Less is More? Antibiotic Treatment Duration in Pseudomonas aeruginosa Ventilator-associated Pneumonia

alexandrossfakianakis shared this article with you from Inoreader Less is More? Antibiotic Treatment Duration in Pseudomonas aeruginosa Ventilator-associated Pneumonia via Clinical Infectious Diseases Advance Access Abstract Recommended antimicrobial treatment durations for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa have evolved over the past few decades. In this Viewpoint, we provide a narrative review of landmark trials investigating antimicrobial treatment durations for VAP caused by P. aeruginosa, and appraise iterations of expert consensus guidelines based on these data. We highligh t strengths and weaknesses of existing data on this topic and provide recommendations for future avenues of study. View on Web

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Incidence of occult cleft palate on prenatal magnetic resonance images obtained for non-cleft indications

alexandrossfakianakis shared this article with you from Inoreader Incidence of occult cleft palate on prenatal magnetic resonance images obtained for non-cleft indications via International Journal of Oral and Maxillofacial Surgery via MedWorm.com Prenatal diagnosis of craniofacial anomalies has improved family education and preparedness. Isolated cleft palate, however, remains difficult to identify sonographically. The aim of this study was to investigate the rate of incidental cleft palate identified on fetal magnetic resonance imaging (MRI) following the ultrasound detection of non-cleft abnormalities. This was a retrospective study of pregnant women who had fetal MRI performed between 2003 and 2017. To be included, the woman had to have been referred for fetal imaging for a non-cleft indication, with subsequent identification of an isolated cleft palate on MRI. (Source: International Journal of Oral and Maxillofacial Surgery) View on Web

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Somatic loss of the Y chromosome is associated with arsenic exposure among Bangladeshi men

alexandrossfakianakis shared this article with you from Inoreader Somatic loss of the Y chromosome is associated with arsenic exposure among Bangladeshi men via International Journal of Epidemiology - Advance Access Abstract Background Arsenic exposure increases the risk of several cancers in humans and contributes to genomic instability. Somatic loss of the Y chromosome (LoY) is a potential biomarker of genomic instability and cancer risk. Smoking is associated with LoY, but few other carcinogens have been investigated. We tested the cross-sectional association between arsenic exposure and LoY in leukocytes among genotyped Bangladeshi men (age 20–70 years) from the Health Effects of Arsenic Longitudinal Study. Methods We extracted the median of logR-ratios from probes on the Y chromosome (mLRR-chrY) from genotyping arrays (n = 1364) and estimated the percentage of cells with LoY (% LoY) from mLRR-chrY. We evaluated the association between arsenic exposure (measured in drinking water and urine) and LoY using multivariable linear and logistic regression models. T he association between LoY and incident arsenic-induced skin lesions was also examined. Results Ten percent of genotyped men had LoY in at least 5% of cells and % LoY increased with age. Among men randomly selected for genotyping (n = 778), higher arsenic in drinking water, arsenic consumed and urinary arsenic were associated with increased % LoY (P = 0.006, P = 0.06 and P = 0.13, respectively). LoY was associated with increased risk of incident skin lesions (P = 0.008). Conclusion Arsenic exposure was associated with increased LoY, providing additional evidence that arsenic contributes to genomic instability. LoY was associated with developing skin lesions, a risk factor for cancer, suggesting that LoY may be a biomarker of susceptibility in arsenic-exposed populations. The effect of arsenic on somatic events should be further explored in cancer-prone tissue types. View on Web

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Control of Pre‐phonatory Glottal Shape by Intrinsic Laryngeal Muscles

alexandrossfakianakis shared this article with you from Inoreader Control of Pre‐phonatory Glottal Shape by Intrinsic Laryngeal Muscles via The Laryngoscope Complex interactions between intrinsic laryngeal muscles and their effects on the vocal fold pre-phonatory posture were studied. The thyroarytenoid (TA) was primarily responsible for the rectangular shape of the adducted glottis with synergistic contribution from the lateral cricoarytenoid (LCA). The cricothyroid (CT) contributed minimally to vocal fold medial shape but elongated the glottis. Objectives Surgical manipulations to treat glottic insufficiency aim to restore the physiologic pre-phonatory glottal shape. However, the physiologic pre-phonatory glottal shape as a function of interactions between all intrinsic laryngeal muscles (ILMs) has not been described. Vocal fold posture and medial surface shape were investigated across concurrent activation and interactions of thyroarytenoid (TA), cricothyroid (CT), and lateral cricoarytenoid/interarytenoid (LCA/IA) muscles. Study Design In vivo canine hemilarynx model. Methods The ILMs were stimulated across combinations of four graded levels each from low-to-high activation. A total of 64 distinct medial surface postures (4 TA × 4 CT × 4 LCA/IA levels) were captured using high-speed video. Using a custom 3D interpolation algorithm, the medial surface shape was reconstructed. Results Combined activation of ILMs yielded a range of unique pre-phonatory postures. Both LCA/IA and TA activation adducted the vocal fold but with greater contribution from TA. The transition from a convergent to a rectangular glottal shape was primarily mediated by TA muscle activation but LCA/IA and TA together resulted in a smooth rectangular glottis compared to TA alone, which caused rectangular glottis with inferomedial bulging. CT activation resulted in a lengthened but slightly abducted glottis. Conclusions TA was primarily responsible for the rectangular shape of the adducted glottis with synergistic contribution from the LCA/IA. CT contributed minimally to vocal fold medial shape but elongated the glottis. These findings further refine laryngeal posture goals in surgical correction of glottic insufficiency. Level of Evidence N/A, Basic science Laryngoscope, 2022 View on Web

