Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms in a cohort of Egyptian patients with immune thrombocytopenia (ITP).

BACKGROUND: Immune thrombocytopenia (ITP) is characterized by immune response dysregulations. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays a central role in immune checkpoint pathways and preventing autoimmune diseases by regulating immune tolerance. We aimed to explore the potential association between CTLA-4 gene polymorphisms and ITP as well as study their impact on the response to therapy. METHODS: We investigated two CTLA-4 single-nucleotide polymorphisms (SNPs; rs: 231775 and rs: 3087243) using real-time PCR as well as the plasma levels of CTLA-4 by ELISA in 88 patients with ITP and 44 healthy participants (HC). RESULTS: CTLA-4 (rs: 3087243) A > G polymorphism analysis showed most HC had the homozygous AA genotype, which was statistically significant compared to patients with ITP. Plasma levels of CTLA4 were statistically lower in patients with acute ITP. There was no correlation between CTLA-4 (rs: 231775 and rs: 3087243) A/G SNPs were not correlated to the response to all lines of therapy assessed (corticosteroids, thrombopoietin receptor agonists, splenectomy, and rituximab). CONCLUSION: CTLA-4 CT 60 A/G may affect the susceptibility of ITP, but both CTLA-4 + 49 A/G and CT60 A/G did not impact the response of patients with ITP to different lines of therapy.

IL-4Rα (rs1801275) A>G polymorphism in Egyptian immune thrombocytopenia (ITP) patients: a single center experience.

INTRODUCTION: Chronic immune thrombocytopenia (cITP) is characterized by dysregulation of the immune response. Until recently, the role of Th2-related cytokine gene polymorphisms was unclear. Interleukin 4 (IL-4) exerts its functions by binding to three types of IL-4 receptor (IL-4R) complexes. We aimed to explore the potential association between the gene polymorphism of IL-4Rα and cITP. METHODS: We investigated the clinical impact of the IL-4Rα (rs1801275) A>G single nucleotide polymorphism (SNP) using the polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism (RFLP) method in 82 cITP patients and 60 healthy controls (HCs). RESULTS: The IL-4Rα (rs1801275) A>G polymorphism analysis showed the mutant GG genotype was significantly higher in control females (p = 0.033). The wild AA genotype had a higher bleeding score (p = 0.02) in the adulthood onset group. Furthermore, the wild AA genotype in the cITP childhood onset group was significantly associated with the disease severity, as well as the response to treatment (p = 0.040). CONCLUSION: The mutant G allele is protective against the susceptibility to cITP in the Egyptian females. The IL-4Rα (rs1801275) A>G polymorphism may affect the clinical severity of cITP and treatment response in the Egyptian population.

Comparison of Renal Function before and after Autologous Stem Cell Transplantation in Egyptian Patients with Multiple Myeloma and Renal Insufficiency: A Retrospective Study.

Renal failure is a common feature of multiple myeloma (MM) that occurs in 20%-40% of newly diagnosed patients with MM and is the result of monoclonal immunoglobulin light chains. Many studies have examined the effect of autologous stem cell transplantation (ASCT) in MM patients with renal impairment and the safety of performing the transplantation in patients with renal failure. This study aimed to compare renal function before and after ASCT in Egyptian MM patients with renal insufficiency to evaluate the effect of ASCT on renal recovery. Our study included 31 MM patients with renal impairment out of 400 patients who met the criteria of the International Myeloma Working Group for symptomatic MM. The estimated glomerular filtration rate (eGFR) calculated by the Modification of Diet in Renal Disease formula was compared before and after the transplant. Only four patients (12.9%) were dependent on dialysis. Six of those with a history of hemodialysis (HD) who were either dependent on dialysis or dialyzed according to need achieved independence from HD. There was no significant correlation between the degree of renal impairment and the disease's status at the time of transplantation (P = 0.86). The study showed significant improvements in serum creatinine levels compared with its value before the transplant (P = 0.016) and in eGFR (P = 0.004). In total, 45% of patients achieved renal improvement, shown by a 25% increase in GFR above the baseline. There was a significant improvement of renal function after ASCT in MM patients with renal impairment.

