Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

Recombinant Lysyl Oxidase Propeptide Protein Inhibits Growth and Promotes Apoptosis of Pre-Existing Murine Breast Cancer Xenografts

Lysyl oxidase propeptide (LOX-PP) ectopic overexpression inhibits the growth of cancer xenografts. Here the ability and mode of action of purified recombinant LOX-PP (rLOX-PP) protein to inhibit the growth of pre-existing xenografts was determined. Experimental approaches employed were direct intratumoral injection (i.t.) of rLOX-PP protein into murine breast cancer NF639 xenografts, and application of a slow release formulation of rLOX-PP implanted adjacent to tumors in NCR nu/nu mice (n = 10). Tumors were monitored for growth, and after sacrifice were subjected to immunohistochemical and Western blot analyses for several markers of proliferation, apoptosis, and for rLOX-PP itself. Direct i.t. injection of rLOX-PP significantly reduced tumor volume on days 20, 22 and 25 and tumor weight at harvest on day 25 by 30% compared to control. Implantation of beads preloaded with 35 micrograms rLOX-PP (n = 10) in vivo reduced tumor volume and weight at sacrifice when compared to empty beads (p<0.05). A 30% reduction of tumor volume on days 22 and 25 (p<0.05) and final tumor weight on day 25 (p<0.05) were observed with a reduced tumor growth rate of 60% after implantation. rLOX-PP significantly reduced the expression of proliferation markers and Erk1/2 MAP kinase activation, while prominent increases in apoptosis markers were observed. rLOX-PP was detected by immunohistochemistry in harvested rLOX-PP tumors, but not in controls. Data provide pre-clinical findings that support proof of principle for the therapeutic anti-cancer potential of rLOX-PP protein formulations

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1

PURPOSE: Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. METHODS: STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-α, IFN-γ or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. RESULTS: Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61 %). Out of 39 familial cases from 11 families, 26 patients (67 %) from 9 families and out of 18 sporadic cases, 9 patients (50 %) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. CONCLUSION: STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing

Cephalometric findings of the patients with Sagliker syndrome: Uglifying human face appearances in CKD

WOS: 000254992000134

Condyle position in Class II Division 1 malocclusion patients: Correlation between MPI records and CBCT images

Background: This study was designed to test the hypothesis that condyle position, as measured by cone beam computed tomography (CBCT), is correlated with the amount and direction of centric slide, determined using a mandibular position indicator (MPI). Methods: In this descriptive study, 40 Class II Division 1 patients with no signs or symptoms of temporomandibular joint disorder were evaluated. Power centric registration and CBCT imaging were performed for each patient. Mandibular position registrations were performed using a mandibular position indicator (MPI). The concentric positions of the condyles were assessed using CBCT imaging. Results: Based on the MPI findings, 57.5% of the patients studied showed a centric relation-centric occlusion discrepancy of ?2 mm in at least one direction at the level of the condyles. Eighty-two percent of the condylar distractions were found to be in the vertical inferior direction. Based on CBCT image tracing, nearly 87.5% of the condyle positions were found to be nonconcentric for the right and left sides. Significant anterior positioning of the condyles was revealed. No relationship was found between the MPI findings and the CBCT measurements. Conclusions: The hypothesis was rejected. The concentricity of the condyle in the mandibular fossa as determined using CBCT measurements cannot be used to predict the centric relation-centric occlusion changes at the level of the condyles. © 2013 World Federation of Orthodontists

THE IMPACT OF CONTACT LENS DURATION ON OCULAR DISCOMFORT

Objectives: To compare contact lens discomfort (CLD) using the Contact Lens Dry Eye Questionnaire-8 (CLDEQ8) in short and long-term CL wearers. Materials and Methods: This prospective study included 98 patients who applied to the Department of Ophthalmology of Ufuk University between January 2020 and January 2021 and had a history of wearing contact lenses for over a month. Participants who wore contact lenses (CL) for six months or less were categorized as short-term CL users, while those who wore them for more than six months were categorized as long-term CL users. Contact lens compliance and the CLDEQ-8 questionnaire results were compared between the groups. Results: The mean age was 21.70±2.81 years in 55 short-term CL wearers, and 80% were female. In 43 long-term CL wearers, the mean age was 28.69±8.48 years, and 86% were female (respectively, p<0.001, p=0.592). The duration of CL wear was 2.36±1.06 months in short-term CL wearers and 10.11±5.6 months in long-term CL wearers (p<0.001). The mean CLDEQ-8 score was 11.52±6.59 in short-term CL wearers and 14.37±6.55 in long-term CL wearers (p=0.015). In addition, 40% of short-term and 65.1% of long-term users had a CLDEQ-8 score greater than 12 (p=0.016). Conclusion: Long-term CL wearers experienced much more CLD, and several considered removing their lenses at various times. Contact lens discomfort has to be investigated, especially in long-term CL users, and solutions should be developed to avoid CL dropout. © Annals of Translational Medicine. All rights reserved