The effect of systemic sclerosis and its subtypes on ocular anterior and posterior segment parameters.

PURPOSE: To evaluate anterior and posterior segment parameters in the eyes of patients with systemic sclerosis (SSc) and examine the effect of disease and disease subtypes on these parameters. METHODS: This cross-sectional study included 54 eyes of 27 SSc patients and 54 eyes of 27 age- and sex-matched healthy controls. In addition to a complete ophthalmologic examination, all patients were examined using a Scheimpflug camera, specular microscopy, and spectral domain optical coherence tomography. RESULTS: The mean age of the patients was 52.5 ± 11.4 years and 19 patients were female. Anterior chamber volume, central corneal thickness, and central macular thickness (CMT) were significantly lower in the eyes of SSc patients compared to healthy controls (p = 0.01, p = 0.03, and p = 0.006, respectively). When evaluated according to SSc subtype, CMT was lower in diffuse SSc patients (p = 0.001), while mean retinal nerve fiber layer (RNFL) and inferior quadrant RNFL values were lower in limited SSc (p = 0.003 and p = 0.005, respectively). CONCLUSION: In the eyes of patients with SSc, some ocular parameters may show decreases compared to healthy individuals, presumably secondary to disease-related vasculopathy and fibrosis. CMT and RNFL parameters may be affected differently according to disease subtype.

Label-Free Identification of Exosomes using Raman Spectroscopy and Machine Learning.

Exosomes, nano-sized extracellular vesicles (EVs) secreted from cells, carry various cargo molecules reflecting their cells of origin. As EV content, structure, and size are highly heterogeneous, their classification via cargo molecules by determining their origin is challenging. Here, a method is presented combining surface-enhanced Raman spectroscopy (SERS) with machine learning algorithms to employ the classification of EVs derived from five different cell lines to reveal their cellular origins. Using an artificial neural network algorithm, it is shown that the label-free Raman spectroscopy method's prediction ratio correlates with the ratio of HT-1080 exosomes in the mixture. This machine learning-assisted SERS method enables a new direction through label-free investigation of EV preparations by differentiating cancer cell-derived exosomes from those of healthy. This approach will potentially open up new avenues of research for early detection and monitoring of various diseases, including cancer.

Werner helicase is required for proliferation and DNA damage repair in multiple myeloma.

BACKGROUND: Multiple myeloma (MM), characterized by extensive genomic instability and aberrant DNA damage repair, is a plasma cell malignancy due to the excessive proliferation of monoclonal antibody-producing plasma cells in the bone marrow. Despite the significant improvement in the survival of patients with the development of novel therapeutic agents, MM remains an incurable disease. Werner (WRN) helicase, a member of the RecQ helicase family that contributes to DNA replication, recombination, and repair, has been highlighted in cancer cell survival, yet the role and mechanism of WRN in MM remain unclear. METHODS AND RESULTS: Increased mRNA expression of WRN in newly diagnosed and relapsed CD138+ myeloma plasma cells than normal CD138+ plasma cells and their matched CD138- non-tumorigenic cells were detected by qPCR. Using NSC19630, a specific WRN helicase inhibitor, we further showed decreased cell viability, proliferation, and DNA repair and increased DNA damage and apoptosis in MM cells by MTT assay, cell cycle assay, apoptosis assay, and Western blotting. CONCLUSIONS: The results of the present study demonstrate that WRN is essential in MM cell viability, proliferation, and genomic stability, indicating its inhibition may enhance the efficacy of chemotherapy in MM.

Endogenous Retroviral Elements Generate Pathologic Neutrophils in Pulmonary Arterial Hypertension.

