is the current standard of care of PAP, however it is not a standardized procedure and the total amount of fluid used to wash each lung is still debated. Considering ICU hospitalization associated risks, a "mini-WLL" with anticipated manual clapping and reduced total infusion volume and has been proposed in our center. The aim of the study is to retrospectively analyze the efficacy of mini-WLL compared to standard WLL at the Pavia center. METHODS: 13 autoimmune PAP patients eligible for WLL were included: 7 patients were admitted to mini-WLL (9 L total infusion volume for each lung) and 6 patients underwent standard WLL (14 L of infusion volume). Functional data (VC%, FVC%, TLC%, DLCO%) and alveolar-arterial gradient values (A-aO2) were collected at the baseline and 1, 3, 6, 12, 18 months after the procedure. RESULTS: A statistically significant improvement of VC% (p = 0.013, 95%CI 3.49-30.19), FVC% (p = 0.016, 95%CI 3.37-32.09), TLC% (p = 0.001, 95%CI 7.38-30.34) was observed in the mini-WLL group in comparison with the standard WLL group, while no significant difference in DLCO% and A-aO2 mean values were reported. CONCLUSION: Mini-WLL has demonstrated higher efficacy in ameliorating lung volumes, suggesting that a lower infusion volume is sufficient to remove the surfactant accumulation and possibly allows a reduced mechanical insult of the bronchi walls and the alveoli. However, no statistically significant differences were found in terms of DLCO% and Aa-O2.

Renal Outcomes of Dialysis-Dependent Acute Kidney Injury in Noncritically Ill Patients: A Retrospective Study.

INTRODUCTION: Acute kidney injury (AKI) is a common complication among hospitalized patients, potentially affecting short- and long-term clinical outcomes. In this retrospective study, we evaluated renal outcomes in noncritically ill patients who required acute hemodialysis (HD) because of an AKI episode occurring during hospitalization. METHODS: Sixty-three hemodynamically stable patients with AKI undergoing acute intermittent HD were included. Kidney function was evaluated at baseline control (pre-AKI), at AKI diagnosis and during the follow-up. According to serum creatinine and the estimated glomerular filtration rate (eGFR), we defined three clinical conditions: renal recovery, different stages of acute kidney disease (AKD), and chronic kidney disease (CKD). RESULTS: Among the 63 patients evaluated, 34 patients (54%) had a history of CKD. Six patients (10%) presented early full renal recovery. HD treatment was stopped in 38 patients (60%), while 25 patients (40%) required maintenance HD. Dialysis-independent patients presented lower comorbidity and higher baseline eGFR and delta creatinine, compared to dialysis-dependent patients. Baseline CKD, previous AKI episodes, and parenchymal causes of AKI were associated with a significant risk of dialysis dependence. At 1-month control, 15 patients (39%) presented AKD stage 0, 6 patients (16%) AKD stage 1, and 17 patients (44%) AKD stage 2-3. At 3-month control, 29 out of 38 patients recovering from AKI (76%) presented CKD. AKD stage was significantly correlated with the risk of CKD development, which, resulted higher in patients with lower baseline eGFR. CONCLUSIONS: AKI might represent a risk factor for the development of chronic kidney damage, even in noncritically ill patients.

A Pre-Release Algorithm With a Confidence Map for Estimating the Attenuation Coefficient for Liver Fat Quantification.

OBJECTIVES: To compare the estimates of attenuation coefficient (AC) for liver fat quantification between 2 Ultrasound systems and to evaluate the quality measure of a pre-released software. METHODS: AC were obtained in 30 participants in this single-center IRB-approved, HIPAA compliant study. Images were obtained on the Philips Epiq Elite system using experimental software and the Canon Medical Systems Aplio i800 with released software. Five AC measurements were taken and the median and IQR/M were calculated. Region of interest placement was based on a confidence map. ROI was at the same depth and size for each system. The concordance was estimated using the Lin's concordance correlation coefficient (CCC), the r Pearson's correlation coefficient, the bias-correction factor (Cb), and the Bland-Altman method. RESULTS: The ACs varied from 0.45 to 1.0 dB/cm/MHz for the Philips system and 0.30 to 0.96 dB/cm/MHz for the Canon system. The CCC (95% CI) was 0.792 (0.666-0.918), Pearson's r was 0.839 with Cb of 0.944, and the mean difference was 0.03 (-0.101; 0.162) suggesting the 2 methods are considered to be in agreement. Based on a Philips confidence map to determine the best location for performing the measurements, a depth of 3.5 to 4.0 cm from the liver capsule was determined, which might be significantly different than that of the Canon system. CONCLUSIONS: Estimation of the AC of the 2 systems showed a high agreement, that is, a similar trend. Assessment of the placement of the measurement box based on the quality of the measurement might be different between the 2 systems.

