Adequate Repair Research Articles

Five Year Experience of Mitral Valve Repair Surgery at Armed Force Institute of Cardiology

Objective: Experience of the conventional and a de novo Mitral repair techniques for the treatment of Severe Mitral Regurgitation (MR) in a Tertiary Care Cardiac Hospital of Pakistan.
 Study Design: Descriptive cross sectional
 Place and Duration of Study: Cardiac Surgical Division, Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, Pakistan
 Methodology: This was a cross sectional study conducted over a period of 5 years from 2016 to 2020, which included SeventyFive (n=75) patients in the trial, 55 females and 20 males. The mean age was 23±9.5 years (range from 16 to 52 years). Amongst all cases of mitral regurgitation (MR) were five (6%) myxomatous degenerative changes, three (4%) ischemic MR & Sixtyseven (91%) patients had rheumatic aetiology. Five (05) patients with myxomatous diseases required only ring annuloplasty. In patients with ischemic MR, two required chordal shortening for anterior leaflet resuspension, and one required quadrangular resection of the posterior leaflet. Restrictive annuloplasty±Coronary Artery Bypass Grafting (CABG) was alsoperformed as part of the procedures. Sixty-seven (91%) patients having severe Mitral Regurgitation with rheumatic aetiology, required a myriad of procedures; including neo-chordae suspension for anterior & posterior mitral leaflets, quadrangular resection & reattachment of the posterior mitral leaflet. A novel innovative procedure, “Posterior annulus-sliding-plasty” (Nasir’s Technique) was adopted in patients with relatively fixed posterior mitral leaflet. Semi-rigid rings (Carbomedics® or Medtronic CG future®) were used in all the patients to stabilize our repair.
 Results: There was no operative mortality. Patients were followed up for 01-year. Most of the patients have been found to have adequate intact Mitral Valve Repair. Only 01 patient developed Grade-II MR after 06 months (ischemic aetiology). This patient is being followed up at 06 monthly intervals with transthoracic echo and is being treated as per guideline-directed medical therapy (GMDT) for functional MR.
 Conclusion: Mitral Valve Repair in the carefully selected subset of patients with severe MR, irrespective of aetiology can effectively be treated with satisfactory short-term and medium-term results.

Surgical Management of Endometriosis of the Bladder and Ureter

<h3>Study Objective</h3> To demonstrate a step-by-step approach for the surgical management of urinary tract endometriosis using conventional laparoscopy for partial cystectomy and robotic-assisted laparoscopy for ureteroneocystostomy. <h3>Design</h3> Surgical video. <h3>Setting</h3> Academic tertiary referral center for endometriosis. <h3>Patients or Participants</h3> The first patient was a 38-year-old G3P3 with a history of hysterectomy presenting with dysuria had an MRI which revealed a T2 hypointense bladder nodule consistent with endometriosis. The second patient was a 25-year-old nulliparous woman with history of stage IV endometriosis with DIE into the bowel and both ureters causing subsequent hydronephrosis requiring bilateral ureteral stents and subsequently bilateral percutaneous nephrostomy tubes. <h3>Interventions</h3> In the first case, a cystoscopy was performed to confirm MRI findings of bladder lesion and to delineate borders and depth of invasion. Conventional laparoscopy was utilized to perform bilateral ureterolysis, bladder mobilization, partial cystectomy for complete excision of the lesion, and two-layered bladder closure. Use of indigo carmine assisted with ureteral orifice identification. In the second case, cystoscopy was performed with injection of ICG to assist with ureteral identification. After ureterolysis, distal ureteric obstruction due to extensive disease was confirmed on laparoscopy and ureteroscopy. Bilateral ureteroneocystostomy with placement of Double-J ureteral stents was performed using a robotic-assisted approach. Each patient had indwelling foley catheter for bladder decompression during recovery. <h3>Measurements and Main Results</h3> Both patients had an uneventful postoperative course. A postoperative retrograde cystogram confirmed adequate repair prior to removal of each foley catheter. Patient two had office stent removal 6 weeks postoperative. <h3>Conclusion</h3> Endometriosis is an increasingly common condition. It is important for gynecological surgeons to have the proper understanding of anatomy, surgical technique, and multidisciplinary care needed with urology for safe and complete excision of bladder and ureter endometriosis.

Robotic-Assisted Laparoscopic Repair of Iatrogenic Vesico-Vaginal Fistula

<h3>Study Objective</h3> This video highlights the principles of robotic assisted laparoscopic repair of iatrogenic vesico-vaginal fistula <h3>Design</h3> Surgical video presentation. <h3>Setting</h3> Academic tertiary care center. <h3>Patients or Participants</h3> We present 2 cases of iatrogenic vesico-vaginal fistula repaired robotically. Case 1 is a 49-year-old patient with a vesico-vaginal fistula after an open supracervical hysterectomy with incidental cystotomy and repair. Case 2 is a 61-year-old patient who was referred for management of a supra-trigonal vesico-vaginal fistula as a complication of vaginal hysterectomy. <h3>Interventions</h3> Case 1 started with cystoscopy and placement of ureteral stents. The peritoneum above the vaginal cuff was incised and an anterior colpotomy was created. The bladder was dissected until the fistula was identified and the injured area was 4 cm away from the colpotomy. The fistulous margins where dissected. The bladder mucosa was repaired in 2 layers in a running fashion. The bladder was retrogradely filled, confirming the repair was watertight. The colpotomy was closed in 2 layers. The repair was reinforced with omental interposition. For case 2, a stent was placed through the vaginal fistulous opening. The stent was identified transvesically with cystoscopy. Bilateral ureteral stents were placed. Similar steps from case 1 were carried out. Cystoscopy was performed confirming an adequate repair. Bilateral ureteral stents were removed. A Foley catheter was inserted to remain in place for 3 weeks. <h3>Measurements and Main Results</h3> Both patients were discharged on post-operative day 1. The patient in case 1 had a voiding cystogram showing no evidence of residual or recurrent fistula on post-operative week 3, and urine leakage was resolved. The patient in case 2 is scheduled for follow up on post-operative week 3. <h3>Conclusion</h3> Robotic assisted repair offers optimal surgical exposure and is ideal for supra-trigonal and complex vesico-vaginal fistulas, affording good outcomes for patients.

Building Facade Failures due to Rainwater Entry in Turkey

Facade failures due to rainwater entry are common in Turkey although, few systematic studies have been completed to determine the types of defects and failures and their causes as would permit developing appropriate repair solutions. The intent of this study is to determine the types of defects and failures caused by rainwater ingress to building facades based on case studies of failure in Turkey. Thus, defects and failures can be characterized and classified, such that the most common types of failure can be revealed and adequate repair solutions proposed. A review of literature was conducted of studies undertaken in Turkey on rainwater entry and building defects. Additionally, field inspections were carried out for 16 public buildings in Istanbul and information regarding failures was gathered from local authorities. Based on data evaluated from previous research and field inspections, it was determined that majority of the buildings had cladding walls with stucco being the most common cladding material. Failures occurred in cladding facades with stucco included detachment of cladding, staining, and cracks; the most common failure was blistering and exfoliation. Air and rainwater leakage due to defects in sealants was the most common failure in buildings with panel and stick wall systems.

Training on Emotional Intelligence for Caregivers of Patients with Acquired Brain Injury and Cognitive Impairment: A Quasi-Experimental Study.

Cognitive-behavioral alterations can occur after an acquired brain injury (ABI). To develop and evaluate a synchronous online training program on emotional intelligence (EI) for the caregivers of adult patients with cognitive-behavioral impairment due to ABI. Quasi-experimental study. Ten caregivers attended a one-month virtual synchronous course about EI. The emotional status of the caregivers was registered one-month-previous and one-month-post program using comparative measures: The Trait Meta-Mood Scale (TMMS-24), the Positive and Negative Affect Schedule (PANAS), Caregiver Burden Interview, the 10-item Connor-Davidson Resilience Scale, and the Emotional Health Survey. After the training course, the favorable changes related to emotional affect measured with the PANAS questionnaire were found; both positive (increase; Mdn = 39.5; effect size -12.79; adjusted variance 95.75) and negative (decrease; Mdn = 14.5; effect size 0.73; adjusted variance 95.50) presented a statistical significance of p &lt; 0.05. The TMMS-24 post-test showed that 90% of the caregivers reported an adequate or excellent emotional repair (p &lt; 0.05; effect size -0.68; adjusted variance 94.75). No other significant differences were found. After this training in EI, the caregivers had a more positive mood and improved aspects of their emotional intelligence, such as emotional regulation. More studies need to be conducted.

All-Inside Technique for Ramp Lesion Repair: Arthroscopic Suture With Knee Scorpion Suture Passer

Ramp lesions are peripheral tears of the posterior horn of the medial meniscus that involve the meniscocapsular attachments. They are commonly associated with anterior cruciate ligament injury and frequently not diagnosed. There are several suture techniques for ramp lesions. However, most have a long learning curve to be performed adequately and to minimize the risks of neurovascular lesions, cartilage injury, as well as damage to the meniscotibial ligament and meniscus. Thus, as an alternative to minimize costs and provide adequate ramp lesion repair, we present a simple, easy-to-reproduce technique using a Scorpion Suture Passer and all-inside sutures, without the need to leave devices inside the knee, causing no additional lesions and making it less costly than conventional methods. Our technique, which consists of a biomechanically strong suture, with no internal devices, is cheaper, allows several sutures with the same thread and produces satisfactory clinical results.

Midpalatal suture bone repair after miniscrew-assisted rapid palatal expansion in adults

BackgroundMidpalatal suture (MPS) repair in growing patients after RPE has been previously reported. However, differences between young and adult patients for timing and pattern of MPS repair after rapid maxillary expansion are expected. The aim of this study was to evaluate the midpalatal suture repair pattern after miniscrew-assisted rapid palatal expansion (MARPE) in adult patients.Materials and methodsThe study included 21 patients (six males, 15 females) successfully treated with MARPE with a mean initial age of 29.1 years of age (SD = 8.0; range = 20.1–45.1). MPS repair was evaluated using maxillary axial and coronal sections derived from CBCT exams taken 16 months after the expansion (SD = 5.9). Objective and subjective assessments of MPS repair were performed. Objective assessments were performed measuring MPS bone density at anterior, median and posterior region of hard palate. Pre-expansion and post-retention bone density changes were evaluated using paired t tests (p < 0.05). Midpalatal suture bone repair was scored 0 to 3 considering, respectively, the complete absence of bone repair in the MPS, the repair of less than 50% of the MPS, the repair of more than 50% of the MPS and the complete repair of the MPS. Intra- and interexaminer reliability evaluation were assessed using Kappa coefficient.ResultsThe objective evaluation showed a significant higher bone density at the pre-expansion stage in all palatal regions. The reliability of the subjective method was adequate with intra- and interexaminer agreements varying from 0.807 to 0.904. Scores 1, 2 and 3 were found in 19.05%, 38.09% and 42.86% of the sample, respectively. The most common region demonstrating absence of bone repair was the middle third. The anterior third of the midpalatal suture was repaired in all patients.ConclusionsA decreased bone density was observed after the retention period when compared to pre-expansion stage. Most adult patients demonstrated incomplete repair of the midpalatal suture 16 months after MARPE. However, adequate bone repair covering more than half of the hard palate extension was observed in 80.95% of the patients.

Application of Phyllanthus emblica extract in manufacturing pharmaceutical composition for repairing liver damage

The objective of this study was to prepare a medicinal formulation with the extract of Phyllanthus emblica to repair liver damage. The hepatocyte cell line Hep-G2 was used in the experiment. The experimental sample was prepared by adding 20,000 hepatocytes to each well of a 24-well Seahorse XF24 analyzer special cell culture plate and cultured for 24 hrs. Subsequently, the culture medium from each well was removed. The hepatocytes in the wells were processed according to the conditions of the experimental, control, or comparator group. The oxygen consumption of the hepatocytes in the experimental, control, and comparator groups in the wells of the cell culture plate was measured using the Seahorse XF24 analyzer bioenergy meter. Treating cells with hydrogen peroxide can simulate the intracellular oxidation of free radicals, permitting examination of the mitochondrial activity of cells under oxidative stress. The mitochondrial activity in the hepatocytes was maintained. The mitochondria produced a sufficient amount of adenosine triphosphate (ATP), allowing the hepatocytes to maintain their normal metabolic functions. Owing to the improved synthesis efficiency and capability of triphosphate required for cell damage repair, damaged hepatocytes were able to obtain adequate energy for repair. Thus, liver repair was accelerated, and it returned to its normal condition.

The incidence of hip dislocation after posterior approach primary total hip arthroplasty: comparison of two different posterior repair techniques.

Total hip arthroplasty (THA) remains one of the most successful orthopedic surgical procedures. The posterior approach is associated with a higher incidence of post-operative dislocations than others. Adequate posterior soft tissue repair techniques, including capsulorrhaphy and transosseous bone sutures in the greater trochanter effectively reduce the dislocation rate. Post-operative "posterior hip precautions" were historically believed to reduce dislocation risks, although not clearly proven. The first protocol consists of capsulorrhaphy with the prescription of post-operative posterior hip precautions (TT) and the second, transosseous bone sutures without precautions (TB). This study aims to determine the optimal protocol to decrease the dislocation rate following posterior approach primary THA. A 10-year retrospective case-control chart review analyzed demographic, pre-, intra-, and post-surgical parameters. Primary outcomes were the difference in dislocation and revision surgery rates between protocols. Secondary outcomes included the incidence of recurrent dislocations and the identification of predictors of dislocation. 2,242 THAs were reviewed and 26 (1.2%) resulted in dislocation. Increased age (p = 0.04) ASA score (p = 0.03) and larger acetabular cup size (p < 0.001) were associated with heightened risk. Tendon to tendon (TT) repair saw a 1.62% dislocation rate versus 0.98% for tendon-to-bone (TB) repair, although statistically insignificant (p = 0.2). Transosseous repair resulted in recurrent dislocations for 8/16 (50%) patients compared to 6/10 (60%) in the suture group (p ≤ 0.001). No significance was found for prescription of posterior hip precautions. To our knowledge, this is the first study to perform a direct comparison of TT repair with posterior precautions to TB repair without posterior precautions. Similarity in dislocation rate, decreased recurrent events and the alleviated patient burden from precautions leads the authors to recommend the TB repair without precautions for a successful THA.

Vibration therapy as an effective approach to improve bone healing in diabetic rats.

ObjectiveTo investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats.Methods148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression.ResultsOur results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (Runx2, Col1a1, Osx), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L).ConclusionsDiabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.

ODONTOGENIC KERATOCYST IN THE MAXILLA: CASE REPORT

A 32-year-old female patient was referred to the oral and maxillofacial surgery service with pain in the jaw for approximately 1 year. On extraoral and intraoral examination, there were no apparent changes or asymmetry. Cone beam computed tomography evidenced an extensive cystic lesion in the left maxillary bone, hypodense, with well-defined limits, extending to the maxillary sinus and involving the impacted tooth 28. Surgical treatment was performed under general anesthesia through enucleation followed by curettage of the entire lesion and removal of the involved impacted tooth. Histopathologic analysis of the specimen resulted in the diagnosis of odontogenic keratocyst. At 10-day follow-up, the surgical site showed adequate tissue repair process. In the postoperative clinical and radiographic follow-up at 1 year and 2 months, a complete bone regeneration was observed and there was no signs of lesion recurrence.

Total anomalous pulmonary venous connection: 16 years of surgical results in a single center.

The aim of the study was to analyze the surgical outcome of patients with total anomalous pulmonary venous connection (TAPVC) who underwent cardiac surgery. A retrospective study was carried out. Patients with diagnosis of TAPVC undergoing cardiac surgery at the National Institute of Cardiology Ignacio Chávez, from January 1, 2003 and June 30, 2019 were included. Descriptive statistics were calculated, as well as a bivariate analysis of the variables associated with mortality. A logistic regression model was included to determine risk factors associated with the main outcome and survival was analyzed using the Kaplan-Meier method. A total of 5314 patients diagnosed with congenital heart disease (CHD) underwent surgery, 414 (7.8%) were patients with TAPVC, with an average age of 17.1 ± 34.6 months, 58.2% were male. It was frequent in infants (61.6%) and preschool (19.6%). Predominant type was supracardiac TAPVC (47.4%). Pulmonary venous obstruction (PVO) occurred in 32.1%. Risk factors associated with mortality were infracardiac TAPVC (odds ratio [OR]: 3.26; 95% confidence interval [CI]: 1.17-9.03; p = .02), PVO (OR: 2.56; 95% CI: 1.05-6.22; p = .03) and postoperative mechanical ventilation (OR: 1.005; 95% CI: 1.002-1.008; p = .01). Overall survival was 87.2%, with better outcomes in adolescents (100%), children (94.1%), mixed TAPVC (96%), and cardiac TAPVC (91.9%;p < .001). The survival of our institution after surgical correction of TAPVC is similar to that of other referral centers, where patients with infracardiac TAPVC and newborns worse outcomes. All patients must undergo a rigorous evaluation to determine an adequate repair strategy.

A Mild Case of Autosomal Recessive Osteopetrosis Masquerading as the Dominant Form Involving Homozygous Deep Intronic Variations in the CLCN7 Gene

Osteopetrosis is a heterogeneous group of rare hereditary diseases characterized by increased bone mass of poor quality. Autosomal-dominant osteopetrosis type II (ADOII) is most often caused by mutation of the CLCN7 gene leading to impaired bone resorption. Autosomal recessive osteopetrosis (ARO) is a more severe form and is frequently accompanied by additional morbidities. We report an adult male presenting with classical clinical and radiological features of ADOII. Genetic analyses showed no amino-acid-converting mutation in CLCN7 but an apparent haploinsufficiency and suppression of CLCN7 mRNA levels in peripheral blood mononuclear cells. Next generation sequencing revealed low-frequency intronic homozygous variations in CLCN7, suggesting recessive inheritance. In silico analysis of an intronic duplication c.595-120_595-86dup revealed additional binding sites for Serine- and Arginine-rich Splicing Factors (SRSF), which is predicted to impair CLCN7 expression. Quantitative backscattered electron imaging and histomorphometric analyses revealed bone tissue and material abnormalities. Giant osteoclasts were present and additionally to lamellar bone, and abundant woven bone and mineralized cartilage were observed, together with increased frequency and thickness of cement lines. Bone mineralization density distribution (BMDD) analysis revealed markedly increased average mineral content of the dense bone (CaMean T-score + 10.1) and frequency of bone with highest mineral content (CaHigh T-score + 19.6), suggesting continued mineral accumulation and lack of bone remodelling. Osteocyte lacunae sections (OLS) characteristics were unremarkable except for an unusually circular shape. Together, our findings suggest that the reduced expression of CLCN7 mRNA in osteoclasts, and possibly also osteocytes, causes poorly remodelled bone with abnormal bone matrix with high mineral content. This together with the lack of adequate bone repair mechanisms makes the material brittle and prone to fracture. While the skeletal phenotype and medical history were suggestive of ADOII, genetic analysis revealed that this is a possible mild case of ARO due to deep intronic mutation.

Myeloid Expressed Epidermal Growth Factor Receptor (EGFR) is Critical to Heart Homeostasis and Limits Adverse Outcomes Following Ischemic Attack

The healthy heart comprises immune cells, mainly macrophages of differing class and origin. While these myeloid cells remain an area of continuous investigation, we have come to appreciate that a subset of tissue residing macrophages (TRMs) seed the heart during development and are maintained through self‐renewal. Further, TRMs continue to be linked to the maintenance of cardiac homeostasis, for instance, through facilitating crosstalk with other cardiac cells, and participating in immunosurveillance. In the case of injury however, such as a myocardial infarction (MI), TRMs are largely replaced by circulating and recruited myeloid cells. Post‐infarct macrophages (mf) are greater in number and class, and functionally, debris clearance and initiation of cardiac repair mechanisms becomes their utmost priority to limit the severity of heart failure (HF). Given these significant roles, it has become critical to understand how cardiac myeloid cells are regulated, and what mechanisms contribute to their known functions both at steady‐state and following injury. Epidermal growth factor receptor (EGFR) is a cell surface tyrosine kinase receptor known to govern cell function through myriad processes. Although historically studied as an oncogene, EGFR has been shown to regulate cardiac physiology, and notably mf activation, survival and function. However, it is currently unknown whether EGFR influences myeloid homeostasis within the heart. Thus, we have generated myeloid‐specific EGFR knockout mice (EGFRmylKO) by crossing floxed EGFR (EGFRf/f) with LysM Cre mice and performed comparative analyses between the lines at baseline and following injury. In response to MI, EGFRmylKO mice exhibit altered inflammatory responses, resulting in aggravated cardiac dysfunction, exacerbated hypertrophic remodeling, and limited angiogenic repair. These functional and structural outcomes are preceded by a disruption in the post‐injury myeloid cell infiltration continuum that favors adequate repair, resulting in decreased transcripts of reparative factors including IL‐10. Additionally, EGFRmylKO mouse hearts show modest signs of stress at baseline, in the absence of injury, including cardiomyocyte hypertrophy with an associated increase in expression of signature fetal gene transcripts. Whole transcriptome analysis of cardiac resident myeloid (Cd11b+) cells by RNASeq revealed over 700 differentially expressed genes that were significantly altered between EGFRmylKO and EGFRf/f control mice. Among these are IGFBP family members 5 and 7, each known to regulate IGF availability, which itself has been recently shown to influence cardiac hypertrophy. In sum, our results reveal that myeloid cell‐expressed EGFR plays previously unknown roles in the regulation of the cardiac homeostasis baseline as well as the chronic remodeling response to ischemic injury.

TNF hampers intestinal tissue repair in colitis by restricting IL-22 bioavailability

Successful treatment of chronic inflammatory diseases integrates both the cessation of inflammation and the induction of adequate tissue repair processes. Strikingly, targeting a single proinflammatory cytokine, tumor necrosis factor (TNF), induces both processes in a relevant cohort of inflammatory bowel disease (IBD) patients. However, the molecular mechanisms underlying intestinal repair following TNF blockade during IBD remain elusive. Using a novel humanized model of experimental colitis, we demonstrate that TNF interfered with the tissue repair program via induction of a soluble natural antagonist of IL-22 (IL-22Ra2; IL-22BP) in the colon and abrogated IL-22/STAT3-mediated mucosal repair during colitis. Furthermore, membrane-bound TNF expressed by T cells perpetuated colonic inflammation, while soluble TNF produced by epithelial cells (IECs) induced IL-22BP expression in colonic dendritic cells (DCs) and dampened IL-22-driven restitution of colonic epithelial functions. Finally, TNF induced IL-22BP expression in human monocyte-derived DCs and levels of IL22-BP correlated with TNF in sera of IBD patients. Thus, our data can explain how anti-TNF therapy induces mucosal healing by increasing IL-22 availability and implicates new therapeutic opportunities for IBD.

Specific Human ATR and ATM Inhibitors Modulate Single Strand DNA Formation in Leishmania major Exposed to Oxidative Agent.

Leishmania parasites are the causative agents of a group of neglected tropical diseases known as leishmaniasis. The molecular mechanisms employed by these parasites to adapt to the adverse conditions found in their hosts are not yet completely understood. DNA repair pathways can be used by Leishmania to enable survival in the interior of macrophages, where the parasite is constantly exposed to oxygen reactive species. In higher eukaryotes, DNA repair pathways are coordinated by the central protein kinases ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR). The enzyme Exonuclease-1 (EXO1) plays important roles in DNA replication, repair, and recombination, and it can be regulated by ATM- and ATR-mediated signaling pathways. In this study, the DNA damage response pathways in promastigote forms of L. major were investigated using bioinformatics tools, exposure of lineages to oxidizing agents and radiation damage, treatment of cells with ATM and ATR inhibitors, and flow cytometry analysis. We demonstrated high structural and important residue conservation for the catalytic activity of the putative LmjEXO1. The overexpression of putative LmjEXO1 made L. major cells more susceptible to genotoxic damage, most likely due to the nuclease activity of this enzyme and the occurrence of hyper-resection of DNA strands. These cells could be rescued by the addition of caffeine or a selective ATM inhibitor. In contrast, ATR-specific inhibition made the control cells more susceptible to oxidative damage in an LmjEXO1 overexpression-like manner. We demonstrated that ATR-specific inhibition results in the formation of extended single-stranded DNA, most likely due to EXO1 nucleasic activity. Antagonistically, ATM inhibition prevented single-strand DNA formation, which could explain the survival phenotype of lineages overexpressing LmjEXO1. These results suggest that an ATM homolog in Leishmania could act to promote end resection by putative LmjEXO1, and an ATR homologue could prevent hyper-resection, ensuring adequate repair of the parasite DNA.

Prospects and Applications of Natural Blood-Derived Products in Regenerative Medicine.

Currently, there are a number of therapeutic schemes used for the treatment of various types of musculoskeletal disorders. However, despite the use of new treatment options, therapeutic failure remains common due to impaired and delayed healing, or implant rejection. Faced with this challenge, in recent years regenerative medicine started looking for alternative solutions that could additionally support tissue regeneration. This review aims to outline the functions and possible clinical applications of, and future hopes associated with, using autologous or heterologous products such as antimicrobial peptides (AMPs), microvesicles (MVs), and neutrophil degranulation products (DGP) obtained from circulating neutrophils. Moreover, different interactions between neutrophils and platelets are described. Certain products released from neutrophils are critical for interactions between different immune cells to ensure adequate tissue repair. By acting directly and indirectly on host cells, these neutrophil-derived products can modulate the body’s inflammatory responses in various ways. The development of new formulations based on these products and their clinically proven success would give hope for significant progress in regenerative therapy in human and veterinary medicine.

97 An unusual combination of rare congenital heart defects in a 70 years old lady complaining worsening dyspnea

Abstract Methods and results A 70-year-old woman presented to our outpatient clinic complaining of worsening dyspnoea in the last 3 months. She had a medical history of hypertension, diabetes, dyslipidemia, and paroxysmal atrial fibrillation. We performed a comprehensive evaluation starting with a transthoracic echocardiogram that showed a dilatation of right ventricle with normal function, severe pulmonary regurgitation, and moderate tricuspid regurgitation with estimated pulmonary artery systolic pressure of 55 mmHg; the left ventricle had normal dimension and function, with mild aortic and mitral regurgitation, and a subaortic membrane which caused a mild obstruction (maximum gradient 17 mmHg). The cardiac magnetic resonance (CMR) confirmed the enlargement of the right ventricle and of the pulmonary artery trunk (51 mm) and the severity of pulmonary regurgitation (regurgitant fraction of 41%). CMR also clearly showed the VSD just below the subaortic membrane and the left to right shunt with a jet that appeared to proceed straight from the left ventricle through the pulmonary valve (Figure 1A). The estimated Qp/Qs was 1.6 and no intramyocardial late enhancement was present. Pulmonary pressures and pulmonary vascular resistance were normal at the right heart catheterization and the Qp/Qs ratio calculated invasively was 1.45. Considering patient high-risk profile for coronary artery disease, a coronary angiography was also performed showing an abnormal origin of the right coronary artery (RCA) from the mid-portion of the left anterior descending coronary artery (LAD) with two significant stenosis: one involving the bifurcation of RCA and the other the mid-portion of the LAD (Figure 1B). The coronary computed tomography angiography (CCTA) showed a benign course of the RCA anterior to the pulmonary artery towards the auriculoventricular groove (Figure 1C, D). Taking into account all these findings, multidisciplinary heart team decided to perform a cardiac surgery intervention of pulmonary valve and trunk replacement, closure of ventricular septal defect and two coronary bypass grafts on LAD and RCA. Conclusions This case represents a combination of some rare congenital heart abnormalities where multimodality cardiovascular imaging techniques were essential to establish a proper diagnosis and to plan an adequate surgical repair. We hypothesize that the peculiar orientation of the VSD jet may have caused the pulmonary trunk dilatation considering that neither the shunt, nor the pulmonary pressure appear to have been of sufficient magnitude to cause it. Pulmonary ectasia and the damage inflicted by the jet to the cusps of the valve have led to the severe valvular insufficiency. While aortic and tricuspid regurgitation are known to be associated with VSD, to the best of our knowledge this is the first report of pulmonary regurgitation secondary to VSD.

Colostomy-Free Bowel Injury Repair.