Rationale: The role of neutrophils and their extracellular vesicles (EVs) in the pathogenesis of pulmonary arterial hypertension is unclear. Objectives: To relate functional abnormalities in pulmonary arterial hypertension neutrophils and their EVs to mechanisms uncovered by proteomic and transcriptomic profiling. Methods: Production of elastase, release of extracellular traps, adhesion, and migration were assessed in neutrophils from patients with pulmonary arterial hypertension and control subjects. Proteomic analyses were applied to explain functional perturbations, and transcriptomic data were used to find underlying mechanisms. CD66b-specific neutrophil EVs were isolated from plasma of patients with pulmonary arterial hypertension, and we determined whether they produce pulmonary hypertension in mice. Measurements and Main Results: Neutrophils from patients with pulmonary arterial hypertension produce and release increased neutrophil elastase, associated with enhanced extracellular traps. They exhibit reduced migration and increased adhesion attributed to elevated ß1-integrin and vinculin identified by proteomic analysis and previously linked to an antiviral response. This was substantiated by a transcriptomic IFN signature that we related to an increase in human endogenous retrovirus K envelope protein. Transfection of human endogenous retrovirus K envelope in a neutrophil cell line (HL-60) increases neutrophil elastase and IFN genes, whereas vinculin is increased by human endogenous retrovirus K deoxyuridine triphosphate diphosphatase that is elevated in patient plasma. Neutrophil EVs from patient plasma contain increased neutrophil elastase and human endogenous retrovirus K envelope and induce pulmonary hypertension in mice, mitigated by elafin, an elastase inhibitor. Conclusions: Elevated human endogenous retroviral elements and elastase link a neutrophil innate immune response to pulmonary arterial hypertension.

Antioxidant and inflammatory biomarkers in herpes zoster.

The risk of herpes zoster (HZ) increases as cell-mediated immunity declines with age. Even though oxidative stress plays a crucial role in the development of HZ, there are few serum biomarkers of the disease's antioxidant activity. The purpose of this study is to investigate the blood levels of major antioxidants in HZ patients. To the best of our knowledge, this is the first study on this issue in the literature. The serum levels of antioxidants including uric acid (UA), total bilirubin (TBIL), albumin (ALB), vitamin D levels, and inflammatory markers such as homocysteine (Hcy) and C-reactive protein (CRP) was retrospectively analyzed in 53 patients with HZ and 53 age-and sex-matched healthy controls (HCs). The relationships between these markers and postherpetic neuralgia (PHN) and the clinical severity of HZ were also evaluated. Serum levels of UA, TBIL, and ALB in patients with HZ were significantly lower than those in the HCs (p < 0.001), while no statistical differences were found in vitamin D levels between the groups. Hcy and CRP levels were significantly increased in HZ patients compared to HCs. Significant differences were observed in the serum levels of UA, Hcy, CRP, and vitamin D in the PHN group versus the non-PHN group (p < 0.001). The presence of inflammatory markers was found to be positively related to disease activity. Furthermore, when compared to the mild or moderate clinical types of HZ, these biomarkers were statistically significant in the severe clinical type. These results suggest that uncontrolled varicella-zoster virus reactivation, acute nerve damage, and PHN may all be associated with low antioxidant levels. These biomarkers may be a protective factor for HZ, but more research is needed to clarify the underlying mechanism.

Frontal QRS/T angle can predict mortality in COVID-19 patients.

AIMS: The frontal QRS-T (fQRS) angle has been investigated in the general population, including healthy people and patients with heart failure. The fQRS angle can predict mortality due to myocarditis, ischaemic and non-ischaemic cardiomyopathies, idiopathic dilated cardiomyopathy, and chronic heart failure in the general population. Moreover, no studies to date have investigated fQRS angle in coronavirus disease 2019 (COVID-19) patients. Thus, the purpose of this retrospective multicentre study was to evaluate the fQRS angle of COVID-19 patients to predict in-hospital mortality and the need for mechanical ventilation. METHODS AND RESULTS: An electrocardiogram was performed for 327 COVID-19 patients during admission, and the fQRS angle was calculated. Mechanical ventilation was needed in 119 patients; of them, 110 died in the hospital. The patients were divided into two groups according to an fQRs angle >90° versus an fQRS angle ≤90°. The percentages of mortality and the need for mechanical ventilation according to fQRS angle were 67.8% and 66.1%, respectively, in the fQRs >90° group and 26.1% and 29.9% in the fQRS ≤90°group. Heart rate, oxygen saturation, fQRS angle, estimated glomerular filtration rate, and C-reactive protein level were predictors of mortality on the multivariable analysis. The mortality risk increased 2.9-fold on the univariate analysis and 1.6-fold on the multivariate analysis for the fQRS >90° patient group versus the fQRS ≤90° group. CONCLUSION: In conclusion, a wide fQRS angle >90° was a predictor of in-hospital mortality and associated with the need for mechanical ventilation among COVID-19 patients.

