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Background: Occupational exhaustion, or burnout, is characterized with three components: emotional exhaustion, depersonalization, and sense of decreased personal accomplishment. Advanced practice providers (APPs) in oncology care are at particular risk for burnout., Methods: This was a prospective, comparative, descriptive study utilizing a convenience sample of oncology APPs who completed the Advanced Practice Provider Oncology Web Education Resource (AP-POWER; formerly Oncology Nurse Practitioner Web Education Resource, or ONc-PoWER), developed to provide educational content for new oncology APPs. The study purpose was to utilize the AP-POWER alumni to describe the level of burnout (Maslach Burnout Inventory) as well as resilience (Brief Resilience Scale) after at least 1 year in oncology practice, and to compare these scores according to the number of APP oncology practice years., Results: Of the 133 questionnaires emailed, 30 were returned (22.6% response) and 27 completed (20.3%). Within the Maslach Burnout Inventory, the mean score of the emotional exhaustion subscale was 25.19 (standard deviation [SD] 12.74; high degree of occupational exhaustion), depersonalization 7.74 (SD 5.98; moderate degree), and personal achievement 31.85 (SD 6.20; low degree). The resilience scores had a mean of 22.52 (SD 3.37; normal range). Resiliency was positively associated with personal accomplishment. There was no difference in burnout among newer (< 3 years) and more experienced (> 3 years) oncology APPs., Discussion: Oncology APPs report key indications of burnout, including a high degree of emotional exhaustion and moderate depersonalization, which was not mitigated through resiliency., Conclusions/implications: The results are worrisome. Burnout scores for oncology APPs are high. Resiliency is present but is not protective for burnout. Strategies must be developed institutionally to support these key cancer care providers., Competing Interests: The authors have no conflicts of interest to disclose., (© 2024 BroadcastMed LLC.)

Objective: To identify and measure radiolucencies at the solear margin of the distal phalanx in radiographs of healthy and laminitic hooves., Sample: Clinical records and dorsoproximal-palmarodistal radiographs of equine forelimbs with radiological diagnoses of either laminitis (n = 40, L) or navicular syndrome (n = 40, NS)., Methods: Outlines of the radiolucent structures at the solar margin were drawn in ImageJ, and a customized novel plugin "Arteries Analyzer/ImageJ" was used for measurements. The diverging radiolucencies outside the terminal arc of the distal phalanx were differentiated as arterial channels (open at the solear margin) and ellipses (closed at the solear margin). Comparisons between L and NS, between distal phalanges with and without ellipses, and of arterial channels and ellipses in areas were compared using Wilcoxon and the Mann-Whitney U tests, respectively. The reliability and repeatability of the method were tested using Friedman's test., Results: Fewer arterial channels but more ellipses were identified in L than in NS. In phalanges with ellipses (n = 47), the number of ellipses and the number of arterial channels were negatively correlated (PCC -0.181, P = .224). The number of ellipses correlated positively with the severity of laminitis (PCC 0.495, P < .001; n = 80) and with the degree of rotation of the distal phalanx (PCC 0.392, P < .001; n = 80)., Clinical Relevance: The software tool successfully measured arterial channels and ellipses outlined by the evaluators. Results indicate that healthy arteries develop into pathological ellipses in laminitic feet. This may be used to complement the interpretation of radiographs and support clinical decision-making.

