Effect of autologous serum after amniotic membrane transplantation for persistent corneal ulcers

AIM:To investigate the effect of adding autologous serum eye drops to the postoperative regime after amniotic membrane transplantation for severe persistent corneal ulcers.METHODS:Forty eyes of 40 patients with persistent corneal ulcers were randomly assigned to artificial tears(sodium hyaluronate 0.2%,ATs group,n=20)or autologous serum eye drops(ASEDs,n=20)following treatment with amniotic membrane transplantation.Digital slit lamp images were acquired from all patients before and 30d post treatment.The area with fibrovascular tissue was calculated using Image J.Central corneal sensitivity was assessed by Cochet-Bonnet aesthesiometry before and one month after treatment.Scar tissue transparency was assessed with a novel optical densitometry.RESULTS:Mean age of patients was 61.65±16.47y and 57.3±19.11y in the ATs group and ASEDs group,respectively.Twenty-two male and 18 female patients were included in the study.The improvement in visual acuity was significantly greater in the ASEDs group(0.14±0.04)than the ATs(0.08±0.04;P=0.00046).Cochet-Bonnet aesthesiometry improved significantly after treatment with a similar rate between groups.There were no statistically significant differences in the area of postoperative fibrovascular tissue between the two groups(P=0.082).The success rate in the two groups was similar.The difference in densitometry between the ATs and ASEDs group was statistically significant(P=0.042)with greater reduction from baseline in the ASEDS group.CONCLUSION:Autologous serum eye drops can lead to better visual acuity,more stable results and improved densitometry and should be considered in the postoperative care following amniotic membrane transplantation.

Erratum to “Identification of Novel Nonsense RPGR Variant Causing Mild X-Linked Cone-Rod Dystrophy and Myopia” [Case Reports in Clinical Medicine Volume 11 (2022) 422-434]

The original online version of this article (Kamenarova, K., Cherninkova, S., Mihova, K., Georgiev, R., Nikolaeva, Y. and Kaneva, R. (2022) Identification of Novel Nonsense RPGR Variant Causing Mild X-Linked Cone-Rod Dystrophy and Myopia. Case Reports in Clinical Medicine, 11, 422-434. DOI: 10.4236/crcm.2022.1110059) unfortunately contains a mistake. The authors need to replace Figure 1.

Increased intestinal permeability in inflammatory bowel diseases assessed by iohexol test

AIM:To study intestinal permeability(IP) and its relationship to the disease activity in patients with inflammatory bowel diseases(IBD)-Crohn's disease(CD) and ulcerative colitis(UC).METHODS:Fifty-eight patients with active IBD(32 with CD and 26 with UC) and 25 healthy controls consented to participate in the study.The clinical activity of CD was estimated using the Crohn's Disease Activity Index(CDAI),and the endoscopic activity of UC using the Mayo scoring system.IP was assessed by the rise in levels of iohexol,which was administered orally(25 mL,350 mg/mL) 2 h after breakfast.Three and six hours later serum(SIC mg/L) and urine(UIC g/mol) iohexol concentrations were determined by a validated HPLC-UV technique.RESULTS:In the CD group,SIC values at 3 h(2.95 ± 2.11 mg/L) and at 6 h after ingestion(2.63 ± 2.18 mg/L) were significantly higher compared to those of healthy subjects(1.25 ± 1.40 mg/L and 1.11 ± 1.10 mg/L,respectively,P < 0.05).UIC(g/mol) values were also higher in patients,but the differences were significant only for UIC at 6 h.Significant positive correlation(P < 0.05) was found between the CDAI and IP,assessed by SIC at 3 h(r = 0.60) and 6 h(r = 0.74) after the ingestion.In comparison to controls,SIC and UIC of UC patients were higher in the two studied periods,but the differences were significant at 6 h only.Significantly higher values of SIC(P < 0.05) were found in patients with severe endoscopic activity of UC compared to those of patients with mild and moderate activity(3.68 ± 3.18 vs 0.92 ± 0.69 mg/L).CONCLUSION:Serum levels of iohexol at 3 h and 6 h after its ingestion reflect increased IP,which is related to the disease activity in patients with IBD.