An Assessment of Anxiety about the Viral Epidemic and Work-Related Stress in Family Physicians in Turkey: How Does COVID-19 Vaccination Period Affect Anxiety and Stress?

BACKGROUND: Our study aimed to evaluate the extent of family physicians' anxiety about the viral epidemic and work-related stress associated with the viral epidemic as well as examining the effects of COVID-19 vaccination period on such situations. SUBJECTS AND METHODS: Data collection forms including the SAVE-9 scale, prepared for this cross-sectional study, were converted into online questionnaires and sent to family physicians in order to evaluate and examine the extent of anxiety and stress of family physicians working as family physicians in different provinces of Turkey via e-mails and communication groups between December, 2020 and March, 2021. The responses of 500 family physicians who were accessible in this way and volunteered to participate in the study were recorded to be analysed. Of all the 500 physicians, the SAVE-9 scale was re-administered to the subgroup of 50 family physicians in the post-vaccination period. The responses were compared with those received in the pre-vaccination period. RESULTS: Of all the 500 family physicians in this study, 40.6% of them were found to be in a state of anxiety about the viral epidemic. In particular, the scores of anxiety about the viral epidemic and of work-related stress were found much higher in female physicians and in those reporting that they had inadequate income. While there was a significant decline in the scores of anxiety about the viral epidemic in the subgroup in the post-vaccination period of health care workers, no statistically significant change was found in work-related stress scores. CONCLUSION: Family physicians have been suffering anxiety due to the pandemic. The vaccination period has a positive impact on anxiety levels.

CHA2DS2-VASc score and modified CHA2DS2-VASc score can predict mortality and intensive care unit hospitalization in COVID-19 patients.

In this study, we investigated whether the CHA2DS2-VASc score could be used to estimate the need for hospitalization in the intensive care unit (ICU), the length of stay in the ICU, and mortality in patients with COVID-19. Patients admitted to Merkezefendi State Hospital because of COVID-19 diagnosis confirmed by RNA detection of virus by using polymerase chain reaction between March 24, 2020 and July 6, 2020, were screened retrospectively. The CHA2DS2-VASc and modified CHA2DS2-VASc score of all patients was calculated. Also, we received all patients' complete biochemical markers including D-dimer, Troponin I, and c-reactive protein on admission. We enrolled 1000 patients; 791 were admitted to the general medical service and 209 to the ICU; 82 of these 209 patients died. The ROC curves of the CHA2DS2-VASc and M-CHA2DS2-VASc scores were analyzed. The cut-off values of these scores for predicting mortality were ≥ 3 (2 or under and 3). The CHA2DS2-VASc and M-CHA2DS2-VASc scores had an area under the curve value of 0.89 on the ROC. The sensitivity and specificity of the CHA2DS2-VASc scores were 81.7% and 83.8%, respectively; the sensitivity and specificity of the M-CHA2DS2-VASc scores were 85.3% and 84.1%, respectively. Multivariate logistic regression analysis showed that CHA2DS2-VASc, Troponin I, D-Dimer, and CRP were independent predictors of mortality in COVID-19 patients. Using a simple and easily available scoring system, CHA2DS2-VASc and M-CHA2DS2-VASc scores can be assessed in patients diagnosed with COVID-19. These scores can predict mortality and the need for ICU hospitalization in these patients.