Introduction: Skeletal abnormalities and malocclusions have varied features that impact populations globally, impairing aesthetics and lowering life quality. The prevalence of the Skeletal Class III disease is the lowest among all angle malocclusions, with varied prevalence across nations. Environmental, genetic, and societal factors play a role in its numerous etiologies. In this study, we conducted a thorough search across the published data relating to quantitative trait loci (QTL) and the genes associated with Class III progression in humans, discussed these findings and their limitations, and proposed future directions and strategies for studying this phenotype., Methods: An inclusive search of published papers in the PubMed and Google Scholar search engines using the following terms: 1. Human skeletal Class III; 2. Genetics of Human skeletal Class III; 3. QTL mapping and gene associated with human skeletal Class III; 4. enriched skeletal Class-III-malocclusion-associated pathways., Results: Our search has found 53 genes linked with skeletal Class III malocclusion reported in humans, genes associated with epigenetics and phenomena, and the top 20 enriched pathways associated with skeletal Class III malocclusion., Conclusions: The human investigations yielded some contentious conclusions. We conducted a genome-wide association study (GWAS), an epigenetics-wide association study (EWAS), RNA-seq analysis, integrating GWAS and expression quantitative trait loci (eQTL), micro- and small-RNA, and long non-coding RNA analysis in tissues connected to skeletal Class III malocclusion phenotype in tissues connected with the skeletal phenotype. Finally, we invite regional, national, and international orthodontists and surgeons to join this effort by contributing human samples with skeletal Class III malocclusion following the accepted Helsinki ethical protocol to challenge these phenomena jointly.

Background: Implant neck characteristics may affect initial implant stability, soft tissue healing, and early marginal bone loss (EMBL) at second-stage surgery. The null hypothesis was that, following two-stage implant insertion, rough surface, non-screw-type collar implants will present lower EMBL at 2nd-stage surgery than rough-surface, screw-type collar implants., Methods: The study comprised seven male beagle dogs (mean weight 10.57 ± 2.8 kg; range 9-17 kg). A novel implant design was developed, composed of 2 parts: an apical part resembling a regular threaded implant, and a coronal non-screw-type collar, 4.2 mm long, served as the study group, whereas standard threaded implants served as control. Twenty-eight implants were placed: two on each side of the mandible. All implants were sand-blasted/acid-etched and of similar dimensions. Each dog received four implants. To assess location (anterior vs. posterior) impact on the outcomes, implants were placed as follows: group I-posterior mandible right-non-screw-type collar implants; group II-anterior mandible right-similar non-screw-type collar implants. To assess the collar-design effect on the outcomes, implants were placed as follows-Group III-anterior mandible left-control group, screw-type collar implants; Group IV-study group, posterior mandible left-non-screw-type collar implants. The following parameters were measured and recorded: insertion torque, soft tissue healing, early implant failure, and EMBL at 2nd-stage surgery., Results: No statistically significant differences were noted between groups I and II regarding all outcome parameters. At the same time, although insertion torque (55 N/cm) and early implant failure (0) were similar between groups III and IV, group III presented significantly poorer soft tissue healing (1.43 vs. 0.14) and increased marginal bone loss (0.86 vs. 0 mm)., Conclusions: When a two-stage implant protocol was used, rough-surface non-screw-type collar implants led to superior outcomes at 2nd-stage surgery. Implant location did not affect the results. The significance of this result in preventing EMBL awaits further research.

Sialography is used for diagnosis of obstructive salivary gland diseases and prior to sialendoscopy. Three-dimensional cone beam computerized tomography (CBCT) sialography allows imaging and measurement of salivary duct structures. Salivary gland endoscopy has a long learning curve. The aim of this retrospective study is to create an anatomical quantitative guide of different distances and angles significant for endoscopy. Twenty-six CBCT sialographies of healthy parotid ducts were included. Outcome parameters included diameters, distances, angles and number of minor tributaries. Results show the average distance from the papilla to the curvature of the gland was 41.5 mm (Q1 36.97 mm-Q3 45.32 mm), with an angle of 126.9° (Q1 107.58°-Q3 135.6°) of the curvature and a distance of 35.25 mm (±7.81 mm) between the curvature and the hilus. The mean width of the duct was 0.8 mm (Q1 0.7 mm-Q3 1.15 mm) at its narrowest and 2 mm (Q1 1.4 mm-Q3 2.2 mm) at its widest. This is the first anatomical quantitative study of the parotid duct in relation to sialendoscopy.