Evaluation of Serum Visfatin as a Biomarker of Lupus Nephritis in Egyptian Patients with Systemic Lupus Erythematosus.

One of the most significant consequences of systemic lupus erythematosus (SLE) is lupus nephritis (LN). Visfatin, an adipokine that is significantly expressed in visceral fat and is a marker of endothelial dysfunction in chronic kidney disease, has multiple proinflammatory actions. We aimed to evaluate the state of serum visfatin in SLE patients and to detect its possible correlation with the disease's activity and effects on the kidney affection. Fifty patients with active LN, 50 patients with inactive lupus, and 50 healthy people had their serum visfatin levels tested. Chemical and immunological markers of SLE and LN were measured. The SLE Disease Activity Index (SLEDAI) was used to measure the disease's activity. Renal biopsies from the LN subgroup were collected and classified using the modified classification of the World Health Organization. The serum visfatin of patients with active LN was significantly greater than that of inactive lupus patients and the healthy controls (20.56 ± 1.07 ng/mL, 16.77 ± 1.02 ng/mL, and 9.96 ± 1.46 ng/mL, P <0.001). SLEDAI and serum visfatin levels were shown to be significantly correlated (P = 0.000057). Serum visfatin levels were likewise significantly correlated with the index of histological activity in the active group (P <0.00001). Serum visfatin was raised in individuals with active LN and was related to the SLEDAI and disease severity scores. Serum visfatin could be utilized as a noninvasive biomarker for evaluating the severity of LN and risk stratification of the risk.

Hemostatic system and COVID-19 crosstalk: A review of the available evidence.

Since the discovery of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant coronavirus disease 2019 (COVID-19) pandemic, respiratory manifestations have been the mainstay of clinical diagnosis, laboratory evaluations, and radiological investigations. As time passed, other pathological aspects of SARS-CoV-2 have been revealed. Various hemostatic abnormalities have been reported since the rise of the pandemic, which was sometimes superficial, transient, or fatal. Mild thrombocytopenia, thrombocytosis, venous, arterial thromboembolism, and disseminated intravascular coagulation are among the many hemostatic events associated with COVID-19. Venous thromboembolism necessitating therapeutic doses of anticoagulants is more frequently seen in severe cases of COVID-19, especially in patients admitted to intensive care units. Hemorrhagic complications rarely arise in COVID-19 patients either due to a hemostatic imbalance resulting from severe disease or as a complication of over anticoagulation. Although the pathogenesis of coagulation disturbance in SARS-CoV-2 infection is not yet understood, professional societies recommend prophylactic antithrombotic therapy in severe cases, especially in the presence of abnormal coagulation indices. The review article discusses the various available evidence on coagulation disorders, management strategies, outcomes, and prognosis associated with COVID-19 coagulopathy, which raises awareness about the importance of anticoagulation therapy for COVID-19 patients to guard against possible thromboembolic events.

Albuminuria as a predictor of mortality in type II diabetic patients after living-donor liver transplantation.

PURPOSE: Diabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection. Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality. This study evaluated albuminuria as a predictor of the outcome of living donor liver transplantation (LDLT) in patients with pre-existing DM. METHODS: This retrospective study involved 103 type II diabetic patients with end-stage liver disease who received LDLT. Preoperative spot urine albumin: creatinine ratio was used to determine the degree of albuminuria. The primary outcome measure was the impact of urinary albumin excretion on the 3-year mortality rate after LDLT in this diabetic cohort. RESULTS: Hepatitis C virus infection was the main cause of cirrhosis. Albuminuria was detected in 41 patients (39.8%); 15 had macroalbuminuria, while 26 had microalbuminuria. Patients with microalbuminuria were significantly older than those with macroalbuminuria and normal albumin in urine. After 3 years, twenty-four patients (23.3%) died within 3 years after LT. Myocardial infarction was the leading cause of death (25%). Albuminuria was an independent factor affecting 3-year mortality with an odds ratio of 5.17 (95% CI: 1.86-14.35). CONCLUSION: Preoperative albuminuria is an independent factor affecting mortality within 3 years after LDLT in type II diabetic patients. Myocardial infarction was the leading cause of death in 25% of cases, followed by hepatocellular carcinoma recurrence, sepsis, and graft failure.KEY MESSAGESDiabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection.Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality.Preoperative albuminuria is a significant predictor of mortality within 3 years after LDLT in diabetic patients.