Hydroxychloroquine/azithromycin treatment, QT interval and ventricular arrhythmias in hospitalised patients with COVID-19.

BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZM) are widely used in off-label treatment of novel coronavirus disease (COVID-19). However, cardiac safety of these drugs is still controversial in COVID-19. Therefore, we aimed to evaluate association of HCQ or HCQ + AZM treatment regimens, corrected QT (QTc) interval and malignant ventricular arrhythmias in hospitalized patients. METHODS: This is a single-center, retrospective and observational study. All data were extracted from the electronic medical records. The initial and post-treatment mean QTc intervals were calculated and compared in patients with HCQ alone or HCQ + AZM therapy. Associated factors with QTc prolongation, the incidence of ventricular arrhythmia during treatment and in-hospital mortality because of ventricular arrhythmias were evaluated. RESULTS: Our cohort comprised 101 hospitalized COVID-19 patients (mean age of 49.60 ± 18 years, 54.4% men). HCQ + AZM combination therapy group (n = 56) was more likely to have comorbidities. After 5-days treatment, 19 (18.8%) patients had QTc prolongation, and significant increase in the QTc interval was observed in both two groups (P < .001). However, HCQ + AZM combination group had significantly higher ΔQTc compared to HCQ group (22.5 ± 18.4 vs 7.5 ± 15.3 ms, P < .001). All of 101 patients completed the 5-days treatment without interruption. Also, no malignant ventricular arrhythmia or death secondary to ventricular arrhythmia occurred during the treatment in both groups. CONCLUSIONS: The present study revealed that although HCQ + AZM treatment was independently associated with QTc prolongation, none of patients experienced malignant ventricular arrhythmia or death during treatment. Further prospective studies are needed to determine the exact implications of these drugs on arrhythmias in patients with COVID-19.

Prognostic value of C-reactive protein/albumin ratio in hypertensive COVID-19 patients.

OBJECTIVES: The aim of this study was to investigate the relationship between the C-reactive protein/albumin ratio and the prognosis of hypertensive COVID-19 patients. METHODS: It was designed as a single center retrospective study. PCR positive COVID-19 patients who were followed up in the intensive care unit (ICU) and received antihypertensive treatment were included in the study. The patients were divided into two groups as survivor and non-survivor. C-reactive protein/albumin (CAR) ratios of the patients were compared. The cut-off value was determined as a mortality predictor. The effect of CAR on mortality was evaluated using Logistic Regression analysis. RESULTS: 281 patients were included in the study. Groups consisted of 135 (non-survivor) and 146 (survivor) patients. CAR was significantly higher in the non-survivor group (p<0.001). The area under the ROC curve for CAR for mortality was 0.807, with sensitivity of 0.71 and specificity of 0.71. The cut-off value for CAR was calculated as 56.62. In logistic regression analysis, CAR increases mortality 4.9 times compared to the cut-off value. CONCLUSION: CAR is a powerful and independent prognostic marker for predicting mortality and disease progression in hypertensive COVID-19 patients.

Type 1 Kounis Syndrome Induced by Inactivated SARS-COV-2 Vaccine.