Treatment of partial rotator cuff lesions is associated with a higher frequency of post-operative shoulder stiffness. A prospective investigation on the role of surgery-related risk factors for this complication.

PURPOSE: Post-operative shoulder stiffness (SS) is a common complication after arthroscopic rotator cuff (RC) repair. The aim of this prospective study is to evaluate the role of surgical risk factors in the development of this complication, with special focus on the characteristics of the RC tears. METHODS: Two-hundred and twenty patients who underwent arthroscopic RC repair for degenerative posterosuperior RC tears were included. Surgery-related risk factors for development of post-operative SS belonging to the following five categories were documented and analyzed: previous surgery, RC tear characteristics, hardware and repair type, concomitant procedures, time and duration of surgery. The incidence of post-operative SS was evaluated according to the criteria described by Brislin and colleagues. RESULTS: The incidence of post-operative SS was 8.64%. The treatment of partial lesions by tear completion and repair technique was significantly associated with development of post-operative SS (p = 0.0083, pc = 0.04). A multivariate analysis revealed that treatment of partial lesions in patients younger than 60 years was associated to a higher risk of developing post-operative SS (p = 0.007). Previously known pre-operative risk factors such as female sex and younger age were confirmed. No other significant associations were documented. CONCLUSION: The treatment of partial lesions of the RC may lead to a higher risk of post-operative SS than the treatment of complete lesions, in particular in patients younger than 60 years. Possible explanations of this finding are the increased release of pro-inflammatory cytokines caused by the additional surgical trauma needed to complete the lesion and the different pain perception of the subgroup of patients who require surgical treatment already for partial tears. EVIDENCE: A higher risk of post-operative SS should be expected after tear completion and repair of partial lesions, especially in young patients. Appropriate pre-operative counseling and post-operative rehabilitation should be considered when approaching this subgroup of RC tears. LEVEL OF EVIDENCE: Prognostic study, level II.

ABCC4 single-nucleotide polymorphisms as markers of tenofovir disoproxil fumarate-induced kidney impairment.

Recently, the use of antiretroviral drug tenofovir disoproxil fumarate (TDF) is increased, thanks to the new co-formulation with doravirine, the availability of booster-free regimens, and its advantageous lipid-lowering effect. The aim of our study was to identify genetic markers that contribute to assess the risk of TDF-related renal toxicity. We have retrospectively investigated, in 179 HIV positive patients treated with TDF, the association between the main variants in ABCC2, ABCC4, and ABCC10 genes and four safety endpoints, three clinically relevant as renal outcomes and a higher tenofovir plasma concentration. In patients with an annual eGFR decline >5 mL/min/1.73 m2 a difference in genotype frequencies was observed for ABCC10 c.1875 + 526 G>A (3 subjects AA vs. 44 GG + GA, p = 0.045). In patients with an eGFR decrement >25%, plus a decline in GFR category and TDF discontinuation, a difference was observed for ABCC4 c.*38T>G (35 subjects TG + GG vs. 18 TT, p = 0.052). At univariate analysis OR was 1.39 [(95% CI 1.00-1.96) p = 0.054] and at multivariate analysis OR was 1.49 [(95% CI 1.00-2.22) p = 0.049]. The stronger associations were found between the tenofovir accumulation and ABCC4 c.*38T>G and c.3348G>A: the percentage of these patients was higher in the TG + GG (p = 0.011) and in the AA (p = 0.004) genotype, respectively. The logistic regression analysis confirmed these significant relationships. No significant association was observed in patients with eGFR < 60 mL/min/1.73m2 and with the studied ABCC2 polymorphisms. Our results show a major role for a combined determination of ABCC4/ABCC10 variants as an indicator of tenofovir toxicity in the clinical practice.