Background: Within medicine, it is common to use risk prediction tools towards clinical decision making. One of the most widely accepted assessment tools is the American Society of Anesthesiologists Physical Status (ASA PS) classification. Oral and maxillofacial procedures performed in an ambulatory setting would be considered low risk for the procedure itself. However, little is known concerning the impact of ASA PS on surgical outcomes. The aim of the present research was to evaluate the effect of ASA PS classification on early implant failure (EIF)., Methods: Retrospective cohort study based on dental records. All treatments were performed by experienced oral and maxillofacial surgeons and experienced prosthodontists., Inclusion Criteria: ASA physical status 1,2,3, consecutive individuals. Variables included the following: age, gender, implant location, implant length, implant width, smoking, and early implant failure., Results: Univariate tests at the patient level showed no statistically difference between the different classifications of ASA PS (1,2,3). Multivariate model using logistic regression at individual level showed that two factors were found to be associated with an increased risk for EIF-augmented bone and implant brand., Conclusions: ASA PS 3 is not a contraindication for implant-supported prostheses. EIF in ASA PS 3 is not significantly different from ASA PS 1,2. In contrast, factors such as bone augmentation and implant brand might be significant risk factors for EIF, regardless of ASA PS.

Purpose: Evaluate the esthetic outcome of ridge augmentation using cancellous bone-block allografts, late implant placement, and immediate loading in the atrophic anterior maxilla, by PES (pink esthetic score) and WES (white esthetic score) indexes. Materials and Methods: Retrospective cohort study. Inclusion criteria were bone loss of at least 3 mm horizontally and 3 mm vertically according to preliminary CBCT; ridge augmentation using cancellous bone-block allografts; six months later the implant insertion and immediately loaded. PES-WES index was used for esthetic assessment of soft tissues surrounding the final implant-supported prosthesis (ISP). Results: All twenty-five successive individuals were included. The mean follow-up was 12.1 ± 56 months (range, 42−90 months). The mean PES index and WES index were 7 ± 1.74 (range: 5−10) and 8.4 ± 2.12 (range: 5−10), respectively. The mean total combination of PES index and WES index (PES/WES) was 15.3 ± 2.85 (range: 12−20). All ISPs had an overall score >12 (the defined threshold of clinical acceptability). Conclusions: Ridge augmentation in the atrophic anterior maxilla using cancellous bone-block allografts and immediate loading allows a stable esthetic result of the soft and hard tissues over the years (follow-up of 42−90 months).

Space radiation presents a substantial threat to travel beyond Earth. Relatively low doses of high-energy particle radiation cause physiological and behavioral impairments in rodents and may pose risks to human spaceflight. There is evidence that 56 Fe irradiation, a significant component of space radiation, may be more harmful to males than to females and worsen Alzheimer's disease pathology in genetically vulnerable models. Yet, research on the long-term, sex- and genotype-specific effects of 56 Fe irradiation is lacking. Here, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like APP/PS1 mice with 0, 0.10, or 0.50 Gy of 56 Fe ions (1GeV/u). Mice underwent microPET scans before and 7.5 months after irradiation, a battery of behavioral tests at 11 months of age and were sacrificed for pathological and biochemical analyses at 12 months of age. 56 Fe irradiation worsened amyloid-beta (Aβ) pathology, gliosis, neuroinflammation and spatial memory, but improved motor coordination, in male transgenic mice and worsened fear memory in wild-type males. Although sham-irradiated female APP/PS1 mice had more cerebral Aβ and gliosis than sham-irradiated male transgenics, female mice of both genotypes were relatively spared from radiation effects 8 months later. These results provide evidence for sex-specific, long-term CNS effects of space radiation.