Background Vaccination is the most important way out of the novel coronavirus disease 2019 (COVID-19) pandemic. Vaccination practices have started in different countries for community immunity. In this process, health authorities in different countries have preferred different type of COVID-19 vaccines. Inactivated COVID-19 vaccine is one of these options and has been administered to more than 7 million people in Turkey. Inactivated vaccines are generally considered safe. Kounis syndrome (KS) is a rare clinical condition defined as the co-existence of acute coronary syndromes and allergic reactions. Case Report We present the case of a 41-year-old woman with no cardiovascular risk factors who was admitted at our emergency department with flushing, palpitation, dyspnea, and chest pain 15 min after the first dose of inactivated CoronaVac (Sinovac Life Sciences, Beijing, China). Electrocardiogram (ECG) showed V4-6 T wave inversion, and echocardiography revealed left ventricular wall motion abnormalities. Troponin-I level on arrival was elevated. Coronary angiography showed no sign of coronary atherosclerosis. She was diagnosed with type 1 KS. The patient's symptoms resolved and she was discharged from hospital in a good condition. Why Should an Emergency Physician Be Aware of This? To the best of our knowledge, this is the first case of allergic myocardial infarction secondary to inactivated coronavirus vaccine. This case demonstrates that KS can occur after inactivated virus vaccine against COVID-19. Although the risk of severe allergic reaction after administration of CoronaVac seems to be very low, people who developed chest pain after vaccine administration should be followed by ECG and troponin measurements.

Loss of Endothelium-Derived Wnt5a Is Associated With Reduced Pericyte Recruitment and Small Vessel Loss in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disorder of the pulmonary circulation associated with loss and impaired regeneration of microvessels. Reduced pericyte coverage of pulmonary microvessels is a pathological feature of PAH and is caused partly by the inability of pericytes to respond to signaling cues from neighboring pulmonary microvascular endothelial cells (PMVECs). We have shown that activation of the Wnt/planar cell polarity pathway is required for pericyte recruitment, but whether production and release of specific Wnt ligands by PMVECs are responsible for Wnt/planar cell polarity activation in pericytes is unknown. METHODS: Isolation of pericytes and PMVECs from healthy donor and PAH lungs was carried out with 3G5 or CD31 antibody-conjugated magnetic beads. Wnt expression profile of PMVECs was documented via quantitative polymerase chain reaction with a Wnt primer library. Exosome purification from PMVEC media was carried out with the ExoTIC device. Hemodynamic profile, right ventricular function, and pulmonary vascular morphometry were obtained in a conditional endothelium-specific Wnt5a knockout ( Wnt5aECKO) mouse model under normoxia, chronic hypoxia, and hypoxia recovery. RESULTS: Quantification of Wnt ligand expression in healthy PMVECs cocultured with pericytes demonstrated a 35-fold increase in Wnt5a, a known Wnt/planar cell polarity ligand. This Wnt5a spike was not seen in PAH PMVECs, which correlated with an inability to recruit pericytes in Matrigel coculture assays. Exosomes purified from media demonstrated an increase in Wnt5a content when healthy PMVECs were cocultured with pericytes, a finding that was not observed in exosomes of PAH PMVECs. Furthermore, the addition of either recombinant Wnt5a or purified healthy PMVEC exosomes increased pericyte recruitment to PAH PMVECs in coculture studies. Although no differences were noted in normoxia and chronic hypoxia, Wnt5aECKO mice demonstrated persistent pulmonary hypertension and right ventricular failure 4 weeks after recovery from chronic hypoxia, which correlated with significant reduction, muscularization, and decreased pericyte coverage of microvessels. CONCLUSIONS: We identify Wnt5a as a key mediator for the establishment of pulmonary endothelium-pericyte interactions, and its loss could contribute to PAH by reducing the viability of newly formed vessels. We speculate that therapies that mimic or restore Wnt5a production could help prevent loss of small vessels in PAH.

The Relationship between Vitamin D Levels and Iron Deficiency and Anemia in Adults Applied for Periodic Medical Examination.

