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A term large-for-gestational-age neonate was born via an uncomplicated normal vaginal delivery at a peripheral hospital. The neonate was referred to our tertiary centre due to concerns regarding the appearance of the right hand. On examination at 6 hours of life there was cyanotic discolouration

Implementation of evidence-based practice (EBP) is essential for ensuring high-quality nursing care. In Portugal, nurses are responsible for care delivery to patients who require peripheral intravenous access. However, recent authors emphasized the predominance of a culture based on outdated professional vascular access practices in Portuguese clinical settings. Thus, the aim of this study was to map the studies conducted in Portugal on peripheral intravenous catheterization. A scoping review was conducted based on the Joanna Briggs Institute recommendations, with a strategy adapted to different scientific databases/registers. Independent reviewers selected, extracted, and synthesized the data. Of the 2128 studies found, 26 were included in this review, published between 2010 and 2022. Previous research shows that Portuguese nurses' implementation of EBP was found to be relatively low overall, while most studies did not attempt to embed EBP change into routine care. Although nurses are responsible for implementing EBP at an individual patient level, the studies conducted in Portugal report nonstandardized practices among professionals, with significant deviations from recent evidence. This reality, combined with Portugal's absence of government-endorsed evidence-based standards for peripheral intravenous catheter (PIVC) insertion and treatment and vascular access teams, may explain the country's unacceptably high incidence of PIVC-related complications reported over the last decade.

Melanocortin-4 receptor (MC4R), the most important monogenetic cause of human metabolic disorders, has been of great interest to many researchers in the field of energy homeostasis and public health. Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes, previous studies have mainly focused on the central, rather than the peripheral, roles of MC4R. Thus, the local expression of MC4R and its behavioral regulation remain unclear. In an attempt to shed light on different directions for future studies of MC4R signaling, we review in this article a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons.

Aim the aim of this contemporary paper is to try and demonstrate that infants who are born prematurely, before 32 weeks’ gestation, react to sepsis by widening the gradient between core (oesophageal) and peripheral (foot) temperature. Design Exploratory descriptive, non-experimental observational prospective study on infants born at or before 32 weeks’ gestation, admitted to the neonatal intensive care. Method All infants born at or before 32 weeks’ gestation, admitted to the NICU, received parental consent were enrolled in the study. Conclusion Inconclusive results. Although this study does not show any significant differences between core and peripheral temperature, discussing issues which were raised whilst conducting the study may have some benefits to other researchers. The study would have continued, giving us a larger cohort of infants if Philips had not discontinued the manufacturing of the InnerSense oesophageal temperature probe.

Publisher Summary This chapter discusses the epidemiology and classification of traumatic peripheral nerve injuries, the effects of these injuries on nerve and muscle, and how electrodiagnosis is used to help classify the injury. Traumatic injury to peripheral nerves results in considerable disability across the world. In peacetime, peripheral nerve injuries result commonly from motor vehicle accident trauma and less commonly from penetrating trauma, such as falls and industrial accidents. If plexus and root injuries are also included, the incidence is about 5%. In the upper limb, the nerve injured most commonly is the radial nerve, followed by the ulnar and median nerves. Lower limb peripheral nerve injuries are less common, and the sciatic nerve is injured most frequently, followed by the peroneal and rarely the tibial or femoral nerves. Peripheral nerve injuries may be seen in isolation, but they also often accompany central nervous system (CNS) trauma. Peripheral nerve injuries have significant impact, as they impede the recovery of function and return to work. There is also a risk of secondary disability from falls, fractures, or other injuries.

Background : The utility, diagnostic yield and accuracy of lung biopsies in pediatric oncology patients are variable. Here we describe our preliminary results using intraoperative electromagnetic navigation bronchoscopy (IENB) for peripheral lung lesions to increase the surgical yield and accuracy in pediatric oncology patients. Methods : From May 2018 until October 2020 all surgical lung biopsies on pediatric oncology patients were performed using IENB technology. IENB and tattooing with methylene blue dye, Indocyanine green dye or both followed by Video-assisted Thoracoscopic Surgery (VATS) was performed in the same setting. Data were collected retrospectively. Data points included diagnosis, technical success, pathologic diagnosis and alteration in treatment management and complications. Results : A total of 10 biopsy procedures were performed on 8 patients during the study. The youngest patient was 7 years old. All had successful IENB with tattooing. All biopsies were diagnostic. No procedures were converted to open. There were no technical failures or procedure complications. One patient had a total of 11 biopsies, 6 from the right lung and 5 from the left, performed at 2 separate procedures. Another had 2 biopsies, one from the right lung and one from the left performed at the same operation. In 7 of the 8 patients treatment changes were made based on results of their biopsy. Conclusion : Here we present the first described experience of IENB and tattooing of peripheral lung lesions in the pediatric population. We have shown that IENB for peripheral lung lesion localization is a safe and effective technique in pediatric oncology.

Introduction It is purported that patients with peripheral arterial disease (PAD) may have impaired cognitive function due to concomitant cerebrovascular disease. Such disease may be clinically unrecognized but can impact on a patient's recovery and prognosis. The purpose of this systematic review was to interrogate the body of published evidence on undiagnosed cognitive impairment in PAD patients. Methods A search strategy encompassing MEDLINE, Scopus, and the Cochrane database was developed to identify peer-reviewed articles examining rates of undiagnosed cognitive impairment in patients with PAD. The following search terms were used: ‘PAD’; ‘PVD’; ‘dementia’; ‘peripheral arterial disease’; ‘peripheral vascular disease’; ‘cognitive impairment'; 'alzheimer's disease’ and ‘cogniti∗’. Our primary outcome was the incidence of previously undiagnosed cognitive impairment in patients with PAD. Results The initial search yielded 1492 titles. After removal of duplicates, 961 abstracts were screened to ascertain if they were eligible for inclusion. Abstract review yielded 62 full texts for further evaluation. Eight case–control studies consisting of 1161 patients were included. Analysis of these studies revealed that PAD patients performed significantly worse than controls on a variety of neuropsychological measures. Conclusion Our review indicated that PAD patients are more likely to suffer with undiagnosed cognitive impairment than healthy controls.

Contrary to many international settings, there are no clinical guidelines for peripheral intravenous catheter (PIVC) insertion and maintenance in Portugal. We sought to derive an international consensus on a PIVC bundle that could guide Portuguese nurses’ clinical decision-making in this scope. Methods: Two international vascular access specialist groups participated in an online Delphi panel. During the first round, specialists (n = 7) were sent a summary report from a previous observational study conducted in a surgical ward in Portugal. Based on the report findings, specialists were asked to provide five to eight PIVC insertion and maintenance interventions. Then, another set of specialists (n = 7) scored and revised the recommendations until a consensus was reached (≥70% agreement). The PIVC bundle was made available and discussed with the surgical ward’s nurses. Results: After three rounds, a consensus was achieved for five evidence-informed interventions: (i) involve the person and assess the peripheral venous network; (ii) maintain an aseptic no-touch technique; (iii) ensure proper catheter dressing and fixation; (iv) perform catheter flush & lock; (v) test the peripheral venous catheter’s functionality and performance at each shift. Conclusion: The final version of the PIVC bundle achieved consensus among international experts. Despite the positive feedback provided by the ward nurses, future studies are warranted to assess its effectiveness in standardizing PIVC care delivery and its potential implications for care outcomes in Portuguese clinical settings.