Purpose: The purpose of this randomized controlled trial was to compare the surgical site infection rate with short (24 hours) vs extended (7 days) antibiotic prophylaxis for maxillary sinus floor augmentation surgery., Materials and Methods: Eighty-five patients who were candidates for unilateral or bilateral maxillary sinus floor augmentation surgery were randomly assigned to short or extended antibiotic prophylaxis. Patients were evaluated on days 7, 14, 30, 60, and 180 after surgery for symptoms and signs of infection. The primary study endpoint was the development of surgical site infection up to day 180 postoperatively., Results: Patients underwent a total of 117 maxillary sinus floor augmentation surgeries, 62 in the short prophylaxis arm and 55 in the extended prophylaxis arm. Fifty-three patients (62%) had unilateral surgery, and 32 (38%) had bilateral surgery. Three patients developed a surgical site infection by 180 days postsurgery (overall rate, 2.6%): one patient (1.6%) in the 24-hour arm and two (3.6%) in the extended prophylaxis arm. All three patients received antibiotic treatment, and the infections resolved entirely., Conclusion: A low rate of surgical site infection was observed after maxillary sinus floor augmentation, and there was no apparent advantage to extended (7 days) vs short (24 hours) duration of antibiotic prophylaxis. The findings do not support the use of extended postprocedural chemoprophylaxis for patients undergoing maxillary sinus floor augmentation.

Objectives: Assess clinical, imaging, operative, and post-operative characteristics of drug-induced vs. non-drug-induced sialolithiasis that are termed 'other etiologies of sialolithiasis.', Materials and Methods: Data collected from a retrospective cohort of 96 patients who underwent intra-oral sialolith removal operations were categorized as patient disease characteristics, physical examination results, and imaging and therapeutic features. Patients were divided into two groups based on having drug-induced sialolithiasis (DIS) vs. other etiologies of sialolithiasis (OES). Patients who consumed any medication for chronic conditions were regarded as DIS. Statistical analyses were conducted to elucidate differences and similarities between the two groups., Results: There were 60 patients in the DIS group and 36 in the OES group. DIS patients were significantly older (average age 57.9 vs. 39.8 years, respectively), with no gender predilection. Statins and anti-hypertensive medications were most commonly consumed. Presenting symptoms including number of past swellings, salty tasting saliva, pain, and antibiotic treatment were similar between the groups; mealtime-related swelling of the gland was noted in a higher proportion of OES patients (51.5% vs. 37%, respectively). Analysis of sialolith size and location from fixed anatomical landmarks on the mandible were not different between groups, and the most frequent sialolith location was the hilus gland in DIS vs. intra-glandular in OES patients. Sialolith removal operation time was significantly shorter for DIS patients (45 ± 11.5 vs. 61.1 ± 18.1 minutes)., Conclusion: Drug-induced sialolithiasis may be regarded as a unique entity with a typical clinical age, presenting symptoms, imaging characteristics, and surgery duration., Clinical Relevance: Clinicians should be aware of the above-mentioned differences when treating patients with sialolithiasis and anticipate a more challenging sialolith removal procedure for other etiologies of sialolithiasis, possibly due to underlying anatomical factors of the duct system. When treating drug-induced sialolithiasis, clinicians can expect a shorter operation time with a similar success rate and hospitalization time as with a younger, healthier population with other sialolithiasis etiologies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Angiolipoma, distinguishable from other lipomas by its excessive degree of vascular vessels, are rare in the head and neck and require unique management. A slow growing mass, located underneath the inferior border of the right mandibular angle of a 51-year-old female, was excised under general anesthesia. Unexpected excessive bleeding during the excision was observed and the histological specimen was diagnosed as angiolipoma. As shown in this case report, pre-operative imaging modalities have a crucial influence and are sufficient to diagnose and manage angiolipomas. The "Gold standard" treatment is excision with clear margins and bleeding management should be taken into account according to appropriate differential diagnosis., Competing Interests: The authors declare no conflict of interest.