BACKGROUND: Anemia and vitamin D deficiency are two important public health issues that may accompany many acute and chronic diseases. Several studies conducted in recent years have suggested that vitamin D deficiency is associated with anemia in healthy and patient populations. The aim of the study is to investigate the relationship between vitamin D deficiency and anemia. METHODS: The data of 9,590 adults aged 18 - 64, who applied for periodic medical examination to family medicine polyclinics of a training hospital between 2016 and 2018, were evaluated retrospectively. Individuals were classified into three groups as iron deficiency, iron deficiency anemia, and anemia; and 25 hydroxy vitamin D (25(OH)D) levels were classified into three groups as deficiency, insufficiency, and sufficiency. The groups were compared with respect to study parameters. RESULTS: Of the participants, 2,395 were male (25.0%) (mean age = 43.75 ± 13.43) and 7,195 (75.0%) were female (mean age = 42.93 ± 12.85). The number of anemic patients was 1,470 (15.3%) while the number of patients having no symptoms of anemia was 8,120 (84.7%). Serum hemoglobin (Hgb), iron, and ferritin levels were found to be significantly lower in the group with 25(OH)D deficiency than in the group of those with no deficiency. The mean 25(OH)D levels were observed to be significantly lower in those having anemia (17.4 ng/mL) than in those who do not (20.2 ng/mL), in those having iron deficiency (18.2 ng/mL) than in those who do not (20.5 ng/mL), and in those having iron deficiency anemia (16.6 ng/mL) than in those who do not (20.1 ng/mL) (all p-values are < 0.001). CONCLUSIONS: The findings of this large study population, who live in a Mediterranean city which is sunny for 300 days of the year, indicate that 25(OH)D deficiency is significantly associated with iron deficiency and/or anemia.

Are mechanical and chemical trauma the reason of meatal stenosis after newborn circumcision?

Mechanical and chemical trauma are a widely accepted theories to explain the pathogenesis of meatalstenosis after newborn circumcision. The aim of the present study was to explore the theory that an exposed glans is prone to meatal stenosis. This was done by a novel investigation of boys who were born with "hooded prepuce", a condition in which the glans is completely exposed. Physical examination, lower urinary tract symptoms, urethral meatus configuration, and surgical procedures of 18 children admitted for routine circumcision, who had congenital hooded prepuce with normally located urethral meatus, were analyzed. The study period was 2013 and 2018. All the cases have been seen because of neonatal circumcision request, but was postponed due to hooded prepuce. The only presenting complaint in children was a cosmetically unattractive appearance. There were no symptoms associated with meatal stenosis, they circumcised in an average of 6 years and non of them required any additional procedure.Conclusion: Meatal stenosis did not occur in cases whose glans penis are naked with hooded prepuce. These findings do not support the default chemical and mechanical trauma theories. Hooded prepuce without any penile anomalies is only a cosmetically unattractive appearance and circumcision can correct this. What is known: • The common theory of meatal stenosis etiology is that the meatus undergoes irritation with chemical/mechanical trauma in the absence of a prepuce after newborn circumcision. • Circumcision is usually postponed in newborns with hooded prepuce. What is new: • We did not notice meatal stenosis in cases whose urethral meatus were not covered with a prepuce congenitally. Ammoniacal dermatitis or mechanical trauma theories may not explain the cause of meatal stenosis. • Hooded prepuce is not a handicap to newborn circumcision. It is just a cosmetic problem and circumcision can solve it.

Pre-Diabetics with Hypovitaminosis D Have Higher Risk for Insulin Resistance.

