X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Common variable immune deficiency (CVID), one of the most common primary immunodeficiency diseases presents in adults, whereas X-linked agammaglobulinemia (XLA), an inherited humoral immunodeficiency, is usually diagnosed early in life after maternal Igs have waned. However, there have been several reports in the world literature in which individuals have either had a delay in onset of symptoms or have been misdiagnosed with CVID and then later found to have mutations in Bruton's tyrosine kinase (BTK) yielding a reclassification as adult-onset variants of XLA. The typical finding of absent B cells should suggest XLA rather than CVID and may be a sensitive test to detect this condition, leading to the more specific test (Btk mutational analysis). Further confirmation may be by mutational analyses.</p> <p>Methods</p> <p>The records of 2 patients were reviewed and appropriate clinical data collected. BTK mutational analysis was carried out to investigate the suspicion of adult-presentation of XLA. A review of the world literature on delayed diagnosis of XLA and mild or "leaky" phenotype was performed.</p> <p>Results</p> <p>2 patients previously diagnosed with CVID associated with virtual absence of CD19⁺B cells were reclassified as having a delayed diagnosis and adult-presentation of XLA. <b>Patient 1</b>, a 64 yr old male with recurrent sinobronchial infections had a low level of serum IgG of 360 mg/dl (normal 736–1900), IgA <27 mg/dl (normal 90–474), and IgM <25 mg/dl (normal 50–415). <b>Patient 2</b>, a 46 yr old male with recurrent sinopulmonary infections had low IgG of 260 mg/dl, low IgA <16 mg/dl, and normal IgM. Mutational analysis of BTK was carried out in both patients and confirmed the diagnosis of XLA</p> <p>Conclusion</p> <p>These two cases represent an unusual adult-presentation of XLA, a humoral immunodeficiency usually diagnosed in childhood and the need to further investigate a suspicion of XLA in adult males with CVID particularly those associated with low to absent CD19⁺B cells. A diagnosis of XLA can have significant implications including family counseling, detecting female carriers, and early intervention and treatment of affected male descendents.</p

Diagnostic performance of FDG-PET/CT of post-transplant lymphoproliferative disorder and factors affecting diagnostic yield

PURPOSE: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, requiring a timely and accurate diagnosis. In this study, we evaluated the diagnostic performance of FDG-PET/CT in patients with suspected PTLD and examined if lactate dehydrogenase (LDH) levels, Epstein-Barr virus (EBV) load, or timing of FDG-PET/CT relate to detection performance of FDG-PET/CT. METHODS: This retrospective study included 91 consecutive patients with clinical suspicion of PTLD and a total of 97 FDG-PET/CT scans within an 8-year period. Pathology reports and a 2-year follow-up were used as the reference standard. Diagnostic performance of FDG-PET/CT for detection of PTLD as well as logistic regression analysis for factors expected to affect diagnostic yield were assessed. RESULTS: The diagnosis of PTLD was established in 34 patients (35%). Fifty-seven FDG-PET/CT scans (59%) were true negative, 29 (30%) were true positive, 6 (6%) false positive, and 5 (5%) false negative. Sensitivity of FDG-PET/CT for the detection of PTLD was 85%, specificity 90%, positive predictive value 83%, and negative predictive value 92%, with good inter-observer variability (k = 0.78). Of the parameters hypothesized to be associated with a true positive FDG-PET/CT result for the diagnosis of PTLD, only LDH was statistically significant (OR 1.03, p = 0.04). CONCLUSION: FDG-PET/CT has a good diagnostic performance in patients suspected of PTLD, with a good inter-observer agreement. Only LDH levels seemed to influence the detection performance of FDG-PET/CT. EBV-DNA load and timing of FDG-PET/CT after transplantation did not affect FDG-PET/CT diagnostic yield

Smoking and its effect on scar healing

Scar formation is influenced by several factors such as wound infection, tension, wound depth and anatomical localization. Hypertrophic scarring is often the result of an imbalance in the wound and scar healing process. The exact underlying pathophysiological mechanism remains unclear. Smoking has a higher risk of postoperative complications probably due to a diminished macrophage induction. Following our clinical impression that smokers without postoperative wound infections show esthetically better scars, we evaluated the scars after a reduction mammaplasty in smoking and nonsmoking patients in a prospective clinical trial. Between July 2006 and September 2007, 13 smokers and 30 non smokers with a reduction mammaplasty were included. They were recruited from Viecuri Medical Centre and Atrium Medical Centre in the Netherlands after written consent. Surgical data and data of the patients' condition were collected. Follow-up for erythema values of the scars was done with a colorimeter (The Minolta CR-300, Minolta Camera Co., Ltd., Osaka Japan) at 1, 3, 6 and 9 months postoperatively on four standardized postsurgical sites. ANOVA and Chi-square test were used for statistical analysis. In the smoking group, the scars were significantly less red compared to the nonsmoking group. No significant differences were found in BMI, resection weight and drain production between both groups. Although smoking is certainly not recommended as a preventive therapy to influence scar healing, this study confirms our assumption that smokers tend to have faster and less erythemateous scar healing to nonsmokers. Further research is needed to understand the mechanism of the effect of smoking on scars