Chimeric antigen receptor (CAR) T-cell therapy has recently emerged as a groundbreaking treatment for CD19-expressing hematologic malignancies and received rapid approval by the U.S. Food & Drug Administration. Tisagenlecleucel and axicabtagene ciloleucel are now widely available at CAR T-cell therapy centers around the United States. Many patients have achieved complete response or remission despite failing multiple previous lines of therapy, but some patients endure the severe risks of cytokine release syndrome, neurotoxicity, and other immunologic effects. As more patients receive this therapy, they will present to their primary oncologists in the community setting for continued follow-up. Oncology-trained advanced practitioners must then have a working knowledge of CAR T-cell therapy, its toxicities, and follow-up care. This review presents the CAR T-cell therapy development and infusion process with associated immediate management. In addition, patient assessment and disease monitoring, relevant diagnostics, unique grading systems to CAR T-cell therapy toxicities, indications for hospitalization, infection prophylaxis, and management of nonneutropenic and neutropenic fever are presented., Competing Interests: The author has no conflicts of interest to disclose., (© 2020 Harborside™.)

Background: The treatment of patients with advanced head and neck cancers requires an extensive oromandibular and craniomaxillofacial resection in many cases. The reconstruction after these extensive resections presents many challenges to the reconstructive surgical team. The purpose of the reconstruction is not only to rehabilitate the physical facial appearance, but also to rehabilitate function, in order to improve future quality of life. To achieve this goal, the use of free tissue reconstruction is often required. The main challenge with osseous free flap reconstruction of the facial bones is the need of perfect alignment at the defect site. The use of different 3D technologies including computerized models and printed 3D stereolithographic models in the preoperative setting improves the accuracy and the outcome of the reconstruction.

Background: Women with metastatic breast cancer (MBC) experience unique symptom management and psychosocial needs due to aggressive, yet palliative treatment with a progressive, chronic illness., Objective: This article describes the effect of a quality improvement project for coordination of supportive care in MBC. Program evaluations included referral rates for supportive services, patient-reported outcomes of symptom distress, generalized anxiety, and overall well-being., Design: An interdisciplinary Support, Education and Advocacy Program (MBC-SEA) was developed. The 1-hour, weekly, patient review included collaborative assessments to determine needs for social service, psychological counseling, and palliative care. A prospective pre- and postexperimental cohort design with convenience sampling was used. Analysis was conducted with paired t test analysis of pre- and postimplementation outcomes., Setting/participants: Program outcomes of 118 women with MBC visiting an urban outpatient breast cancer clinic during September 2016 to November 2016 (pre) and January 2017 to March 2017 (post) were evaluated., Measurements: Referral rates to social work and palliative care, symptom, anxiety, and overall well-being scores., Results: Following program implementation, referrals to palliative care and social work supportive services increased significantly including patient-reported outcomes symptom distress scores mean difference 1.4 (95% confidence interval [CI]: 0.4306-2.6428), P = .004; generalized anxiety scores mean difference 1.5 (95% CI: 0.5406-2.5781), P = .003; and overall well-being mean difference of -0.7 (95% CI: -1.3498 to -0.0570), P = .03., Conclusions: Purposeful nurse-led assessment for social service and palliative care needs increases referrals with improvement in patient-reported outcomes.

Space travel will expose people to high-energy, heavy particle radiation, and the cognitive deficits induced by this exposure are not well understood. To investigate the short-term effects of space radiation, we irradiated 4-month-old Alzheimer's disease (AD)-like transgenic (Tg) mice and wildtype (WT) littermates with a single, whole-body dose of 10 or 50 cGy 56 Fe ions (1 GeV/u) at Brookhaven National Laboratory. At ~1.5 months post irradiation, behavioural testing showed sex-, genotype-, and dose-dependent changes in locomotor activity, contextual fear conditioning, grip strength, and motor learning, mainly in Tg but not WT mice. There was little change in general health, depression, or anxiety. Two months post irradiation, microPET imaging of the stable binding of a translocator protein ligand suggested no radiation-specific change in neuroinflammation, although initial uptake was reduced in female mice independently of cerebral blood flow. Biochemical and immunohistochemical analyses revealed that radiation reduced cerebral amyloid-β levels and microglia activation in female Tg mice, modestly increased microhemorrhages in 50 cGy irradiated male WT mice, and did not affect synaptic marker levels compared to sham controls. Taken together, we show specific short-term changes in neuropathology and behaviour induced by 56 Fe irradiation, possibly having implications for long-term space travel.