BACKGROUND: Various studies have been reported on the relationship between vitamin D, whose deficiency has been identified in a pandemic way, and metabolic-endocrine diseases, including insulin resistance. Insulin resistance is an important public health issue since it is a common cause of death as it transforms into metabolic syndrome and type 2 diabetes mellitus (DM). In this study, the aim is to investigate the relationship between the level of serum 25 hydroxy vitamin D (25(OH)D) and insulin resistance. METHODS: A retrospective study was carried out including 2,008 patients aged between 18 - 67 chosen from among the patients who had applied to Saglik Bilimleri University Antalya Training and Research Hospital. Patients were divided into three groups as non-diabetic, pre-diabetic, and diabetic according to their blood glucose profile and into three categories according to their 25(OH)D levels. The relationship between serum vitamin D levels and insulin resistance was compared between the groups. Individuals with homeostasis model assessment of insulin re-sistance (HOMA-IR) > 2.5 were considered to have insulin resistance. RESULTS: The study was composed of 2,008 patients, 1,614 were female (80.4%). Of the participants, 216 (10.6%) were diabetics, 849 (42.3%) were pre-diabetics, and 943 (47.1%) were non-diabetics. It was identified that age, fasting blood glucose, HbA1c, triglyceride (Tg), very-low-density lipoprotein cholesterol (VLDL-C), fasting insulin, and HOMA-IR levels were significantly higher in diabetic patients than in pre-diabetic patients (all p < 0.001) and similarly higher in pre-diabetics than in non-diabetics. Tg, VLDL, fasting insulin, and HOMA-IR levels were significantly lower in the group with 25(OH)D ≥ 30 ng/mL. Especially in pre-diabetic individuals, a significant negative correlation was observed between the 25(OH)D level and HbA1c (p = 0.020), Tg (p = 0.001), VLDL-C (p = 0.001), fasting insulin (p < 0.001) and HOMA-IR (p < 0.001). While high HOMA-IR was positively associated with fasting blood glucose and total cholesterol values (all p < 0.001), it was negatively associated with age (p < 0.001), LDL-cholesterol (p < 0.001), HDL-cholesterol (p < 0.001) and 25(OH)D (p = 0.001). CONCLUSIONS: Diabetic subjects have lower plasma 25(OH)D levels and pre-diabetics with hypovitaminosis D have higher risk for insulin resistance. Thus, HOMA-IR must be well evaluated in pre-diabetic individuals with vitamin D deficiency/insufficiency, if there is associating abdominal obesity.

A Rare Non-Hemolytic Case of Idiopathic Cold Agglutinin Disease.

BACKGROUND: Cold agglutinin disease is a very rare condition associated with agglutination of erythrocytes in cold environment usually due to IgM type antibodies. Other than hemolytic anemias, it may interfere with routine hemogram tests due to miscalculation of red blood cell count (RBC) and other hemogram parameters calculated with involvement of RBC. Awareness of the condition is important to overcome laboratory errors. METHODS: We studied a peripheral blood smear and repeated the hemogram test at 37°C to establish the diagnosis of cold agglutinin disease. RESULTS: Initial hemogram test results of the fifty-eight year-old man was as follows: RBC: 1.34 M/µL, hemoglobin (Hb): 12.4 g/dL, hematocrit (Htc): 11.8%, mean corpuscular hemoglobin (MCH): 92.4 pg, and mean corpuscular hemoglobin concentration (MCHC): 105 gr/dL. Despite the standard indirect Coombs test being negative, repeated tests at room temperature was 4+. We suspected cold agglutinin disease and repeated the hemogram test using the Bain-Marie method at 37°C and the test results showed RBC: 3.4 M/µL, hemoglobin: 12.6 g/dL, hematocrit: 30.2%, MCH: 31.7 pg, and MCHC: 41.8 g/dL. CONCLUSIONS: Inappropriate hemogram results may be a sign of underlying cold agglutinin disease. Hemolytic anemia not always accompanies the disease; however, cold exposure may trigger erythrocyte agglutination in vitro and may cause erratic laboratory results.

Multitarget, quantitative nanoplasmonic electrical field-enhanced resonating device (NE2RD) for diagnostics.

