DNA Repair Expression Profiling to Identify High-Risk Cytogenetically Normal Acute Myeloid Leukemia and Define New Therapeutic Targets

This study presents the results of surgery in the elderly for primary hyperparathyroidism (PHPT) from a single institution's experience. We retrospectively analyzed 898 cases of surgically treated PHPT, divided into two groups: 135 elderly patients (A) and 763 patients younger than 65 years (B). PHPT was symptomatic in 68.8 per cent patients in group A and in 81.6 per cent in group B. Unilateral temporary recurrent laryngeal nerve palsy was observed in 0.9 per cent in group A and 0.1 per cent in group B (P > 0.05). No cervical hematomas, mortality or major cardiovascular, neurological, respiratory or metabolic postoperative complications were registered. All the patients evaluated at one year had improvement in the quality of life, with increase of bone mineral density (BMD) in 85.6 per cent and 79.8 per cent of patients in groups A and B, with no significant differences between symptomatic and asymptomatic patients. Parathyroidectomy in elderly PHPT patients is safe, with rate of morbidity similar to what observed in younger individuals. Further investigations are recommended to confirm the role of surgery as an effective approach in elderly PHPT patients.

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LASIK-induced Corneal Changes after Correction of Hyperopia with and without Application of Mitomycin-C

10.21203/rs.2.356/v1 ◽

2019 ◽

Author(s):

Ehab M. Moawad ◽

Ahmed A. Abd Elghany ◽

Amr A. Gab-Alla ◽

Osama M. Elbassiouny ◽

Mohsen S. Badawy

Keyword(s):

Mitomycin C ◽

Clinical Trial Registry ◽

Uncorrected Distance Visual Acuity ◽

Group A ◽

Randomized Control ◽

One Year ◽

Group B ◽

Control Study

Abstract Background The study aimed to assess the role of intraoperative mitomycin-C (MMC) application during hyperopic LASIK correction (+1.00 D to +6.00 D) by examining topographic corneal changes and incidence of regression over a one-year follow-up period. Methods This comparative randomized control study included 136 eyes of 68 hyperopic patients divided into two groups; Group A included 68 eyes of 34 patients that had LASIK with the application of 0.02% MMC for 10 seconds on the stromal bed after excimer laser treatment, and group B included 68 eyes of 34 patients that had LASIK without MMC application. Uncorrected distance visual acuity (UDVA), refraction, keratometry and topography were recorded at 1st week and 1st, 3rd, 6th, and 12th months postoperation. Predictability and treatment efficacy were also recorded at the end of the follow-up period. Results Better predictability was noted in group A than in group B at the 6 month and 12 month follow-up visits, with a mean cycloplegic refraction SE of +0.5 ± 0.31 D in group A and +0.67 ± 0.39 D in group B at the 6 month visit, and +0.63 ± 0.37 D in group A and +0.89 ± 0.48 D in group B at the 12 month visit. The efficacy of the treatment at the end of the follow up period was better in group A than in group B. Group A showed fewer topographic corneal changes than group B. Conclusions Intraoperative MMC application during hyperopic LASIK achieves better predictability and efficacy and induces fewer topographic changes and lower regression rate of hyperopia during the first postoperative year. Trial registration: the Pan African Clinical Trial Registry PACTR201901543722087, on 29 January 2019.

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Role of Prophylactic Dimenhydrinate Versus Ondansetron as an Adjunct to Dexamethasone on Post-Operative Nausea and Vomiting in Laparoscopic Abdominal Procedures

Proceedings of Shaikh Zayed Medical Complex Lahore - October to December ◽

10.47489/p000s343z7581-6mc ◽

2020 ◽

Vol 34 (3) ◽

pp. 29-34

Author(s):

Aaifa Khalid Niazi

Keyword(s):