Intravascular lithotripsy (IVL) is a novel tool for the treatment of calcified vascular stenosis. Recently, IVL has been successfully used for modification of calcified plaque in coronary and lower extremity peripheral arteries with promising results. However, experience in subclavian and innominate peripheral arterial disease is limited. This study aims to report our initial experience of IVL use in calcified subclavian and innominate vasculature.This was a retrospective review of all the cases of IVL performed in subclavian and innominate arteries at the Miriam Hospital, Providence, between January 2019 and May 2020. Data on the baseline and procedural characteristics were collected. The primary endpoint was procedural success defined as residual stenosis of20% after stenting. Other endpoints of interest were; 1) procedural complications, including dissections, perforations, abrupt closure, slow or no-reflow, thrombosis, and distal embolization; 2) in-hospital major adverse cardiac events (MACE) defined as a composite of death, myocardial infarction, or stroke/transient ischemic attack.A total of 7 patients with 13 lesions undergoing IVL were included. Of these, 5 (71%) were women, the mean age was 74.6 ± 12.9, and the mean BMI was 25.1 ± 6.7. IVL was successfully delivered to all the target lesions with a mean 252.9 ± 54.4 pulses delivered per patient. Procedural success was achieved in 100% of the treated lesions. No procedure-related complications or in-hospital MACE occurred in any of the patients.In this single-center retrospective analysis, IVL facilitated acute procedural success without any procedural complications in severely calcified stenoses of the subclavian and innominate vasculature. Larger studies with an active comparator and longer follow-up are needed to establish the relative efficacy and safety of IVL use in this vascular bed.

Observing the dynamic progress of the brain in response to peripheral nerve stimulation as a whole is the basis for a deeper understanding of overall brain function; however, it remains a great challenge. In this work, a novel mini-invasive orthogonal recording method is developed to observe the overall evoked cortex potential (ECP) in rat brain. A typical ECP atlas with recognizable waveforms in the rat cortex corresponding to the median, ulnar, and radial nerve trunks and subdivided branches is acquired. Reproducible exciting temporal–spatial progress in the rat brain is obtained and visualized for the first time. Changes in the ECPs and exciting sequences in the cortex four months after median nerve transection are also observed. The results suggest that the brain’s response to peripheral stimulation has precise and reproducible temporal–spatial properties. This resource can serve as a testbed to explore the overall functional interaction and dynamic remodeling mechanisms between the peripheral and central nervous systems over time.

Ameloblastic fibro-odontoma (AFO) is a rare benign mixed odontogenic tumor that affects children and young adults. AFO occurs mainly intraosseous. Extraosseous AFO is extremely rare. We report 2 cases of rare peripheral ameloblastic fibro-odontoma in 2- and 12-year-old female patients. Microscopic examination revealed a benign proliferation of odontogenic epithelium associated with a dentinoid material distributed within a cell-rich mesenchymal stroma resembling dental papilla. Simple surgical excision of the lesion is usually curative. There was no recurrence after a short period of follow-up. Clinicians should be cognizant of this rare entity, which can be considered in a differential diagnosis of gingival growths that are noted in early childhood.

BackgroundAltered peripheral immune/inflammatory system and brain volumetric changes have been implicated in the pathophysiology of bipolar disorder (BD). This study aimed to evaluate how peripheral levels of cytokines are related to volumetric brain changes in euthymic patients with BD.MethodsEuthymic patients with BD (n = 21) and healthy controls (n = 22) were enrolled in this exploratory study. Blood samples were collected on the same day of clinical assessment and neuroimaging. Cytokines were measured through cytometric bead array method. Neuroimaging data were acquired using a sagittal three-dimensional magnetic resonance imaging T1-weighted fast field echo sequence and was processed using FreeSurfer.ResultsCompared to controls, BD patients had significantly lower volumes in the cingulate, medial-orbitofrontal (MOF) and parahippocampal regions. We found a negative correlation between right MOF volume and interferon-gamma levels (β = −0.431, P = .049) and a positive correlation between interleukin-10 levels and left posterior cingulate volume (β = 0.457, P = .048).ConclusionOur results support the involvement of inflammatory pathways in structural brain changes in BD.

How do attentional networks influence conscious perception? To answer this question, we used magnetoencephalography (MEG) in human participants, and assessed the effects of spatially nonpredictive or predictive supra-threshold peripheral cues on the conscious perception of near-threshold Gabors. Three main results emerged. (1) As compared with invalid cues, both nonpredictive and predictive valid cues increased conscious detection. Yet, only predictive cues shifted the response criterion towards a more liberal decision (i.e., willingness to report the presence of a target under conditions of greater perceptual uncertainty) and affected target contrast leading to 50% detections. (2) Conscious perception following valid predictive cues was associated to enhanced activity in frontoparietal networks. These responses were lateralized to the left hemisphere during attentional orienting, and to the right hemisphere during target processing. The involvement of frontoparietal networks occurred earlier in valid than in invalid trials, a possible neural marker of the cost of re-orienting attention. (3) When detected targets were preceded by invalid predictive cues, and thus reorienting to the target was required, neural responses occurred in left hemisphere temporo-occipital regions during attentional orienting, and in right hemisphere anterior insular and temporo-occipital regions during target processing. These results confirm and specify the role of frontoparietal networks in modulating conscious processing, and detail how invalid orienting of spatial attention disrupts conscious processing.Significance StatementDo we need to pay attention to external objects in order to become aware of them? Characterizing the spatiotemporal dynamics of attentional effects on visual perception is critical to understand how humans process and select relevant information. Participants detected near-threshold visual targets preceded by supra-threshold spatial cues with varying degrees of predictivity, while their brain activity was recorded using magnetoencephalography. Results demonstrated that valid predictive cues biased participants’ conscious perception through an early recruitment of frontoparietal regions, and that attentional costs associated to invalid predictive cues were related to activation of the right hemisphere ventral network. This work characterizes the neural dynamics associated with the cost of attentional reorienting on conscious processing.

To investigate the association between cytokine peripheral levels and the risk of cardiovascular disease in patients with schizophrenia and controls.A sample of 40 patients and 40 control subjects participated in the study. Psychiatric diagnosis was established following structured clinical assessment. The Framingham Score was used to assess cardiovascular risk (CVR). Serum levels of the cytokines IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were determined by cytometric bead array (CBA) technique, and the serum levels of IL-33, sST2, sTNFR1, sTNFR2, Leptin and Adiponectin by Enzyme-Linked Immunosorbent assay (ELISA).Patients with schizophrenia showed greater frequency of moderate CVR when compared with controls (p = 0.14). In addition, patients showed higher levels of sTNFR2 and Adiponectin compared to controls (p = 0.007 and p 0.001, respectively). Adiponectin and sTNFR2 were associated with CVR only in patients (p = 0.0002 and p = 0.033, respectively). In multivariate analysis controlling for socio-demographic and clinical confounders, illness duration (r = 0.492; p 0.002) and sTNFR2 (r = 0.665; p 0.004) were independent predictors of CVR.Our results reinforce the concept that patients with schizophrenia are at greater risk to develop cardiovascular diseases, and suggest that the associated chronic low-grade inflammation might play a role in this process.

BACKGROUND: The presence of severe calcific atherosclerosis at the iliofemoral axis may preclude transcatheter aortic valve implantation (TAVI) by the transfemoral (TF) approach. Intravascular lithotripsy (IVL) is a novel technology that fractures intimal/medial calcium and increases vessel compliance allowing TF TAVI in selected patients with peripheral artery disease (PAD). AIMS: The aim of this study was to report on the safety and efficacy of IVL-assisted TF TAVI in an all-comers population. METHODS: Clinical, imaging and procedural data on all consecutive patients treated by IVL-assisted TF TAVI in six high-volume European centres (2018-2020) were collected in this prospective, real-world, multicentre registry. RESULTS: IVL-assisted TF TAVI was performed in 108 patients, increasing from 2.4% to 6.5% of all TAVI from 2018 to 2020, respectively. The target lesion was most often localised at the common and/or external iliac artery (93.5% of cases; average TL-MLD 4.6±0.9 mm with 318 degrees of calcium arc). Transfemoral aortic valve delivery was successful in 100% of cases; final procedural success in 98.2% (two conversions to cardiac open surgery for annular rupture and valve migration). Complications of the IVL-treated segments consisted of 1 perforation and 3 major dissections requiring stent implantation (2 covered stents and 2 BMS). Access-site-related complications included 3 major bleedings. Three in-hospital deaths were recorded (2.8%, 1 failed surgical conversion after annular rupture, 1 cardiac arrest after initial valvuloplasty, 1 late hyperkalaemia in renal dysfunction). CONCLUSIONS: IVL-assisted TF TAVI proved to be a safe and effective approach, which helps to expand the indications for TF TAVI in patients with severe calcific PAD. However, these patients continue to have a higher-than-average incidence of periprocedural complications.

Signals from the peripheral retina are important for myopia development. Unlike temporal vision, deficits in peripheral spatial visual functions of myopes have been investigated previously. This study investigated temporal contrast thresholds in emmetropes and myopes at different retinal eccentricities.Forty-four young adults (mean age 23 ± 3 years) including 21 emmetropes (Spherical Equivalent (SE): +0.01 ± 0.30D) and 23 myopes (SE: -3.98 ± 2.41D) participated in this prospective study. Flicker modulation thresholds (FMT) were determined monocularly (right eye) for 15 Hz flicker stimulus at 0°, nasal (23°, 10°) and temporal (-23°, -10°) retinal eccentricities along the horizontal meridian. FMTs were measured psychophysically using 5-adaptive interleaved staircases and threshold was taken as the average of the last 6 reversals.In both the groups (emmetropes and myopes), there was a naso-temporal asymmetry in FMTs with higher thresholds in the far temporal retina (Median; Interquartile range: 40.97%; 17.06) than the nasal retina (28.07%; 9.36) (p0.001). Flicker modulation thresholds were significantly higher in myopes (30.58%; 12.15) compared to emmetropes (26.77%; 7.74; p = 0.04) at far nasal retina (23°), while at other eccentricities there was no effect (p0.05). Further sub-analysis revealed only high myopes (34.48 %, 21.9) showed significantly higher FMT compared to emmetropes (26.77%; 7.74; p = 0.04).Greater FMTs were seen in high myopes than that of emmetropes in the nasal retina. Further studies exploring the structural aspects of the myopic eye with FMT would provide a better understanding of role of flicker sensitivity in myopiogenesis.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive neoplasms with poor outcomes, commonly affecting older patients with comorbidities. This study aims to describe outcomes of older patients with PTCL in a large international cohort. Patients aged ≥70 years with PTCL diagnosed from 1 January 2010 to 31 December 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. Data on comorbidity were retrospectively collected according to the Charlson Comorbidity Index (CCI), and clinical outcomes were extracted. A total of 891 patients were included (SLR, n = 173; CCR, n = 718). Median age was 77 (SLR) and 78 (CCR) years. Included subtypes were as follows: angioimmunoblastic T-cell lymphoma, n = 226; anaplastic large-cell lymphoma, n = 122; enteropathy-associated T-cell lymphoma (EATL), n = 31; hepatosplenic TCL, n = 7; natural killer–/T-cell lymphoma, n = 62; PTCL not otherwise specified, n = 443. CCI data were available in 775 patients (87%), and CCI scores were divided into the groups CCI = 0 (39%), CCI = 1 (22%), and CCI > 1 (39%). Median age did not differ among the CCI groups (P = .72). Patients with a CCI > 1 had a worse median overall survival (4.4 months) compared with patients with CCI = 0 (11.9 months) and CCI = 1 (8.4 months; P < .001). Comorbidity and advancing age in as little as 5-year increments are important adverse factors in this group. Most patients died of lymphoma within a year from diagnosis, underscoring the importance of developing new treatments.

Objective We aimed to evaluate the clinico-pathological patient features, prognostic factors, treatment options and outcomes of peripheral nodal recurrence (PNR) of endometrial cancer (EC). Material and methods The data of 9 patients with PNR of EC from two institutions were reviewed. The electronic literature was reviewed from 1972 to May 2018 to identify articles about PNR in EC. Finally, 42 cases were evaluated. Results 19 (45.2%) patients were initially diagnosed with either stage I or II disease, whereas 20 (47.7%) patients had stage III or IV disease. The stages were not reported in 3 patients. PNR developed as the first recurrence in 40 (95.2%) patients and as the second recurrence in 2 (4.8%) patients. Isolated PNR appeared in 35 (83.3%) patients. Seven (16.7%) patients had PNR coexisting with multiple other sites of tumoral involvement. In the entire cohort, the 5-year and 10-year post-recurrence survival (PRS) were both 78%. Only the presence of distant hematogenous metastasis concurrent with PNR was significantly related to poor PRS (p=0.005). Among patients with isolated PNR, those who had surgery had 30% higher 5-year PRS than those treated without surgery, however, this difference was not found as statistically significant (80% vs. 50%; p>0.05). Conclusion A concurrent distant hematogenous metastasis was the only factor related to poor survival. A wide range of therapies exist for PNR but none of the therapies appear to be more advantageous over others. However, surgery as a component of treatment can render a survival advantage for patients who have isolated PNR.

Rational and Objectives Ultrasound investigation of peripheral nerves, long used in the adult population, has been shown to be of value in diagnosing a variety of peripheral nerve abnormalities. More recently, nerve sonography has also been shown to be of use in pediatrics. However, normative values for nerve size in children have been lacking. As such, the goal of this research was to establish normative data for cross sectional area (CSA) measurements of the median and ulnar nerves in children. Materials and methods The median and ulnar nerves of 48 children ranging in age from 2 years to 17 years were imaged by ultrasound. CSA measurements were made at 2 separate sites for each nerve and measured independently by 6 pediatric radiologists. Reliability of ultrasound measurements between the radiologists was assessed by calculating intraclass correlation coefficients. Linear mixed-effects modeling was performed to develop prediction models for nerve cross sectional area for each nerve segment; 95% prediction values were generated from these models to approximate normal ranges. Results Agreement in nerve cross-sectional area measurements among the 6 radiologists for all nerve segments was good (ICC 0.82, 95% CI 0.78 to 0.85). CSA for both the median and ulnar nerves is larger in older children. However, statistical models to predict CSA using height perform better rather than those using a child's age. The range of normal nerve segment CSA using these prediction models based on child height are reported. Conclusion Median and ulnar nerve CSA can be reliably measured with ultrasound. Normal reference values for ulnar and median nerve CSA correlate with patient age but may be more optimally determined based on a child's height.

Peripheral T-cell lymphomas are a heterogeneous, and usually aggressive, group of mature T-cell neoplasms with overlapping clinical, morphologic and immunologic features. A large subset of these neoplasms remains unclassifiable with current diagnostic methods ("not otherwise specified"). Genetic profiling and other molecular tools have emerged as widely applied and transformative technologies for discerning the biology of lymphomas and other hematopoietic neoplasms. Although the application of these technologies to peripheral T-cell lymphomas has lagged behind B-cell lymphomas and other cancers, molecular profiling has provided novel prognostic and diagnostic markers as well as an opportunity to understand the biologic mechanisms involved in the pathogenesis of these neoplasms. Some biomarkers are more prevalent in specific T-cell lymphoma subsets and are being used currently in the diagnosis and/or risk stratification of patients with peripheral T-cell lymphomas. Other biomarkers, while promising, need to be validated in larger clinical studies. In this review, we present a summary of our current understanding of the molecular profiles of the major types of peripheral T-cell lymphoma. We particularly focus on the use of biomarkers, including those that can be detected by conventional immunohistochemical studies and those that contribute to the diagnosis, classification, or risk stratification of these neoplasms.

Background and aim: Echinodorus macrophyllus (Kunth.) Micheli is popularly used for acute and chronic inflammatory conditions. The anti-inflammatory activity was previously demonstrated for its flavonoid-enriched fractions. The aim of this work assessed the antinociceptive properties of both aqueous extract and its fractions. Experimental procedure: The antinociceptive activity was determined by acetic acid-induced writhing, formalin test, tail immersion test, hot-plate test, xylene-induced ear edema methods, and the evaluation of its mechanism was performed in the writhing model. The aqueous extract of Echinodorus macrophyllus (AEEm) was fractionated, yielding Fr20, and Fr40. Fr40 composition was determined by HPLC-DAD-ESI-MS. Results and conclusion: Fr20 (all doses) and Fr40 (100 mg/kg) reduced the nociception in the tail-flick model. Both fractions increased the percentage of maximum possible effect with 25 mg/kg, in the hot-plate assay, at 60 min, while AEEm reduced pain only with 50 and 100 mg/kg. There was a reduction in xylene-edema index, with Fr40 (25 mg/kg), AEEm (50 mg/kg) and Fr20 (50 mg/kg). All doses of AEEm, Fr20, and Fr40 reduced both phases of the formalin model. In the abdominal contortion model, Fr40 presented the highest activity, reducing 96% of contortions and its antinociceptive mechanism was evaluated. The results indicated the involvement of NO and adrenergic activation pathways. The main components of Fr40 are swertisin, swertiajaponin, isoorientin 7,3′-dimethyl ether, swertisin-O-rhamnoside, isoorientin, isovitexin, isovitexin-Orhamnoside, and isovitexin-7-O-glucoside. The aqueous extract of E. macrophyllus leaves and its fractions exhibited significant analgesic effect, mediated through both peripheral and central mechanisms being considered a potentially antinociceptive drug.

Introduction: Squamous cell carcinoma of the external auditory canal is a rare entity. Previous studies have suggested predictors for tumor recurrence. However, most of the prognostic factors were from the clinicopathological aspect. Objective: This study aims to analyze the correlation between pre-operative peripheral inflammation markers and survival outcomes, in order to identify prognostic biomarkers for patients with squamous cell carcinoma of the external auditory canal. Methods: We retrospectively analyzed patients diagnosed with squamous cell carcinoma of the external auditory canal who underwent surgery at our institute. The pre-operative circulating inflammatory markers, such as the neutrophil, lymphocyte, platelet, and monocyte counts were measured and their ratios including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were calculated. The prognostic value of the measured hematologic parameters in relation to the survival outcomes was also evaluated. Results: A total of 83 patients were included, of which 26 patients showed tumor recurrence and 57 without recurrence. Neutrophil counts and neutrophil-to-lymphocyte ratio were closely connected with tumor stage. In the patients with recurrence, neutrophil counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were elevated (p< 0.0001, p< 0.0001 and p = 0.001), while lymphocyte counts and lymphocyte-to-monocyte ratio were decreased (p = 0.013 and p = 0.016, respectively). The receiver operating curve analysis indicated that pre-operative neutrophil-to-lymphocyte ratio is a potential prognostic marker for recurrence of squamous cell carcinoma of the external auditory canal (area under curve = 0.816), and the cut-off points was 2.325. Conclusions: Pre-operative neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte are significantly correlated with tumor recurrence in patients with external auditory canal squamous cell carcinoma. Furthermore, neutrophil-to-lymphocyte ratio may be unfavorable prognostic factors of this disease. Resumo Introdução: O carcinoma espinocelular do meato acústico externo é uma doença rara. Estudos anteriores sugeriram preditores de recorrência do tumor. Entretanto, a maioria dos fatores prognósticos se originou do aspecto clínico-patológico. Objetivo: Analisar a correlação entre marcadores inflamatórios periféricos pré-operatórios e os desfechos de sobrevida e identificar biomarcadores prognósticos para pacientes com carcinoma espinocelular do meato acústico externo. Método: Analisamos retrospectivamente pacientes com diagnóstico de carcinoma espinocelular do meato acústico externo submetidos à cirurgia em nosso instituto. Os marcadores inflamatórios circulantes pré-operatórios, como as contagens de neutrófilos, linfócitos, plaquetas e monócitos, foram medidos e as suas relações calculadas, inclusive as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos. O valor prognóstico dos parâmetros hematológicos medidos em relação aos desfechos de sobrevida também foi avaliado. Resultados: Foram incluídos 83 pacientes, entre os quais 26 apresentaram recorrência tumoral e 57 não apresentaram. A contagem de neutrófilos e a relação neutrófilo/linfócito estavam intimamente associadas ao estágio do tumor. Nos pacientes com recorrência, a contagem de neutrófilos, a relação neutrófilos/linfócitos e a relação plaquetas/linfócitos eram elevadas (p < 0,0001, p > 0,0001 e p = 0,001), enquanto a contagem de linfócitos e a relação linfócitos/monócitos estavam diminuídas (p = 0,012 ep = 0,016, respectivamente). A análise da curva, Receiver Operating Characteristic, indicou que a relação neutrófilos/linfócitos pré-operatória era um potencial marcador prognóstico para a recorrência de carcinoma espinocelular do meato acústico externo (Área sob a curva = 0,816) e o ponto de corte foi de 2,325. Conclusão: A contagem pré-operatória de neutrófilos e linfócitos, as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos estão significativamente correlacionadas com a recorrência do tumor em pacientes com carcinoma espinocelular do meato acústico externo. Além disso, a relação neutrófilos/linfócitos pode ser um fator prognóstico desfavorável dessa doença.

Background: This study investigated the efficacy and complications of microwave ablation in combination with chemotherapy in treating peripheral IIIB-IV nonsmall cell lung cancer (NSCLC). Materials...

OBJECTIVE: Opioid use is common among patients with peripheral arterial disease (PAD), given that pain is a defining symptom. Unfortunately, long-term opioid use places patients at dramatically increased risk of overdose and death. Although surgical revascularization is extremely effective in alleviating ischemic pain related to PAD, it is unclear whether this practice results in the discontinuation of opioids after surgery. Therefore, we conducted the following study to investigate trends in opioid use before and after surgical bypass in patients with PAD, as well as the risk factors for continued opioid use after surgery. METHODS: We conducted a retrospective analysis of patients undergoing open lower extremity bypass for claudication or rest pain between June 1, 2017, and March 31, 2021. Patients were grouped according to whether they reported preoperative opioid use at the time of surgery. The primary outcome was continued opioid use at 30-day follow-up after discharge. A multivariable logistic regression was conducted to estimate the association of continued opioid use with patient characteristics, preoperative opioid use, and receiving a postoperative opioid prescription. RESULTS: Among 3873 patients undergoing surgery, the mean age was 65.7 (10.2) years and 2650 (68.4%) patients were male. There were 913 patients (23.6%) who used opioids preoperatively and hydrocodone was the most common preoperative opioid (583 [63.9%]). At discharge, 2506 patients (64.7%) received a postoperative opioid prescription. Postoperative opioid prescriptions were significantly more common for preoperative opioid users than opioid-naïve patients (813 [89.0%] vs 1693 [57.2%]; P < .001) and were significantly larger in size (24.3 [21.1] pills vs 19.9 [10.5] pills; P < .001). On 30-day follow-up, 522 preoperative opioid users (61.3%) and 616 opioid-naïve patients (28.4%) reported that they were still using opioids (P < .001). Continued opioid use at follow-up was associated with preoperative opioid use (adjusted odds ratio, 3.23; 95% confidence interval, 2.70–3.89) and receiving a postoperative opioid prescription (adjusted odds ratio, 10.83; 95% confidence interval, 7.96–15.06). CONCLUSIONS: Most patients with PAD who use opioids preoperatively do not discontinue opioids after lower extremity bypass. Moreover, a significant proportion of previously opioid-naïve patients are still using opioids 1 month after surgery. In both cases, postoperative opioid prescriptions had the strongest association with continued opioid use. These findings underscore the need for improved prescribing practice and increased attentiveness to discontinuation of unnecessary medications after surgery. (J Vasc Surg 2022;75:998–1007.)

There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with HIV (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCLs) in the modern antiretroviral therapy era. North American AIDS Cohort Collaboration on Research and Design and Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study, 52, 64, 101, 500, and 246 PWH with histologic confirmation of TCL, primary central nervous system lymphoma, Burkitt’s lymphoma, diffuse large B-cell lymphoma (DLBCL), and Hodgkin’s lymphoma (HL), respectively, and 450 TCLs without HIV were eligible for analysis. At the time of TCL diagnosis, anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. Although PWH with TCL diagnosed between 1996 and 2009 experienced a low 5-year survival probability at 0.23 (95% confidence interval [CI]: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010 and 2016 (0.69; 95% CI: 0.48, 1; P = .04) in contrast to TCLs among PWoH (0.45; 95% CI: 0.41, 0.51; P = .53). Similarly, PWH with ALCLs diagnosed between 1996 and 2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt’s (0.43; 95% CI:0.33, 0.57; P = .09) and DLBCL (0.17; 95% CI: 0.06, 0.46; P = .11) and behind HL (0.57; 95% CI: 0.50, 0.65; P < .0001). Despite a small number, those diagnosed between 2010 and 2016 experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison with PWoH (0.76; 95% CI: 0.66, 0.87; P = .58). Thus, our analysis confirms improved overall survival for aggressive B- and T-cell malignancies among PWH in the last decade.

Background: Chronic inflammation has been linked to the development and prognosis of neuroendocrine tumors (NETs). The current study intended to evaluate the role of peripheral hematological inflam...

Purpose The single-session dose tolerance of the spinal nerves has been observed to be similar to that of the spinal cord in pigs, counter to the perception that peripheral nerves are more tolerant to radiation. This pilot study aims to obtain a first impression of the single-session dose-response of the brachial plexus using pigs as a model. Methods and Materials Ten Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiotherapy. A 2.5-cm length of the left-sided brachial plexus cords was irradiated. Pigs were distributed in 3 groups with prescription doses of 16 (n = 3), 19 (n = 4), and 22 Gy (n = 3). Neurologic status was assessed by observation for changes in gait and electrodiagnostic examination. Histopathologic examination was performed with light microscopy of paraffin-embedded sections stained with Luxol fast blue/periodic acid-Schiff and Masson's trichrome. Results Seven of the 10 pigs developed motor deficit to the front limb of the irradiated side, with a latency from 5 to 8 weeks after irradiation. Probit analysis of the maximum nerve dose yields an estimated ED50 of 19.3 Gy for neurologic deficit, but the number of animals was insufficient to estimate 95% confidence intervals. No motor deficits were observed at a maximum dose of 17.6 Gy for any pig. Nerve conduction studies showed an absence of sensory response in all responders and absent or low motor response in most of the responders (71%). All symptomatic pigs showed histologic lesions to the left-sided plexus consistent with radiation-induced neuropathy. Conclusions The single-session ED50 for symptomatic plexopathy in Yucatan minipigs after irradiation of a 2.5-cm length of the brachial plexus cords was determined to be 19.3 Gy. The dose-response curve overlaps that of the spinal nerves and the spinal cord in the same animal model. The relationship between the brachial plexus tolerance in pigs and humans is unknown, and caution is warranted when extrapolating for clinical use.

Congenital afibrinogenemia is a rare autosomal recessive blood disorder that accompanies thrombotic complications and is associated with bleeding tendency. The management of these opposing complications remains a challenge. Endovascular treatment (EVT) for peripheral arterial thrombosis has not been described in previous studies. A 57-year-old man with congenital afibrinogenemia developed back pain and left lower leg pain. The cause of the pain was confirmed to be renal infarction and lower extremity arterial thrombosis by Doppler ultrasound and contrast-enhanced computed tomography. He was treated with EVT for the lower extremity arterial thrombosis, leading to an excellent short-term improvement without bleeding.

Acute peripheral nerve injuries are common and can cause physical disabilities with sensory and functional sequelae; they therefore require surgery. The aim of this study was to conduct a systematic review to assess the clinical applicability of end-to-side neurorrhaphy in peripheral nerve reconstruction, based on available evidence. We carried out a systematic review of the literature using MEDLINE/PubMed, EMBASE, Cochrane Library, Web of Science, Scielo and Scopus through March 16, 2021. Most of the selected studies were qualitative and employed nonrandomized groups of patients, without standardized scales for assessing outcomes, which made statistical analysis difficult. Efficacy varied from 24% to 81%. Factors for better outcome included the type of injury, type of injured nerve (sensory, motor or mixed), presence of an epineural window, topography, injury extension1.3 cm, and intervention within 2 weeks of injury. Clinical studies so far lack scientific evidence on end-to-side neurorrhaphy in peripheral nerve lesions.

Impaired temporal resolution of the central auditory system has long been suggested to contribute to speech understanding deficits in the elderly. However, it has been difficult to differentiate between direct age-related central deficits and indirect effects of confounding peripheral age-related hearing loss on temporal resolution. To differentiate this, we measured temporal acuity in the inferior colliculus (IC) of aged CBA/J and C57BL/6 mice, as a model of aging with and without concomitant hearing loss. We used two common measures of auditory temporal processing: gap detection as a measure of temporal fine structure and amplitude-modulated noise as a measure of envelope sensitivity. Importantly, auditory temporal acuity remained precise in the IC of old CBA/J mice when no or only minimal age-related hearing was present. In contrast, temporal acuity was only indirectly reduced by the presence of age-related hearing loss in aged C57BL/6 mice, not by affecting the brainstem precision, but by affecting the signal-to-noise ratio of the neuronal activity in the IC. This demonstrates that indirect effects of age-related peripheral hearing loss likely remain an important factor for temporal processing in aging in comparison to 'pure' central auditory decline itself. It also draws attention to the issue that the threshold difference between ‘nearly normal’ or ‘clinically normal hearing aging subjects in comparison to normal hearing young subjects still can have indirect effects on central auditory neural representations of temporal processing.

BACKGROUND Expression of NKG2D ligand (NKG2DL) plays a major role as a "danger signal" on stressed cells to promote removal of the latter by NKG2D-expressing cytotoxic lymphocytes. NKG2DL expression has been found in peripheral immune cells as well, such as in macrophages; however, the effect of this expression is yet to be determined. METHODS We determined instrumental variables (IVs; R2 0.05), and the results were consistent across the sensitivity analyses. CONCLUSIONS Our study provide novel evidence associating NKG2DL expression with Graves' disease, an autoimmune thyroiditis; direction of the effect indicated the immunoregulatory role of MICA expression in PBMCs, suggesting the importance of further functional assays in inflammatory diseases.

Метою дослідження було порівняльне вивчення впливу двох режимів інтраопераційного рідинного забезпечення на стан центральної гемодинаміки (ЦГД) та величину периферичного капілярного кровотоку у хворих із злоякісною патологією кісток нижніх кінцівок, які піддаються травматичним хірургічним втручанням в ортопедичній онкології. У дослідження ввійшло 70 хворих віком 18–77 років, яким проведено планові хірургічні втручання під комбінованою анестезією, що включала спинномозкову анестезію бупівакаїном і внутрішньовенний пропофоловий наркоз. Сформовано дві групи дослідження. Пацієнтам першої групи (n = 35) забезпечувався рестриктивний режим інтраопераційного введення рідини. Пацієнтам другої групи (n = 35) проводили цілеспрямовану рідинну терапію (ЦРТ) із ретельним моніторингом серцевого викиду та цільовою підтримкою ударного індексу на рівні, що сягає 35 мл/м2, і середнього артеріального тиску на рівні, що не менше 80 мм рт.ст. для осіб молодого та середнього віку, та не менше 90 мм рт.ст. для осіб похилого та старечого віку. Якщо у хворих першої групи серцеве переднавантаження часто моделювалося за допомогою інфузії норадреналіну, то у хворих другої групи його підтримували короткочасними інфузіями розчину гідроксіетилкрохмалю. Кожну з груп було поділено на дві підгрупи: 1) пацієнти віком до 60 років (при обох режимах рідинного забезпечення таких хворих було по 10); 2) пацієнти віком 60 років і старше (при обох режимах рідинного забезпечення таких хворих було по 25). ЦГД вивчали за допомогою методики грудного біореактансу. Спроможність периферичного капілярного кровотоку оцінювали шляхом фотоплетизмометричного визначення величини перфузійного індексу. Результати дослідження показали, що в умовах обмеження рідинної підтримки спостерігається суттєве зменшення показників серцевого викиду, судинного тонусу та величини периферичного капілярного кровотоку. І у хворих віком до 60 років, і у хворих віком 60 років і старше методика ЦРТ забезпечувала вірогідно більші показники артеріального тиску, серцевого викиду та величини перфузійного індексу на травматичному етапі операції та наприкінці дослідження. Всі пацієнти з рестриктивним режимом рідинного забезпечення віком 60 років та старше (100 %) потребували інфузії норадреналіну з метою корекції судинного тонусу та серцевого переднавантаження. Пацієнтам із ЦРТ інфузії норадреналіну не знадобилися.

The article presents a literature review on the application of such method of reflexotherapy acupuncture as myeloacupuncture used in the pathology of the peri­pheral joints and spine. It is theoretically grounded and associated with a positive clinical effect as a result of regenerating influence on the processes of free radical oxidation, imbalance of the cytokine network, growth factors, vascular endothelial function, the system of nitric oxide and pro-inflammatory enzymes (matrix metalloproteinases, cyclooxygenase-2, caspase-3). Achievement of the analgesic effect by acupuncture needle injection into the spinal cord is conducted due to the impact on peripheral, spinal and sub-spinal mechanisms, synthesis of neurotransmitters and neurohormones, neuroacid, that cause vanniloid-1 reception normalization, enhancement of production of endorphins, enkephalins and endomorphins, thyrotropin-releasing hormone and P substance.

Background: Central nervous system disruption of cholinergic (ACh) signaling, which plays a major role in cognitive processes, is well documented in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The expression of muscarinic ACh receptors type 1 and 4 (CHRM1 and CHRM4) has been reported to be altered in the brain of DLB patients. Objective: We aim to assess the peripheral gene expression of CHRM1 and 4 in DLB as a possible marker as compared to AD and healthy control (HC) subjects. Methods: Peripheral blood mononuclear cells were collected from 21 DLB, 13 AD, and 8 HC matched subjects. RT-PCR was performed to estimate gene expression of CHRM1 and CHRM4. Results: Peripheral CHRM1 expression was higher and CHRM4 was lower in DLB and AD compared to HC, whereas both CHRM1 and CHRM4 levels were higher in AD compared to DLB patients. Receiver operating characteristics curves, with logistic regression analysis, showed that combining peripheral CHRM1 and CHRM4 levels, DLB and AD subjects were classified with an accuracy of 76.0%. Conclusion: Alterations of peripheral CHRM1 and CHRM4 was found in both AD and DLB patients as compared to HC. CHRM1 and CHRM4 gene expression resulted to be lower in DLB patients compared to AD. In the future, peripheral CHRM expression could be studied as a possible marker of neurodegenerative conditions associated with cholinergic deficit and a possible marker of response to acetylcholinesterase inhibitors.

Background and Aims Clostridioides difficile infection (CDI) is associated with a range of outcomes and existing prediction models for death among patients with CDI are imprecise. Peripheral eosinopenia has been proposed as a novel risk factor for death among patients with CDI but has not been incorporated into prediction models. This study aimed to develop and validate a prediction model for death among patients hospitalized with CDI that incorporated peripheral eosinopenia. Methods Eosinopenia was defined as 0 eosinophils/uL on the soonest peripheral blood draw within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of three large, unaffiliated hospital networks, tested positive for CDI by stool PCR and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days. Results There were 4,518 unique hospitalized adults with CDI included (2,142 derivation cohort and 2,376 validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts respectively. In the validation cohort, the factors most strongly associated with death were eosinopenia [adjusted OR (aOR) 2.49, 95% CI 1.77-3.50], albumin 1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A six variable clinical prediction model was developed that improved upon existing classification schemes for CDI severity (AUROC of 0.75 vs. 0.68). Conclusions Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification.