Skin autofluorescence is increased in patients with carotid artery stenosis and peripheral artery disease

Advanced glycation end products (AGEs) have a pivotal role in atherosclerosis. We evaluated skin autofluorescence (SAF), a non-invasive measurement of tissue AGE accumulation, in patients with carotid artery stenosis with and without coexisting peripheral artery occlusive disease (PAOD). SAF was measured using the AGE Reader™ in 56 patients with carotid artery stenosis and in 56 age- and sex-matched healthy controls without diabetes, renal dysfunction or known atherosclerotic disease. SAF was higher in patients with carotid artery stenosis compared to the control group: mean 2.81 versus 2.46 (P = 0.002), but especially in the younger age group of 50–60 years old: mean 2.82 versus 1.94 (P = 0.000). Patients with carotid artery stenosis and PAOD proved to have an even higher SAF than patients with carotid artery stenosis only: mean 3.28 versus 2.66 (P = 0.003). Backward linear regression analysis showed that age, smoking, diabetes mellitus, renal function and the presence of PAOD were the determinants of SAF, but carotid artery stenosis was not. SAF is increased in patients with carotid artery stenosis and PAOD. The univariate and multivariate associations of SAF with age, smoking, diabetes, renal insufficiency and PAOD suggest that increased SAF can be seen as an indicator of widespread atherosclerosis

Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE):a multicenter observational study

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and (18)F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341

Relationship between semiquantitative 18F-fluorodeoxyglucose positron emission tomography metrics and necrosis in classical Hodgkin lymphoma

Semiquantitative 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) parameters have been proposed as prognostic markers in classical Hodgkin lymphoma (cHL). In non-Hodgkin lymphoma necrosis as assessed by 18F-FDG PET or computed tomography (CT) (necrosisvisual) correlates with an adverse prognosis. We investigated whether semiquantitative 18F-FDG PET metrics correlate with necrosisvisual, determined the incidence of necrosisvisual and explored the prognostic impact of these factors in cHL. From 87 cHL cases treated with ABVD, (escalated) BEACOPP or CHOP chemotherapy between 2010 and 2017, 71 had both a NEDPAS/EARL accredited 18F-FDG PET and a contrast enhanced CT scan. Semiquantitative 18F-FDG PET parameters were determined using Hermes Hybrid 3D software. Necrosisvisual, defined by photopenic tumor areas on 18F-FDG PET and attenuation values between 10 and 30 Hounsfield units (HUs) on CT, was assessed blinded to outcome. Univariate Cox regression survival analyses of progression free survival (PFS) were performed. Necrosisvisual was observed in 18.3% of cHL patients. Bulky disease (tumor mass >10 cm in any direction) (P = 0.002) and TLG (P = 0.041) but no other semiquantitative parameters were significantly associated with necrosisvisual. In exploratory univariate survival analysis for PFS the covariates IPS, bulky disease, MTV and TLG were prognostic, while necrosisvisual was not

A Prospective Evaluation of Quick Intraoperative Parathyroid Hormone Assay at the Time of Skin Closure in Predicting Clinically Relevant Hypocalcemia after Thyroidectomy

BACKGROUND: Post-thyroidectomy hypocalcemia is a major contributing factor in delayed hospital discharge and dissuading surgeons from ambulatory thyroidectomy. We prospectively evaluated the accuracy and reliability of quick parathyroid hormone level measurement at skin closure (PTH-SC) in predicting clinically relevant hypocalcemia (i.e., patients requiring calcium +/- calcitriol supplements on hospital discharge). METHODS: Of the 117 patients who underwent a total or completion total thyroidectomy and PTH-SC, 17 (14.5 %) had hypocalcemic symptoms or adjusted calcium 1 pmol/L) had a higher specificity (95.0 %) and AUC (0.887) than serial calcium monitoring or PTH-D1 alone. Although 3/98 of patients with PTH-SC >1 pmol/L required calcium supplements on discharge, they required only the minimum amount to maintain normocalcemia. CONCLUSION: PTH-SC is an accurate and reliable means of predicting clinically relevant hypocalcemia. It would be reasonable to discharge those with PTH-SC >1 pmol/L on the same operative day as the risk of life-threatening hypocalcemia would seem unlikely.published_or_final_versio

Preoperative anaemia and outcome after elective cardiac surgery:a Dutch national registry analysis

Background: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. Methods: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. Results: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4–1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3–1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4–2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. Conclusions: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes