Chemokine receptor CXCR4 expression in breast cancer as a potential predictive marker of isolated tumor cells in bone marrow

Interactions between the CXCR4 chemokine receptor in breast cancer cells and the ligand CXCL12/SDF-1α are thought to play an important role in breast cancer metastases. In this pilot study, CXCR4 expression along with other biomarkers including HER2-neu and EGFR, were measured in primary tumor samples of patients with operable breast cancer to test whether any of these biomarkers alone and in combination could indicate breast cancer with high likelihood of metastasizing to bone marrow. Cytokeratin (CK) positive cells in bone marrow were identified by flow-cytometry following enrichment with CK 7/8 antibody-coupled magnetic beads. Primary tumors (n = 18) were stained with specific antibodies for CXCR4, HER2-neu, EGFR, and PCNA using an indirect avidin–biotin horseradish peroxidase method. The majority of the patients had T2/T3 tumors (72%), or lymph node involvement (67%) as pathologic characteristics that were more indicative of high-risk breast cancer. High CXCR4 cytoplasmic expression was found in 7 of 18 patients (39%), whereas 6 of 18 patients (33%) were found to have CK positivity in bone marrow. The median number of CK⁺ cells was 236 (range, 20–847) per 5 × 10⁴ enriched BM cells. The presence of CK⁺ cells in bone marrow was found to be associated with increased expression of CXCR4 alone or in addition to EGFR and/or HER2-neu expression (P = 0.013, P = 0.005, and P = 0.025, respectively) in primary tumors. Furthermore, three patients with high CK positivity (>236 CK⁺ per 5 × 10⁴ enriched bone marrow cells) in bone marrow exclusively expressed high levels of CXCR4 with EGFR/HER2-neu (P = 0.001). Our data suggest that high CXCR4 expression in breast cancer may be a potential marker in predicting isolated tumor cells in bone marrow. CXCR4 coexpression with EGFR/HER2-neu might further predict a particular subset of patients with high CK positivity in bone marrow.     

Impact of anxiety,stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency

Background

Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP).

Methods

This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status.

Results

139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0–45) and 6 (min-max: 0–10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05).

Conclusions

This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

     

T-cell receptor heterogeneity of gamma delta T-cell clones from human female reproductive tissues.

gamma delta T cells were isolated from human decidua parietalis, decidua basalis and cervix and cloned in the presence of interleukin-2 (IL-2). T-cell receptor (TcR) expression was then analysed and compared with that of a panel of gamma delta T-cell clones from peripheral blood. Only 17/40 (42.5%) clones from decidua parietalis were V gamma 9+/V delta 2+ as compared to 68/94 (72%) of peripheral blood clones (P < 0.005). Conversely, 50% of clones from decidua parietalis but only 15% of clones from peripheral blood were V delta 1+ (P < 0.001). At least seven distinct TcR types were identified among the panel of clones from decidua parietalis and at least six different types were expressed by the panel of 17 clones from cervix. This receptor heterogeneity was not a result of interdonor variation as in all instances where more than one clone was obtained from a single sample, individual clones having between two and five receptor types were identified. However, 23/24 (95.8%) of clones from decidua basalis were V gamma 9+/V delta 2+. Most clones from decidua parietalis and cervix, whether V gamma 9+/V delta 2+ or V delta 1+, were positive for the mucosal lymphocyte marker, HML-1, but expression was often heterogeneous within a single clone. In contrast, almost all gamma delta T-cell clones from peripheral blood were HML-1-. Thus, unlike the mouse, gamma delta T cells within these human female reproductive tissues have a diverse TcR repertoire which, in decidua parietalis, is distinct from that of peripheral blood.     

Apolipoprotein E polymorphism and stroke in a population from eastern Turkey

Human apolipoprotein E (apo E) alleles are polymorphic with significantly different frequencies among different ethnic groups and have been associated with increased risk of coronary heart disease, and postulated as a major genetic susceptibility locus for Alzheimer's disease. Studies undertaken in different populations have shown different association patterns between apo E genotype and stroke. The aim of this study was to determine the risk of apo E genotype in stroke patients living in the eastern part of Turkey. The apo E genotypes and allele frequencies of 229 individuals from the same geographic area were determined by polymerase chain reaction and restriction fragment length polymorphism, of which 103 were patients with a documented history of stroke without other apparent dementia and 126 age-matched healthy subjects as a control group. A reduced E3/4 genotype frequency was found in subjects with stroke and the E2/3 genotype frequency was elevated in patients with previous stroke. There was no association between apo E epsilon4 allele and stroke. The APOE alleles had divergent effects in this population. Association between APOE (the gene) alleles and stroke in this population may be altered due to interaction with other genetic effects. The effects of APOE alleles and genotypes require further study in different populations.     

Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Background

Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV₁) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma.

Methods

In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV₁ and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed.

Results

In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P < .001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P = .52/0.15). Across subgroups, pre-BD FEV₁ improved by 0.18-0.22 L/0.19-0.24 L (all P < .05) and 0.23-0.36 L/0.15-0.25 L (all P < .01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P < .05) and 0.38-0.50/0.24-0.30 (all P < .05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P = .09). Dupilumab was also effective in patients taking medium-dose ICS.

Conclusion

Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline.

     

Polyorchidism in ultrasound examination: A case report

Polyorchidism is usually diagnosed incidentally when the patient undergoes imaging or surgery for some other reason. Although we are facing lack of evidence in different steps of diagnostic and therapeutic workup of these patients, this disorder is usually considered benign, not requiring any intervention. We report the case of a man complaining of a palpable mass in his scrotum. We evaluated the patient using ultrasound, MRI and serum tumour marker level measurement. The patient was finally diagnosed with polyorchidism (three testes). For the management, we recommended annual physical examination, US examination and serum tumour marker level measurement.     

Analysis of factors among 30-day and 1-year mortality rates in patients with borderline stable-unstable intertrochanteric hip fracture

ObjectiveThis study aimed to evaluate the possible effects of surgical procedures on mortality and to identify the possible risk factors for mortality in the management of geriatric hip fractures.MethodsA total of 191 patients (105 women and 86 men; mean age 82.26±9.681 [60–108] years) with AO/OTA 31A2.2 intertrochanteric fractures and treated with sliding hip screw, proximal femoral nail, or hemiarthroplasty were included in this retrospective cohort study. The treatment type was decided by the responsible surgeon according to the patients’ pre-injury activity level, bone quality, and features of the fracture. Age, sex, type of fracture, type of surgery performed, American society of anesthesiology (ASA) grade, type of anesthesia, time to surgery, type of physical therapy, length of hospital stay, and number of comorbidities were documented. We evaluated the 30-day and 1-year mortality of patients treated with sliding hip screw (SHS), proximal femoral nail antirotation (PFN-A), or hemiarthroplasty and identified the possible risk factors for mortality.ResultsA total of 49 patients underwent SHS, 58 underwent PFN-A, and 84 underwent hemiarthroplasty. Of these, 2 patients with SHS, 2 with PFN-A, and 11 with hemiarthroplasty died within 30 days after surgery, whereas 7 patients with SHS, 15 with PFN-A, and 23 with hemiarthroplasty died 1 year after surgery. The 30-day and 1-year overall mortality rates were 7.9% and 23.6%, respectively. Both the 30-day and 1-year mortality risks were higher in patients undergoing hemiarthroplasty than in patients undergoing SHS (p=0.068 versus 0.058). The 30-day mortality was higher in patients receiving general anesthesia than in those receiving combined spinal and epidural anesthesia (p=0.009). The 1-year mortality risk was higher in patients with ASA grade 4 than in those with grade 1 and 2 (p=0.045). Advanced age (p=0.022) and male sex (p=0.007) were also found to be the risk factors for 1-year mortality.ConclusionWe demonstrated that higher ASA grade, male sex, general anesthesia, and hemiarthroplasty procedures are associated with higher mortality rates in elderly patients with hip fractures. Thus, we highly recommend orthopedic surgeons to consider all these factors in the management of intertrochanteric hip fractures in the geriatric population.Level of EvidenceLevel IV, Prognostic Study     

Early and late visual prognosis in solar retinopathy

Background: Solar retinopathy was observed in a total of 86 eyes of 58 patients following the solar eclipse over Turkey in April 1976. The visual prognosis and the presence of late complications were evaluated at the early and late periods. Methods: Of the 58 patients, 34 (51 eyes) presented during the first week and came for follow-up examination in the succeeding week, also after 1, 3, 12 and 18 months. After that they were examined at yearly intervals (mean 4.2 years). Twenty-four patients (35 eyes) presented during the period between 1 and 11 years post-eclipse and were followed up for a mean period of 3.4 years. After a period of 15 years, all of the patients were invited for re-examination and nine patients (14 eyes) attended. Results: The improvement in visual acuity was observed to have taken place mostly during the first 2 weeks to 1 month after the eclipse. Further improvement in visual acuity was not observed in any of the eyes after the 18-month examination. The improvement in visual acuity was more prominent and earlier in the eyes that had visual acuity of 0.2 or better initially. Only the eyes with initial visual acuity equal to or better than 0.4 had a chance to improve their acuity to 10/10. Having observed the 51 eyes for mean period of 4.2 years and the 35 eyes for 3.4 years, no change in visual acuity was observed. Among the total of 86 eyes, 9 were found to have pseudolamellar macular holes. Conclusion: Correlation was found between initial visual acuity and the funduscopic appearance after the 2nd week. Fluorescein angiography was not found to be a conclusive test in solar retinopathy. No late complications were observed.     

Isolated Ruptured Inter‐Atrial Septal Cystic Echinococcosis during Pregnancy

Herein, we present a case of asymptomatic isolated cardiac cystic echinococcosis localized entirely to the inter‐atrial septum in a pregnant woman. The patient underwent successful surgery. Cardiac cystic echinococcosis is rarely seen in pregnancy. A high index of suspicion is necessary for the diagnosis of a cardiac cyst hydatid. The treatment of cardiac cyst hydatid is surgical and should not be delayed during pregnancy. Early surgery might prevent septic embolization and cardiac life‐threatening complications and save the lives of both mother and baby as in the present case.