<h3>Study Objective</h3> To examine procedures of bowel repair after accidental bowel injury during gynecologic surgery and consider the role of colostomy. Demonstrate the appropriate management of accidental bowel injuries. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> Urban general hospital in Japan. <h3>Patients or Participants</h3> From January 2010 to December 2020, 7,154 underwent laparoscopic or robotic hysterectomy for benign pathology. From these cases, the videos of surgeries where bowel injury was experienced were viewed. <h3>Interventions</h3> 21 cases suffered an intraoperative bowel injury that may normally be recommended for colostomy. These cases were managed by same-session intraoperative repair. In one case where multiple bowel injuries occurred during vaginal retrieval, a colostomy was performed. In the other 20 cases, intraoperative repair was safely completed, and no patients experienced pan-peritonitis after the original surgery. It is important to suture the bowel in two layers. Needle driving needs to be precise with the driving and pull-through perpendicular to the bowel wall. Tissue involvement needs to be both precise and consistent across all sutures. The seromuscular suture is placed to push the mucosa into the lumen. In very severe cases we use LAR (one case). After trimming of the damaged cut end of the rectum, a double stapling technique is very effective for event free anastomosis. <h3>Measurements and Main Results</h3> One case experienced leakage from the repair site and this was resolved with drainage and no colostomy was required. All other patients had an event-free recovery. <h3>Conclusion</h3> Bowel injuries have been routinely managed by colostomy. In our series, we have examined the effectiveness of our methods of repair without using colostomy and have found that when repair is sound, colostomy is not required. Colostomy-free surgery is more patient friendly and should be practiced in scenarios where repair training is adequate and suture repair can be performed safely.

Cardiac CT derived 3D reconstruction discriminates for complexity and hemodynamic effect of transcatheter mitral valve repair

Abstract Background Transcatheter mitral valve repair (TMVR) is increasingly used to treat mitral regurgitation (MR) in high risk patients. Optimal transseptal access and guiding catheter position are essential to perform adequate repair. Anatomy of the inter-atrial septum (IAS) and mitral annulus (MA) are often complex and difficult to determine from echocardiography. Purpose The aim of the current study was to evaluate whether pre-TMVR cardiac CT and 3D reconstruction of the IAS and MA could discriminate for complexity and hemodynamic effect of TMVR. Methods Patients planned for TMVR, underwent cardiac CT scan (if eligible). Post-processing software was used to segment and reconstruct the aortic root, IAS, fossa ovalis (FO) and MA, resulting in a 3D model. The following parameters were measured in each model: (1) IAS angle (°) (2) Posterior-FO angle (°) (3) FO-perpendicularity angle (°) (4) MA area (cm2). Patient specific anatomy was categorized in 4 groups as either (1) Posterior-perpendicular (PP) FO + limited IAS angle, (2) PP FO + wide IAS angle, (3) non-PP FO + limited IAS angle or (4) non-PP FO + wide IAS angle. PP FO was defined as posterior-FO angle &amp;gt;65° and FO-perpendicularity angle &amp;gt;135°. IAS angle was considered limited if &amp;lt;110°. Device implantation time (min) was used to assess complexity of the procedure and was compared between the different groups. MR reduction (grades), number of clips used and mitral valve (MV) gradient (mmHg) were compared for patients with MA area &amp;lt;14 cm2 vs. ≥14 cm2. Results 46 patients (mean age 75 years, 41% male) were included. Anatomy was classified (1) PP FO + limited IAS angle in 13, (2) PP FO + wide IAS angle in 13, (3) Non-PP FO + limited IAS angle in 8 and (4) Non-PP FO + wide IAS angle in 12. Median device implantation time was 20 min in group 1, compared to 39 min in group 2 (p=0.02), 33 min in group 3 (p=0.03) and 29 min in group 4 (p=0.08). In patients with MA area &amp;lt;14 cm2, MR reduction was greater (2.22 vs. 1.68, p=0.02), number of clips used was lower (1.44 vs. 1.79, p=0.05) and MV gradient was higher, though not significant (3.15 vs. 2.58, p=0.26) Conclusion The current study showed that TMVR seemed less complex in patients with an optimal anatomy. In patients with limited mitral annulus area a more favorable hemodynamic effect was achieved. Cardiac CT and 3D reconstruction could therefore be of strong aid for procedural planning of TMVR. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Abbott Vascular Anatomy and device implantation timeHemodynamic effect of annulus area