Recent advances in biosensing technologies present great potential for medical diagnostics, thus improving clinical decisions. However, creating a label-free general sensing platform capable of detecting multiple biotargets in various clinical specimens over a wide dynamic range, without lengthy sample-processing steps, remains a considerable challenge. In practice, these barriers prevent broad applications in clinics and at patients' homes. Here, we demonstrate the nanoplasmonic electrical field-enhanced resonating device (NE(2)RD), which addresses all these impediments on a single platform. The NE(2)RD employs an immunodetection assay to capture biotargets, and precisely measures spectral color changes by their wavelength and extinction intensity shifts in nanoparticles without prior sample labeling or preprocessing. We present through multiple examples, a label-free, quantitative, portable, multitarget platform by rapidly detecting various protein biomarkers, drugs, protein allergens, bacteria, eukaryotic cells, and distinct viruses. The linear dynamic range of NE(2)RD is five orders of magnitude broader than ELISA, with a sensitivity down to 400 fg/mL This range and sensitivity are achieved by self-assembling gold nanoparticles to generate hot spots on a 3D-oriented substrate for ultrasensitive measurements. We demonstrate that this precise platform handles multiple clinical samples such as whole blood, serum, and saliva without sample preprocessing under diverse conditions of temperature, pH, and ionic strength. The NE(2)RD's broad dynamic range, detection limit, and portability integrated with a disposable fluidic chip have broad applications, potentially enabling the transition toward precision medicine at the point-of-care or primary care settings and at patients' homes.

Subsequent malignancies after allogeneic hematopoietic stem cell transplantation.

We evaluated 979 patients for the development of post-transplant lymphoproliferative disease (PTLD) and solid malignancies after allogeneic hematopoietic stem cell transplantations (allo-HSCT) as a late complication. We found 15 (1.5%) subsequent malignancies; three of these malignancies were PTLD, and twelve were solid tumors. The median time from allo-HSCT to the development of PTLD was 9 (3-20) months and that from allo-HSCT to the development of solid tumors was 93 (6-316) months. The cumulative incidence of evolving subsequent malignancy in patients was 1.3% (±0.5 SE) at 5 years and 3.9% (±1.2 SE) at 10 years. The cumulative incidence of developing subsequent malignancy in patients with benign hematological diseases as the transplant indication was 7.4%±4.2 SE at 5 years. More subsequent malignancy developed in patients having ≥1 year chronic graft-vs-host disease (GVHD; 3.7% in ≥1 year chronic GVHD and 0.7% in <1 year chronic GVHD patient groups, P=.002). Subsequent epithelial tumor risk was higher in ≥1 year chronic GVHD patients than <1 year (3.7% vs 0.1%, P<.001). In multivariate analysis, benign hematological diseases as transplant indication (RR: 5.6, CI 95%: 1.4-22.3, P=.015) and ≥1 year chronic GVHD (RR: 7.1, 95% CI: 2.3-22.5, P=.001) were associated with the development of subsequent malignancy.

The effect of age on peripheral stem cell mobilization in healthy donors, single center experience.

PURPOSE: Peripheral stem cell transplantation is used as a life-saving therapeutic option in hematological malignancies. As previously established, most hematological malignancies are seen in the elderly population. Therefore, possible HLA-identical sibling donors of elderly patients are generally of an advanced age. In this study, we aimed to evaluate the effect of old age on stem cell mobilization and quality in older adult healthy sibling donors. MATERIALS AND METHODS: Between 2006 and 2014, we evaluated 38 healthy donors aged ≥55 years. The granulocyte-colony stimulating factor (G-CSF) analogs were used at a dose of 5 µg/kg/day and administered subcutaneously twice a day for five days. CD34+ cells were estimated in the peripheral blood before collection of the apheresis product. The National Marrow Donor Program selects healthy unrelated donors if they are younger than 60 years. Therefore, we compared the product quality in donors over the age of 60 to that in donors aged 60 years or less. RESULTS: We collected sufficient products from all the donors with one to three apheresis procedures. No serious complication was detected in all donors. Reaching the target CD34+ cell count in one day were detected in 83% of younger and 79% of older donors (P = NS). Collected CD34+ cells x10e6/recipient body weight (kg) was same and 5.1 in the groups (P = NS). There were no correlation between the donor age and these parameters. CONCLUSION: Healthy donor apheresis in older adults can be performed effectively and possible donors should be evaluated regardless of their age. J. Clin. Apheresis 32:16-20, 2017. © 2016 Wiley Periodicals, Inc.