Itch is a universally experienced sensation, and chronic itch can be as diabolically debilitating as pain. Recent advances have not only identified the neuronal itch sensing circuitry, but also have uncovered the intricate interactions between skin and immune cells that work together with neurons to identify itch-inducing irritants. In this review, we will summarize the fundamental mechanisms of acute itch detection in the skin, as well as highlight the recent discoveries relating to this topic.

Purpose Our purpose was to characterize the radiation doses to organs-at-risk (OAR) in the phase I trial (NCT02608385) that established safety/efficacy of stereotactic body radiation therapy (SBRT) using NRG-BR001 dose constraints combined with programmed cell death protein 1 blockade for metastatic disease. Methods and Materials Between January 2016 and May 2018, 73 patients with advanced solid tumors were treated with SBRT followed by pembrolizumab. Tumor volumes (gross tumor volume/internal tumor volume) were delineated for each metastasis, with planning target volume contraction to limit OAR dose per protocol (n = 54) or when gross tumor volume/internal tumor volume > 65 cm3 (n = 19). For 20 OAR, doses were compared with NRG-BR001 constraints. Protocol constraints were considered challenged when the minimum of the highest dose received by ≥6 patients without dose-limiting toxicities (DLTs) ( D m a x 6 t h ) was ≥70% of the protocol constraint. Results A total of 151 metastases were irradiated including 32 peripheral lung, 23 central lung, 13 mediastinal/cervical, 24 liver, 28 abdominal-pelvic, 16 osseous, and 15 spinal metastases. A median of 2 metastases (range, 2-4) with mean volumes of 33.5 cm3 (range, 0.4-391 cm3) were treated using average planning target volumes of 50.7 cm3 (range, 3.2-161 cm3). At least 1 dose constraint from NRG-BR001 was exceeded in 38 of 73 (52%) patients. OAR constraints were challenged in 10 serial organs (gastrointestinal, cardio-pulmonary, musculoskeletal, and nervous systems) and 1 parallel OAR (lung). Grade 3 DLTs occurred in 6 patients, including pneumonitis (n = 3), colitis (n = 2), and hepatic failure (n = 1). In 4 patients, the toxicity could be directly attributed to the planned dose to OAR (ie, pneumonitis due to high lung dose or colitis due to high bowel dose). Conclusions Multisite SBRT in combination with programmed cell death protein 1 blockade was safely tolerated when treating critical central, abdominal-pelvic, and peripheral OAR nearing NRG-BR001 constraints with clinically acceptable toxicity in the corresponding organ systems. The observed relationship between dose and DLTs in 4 of 6 patients indicates that NRG-BR001 dose constraints should be respected in subsequent trials to maintain clinical safety.

Purpose This study aimed to demonstrate the efficacy and safety of the SoundBite® Crossing System‒Peripheral (SCS‒P) to facilitate crossing chronic total occlusions (CTOs) of infrainguinal arteries. Failure to cross CTOs is the main cause of failed endovascular revascularization attempts. The SCS‒P is a newly developed device that uses a 0.018-inch wire to deliver acoustic shock waves and facilitate CTO crossing. Methods This clinical trial was approved by Ethics Committees of all 4 participating centers and enrolled 52 patients with symptomatic de novo infrainguinal CTOs. Technical device success, the primary efficacy endpoint, was defined as the ability to facilitate treatment of the target lesion by crossing a portion or the whole length of the CTO. Freedom from SCS‒P related major adverse events (MAEs) at 30 days post procedure was the primary safety endpoint. Results The SCS‒P met the primary efficacy and safety endpoints in 92.3% (48/52) and 100% (52/52) of subjects, respectively. Technical device success with post-procedural patency and freedom from SCS‒P related MAEs was achieved in 88.5% (46/52) of subjects. Mean CTO crossing time was 20.0 ± 30.8 minutes and the SCS‒P was able to traverse the whole CTO and enter the distal true lumen without the need of any other device in 59.6% (31/52) of subjects. Mean Rutherford category and ankle brachial index improvement at 30 days follow-up was 2.4±1.17 and 0.23±0.22, respectively. Conclusions The SCS‒P demonstrated a satisfactory safety and performance profile to cross peripheral CTOs and enter into the distal true lumen of infrainguinal CTOs.

Despite being an important patient group, adult cystic fibrosis patients with an FEV1 below 40%predicted have been excluded from clinical trials with elexacaftor/tezacaftor/ivacaftor. We conducted a real-life 3 months follow-up study in 14 adult CF patients (median FEV1 34%predicted) demonstrating significant treatment effects in terms of FEV1 (an increase of 12%predicted at 4 weeks, remaining stable thereafter). Corresponding decreases in lung clearance index LCI (by 31%predicted, down from baseline 247%predicted) and ventilation heterogeneity in the acinar compartment (Sacin) (by 411%predicted, down from baseline 798%predicted) suggest a distinct peripheral lung effect. One patient had intermittent treatment interruptions because of drug-induced liver injury. Our real-life data confirm that treatment with elexacaftor/tezacaftor/ivacaftor is effective in severely obstructive patients, and this is the first study to show time evolution of ventilation distribution improvement, pointing to the peripheral lung as the main site of treatment effect.

Background Diffusion-weighted imaging (DWI) provides specific in vivo information about tissue microstructure, which is increasingly recognized for various applications outside the central nervous system. However, standard sequence parameters are commonly adopted from optimized central nervous system protocols, thus potentially neglecting differences in tissue-specific diffusional behavior. Purpose To characterize the optimal tissue-specific diffusion imaging weighting scheme over the b domain in peripheral nerves under physiologic and pathologic conditions. Materials and Methods In this prospective cross-sectional study, 3-T MR neurography of the sciatic nerve was performed in healthy volunteers (n = 16) and participants with type 2 diabetes (n = 12). For DWI, 16 b values in the range of 0-1500 sec/mm2 were acquired in axial and radial diffusion directions of the nerve. With a region of interest-based approach, diffusion-weighted signal behavior as a function of b was estimated using standard monoexponential, biexponential, and kurtosis fitting. Goodness of fit was assessed to determine the optimal b value for two-point DWI/diffusion tensor imaging (DTI). Results Non-Gaussian diffusional behavior was observed beyond b values of 600 sec/mm2 in the axial and 800 sec/mm2 in the radial diffusion direction in both participants with diabetes and healthy volunteers. Accordingly, the biexponential and kurtosis models achieved a better curve fit compared with the standard monoexponential model (Akaike information criterion >99.9% in all models), but the kurtosis model was preferred in the majority of cases. Significant differences between healthy volunteers and participants with diabetes were found in the kurtosis-derived parameters Dk and K. The results suggest an upper bound b value of approximately 700 sec/mm2 for optimal standard DWI/DTI in peripheral nerve applications. Conclusion In MR neurography, an ideal standard diffusion-weighted imaging/diffusion tensor imaging protocol with b = 700 sec/mm2 is suggested. This is substantially lower than in the central nervous system due to early-occurring non-Gaussian diffusion behavior and emphasizes the need for tissue-specific b value optimization. Including higher b values, kurtosis-derived parameters may represent promising novel imaging markers of peripheral nerve disease. ©RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Jang and Du in this issue.

Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.

To use optical modeling to compare a 6.0 mm and 7.0 mm intraocular lens (IOL) optic diameters on peripheral retinal illumination with implications for negative dysphotopsia.Mayo Clinic, Rochester, Minnesota, and Simpson Optics LLC, Arlington, Texas.Model eye.Ray-tracing software was used to simulate retinal illumination from an extended light source for a pseudophakic eye with in-the-bag biconvex IOLs (refractive index [n] = 1.46 and 1.55) and a 2.5 mm pupil. Ray-tracing diagrams and simulated retina illumination profiles were compared using the 6.0 mm and 7.0 mm optic diameter IOLs. Retinal locations were scaled to relative visual angles from 70 to 110 degrees horizontally.A 7.0 mm optic (n = 1.46) expands the image field by 2.8 degrees compared with a 6.0 mm optic. High-angle input light misses a 7.0 mm optic at a larger visual angle than a 6.0 mm optic, shifting illumination of the peripheral retina by this light anteriorly by 5.6 degrees. Consequently, a region of nonilluminated peripheral nasal retina is enlarged and shifted peripherally using a 7.0 mm optic (visual angle, 86.3 to 96.3 degrees) compared with a 6.0 mm optic (visual angle, 83.5 to 90.7 degrees). Similar illumination changes were seen modeling a 1.55 n IOL.A narrow dark region in the nasal retina when using a 6.0 mm optic is changed to a broader, more peripheral dark region when using a 7.0 mm optic. An extended, more peripheral dark nasal region may make a temporal shadow less bothersome and explain lower negative dysphotopsia rates using a 7.0 mm optic.

Background The Center for Medicare and Medicaid Services decreased reimbursement rates for peripheral venoarterial (VA) extracorporeal membrane oxygenation (ECMO) and venovenous (VV) ECMO procedures in October 2018. Limited data are available describing hospital costs and clinical resources required to support ECMO patients. Methods All patients supported on ECMO at our institution between March 2017 and October 2018 were identified. Exclusion criteria were cannulation at referring hospitals, organ transplant recipients, and temporary right ventricular support. The cohort was stratified by the initial cannulation strategy. Outcomes were total hospital cost and clinical resource utilization. Results There were 29 patients supported on central VA, 72 on peripheral VA, and 37 on VV ECMO. Survival at 30 days was 48% for central vs 37% for peripheral vs 51% for VV. Hospital costs were $187,848 for central vs $178,069 for peripheral vs $172,994 for VV (P = .91). Mean hospital stay was 25.8 days for central vs 21.5 days for peripheral vs 26.2 days for VV (P = .49). Mean intensive care unit stay was 14.1 days for central vs 12.8 days for peripheral vs 7.7 days for VV (P = .25). Mean length of ECMO support was 6.5 days for central vs 6.2 days for peripheral vs 7.8 days for VV (P = .38). Mean ventilator time was 13.0 days for central vs 8.2 days for peripheral vs 10.0 days for VV (P = .06). Hemodialysis was used in 41% central patients, 47% peripheral, and 41% VV (P = .75). Theoretical ECMO reimbursement losses ranged from $1,970,698 to $5,648,219 annually under 2018 Center for Medicare and Medicaid Services rates. Conclusions ECMO cannulation strategy has minimal impact on resource utilization and hospital cost.

Breast cancer represents a heterogeneous condition in which the interaction between host immune response and primary oncogenic events can impact disease progression. Ratios of systemic blood-based immunocytes have emerged as clinically-relevant prognostic biomarkers in cancer patients. The NLR (neutrophil-to-lymphocyte ratio) has been shown to be prognostic in a variety of cancers, including breast cancer. However, evaluation of the prognostic value for overall survival (OS) and disease-free survival (DFS) of other key immunocyte ratios—neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-white cell count ratio (NWR), lymphocyte-to-white cell count ratio (LWR), monocyte-to-white cell count ratio (MWR), platelet-tolymphocyte (PLR)—by breast cancer subtypes in a neoadjuvant chemotherapy (NAC) cohort remains to be fully explored. An NAC-treated breast cancer cohort, comprised of Luminal A, Luminal B, HER2-positive, and triple negative/basal breast cancers, treated at a tertiary referral center (minimum 3-year follow-up), was used to calculate immunocyte ratios and immunocyte cut-off values, calculated with >80% specificity (using decision tree modeling). The association with subtype-specific OS, DFS, and tumor grade was analyzed using cut offs calculated using both receiver operating characteristic curves and decision tree modelling. Decision tree calculated ratios showed that LMR (5.29) and MWR (0.06) were significantly associated with Luminal A OS (p = 0.004 and p = 0.022) and DFS (p = 0.004 and p = 0.022), and Luminal B OS (p = 0.027 and p = 0.008) and DFS (p = 0.005 and p = 0.007). NLR (1.79) and LWR (0.30) were significantly associated with HER2-positive OS (p = 0.013 and p = 0.043). NLR (1.79) and NWR (0.62) were significantly associated with DFS (p = 0.035 and p = 0.021). No significant association we observed between any immunocyte ratio in the triple negative cohort. Our results demonstrate the subtype-specific prognostic value of immunocyte ratios in NAC-treated breast cancer patients. Further validation of immunocyte ratios will provide clinicians with a new prognostic aid for disease management and monitoring.

Objectives To examine the cross-sectional association of ascending pain mechanisms (APM), implicated in pain sensitization (PS), and descending pain modulation with pain patterns and unpredictability of pain. Methods The Multicenter Osteoarthritis (OA) Study is a longitudinal cohort of older adults with or at risk of knee OA. Peripheral and central APM were assessed using quantitative sensory tests (QST); pressure pain thresholds (PPTs) using a handheld pressure algometer (knee/peripheral and wrist/central), temporal summation (TS) using weighted probes (wrist/central). Descending modulation was assessed by conditioned pain modulation (CPM) using PPTs and a forearm ischemia test. Pain patterns were characterized based on responses to the Intermittent and Constant OA Pain (ICOAP) questionnaire: 1) no intermittent or constant pain; 2) intermittent pain only; 3) constant pain only; and 4) combined constant and intermittent pain. A question regarding frequency assessed unpredictable pain. We assessed the association of QST measures to pain patterns using regression models with generalized estimating equations. Results There were 2794 participants (mean age 63.9, BMI 29.5 kg/m2 , 57% female). Lower PS (by wrist PPT) OR = 0.80 (95% CI 0.68, 0.93) and adequate CPM, OR = 1.45 (1.10, 1.92) were associated with having constant +/- intermittent pain compared with intermittent pain only. Higher PS (by PPT and TS) was associated with higher likelihood of unpredictable pain. Conclusions Knee pain patterns appear to be related to peripheral +/- central facilitated APM, and descending modulatory mechanisms. These findings highlight the need for a broader approach to understanding pain mechanisms by symptomatic disease progression.