Improvement of Pancreatic Steatosis and Indices of Insulin Resistance After Metabolic Surgery.

Purpose: Obesity is associated with fat accumulation in ectopic sites such as the pancreas, the so-called pancreatic steatosis (PS). Bariatric surgery has been shown to be associated with reducing pancreatic fat. This study investigated the effect of laparoscopic sleeve gastrectomy (LSG) on pancreatic volume and its fat content and glucose homeostasis. Methods: The study enrolled 54 patients subjected to LSG. Metabolic variables and pancreatic exocrine function were assessed immediately before surgery and 12 months after. MRI of the abdomen was performed to measure pancreatic fat content and its total volume and visceral adipose tissue (VAT). Results: Surgery resulted in a significant reduction in body weight and BMI. HbA1c, fasting insulin, C-peptide levels, HOMA-IR, and Hs-CRP levels decreased significantly. Surgery resulted in significant improvement in lipid profile except for HDL-cholesterol and liver function tests. Total VAT volume decreased significantly. Total pancreas volume decreased by a mean of 9.0 cm3 (95% CI: 6.6-11.3). The median change of pancreatic fat was -26.1% (range: -55.6 to 58.3%). Pancreatic lipase decreased significantly (P < 0.001). There was a positive correlation between the percentage of total weight loss and decrease in pancreatic fat volume (r = 0.295, P = 0.030). Conclusion: Weight loss after LSG is associated with a reduction of total VAT volume, total pancreatic volume, and pancreatic fat content. These changes are associated with improved glucose homeostasis, reduced systemic inflammation, and decreased pancreatic lipase secretion.

Sarcoidosis beyond pulmonary involvement: A case series of unusual presentations.

Unusual presentations of sarcoidosis pose a diagnostic challenge and warrant attention. Hematologic associations: Case 1 (37-years-old male): Pancytopenia: myelofibrosis (leading to sepsis and mortality) following a two-year quiescent course of biopsy-proven-sarcoidosis. Case 2 : (38-years-old male): Presentation with thrombocytopenia (5 × 103/cmm): immune thrombocytopenic purpura (histologically associated with megakaryocytic emperipolesis). Biopsied enlarged lymph nodes demonstrated sarcoidosis. Hematologic sarcoid involvement is usually due to granulomatous bone marrow (3.9%) or splenic infiltration (6-30%); however, the presented manifestations are scarcely reported with a potential significance that is yet to be elucidated. Case 3: Neurologic presentation: 48-years-old female: presentation with bilateral sensorineural hearing loss and facial palsy. Brain magnetic resonance imaging showed leptomeningeal thickening. Biopsied enlarged lymph nodes showed sarcoidosis. Case 4: Neurologic and renal manifestations: 13-years-old male (family history of sarcoidosis): Presenting with acute headache, investigations showed elevated serum creatinine (2.1 mg/dL) and angiotensin converting enzyme, and computed tomography chest and abdominal findings characteristic of sarcoidosis. Associated benign increased intracranial and acute tubulointerstitial nephritis (with eosinophils) were diagnosed upon concordant workup. Of sarcoidosis neurologic affection (5-10%), cranial nerve(s) involvement is among the most common (25-50% of neurosarcoid affection), particularly that of the facial nerve (Case 3). Leptomeningeal enhancement is among the most common neurosarcoid radiologic findings (30-40%). Whereas benign increased intracranial tension (Case 4) is much less reported. Among sarcoidosis renal involvement (35-50%), interstitial nephritis usually presents with granulomatous renal lesions, yet its sole association with sarcoidosis is unusual (Case 4). The portrayed atypical hematologic, neurologic, and renal manifestations further emphasize the masquerading nature of sarcoidosis.

Incidence of Silent Thrombosis in Patients Younger Than 60 Years With Myeloproliferative Neoplasms: Single-Center Egyptian Study.