Single Dose ◽

Nausea And Vomiting ◽

Common Complication ◽

Operation Theatre ◽

Risk Patients ◽

Group A ◽

One Year ◽

Group B ◽

Post Operative Nausea

Introduction: Post-operative nausea and vomiting (PONV) is a common complication in patients undergoing surgery. Anti-emetic prophylaxis is recommended for all high risk patients. Combination therapy is considered superior to single dose prophylaxis however its efficacy in varied laparoscopic abdominal surgical situations has not been investigated. Aims & Objectives: To compare the post-operative nausea and vomiting with Dimenhydrinate plus Dexamethasone versus Ondansetron plus Dexamethasone in patients following laparoscopic abdominal procedures. Place and duration of study: Operation Theatre, Shaikh Zayed Hospital Lahore, for one year (1st April 2015 – 31st March 2016). Material & Methods: 464 patients were placed in two groups of 232 each. Group A received prophylaxis with Dexamethasone 8 mg I/V + Dimenhydrinate 50mg I/V and Group B received prophylaxis with Dexamethasone 8 mg I/V + Ondansetron 4 mg I/V. Efficacy was judged with absence of nausea and vomiting in first 24 hours after surgery. Data was analyzed in SPSS version 27. Results: The frequency of nausea was 6% with Dimenhydrinate while was 9% with ondansetron. Similarly, vomiting was 18% vs. 24% respectively. The efficacy of Dimenhydrinate was 88% while and Ondansetron achieved efficacy in 65% cases, which was statistically significant (p<0.05). Conclusion: The combination Dexamethasone & Dimenhydrinate was more efficacious in preventing PONV than the combination Dexamethasone & Ondansetron

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LASIK-induced Corneal Changes after Correction of Hyperopia with and without Application of Mitomycin-C

10.21203/rs.2.356/v3 ◽

2019 ◽

Author(s):

Ehab M. Moawad ◽

Ahmed A. Abd Elghany ◽

Amr A. Gab-Alla ◽

Osama M. Elbassiouny ◽

Mohsen S. Badawy

Keyword(s):

Mitomycin C ◽

Clinical Trial Registry ◽

Uncorrected Distance Visual Acuity ◽

Group A ◽

Randomized Control ◽

One Year ◽

Group B ◽

Control Study

Abstract Background The study aimed to assess the role of intraoperative mitomycin-C (MMC) application during hyperopic LASIK correction (+1.00 D to +6.00 D) by examining topographic corneal changes and incidence of regression over a one-year follow-up period. Methods This comparative randomized control study included 136 eyes of 68 hyperopic patients divided into two groups; Group A included 68 eyes of 34 patients that had LASIK with the application of 0.02% MMC for 10 seconds on the stromal bed after excimer laser treatment, and group B included 68 eyes of 34 patients that had LASIK without MMC application. Uncorrected distance visual acuity (UDVA), refraction, keratometry and topography were recorded at 1st week and 1st, 3rd, 6th, and 12th months postoperation. Predictability and treatment efficacy were also recorded at the end of the follow-up period. Results Better predictability was noted in group A than in group B at the 6 month and 12 month follow-up visits, with a mean cycloplegic refraction SE of +0.5 ± 0.31 D in group A and +0.67 ± 0.39 D in group B at the 6 month visit, and +0.63 ± 0.37 D in group A and +0.89 ± 0.48 D in group B at the 12 month visit. The efficacy of the treatment at the end of the follow up period was better in group A than in group B. Group A showed fewer topographic corneal changes than group B. Conclusions Intraoperative MMC application during hyperopic LASIK achieves better predictability and efficacy and induces fewer topographic changes and lower regression rate of hyperopia during the first postoperative year. Trial registration: the Pan African Clinical Trial Registry PACTR201901543722087, on 29 January 2019.

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LASIK-induced Corneal Changes after Correction of Hyperopia with and without Application of Mitomycin-C

10.21203/rs.2.356/v2 ◽

2019 ◽

Author(s):

Ehab M. Moawad ◽

Ahmed A. Abd Elghany ◽

Amr A. Gab-Alla ◽

Osama M. Elbassiouny ◽

Mohsen S. Badawy

Keyword(s):