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Renal function in abdominal neuroblastoma patients undergoing proton radiotherapy

alexandrossfakianakis shared this article with you from Inoreader Renal function in abdominal neuroblastoma patients undergoing proton radiotherapy via Pediatric Blood & Cancer Abstract Background The purpose of this study is to analyze renal function outcomes in abdominal neuroblastoma patients undergoing proton therapy (PT). Procedure From 2011 to 2019, two single-institution Institutional Review Board-approved protocols prospectively enrolled neuroblastoma patients for data collection. To assess renal function, serum creatinine (Cr), blood urea nitrogen (BUN), and creatinine clearance (CrCl) before proton therapy (pre-PT) were compared with the values at last follow-up. Results A total of 30 children with abdominal neuroblastoma with median age 3.5 years (range, 0.9–9.1) at time of PT were included in this study. All patients underwent chemotherapy and resection of primary tumor prior to PT. Two patients required radical nephrectomy. Median follow-up after PT was 35 months. Mean dose to ipsilateral and contralateral kidney was 13.9 and 5.4 Gy, respectively. No patients developed hypertension or renal dysfunction during follow-up. There was no statistically significant change in serum BUN (p = .508), CrCl (p = .280), or eGFR (p = .246) between pre-PT and last follow-up. Conclusion At a median follow-up of almost 3 years, renal toxicity was uncommon after PT. Longer follow-up and larger patient cohort data are needed to further assess impact of PT on renal function in this population. View on Web

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Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant

alexandrossfakianakis shared this article with you from Inoreader Outcomes of patients who underwent treatment for anti‐HLA donor‐specific antibodies before receiving a haploidentical hematopoietic cell transplant via Pediatric Blood & Cancer Abstract Pediatric and adolescent and young adult (AYA) patients who receive many blood product transfusions, such as individuals with sickle cell disease (SCD), severe aplastic anemia (SAA) or indolent hematologic malignancies, are at high risk for developing donor-specific antibodies (DSA). DSAs with mean fluorescence intensity (MFI) greater than 5000 have been associated with significant graft failure, but lower MFI values between 2000 and 5000 may result in poor graft function after hematopoietic cell transplant (HCT). Desensitization strategies have been developed to reduce the DSA burden in HCT recipients before graft infusion, but the experience with these strategies in the pediatric and AYA populations is not well described in the literature. Here, we describe our experience with successful desensitization by using a combination of treatment strategies in five pediatric and AYA patients, including a novel use of daratumumab in a young adult patient who had refractory DSAs and had s uffered serious side effects from conventional desensitization strategies. The presence of elevated DSAs in pediatric and AYA recipients of a human leukocyte antigen (HLA)-mismatched haploidentical HCT can be overcome by a multipronged treatment strategy. View on Web

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Therapeutic targeting of DNA damage repair pathways guided by homologous recombination deficiency scoring in ovarian cancers

alexandrossfakianakis shared this article with you from Inoreader Therapeutic targeting of DNA damage repair pathways guided by homologous recombination deficiency scoring in ovarian cancers via Fundamental & Clinical Pharmacology Abstract The susceptibility of cells to DNA damage and their DNA repair ability are crucial for cancer therapy. Homologous recombination is one of the major repairing mechanisms for DNA double-strand breaks. Approximately half of ovarian cancer (OvCa) cells harbor homologous recombination deficiency (HRD). Considering that HRD is a major hallmark of OvCas, scholars proposed HRD scoring to evaluate the HRD degree and guide the choice of therapeutic strategies for OvCas. In the last decade, synthetic lethal strategy by targeting poly (ADP-ribose) polymerase (PARP) in HR-deficient OvCas has attracted considerable attention in view of its favorable clinical effort. We therefore suggested that the uses of other DNA damage/repair-targeted drugs in HR-deficient OvCas might also offer better clinical outcome. Here, we reviewed the current small molecule compounds which targeted DNA damage/repair pathways, and discussed the HRD scoring system to guide their clinical uses. View on Web