BACKGROUND: Identification of janus kinase 2 (JAK2) mutation even in absence of myeloproliferative disorders (MPNs) was found to be related to venous thromboembolism occurrence. Venous thrombosis screening is not routinely requested in patients with myeloproliferative neoplasms unless the patient is symptomatic. It has been reported that the incidence of thrombosis in elderly patients is much higher than in young patients. The aim of this work was to screen MPN patients for venous thrombosis and study its correlation with JAK2 allele burden and with MPN 10 score. PATIENTS AND METHODS: We enrolled 73 patients with JAK2-positive MPN from our Hematology Clinic in the period August 2015 to Feb 2017. All patients had been screened for thrombosis in the venous system in lower limbs (LLs), upper limbs, portal, and mesenteric systems using color Doppler ultrasound imaging. RESULTS: Fifty-three (72.6%) patients were younger than 60 years. Twenty-two (30%) had essential thrombocytosis, 35 (47.9%) had polycythemia rubra vera, and 16 (22%) had idiopathic myelofibrosis. Twenty-seven venous thrombotic attacks were reported in 22 (30.1%) patients. Five (6.8%) had thrombosis in 2 sites. Seventeen (23%) had superior mesenteric and portal vein thrombosis. Six (8%) had iliofemoral (8%) and 4 (5%) had combined LL and portal thrombosis. Eight (10.8%) had active thrombosis at screening. Only 3 patients (4%) were symptomatic with abdominal pain during screening. Pruritis (P = .02) and abdominal pain (P = .039) were significantly different between cases with and without thrombosis. There was no significant difference in MPN 10 score between cases with active or previous thrombosis. CONCLUSION: We recommend routine screening for venous thrombosis in any case of MPN when diagnosed and screening for MPNs in any patient with venous thrombosis especially of the portal vein or atypical sites. If MPN patients present with increasing pruritus or abdominal pain, they also should be screened for venous thrombosis. Further research on a large scale in MPN age groups younger than 60 years regarding pathogenesis of thrombosis is highly recommended.

New insights on iron study in myelodysplasia.

OBJECTIVE: Hepcidin plays a pivotal role in iron homeostasis. It is predominantly produced by hepatocytes and inhibits iron release from macrophages and iron uptake by intestinal epithelial cells. Competitive ELISA is the current method of choice for the quantification of serum hepcidin because of its lower detection limit, low costs, and high throughput. This study aims to discuss the role of hepcidin in the pathogenesis of iron overload in recently diagnosed myelodysplasia (MDS) cases. MATERIALS AND METHODS: The study included 21 recently diagnosed MDS patients and 13 healthy controls. Ferritin, hepcidin, and soluble transferrin receptor (sTFR) were measured in all subjects. RESULTS: There were 7 cases of hypocellular MDS, 8 cases of refractory cytopenia with multilineage dysplasia, and 6 cases of refractory anemia with excess blasts. No difference was observed among the 3 MDS subtypes in terms of hepcidin, sTFR, and ferritin levels (p>0.05). Mean hepcidin levels in the MDS and control groups were 55.8±21.5 ng/mL and 19.9±2.6 ng/mL, respectively. Mean sTFR was 45.7±8.8 nmol/L in MDS patients and 31.1±5.6 nmol/L in the controls. Mean ferritin levels were significantly higher in MDS patients than in controls (539.14±83.5 ng/mL vs. 104.6±42.9 ng/mL, p<0.005). There was a statistically significant correlation between hepcidin and sTFR (r=0.45, p=0.039). No difference in hepcidin levels between males and females was observed, although it was lower in males in comparison to females (47.9±27.6 vs. 66.7±35.7, p>0.05). CONCLUSION: Hepcidin may not be the main cause of iron overload in MDS. Further studies are required to test failure of production or peripheral unresponsiveness to hepcidin in MDS cases.

Tissue residues, hematological and biochemical effects of tilmicosin in broiler chicken.