Many proteins are synthesized as precursors, with propeptides playing a variety of roles such as assisting in folding or preventing them from being active within the cell. While the precise role of the propeptide in fungal lipases is not completely understood, it was previously reported that mutations in the propeptide region of the Rhizomucor miehei lipase have an influence on the activity of the mature enzyme, stressing the importance of the amino acid composition of this region. We here report two structures of this enzyme in complex with its propeptide, which suggests that the latter plays a role in the correct maturation of the enzyme. Most importantly, we demonstrate that the propeptide shows inhibition of lipase activity in standard lipase assays and propose that an important role of the propeptide is to ensure that the enzyme is not active during its expression pathway in the original host., Competing Interests: The authors declare the following competing financial interest(s): Novozymes are a commercial enzyme supplier.

Purpose: To compare short- and long-term quality of life (QOL) scores in patients undergoing mandibular resection and reconstruction., Materials and Methods: All the patients who underwent resection and reconstruction of the mandible between 2000 and 2015 at a large tertiary center were retrospectively reviewed. Their QOL was measured by the University of Washington QOL questionnaire. Between 12 and 189 months (median 83.5 months) had elapsed since the end of treatment. The QOL of the short-term (< 5 years) and long-term (> 5 years) follow-up groups was compared and analyzed., Results: Fifty-eight patients completed the questionnaire. The scores for physical function, emotional function, activity, recreation, and taste domains were significantly higher for the long-term follow-up group. The activity and pain domains posed a significant problem for significantly more patients in the short-term follow-up group., Conclusion: Comparison of the short- and long-term QOL scores of patients undergoing mandibular resection and reconstruction revealed that the scores for the latter were significantly higher in several domains. This finding might be indicative of a cumulative effect of time on patients' QOL, even many years post-treatment.

Patients undergoing treatment for cancer often experience stress, fatigue, and pain during their treatment. Medical management of these symptoms can cause additional adverse effects, but it is possible that noninvasive complementary therapies may be able to reduce these symptoms without unwanted adverse effects. The purpose of this study was to assess the feasibility and impact of the Seva Stress Release acupressure protocol on stress, fatigue, pain, and vital signs of patients hospitalized for cancer treatment. Thirty patients receiving cancer treatment and experiencing stress, fatigue, and pain were recruited for the study. After obtaining informed consent, baseline data (survey and vital signs) were obtained, followed by administration of the Seva Stress Release. After the intervention, vital signs were obtained, and patients completed 2 additional surveys. After Seva, patient stress, fatigue, pain, heart rate, and respirations were significantly decreased (P = .000). Sixty-six percent of participants experienced symptom relief for at least 1 to 4 hours. Qualitative findings also indicated that patients reported better sleep and mental clarity after the intervention. The Seva protocol could be taught to nurses and be used as an independent intervention for patients experiencing adverse effects of cancer treatment, to promote comfort and reduce stress and fatigue.

Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects., Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers., Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers., Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression., Conclusions: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Third lower molar partially erupted is commonly encountered in dental practice. This situation challenges clinicians with the dilemma whether to remove or to monitor it, because this molar can cause pathology of the adjacent second molar. The aim of this retrospective study is to evaluate the relationship between third mandibular molar and distal cervical caries in second molar. This retrospective study analyzed 55 digital orthopantograms of adult patients and a total number of 95 mandibular third molars were assessed for eruption status, angulation, radiographic evidence of caries or restoration in the mandibular third molar, and radiographic evidence of caries or restoration in the distal surface of the mandibular second molar. The distal cervical caries in second molar is associated with fully erupted and partially erupted wisdom molar in horizontal, mesioangular and vertical position and less with presence of caries in third molar. There are caries lesions in distal second molars in mesioangular position when adjacent third molar is caries free.