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Two stage, hybrid endovascular and open surgical approach to treat difficult carotid body tumors

alexandrossfakianakis shared this article with you from Inoreader Two stage, hybrid endovascular and open surgical approach to treat difficult carotid body tumors via Head & Neck Abstract Objective Present the feasibility, applicability, clinical effectiveness, and results of complicated Shamblin II or III carotid body tumors treated with a two-stage hybrid surgical approach. Materials and Methods Retrospective, observational, cross-sectional, descriptive study of the successful treatment of 16 cases of difficult Shamblin II or III carotid body tumors, consisting of a two-stage surgical approach. We conducted a retrospective, observational, cross-sectional, descriptive study of a series of patients with complicated Shamblin II or III carotid body tumors, which we treated with a two-stage hybrid surgical procedure, in which we first placed a carotid endoprosthesis and 45 days later performed surgical resection of the tumor, following our originally published technique. This study was conducted from February, 2007 to November, 2019, in a third level care centre. Results We treated 16 patients with a mean age of 50.5 years. All resided at more than 2000 meters above sea level. In all 16 a complete resection was performed. The average duration of surgery was 103.9 min, the average intraoperative bleeding was 69 ml. There were three cases of neuropraxia. The ansa cervicalis nerve had to be sectioned in three cases and there was permanent upper laryngeal nerve injury in two cases. There were no permanent cerebrovascular injuries from placement of the endoprostheses. One patient developed transient cerebral ischaemia (TIA) with no long-term sequelae. There were two cases of asymptomatic late occlusion of the endoprostheses. The average initial volume of the tumors was 54.4 cc. The average tumor volume 35 days after implant of the endoprosthesis was 30.9 cc. Symptoms Presence of tumors in the neck in all cases and two cases of dysphagia. Conclusion This two-stage hybrid technique allowed for the complete resection of difficult Shamblin II or III carotid body tumors, with one case of TIA and two with permanent upper laryngeal nerve injuries and without mortality. View on Web

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Low postoperative lymphocyte count increases risk of progression in human papillomavirus associated oropharyngeal cancer

alexandrossfakianakis shared this article with you from Inoreader Low postoperative lymphocyte count increases risk of progression in human papillomavirus associated oropharyngeal cancer via Head & Neck Abstract Background We aim to explore the prognostic role of absolute lymphocyte count (ALC) before, during, and after treatment on oncologic outcomes in human papillomavirus associated oropharyngeal cancer (HPV(+)OPSCC). Methods Retrospective cohort at a tertiary center, 2006–2018. Multivariable Cox regressions were used to determine the effect of ALC on risk of progression. Univariate linear regression was performed to determine clinical factors associated with lower ALC. Results All 197 patients underwent primary surgery. Mean (SD) ALC nadirs (×109 cells/L) were: baseline (N = 149): 1.69 (0.56); postoperative (N = 126): 1.58 (0.59); post-RT (N = 141): 0.68 (0.35) and long-term (N = 105): 0.88 (0.37). Lower baseline ALC nadir was associated with worse overall survival (HR 3.85, 95%CI: 1.03–14.29, p = 0.04). Lower postoperative ALC nadir was associated with higher risk of progression (HR 2.63, 95%CI: 1.04–6.67, p = 0.04). Conclusions Lower baseline ALC is associated with worse survival, whereas lower postoperative ALC is associated with increased risk of progression in surgically treated HPV(+)OPSCC. Level of Evidence 3 View on Web

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Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection

alexandrossfakianakis shared this article with you from Inoreader Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection via Brain Pathology The human frontal cortex of SAD, FAD, and APOEch is characterized by specific astrocyte phenotypes which define the integrity of Gliovascular unit. ApoE3ch mutation in an E280A carrier might be related to the promotion of astrocytic and gliovascular homeostatisis despite the massive load of Aβ. This study provides new insights into the potential relevance of the gliovascular unit in the development and protection of AD. Abstract In response to brain insults, astrocytes become reactive, promoting protection and tissue repair. However, astroglial reactivity is typical of brain pathologies, including Alzheimer's disease (AD). Considering the heterogeneity of the reactive response, the role of astrocytes in the course of different forms of AD has been underestimated. Colombia has the largest human group known to have familial AD (FAD). This group carries the autosomal dominant and fully penetrant mutation E280A in PSEN1, which causes early-onset AD. Recently, our group identified an E280A carrier who did not develop FAD. The individual was homozygous for the Christchurch mutation R136S in APOE3 (APOEch). Remarkably, APOE is the main genetic risk factor for developing sporadic AD (SAD) and most of cerebral ApoE is produced by astroglia. Here, we characterized astrocyte properties related to reactivity, glutamate homeostasis, and structural integrity of the gliovascular unit (GVU), as factors that could underlie the pathogenesis or protection of AD. Specifically, through histological and 3D microscopy analyses of postmortem samples, we briefly describe the histopathology and cytoarchitecture of the frontal cortex of SAD, FAD, and APOEch, and demonstrate that, while astrodegeneration and vascular deterioration are prominent in SAD, FAD is characterized by hyperreactive-like glia, and APOEch displays the mildest astrocytic and vascular alterations despite having the highest burden of Aβ. Notably, astroglial, gliovascular, and vascular disturbances, as well as brain cell death, correlate with the specific astrocytic phenotypes identified in each condition. This study provides new insights into the potential relevance of the gliovasculature in the development and protection of AD. To our knowledge, this is the first study assessing the components of the GVU in human samples of SAD, FAD, and APOEch. View on Web

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