The aim of this study was to determine the blood and tissue concentrations profile and effect of tilmicosin on some hematological and biochemical parameters in broiler chicken. Fifty clinically healthy Hubbard chickens were orally administered 25 mg/kg BW of tilmicosin once daily for 5 consecutive days. Tissue residues of tilmicosin in slaughtered healthy chicken could not be detected by microbiological assay in all tested tissues except in lung (at 96 hours) and liver and kidneys (at 72 hours) after last administration. Tilmicosin caused temporary decrease in the RBCs and WBCs counts and has no effect on hemoglobin (Hb) and packed cell volume concentration (PCV). Also, the effect of tilmicosin on some biochemical parameters was as follows: the concentrations of creatinine, uric acid, electrolytes (sodium, potassium, and calcium), glucose, AST, ALT, ALP, and HDL-cholesterol in the serum of treated chicken did not change in response to the repeated oral administration of tilmicosin. There were only a temporary significant decrease in total protein and albumin concentrations and a significant increase in cholesterol and triglycerides concentrations. Chicken must not be slaughtered before 4 days from the stopping of tilmicosin administration. Tilmicosin makes temporary changes on hematological and biochemical parameters in broiler chicken.

Risk factors for bronchopleural fistula after right pneumonectomy: does eliminating the stump diverticulum provide protection?

PURPOSE: Bronchopleural fistula (BPF) remains an important source of morbidity and mortality after right pneumonectomy. We reviewed our 18-year institutional experience with right pneumonectomy to identify risks factors for BPF. METHODS: From 1992 to 2010, a total of 145 patients who underwent right pneumonectomy were identified from an institutional database. Median age was 56 years. Most patients (66.2%) underwent surgery for non-small cell lung cancer. Sixty-seven patients (46.2%) received either chemotherapy or radiotherapy before surgery. Medical records were reviewed for 14 variables potentially predictive for BPF, including two airway closure techniques (standard bronchial closure and carinal closure). Variables predictive of BPF by univariate analysis were entered into a logistic regression model. RESULTS: The overall mortality rate was 13.1% (n=19), with 15.9 and 10.5% mortality in the bronchial closure and carinal closure groups, respectively (P=0.33). The overall BPF rate was 7.6% (n=11), with a 3.9% (3 of 76) rate in the carinal closure group compared to 11.6% (8 of 69) in the bronchial closure group (P=0.08). Seven of eight bronchial closure patients who developed BPF required operative repair. Only one of three patients who developed BPF after carinal closure did not spontaneously heal after open drainage. Multivariate analysis identified preoperative radiation dose (P=0.042) and bronchial closure (P=0.041) as independent risk factors for BPF, while the length of postoperative ventilation before development of BPF approached significance (P=0.057). CONCLUSIONS: In our experience, higher preoperative radiation doses are a risk factor for BPF after right pneumonectomy, while carinal closure exerts a protective effect.

Prognostic indicators after surgery for thymoma.

BACKGROUND: We undertook a 20-year retrospective institutional study to investigate prognostic indicators after surgery for thymoma. METHODS: From 1989 to 2009, 83 patients underwent surgical resection of thymoma or thymic carcinoma at our institution. Twelve of these patients were determined to have either World Health Organization type C disease or Masaoka stage IV-B disease and were excluded from analysis. The remaining 71 patients were reviewed. RESULTS: The majority of patients in this series were female 64.7% (n=46) with an overall average age of 51.0 years. The distribution of Masaoka stages I, II, III, and IV-A was 40.8% (n=29), 19.7% (n=14), 18.3% (n=13), and 21.1% (n=15), respectively. Thirteen of the 28 (46.2%) patients who presented with stage III or IV-A disease received preoperative chemotherapy. After a mean follow-up of 66 months (range, 6 to 241 months), 54 (75.3%) patients are alive and well while six are alive with disease. Eleven (16.0%) patients have died, but only 3 (4.3%) of these patients died of thymoma. The overall disease-specific survival was 97% and 89% at 5 and 10 years. Of the variables analyzed, only age was predictive of overall survival (p=0.03). Masaoka stages I to III as compared with stage IV-A was significantly predictive of disease-free survival (p<0.01). CONCLUSIONS: Long-term disease-specific survival can be expected not only after surgery for early stage thymoma but also after surgery for advanced disease, including patients with pleural metastases. However, patients who undergo surgery for stage IV-A disease have reduced disease-free survival. Late mortality due to secondary cancers and associated immunologic disorders was more frequent than mortality from thymoma in this series.