Mitomycin C ◽

Clinical Trial Registry ◽

Uncorrected Distance Visual Acuity ◽

Group A ◽

Randomized Control ◽

One Year ◽

Group B ◽

Control Study

Abstract Background The study aimed to assess the role of intraoperative mitomycin-C (MMC) application during hyperopic LASIK correction (+1.00 D to +6.00 D) by examining topographic corneal changes and incidence of regression over a one-year follow-up period. Methods This comparative randomized control study included 136 eyes of 68 hyperopic patients divided into two groups; Group A included 68 eyes of 34 patients that had LASIK with the application of 0.02% MMC for 10 seconds on the stromal bed after excimer laser treatment, and group B included 68 eyes of 34 patients that had LASIK without MMC application. Uncorrected distance visual acuity (UDVA), refraction, keratometry and topography were recorded at 1st week and 1st, 3rd, 6th, and 12th months postoperation. Predictability and treatment efficacy were also recorded at the end of the follow-up period. Results Better predictability was noted in group A than in group B at the 6 month and 12 month follow-up visits, with a mean cycloplegic refraction SE of +0.5 ± 0.31 D in group A and +0.67 ± 0.39 D in group B at the 6 month visit, and +0.63 ± 0.37 D in group A and +0.89 ± 0.48 D in group B at the 12 month visit. The efficacy of the treatment at the end of the follow up period was better in group A than in group B. Group A showed fewer topographic corneal changes than group B. Conclusions Intraoperative MMC application during hyperopic LASIK achieves better predictability and efficacy and induces fewer topographic changes and lower regression rate of hyperopia during the first postoperative year. Trial registration: the Pan African Clinical Trial Registry PACTR201901543722087, on 29 January 2019.

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DNA Repair Expression Profiling to Identify High-Risk Cytogenetically Normal Acute Myeloid Leukemia and Define New Therapeutic Targets

Cancers ◽

10.3390/cancers12102874 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2874

Author(s):

Ludovic Gabellier ◽

Caroline Bret ◽

Guillaume Bossis ◽

Guillaume Cartron ◽

Jérôme Moreaux

Keyword(s):

Dna Repair ◽

Clinical Outcomes ◽

Prognostic Value ◽

Gene Mutations ◽

Risk Groups ◽

Prognostic Information ◽

Mutational Status ◽

Cox Analysis ◽

Acute Myeloid

Cytogenetically normal acute myeloid leukemias (CN-AML) represent about 50% of total adult AML. Despite the well-known prognosis role of gene mutations such as NPM1 mutations of FLT3 internal tandem duplication (FLT3-ITD), clinical outcomes remain heterogeneous in this subset of AML. Given the role of genomic instability in leukemogenesis, expression analysis of DNA repair genes might be relevant to sharpen prognosis evaluation in CN-AML. A publicly available gene expression profile dataset from two independent cohorts of patients with CN-AML were analyzed (GSE12417). We investigated the prognostic value of 175 genes involved in DNA repair. Among these genes, 23 were associated with a prognostic value. The prognostic information provided by these genes was summed in a DNA repair score, allowing to define a group of patients (n = 87; 53.7%) with poor median overall survival (OS) of 233 days (95% CI: 184–260). These results were confirmed in two validation cohorts. In multivariate Cox analysis, the DNA repair score, NPM1, and FLT3-ITD mutational status remained independent prognosis factors in CN-AML. Combining these parameters allowed the identification of three risk groups with different clinical outcomes in both training and validation cohorts. Combined with NPM1 and FLT3 mutational status, our GE-based DNA repair score might be used as a biomarker to predict outcomes for patients with CN-AML. DNA repair score has the potential to identify CN-AML patients whose tumor cells are dependent on specific DNA repair pathways to design new therapeutic avenues.

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Comparison of one-year prognosis of patients classified as chronic critical lower limb ischaemia according to TASC II or European consensus definition in the COPART cohort

VASA ◽

10.1024/0301-1526/a000432 ◽

2015 ◽

Vol 44 (3) ◽

pp. 0220-0228 ◽

Cited By ~ 4

Author(s):

Marion Vircoulon ◽

Carine Boulon ◽

Ileana Desormais ◽

Philippe Lacroix ◽

Victor Aboyans ◽

...

Keyword(s):

Medical Treatment ◽

Critical Limb Ischaemia ◽

Limb Ischaemia ◽

Medical Group ◽

Consensus Definition ◽

Transcutaneous Oxygen ◽

European Consensus ◽

Group A ◽

One Year ◽

Group B

Background: We compared one-year amputation and survival rates in patients fulfilling 1991 European consensus critical limb ischaemia (CLI) definition to those clas, sified as CLI by TASC II but not European consensus (EC) definition. Patients and methods: Patients were selected from the COPART cohort of hospitalized patients with peripheral occlusive arterial disease suffering from lower extremity rest pain or ulcer and who completed one-year follow-up. Ankle and toe systolic pressures and transcutaneous oxygen pressure were measured. The patients were classified into two groups: those who could benefit from revascularization and those who could not (medical group). Within these groups, patients were separated into those who had CLI according to the European consensus definition (EC + TASC II: group A if revascularization, group C if medical treatment) and those who had no CLI by the European definition but who had CLI according to the TASC II definition (TASC: group B if revascularization and D if medical treatment). Results: 471 patients were included in the study (236 in the surgical group, 235 in the medical group). There was no difference according to the CLI definition for survival or cardiovascular event-free survival. However, major amputations were more frequent in group A than in group B (25 vs 12 %, p = 0.046) and in group C than in group D (38 vs 20 %, p = 0.004). Conclusions: Major amputation is twice as frequent in patients with CLI according to the historical European consensus definition than in those classified to the TASC II definition but not the EC. Caution is required when comparing results of recent series to historical controls. The TASC II definition of CLI is too wide to compare patients from clinical trials so we suggest separating these patients into two different stages: permanent (TASC II but not EC definition) and critical ischaemia (TASC II and EC definition).