Background: A significant amount of common variable immunodeficiency (CVID) patients manifest with autoimmunity. Particularly, autoimmune thrombocytopenia (AITP) is commonly seen. Intravenous immunoglobulins (IVIG) are an established treatment option for both, CVID and AITP. Nonetheless, due to fewer systemic side effects, immunoglobulins are increasingly applied subcutaneously (SCIG)., Objective: To compare the efficacy and safety of IVIG and SCIG treatment in patients with both CVID and clinical relevant thrombocytopenia in the prevention of AITP bouts., Methods: Patients with both CVID and AITP were enrolled at the Centre for Chronic Immunodeficiency in Freiburg, Germany and at the Royal Free Hospital, London, UK. Clinical and laboratory features of patients were collected and analyzed., Results: This retrospective study recruited 61 adult patients between 19 and 71 years of age who had a diagnosis of CVID and at least one bout of thrombocytopenia defined as a platelet count of <50,000/μl if bleeding episodes occurred, or a platelet count of <20,000/μl without bleeding. Thirty patients received immunoglobulin through IVIG, and 31 patients were on SCIG replacement. One patient of the IVIG-group was excluded, because of a diffuse large B-cell lymphoma. We did not find a higher occurrence of thrombocytopenic events in CVID patients who received SCIG, compared to CVID patients who had IVIG, but we identified a low IgG through level as a risk factor for AITP bouts., Conclusion: SCIG is at least as safe as IVIG for patients with CVID and concomitant AITP. However, an IgG through level under 7 g/l is a key factor for the development of AITP.

The diagnosis of lipopolysaccharide-responsive beige-like-anchor-protein (LRBA) deficiency currently relies on gene sequencing approaches that do not support a timely diagnosis and clinical management. We developed a rapid and sensitive test for clinical implementation based on the detection of LRBA protein by flow cytometry in peripheral blood cells after stimulation. LRBA protein was assessed in a prospective cohort of 54 healthy donors and 57 patients suspected of LRBA deficiency. Receiver operating characteristics analysis suggested an LRBA:MFI ratio cutoff point of 2.6 to identify LRBA-deficient patients by FACS with 94% sensitivity and 80% specificity and to discriminate them from patients with a similar clinical picture but other disease-causing mutations. This easy flow cytometry-based assay allows a fast screening of patients with suspicion of LRBA deficiency reducing therefore the number of patients requiring LRBA sequencing and accelerating the treatment implementation. Detection of biallelic mutations in LRBA is however required for a definitive diagnosis.