Telbivudine vs tenofovir in hepatitis B e antigen-negative chronic hepatitis B patients: OPTIMA roadmap study

AIMTo make efficacy and safety comparison of telbivudine-raodmap and tenofovir-roadmap in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. METHODSThis was the first prospective, randomised, two-arm, open-label, non-inferiority study in HBeAg-negative CHB patients that compared telbivudine and tenofovir administered as per roadmap concept. Patients were treated up to 24 wk and, depending on virologic response, continued the same therapy or received add-on therapy up to 104 wk. Eligible patients received an additional 52 wk of treatment in the extension period (i.e., up to 156 wk). Patients who developed virologic breakthrough (VB) while on monotherapy also received add-on therapy. The primary efficacy endpoint was the rate of patients achieving hepatitis B virus (HBV) DNA RESULTSA total of 241 patients were randomised. Non-inferiority of telbivudine arm to tenofovir arm was demonstrated at week 52 (&plusmn; 7 d window), with over 91% of patients in each treatment arm achieving HBV DNA level CONCLUSIONEfficacy was shown for both telbivudine-roadmap and tenofovir-roadmap regimens in HBeAg-negative CHB patients over 156 wk. Telbivudine arm was associated with renal improvement.

Chronic hepatitis C virus infection:Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients

AIM: To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia. METHODS: The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using χ2 and Fisher’s exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis. RESULTS: Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation. Clinical manifestations included fatigue (59.6%), kidney impairment (25.0%), type 2 diabetes (22.8%), paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fi brosis (15.4%), thyroid dysfunction (14.7%), Raynaud’s phenomenon (11.8%), B-cell lymphoma (8.8%), sicca syndrome (6.6%), and lichen planus (5.9%). The biological manifestations included cryoglobulinproduction (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome, and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were: age ≥ 60 years, female gender, virus transmission by blood transfusions, longstanding infection (≥ 20 years), and extensive liver fi brosis. The most signifi cant risks factors (multivariate analysis) were longstanding infection and extensive liver fi brosis. CONCLUSION: We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production. Longstanding infection and extensive liver fi brosis were signifi cant risk factors for the presence of extrahepatic manifestations in HCV patients.

Immunohistochemical Expression of Ki-67, PCNA, pRb, p16, p53, Bcl-2 and Bax in Esophageal Adenocarcinoma and Barrett’s Associated Dysplasia

Background: Esophageal adenocarcinoma (EAC) has an extremely poor prognosis. There is a need to characterize the molecular alterations in the carcinogenesis of EAC in order to improve the diagnosis and treatment. Materials and Methods: We used 7 markers to explore the changes in the cell cycle, proliferation and apoptosis in patients with EAC and Barrett’s esophagus (BE)-associated dysplasia. The protein expression of Ki-67, PCNA, pRb, p16, p53, Bcl-2 and Bax was evaluated by immunohistochemistry in archival tissue samples, collected from 15 patients with EAC and 5 patients with BE-associated dysplasia. We analyzed also lymph-node, omentum and liver metastases from the primary esophageal tumors. Results: Ki-67, PCNA, pRb, p16, p53, Bcl-2 and Bax expression was observed in 100%, 87%, 60%, 40%, 100%, 7% and 93% of tumor samples, and in 100%, 80%, 0%, 80%, 80%, 20% and 100% of dysplasia samples, respectively. Significant difference in the expression of the markers between EAC and BE-associated dysplasia was detected for pRb (p = 0.006). Ki-67 expression was associated with clinicopathological parameter T (p = 0.012;V = 0.585). Ninefold higher risk to develop EAC was established for the patient with strong p53 expression, than the lacking p53 patient. Patients with strong p53 expression survived 6.8 months longer than the patients with weak p53 expression and 8.6 months longer than the patients with moderate p53 expression. No correlation was found between the expression of the other markers and prognosis. Conclusion: The results suggest that Ki-67, PCNA, pRb, p16, p53 and Bax participate in the pathogenesis of EAC, whereas Bcl-2 does not play essential role in EAC and BE-associated dysplasia. The balance between cell proliferation and apoptosis is lost in EAC and BE-associated dysplasia. Abnormal p53 protein expression has predictive and prognostic value in EAC. Larger prospective studies are needed to confirm these findings.

Long-term effectiveness,outcomes and complications of bariatric surgery

Dietary imbalance and overeating can lead to an increasingly widespread disease-obesity.Aesthetic considerations aside,obesity is defined as an excess of adipose tissue that can lead to serious health problems and can predispose to a number of pathological changes and clinical diseases,including diabetes;hypertension;atherosclerosis;coronary artery disease and stroke;obstructive sleep apnea;depression;weight-related arthropathies and endometrial and breast cancer.A body weight 20%above ideal for age,gender and height is a severe health risk.Bariatric surgery is a set of surgical methods to treat morbid obesity when other treatments such as diet,increased physical activity,behavioral changes and drugs have failed.The two most common procedures currently used are sleeve gastrectomy and gastric bypass.This procedure has gained popularity recently and is generally considered safe and effective.Although current data show that perioperative mortality is low and better control of comorbidities and short-term complications is achieved,more randomized trials are needed to evaluate the long-term outcomes of bariatric procedures.This review aims to synthesize and summarize the growing evidence on the long-term effectiveness,outcomes and complications of bariatric surgery.