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DNA Damage-Induced Neurodegeneration in Accelerated Ageing and Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms22136748 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6748

Author(s):

Heling Wang ◽

Sofie Lautrup ◽

Domenica Caponio ◽

Jianying Zhang ◽

Evandro F. Fang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dna Repair ◽

Werner Syndrome ◽

Accelerated Ageing ◽

Genes Encoding ◽

Group A ◽

Group B ◽

Novel Therapeutic Strategies ◽

Energy Deprivation

DNA repair ensures genomic stability to achieve healthy ageing, including cognitive maintenance. Mutations on genes encoding key DNA repair proteins can lead to diseases with accelerated ageing phenotypes. Some of these diseases are xeroderma pigmentosum group A (XPA, caused by mutation of XPA), Cockayne syndrome group A and group B (CSA, CSB, and are caused by mutations of CSA and CSB, respectively), ataxia-telangiectasia (A-T, caused by mutation of ATM), and Werner syndrome (WS, with most cases caused by mutations in WRN). Except for WS, a common trait of the aforementioned progerias is neurodegeneration. Evidence from studies using animal models and patient tissues suggests that the associated DNA repair deficiencies lead to depletion of cellular nicotinamide adenine dinucleotide (NAD+), resulting in impaired mitophagy, accumulation of damaged mitochondria, metabolic derailment, energy deprivation, and finally leading to neuronal dysfunction and loss. Intriguingly, these features are also observed in Alzheimer’s disease (AD), the most common type of dementia affecting more than 50 million individuals worldwide. Further studies on the mechanisms of the DNA repair deficient premature ageing diseases will help to unveil the mystery of ageing and may provide novel therapeutic strategies for AD.

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Tissue Ki67 proliferative index expression and pathological changes in hemodialysis arteriovenous fistulae: Preliminary single-center results

The Journal of Vascular Access ◽

10.1177/11297298211015495 ◽

2021 ◽

pp. 112972982110154

Author(s):

Raffaella Mauro ◽

Cristina Rocchi ◽

Francesco Vasuri ◽

Alessia Pini ◽

Anna Laura Croci Chiocchini ◽

...

Keyword(s):

Morphological Changes ◽

Hot Spot ◽

Wall Thickening ◽

Proliferating Cells ◽

Ki 67 ◽

Group A ◽

The Mean ◽

Set Up ◽

Group B

Background: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes. Materials and methods: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots. Results: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0–65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 ( p = 0.001) and with NA ( p = 0.001). Conclusions: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.

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High Basal Maximal Standardized Uptake Value (SUVmax) in Follicular Lymphoma Identifies Patients with a Low Risk of Long-Term Relapse

Cancers ◽

10.3390/cancers13122876 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2876

Author(s):

Giovanni Manfredi Assanto ◽

Giulia Ciotti ◽

Mattia Brescini ◽

Maria Lucia De Luca ◽

Giorgia Annechini ◽

...

Keyword(s):

Risk Factors ◽

Follicular Lymphoma ◽

Standardized Uptake Value ◽

Metabolic Tumor Volume ◽

Late Relapse ◽

Prognostic Role ◽

Pet Ct ◽

Group A ◽

Group B

Background: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUVmax alone at baseline PET/CT could have a different prognostic role. Patients and Methods: We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUVmax ≤ 6; and (B) Basal SUVmax > 6. Results: Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B (p 0.005). The five-year PFS in the whole cohort was 87.5%. A clear advantage was confirmed in group A in the absence of other risk factors. Patients with SUVmax ≤ 6 and no risk factors showed a 5-year PFS of 73% against 83% for patients with SUVmax > 6 and at least two risk factors. Conclusion: A high FDG uptake favorably correlated with PFS. A low basal SUVmax reflected a higher rate of late relapse requiring a prolonged follow-up. The basal SUVmax is an approachable parameter with prognostic implications.

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