Background: Patients with common variable immunodeficiency (CVID) suffer frequent respiratory tract infections despite immunoglobulin replacement and are prescribed significant quantities of antibiotics. The clinical and microbiological nature of these exacerbations, the symptomatic triggers to take antibiotics, and the response to treatment have not been previously investigated., Objectives: To describe the nature, frequency, treatment, and clinical course of respiratory tract exacerbations in patients with CVID and to describe pathogens isolated during respiratory tract exacerbations., Methods: We performed a prospective diary card exercise in 69 patients with CVID recruited from a primary immunodeficiency clinic in the United Kingdom, generating 6210 days of symptom data. We collected microbiology (sputum microscopy and culture, atypical bacterial PCR, and mycobacterial culture) and virology (nasopharyngeal swab multiplex PCR) samples from symptomatic patients with CVID., Results: There were 170 symptomatic exacerbations and 76 exacerbations treated by antibiotics. The strongest symptomatic predictors for commencing antibiotics were cough, shortness of breath, and purulent sputum. There was a median delay of 5 days from the onset of symptoms to commencing antibiotics. Episodes characterized by purulent sputum responded more quickly to antibiotics, whereas sore throat and upper respiratory tract symptoms responded less quickly. A pathogenic virus was isolated in 56% of respiratory exacerbations and a potentially pathogenic bacteria in 33%., Conclusions: Patients with CVID delay and avoid treatment of symptomatic respiratory exacerbations, which could result in structural lung damage. However, viruses are commonly represented and illnesses dominated by upper respiratory tract symptoms respond poorly to antibiotics, suggesting that antibiotic usage could be better targeted., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Microglial activation is a key pathological feature of Alzheimer's disease (AD). PET imaging of translocator protein 18 kDa (TSPO) is a strategy to detect microglial activation in vivo . Here we assessed flutriciclamide ([ 18 F]GE-180), a new second-generation TSPO-PET radiotracer, for its ability to monitor response to LM11A-31, a novel AD therapeutic in clinical trials. AD mice displaying pathology were treated orally with LM11A-31 for 3 months. Subsequent [ 18 F]GE-180-PET imaging revealed significantly lower signal in cortex and hippocampus of LM11A-31-treated AD mice compared to those treated with vehicle, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining. In addition to detecting decreased microglial activation following LM11A-31 treatment, [ 18 F]GE-180 identified activated microglia in AD mice with greater sensitivity than another second-generation TSPO radiotracer, [ 18 F]PBR06. Together, these data demonstrate the promise of [ 18 F]GE-180 as a potentially sensitive tool for tracking neuroinflammation in AD mice and for monitoring therapeutic modulation of microglial activation., Competing Interests: Competing interests: Dr. Longo is listed as an inventor on patents relating to LM11A-31, which are assigned to UNC and UCSF. Dr. Longo is eligible for royalties distributed by the assigned universities. Dr. Longo has financial interest in PharmatrophiX, a company focused on the development of small molecule ligands for neurotrophin receptors, which has licensed several of these patents.

There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF ≤ 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per-oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean ± SD age of 53.5 ± 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9 %), foreign body in sinus (n = 10, 22.2 %) nasal congestion (n = 7, 15.5 %), halitosis (n = 6, 13.3 %) and pain (n = 5, 12.2 %). Surgical complications included local pain (n = 2, 4.4 %), persistent rhinitis (n = 2, 4.4 %) and synechia (n = 1, 2.2 %). One patient required revision surgery due to an unresolved OAF. The OAF of all the other 44 patients (97.8 %) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 ± 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis.

Objectives: To report our experience with combined one-stage double-team maxillary sinus floor elevation (SFE) and endonasal endoscopic sinus surgery (ESS) procedure for concomitant inflammatory sinonasal pathologies., Material and Methods: Clinical records of all patients that underwent maxillary SFE in conjunction with endonasal ESS for the treatment of inflammatory sinonasal pathologies between 2011 and 2013 were retrospectively reviewed. All included patients had a sinonasal-related pathology that was first suggested by the referring physician and was later confirmed clinically and radiographically by our combined team comprised of otorhinolaryngologist and maxillofacial surgeons., Results: Fifteen combined SFE+ESS surgeries were performed using either xenograft-allograft mixture or autograft-xenograft-allograft mixture. The study group included seven males and eight females, whose median age was 55 years (range, 45-78 years). Seven patients underwent a unilateral SFE, and eight patients underwent bilateral SFEs. During the same session, four patients also underwent septoplasty for deviated nasal septum, five patients underwent bilateral maxillary antrostomy, 10 patients underwent unilateral maxillary antrostomy, and six patients underwent maxillary sinus cyst resection. Seven combined procedures were performed under active infection. There were no intra-operative complications, and all SFE+ESS combined procedures were successful. Three patients required extended postoperative antibiotic treatment for persistent sinusitis. One patient reported infraorbital hypoesthesia., Conclusions: We first report the promising outcomes of the double-team one-stage SFE+ESS procedure performed by a combined team of otorhinolaryngologist and maxillofacial surgeons, including on patients presenting with an infection of the sinuses at the time of surgery., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)