Sexual Function in Patients with PCOS and/or Obesity before and after Metformin Treatment

The clinical signs of hyperandrogenemia, commonly seen in polycystic ovarian syndrome (PCOS) patients combined with obesity and infertility can cause emotional distress. There are however few data about the psychosocial and sexual function of patients with PCOS. Objectives: The aim of the study was to investigate the sexual function in patients with obesity and/or PCOS using Female sexual function inventory (FSFI) before and after metformin treatment. Design and Methods: In the present study were included 79 patients divided into three groups—group 1 Obese (n = 22);group 2 Lean PCOS (n = 41) and group 3 Obese PCOS (n = 16). All of the subjects completed FSFI questionnaire. In patients who had insulin resistance (OGTT + IRI) metformin treatment was started in dose 1700 - 3000 mg/day. Results: Obese women without PCOS showed significantly higher scores on total FSFI and all domains except from desire compared to lean PCOS subjects. Although the differences do not reach statistical significance, lean PCOS patients have the lowest scores on all domains. FSFI score correlates negatively only with androstendione levels. Women with and without hyperandrogenemia do not show differences in FSFI score. It is interesting to note that LH but not FSH shows moderate positive correlation to all domains of FSFI. FSFI scores do not show correlation to the indices of carbohydrate metabolism (blood glucose and IRI during OGTT), lipid profile, and arterial pressure. After metformin treatment there was an increase in all FSFI domain scores although statistical significance was noted only for the total FSFI score and the domains lubrication and pain, probably because of the small number of patients. Conclusions: Lean PCOS patients have lower scores on FSFI than obese patients with or without PCOS. The hyperandrogenemia is not a determinant for sexual dysfunction in PCOS women. Metformin treatment has a favorable effect on sexual function.

Islet transplantation-immunological challenges and current perspectives

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.

Effectiveness and safety of COVID-19 vaccines in patients with diabetes as a factor for vaccine hesitancy

Diabetes mellitus is one of the most common comorbid conditions encountered in patients with severe acute respiratory syndrome coronavirus 2 infection accompanied by significantly increased mortality,prolonged hospital stay,and requirement of invasive mechanical ventilation.This review aims to present the effectiveness and safety profile of available coronavirus disease 2019(COVID-19)vaccines in people with diabetes as a potential cause of hesitancy for vaccination.Data from published research proves a robust immune response following immunization for COVID-19 in diabetic patients with substantial production of virus-neutralizing antibodies;however,the observed immune response was unequivocally weaker than that in individuals without diabetes.This observation was further enhanced by the findings that worse glycemic control was associated with more suppressed antibody production.In contrast,individuals with optimal glycemic control performed similarly to healthy controls.In addition to the need for strict glucose monitoring and adequate diabetes treatment,those findings reinforce the concept of diabetes-induced secondary immune deficiency and necessitate the application of booster doses to diabetic patients with priority.Nevertheless,after vaccination,reported adverse events were not different from those in the general population.No increase in severe adverse events was documented.While single case reports detected transient increases in blood glucose post-vaccination,more extensive trials could not replicate such a relationship.

Identification of Novel Nonsense RPGR Variant Causing Mild X-Linked Cone-Rod Dystrophy and Myopia

Background: Mutations in the RPGR gene are associated with rod-cone or cone-rod dystrophy, the latter associated with mutations at the distal end. Cone-rod dystrophy (CRD) is a subgroup of hereditary retinal disorders characterized by the primary degeneration of cone photoreceptors often followed by progressive loss of rod photoreceptors in the peripheral visual field. Purpose: The aim of this study was to describe the milder CRD phenotype associated with a novel pathogenic variant c.1905 + 223C > T (p.Q710X) found in RPGR which results in shortening of the photoreceptor specific isoform RPGR ORF15. Method: An 11-year-old boy with symptoms of CRD and two female relatives were referred for detailed ophthalmic examinations. Genetic testing was performed by next-generation sequencing of clinical exome followed by Sanger sequencing for segregation analysis. Results: Genetic analysis identified a novel variant in ORF15 of the RPGR gene (c.1905 + 223C > T, p.Q710X) in the proband considered as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards. Segregation study identified the mutation in a heterozygous state in the mother and her sister. Detailed ophthalmological examination revealed slightly reduced color vision and scattered grayish point-like deposits in the posterior pole of the fundus in the male patient. All mutation carriers were myopic. Conclusion: We report a novel pathogenic RPGR variant in a Bulgarian patient with clinical features compatible with the CRD diagnosis. This condition is inherited as an X-linked dominant trait in its familial form presenting with a mild CRD phenotype in the male hemizygous proband and a moderate to high myopia in the female heterozygous carriers.