Antibacterial activity of Ricinus communis plant extract against antibiotic resistant Helicobacter pylori and Gluconobacter oxydans isolated from fresh apple juices samples

Abstract Bacteria were isolated from samples of Fresh Apple juices from shops of three different localities of Lahore. Analysis of samples from Liberty, Anarkali and Yateem khana Markets show different levels of contamination. There were pathogenic and non-pathogenic bacteria in all samples and were identified by the morphological and biochemical tests. Most of the plasmids of pathogenic bacteria were 4kb in their molecular size. Ribotyping of 16S ribosomal RNA gene sequencing was done to confirm Helicobacter pylori strain and Gluconobacter oxydans. The highest sensitivity of 210mm was shown by Enterobacter sp. against Aztheromysine disk (15µg) while Micrococcus sp. was highly resistant against all of the Antibiotics applied. The antibiotic resistance of pathogenic bacteria was also checked against Ricinus communis plant's extracts, all isolated bacterial pathogens were resistant but only, E.coli was inhibited at 300µl of the extracts. Presence of pathogenic bacteria in Apple juice samples was due to contamination of sewage water in drinking water while some of these pathogenic bacteria came from Apple's tree and other from store houses of fruits.

Resumo As bactérias foram isoladas de amostras de suco de maçã fresco de lojas de três diferentes localidades de Lahore. A análise de amostras dos mercados Liberty, Anarkali e Yateem khana mostram diferentes níveis de contaminação. Havia bactérias patogênicas e não patogênicas em todas as amostras e foram identificadas pelos testes morfológicos e bioquímicos. A maioria dos plasmídeos de bactérias patogênicas tinha 4 kb em seu tamanho molecular. A ribotipagem do sequenciamento do gene do RNA ribossômico 16S foi realizada para confirmar a cepa de Helicobacter pylori e Gluconobacter oxydans. A maior sensibilidade de 210 mm foi mostrada por Enterobacter sp. contra disco de azteromisina (15µg) enquanto Micrococcus sp. foi altamente resistente a todos os antibióticos aplicados. A resistência a antibióticos de bactérias patogênicas também foi verificada contra extratos de plantas de Ricinus communis, todos os patógenos bacterianos isolados foram resistentes, mas apenas E. coli foi inibida em 300µl dos extratos. A presença de bactérias patogênicas nas amostras de suco de maçã deveu-se à contaminação da água de esgoto na água potável, enquanto algumas dessas bactérias patogênicas vieram da árvore da maçã e outras de armazéns de frutas.

Variability in indigenous Pakistani tomato lines and worldwide reference collection for Tomato Mosaic Virus (ToMV) and Tomato Yellow Leaf Curl Virus (TYLCV) infection

Abstract Local and exotic germplasm of tomato remains a major source for genetic improvement. Assessment of such lines for biotic stresses particularly viral diseases are the most important criteria for selection in Pakistan, where Tomato Yellow Leaf Curl Virus (TYLCV) and Tomato Mosaic Virus (ToMV) are the major diseases/viruses. A set of 40 accessions (including indigenous Pakistani lines and exotic germplasm from Europe, the United States, and Asia) were evaluated for their resistance/infection response to ToMV with artificial inoculation under greenhouse conditions. Infection response was quantified through disease scoring and DAS-ELISA test (for ToMV). A subset of 24 lines, was further screened for TYLCV using disease scoring and TAS-ELISA. The tested lines showed significant variability for resistance to ToMV. Only one accession (Acc-17878) was resistant to the ToMV whereas seven accessions i.e. Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352, and CLN-362 expressed resistance to TYLCV. Correlation between phenotypic evaluation was confirmed by the ELISA results in both diseases, although both tools complemented to assess the viral infection status. In future, tomato breeding programs must consider breeding for ToMV and TYLCV resistance (using identified germplasm in our study) so as to deliver virus resistant tomato varieties.

RESUMO O germoplasma local e exótico do tomate continua sendo uma importante fonte de melhoramento genético. A avaliação de linhagens para estresses bióticos, particularmente as doenças virais, é o critério mais importantes para seleção no Paquistão, onde o vírus da folha amarela do tomate (TYLCV) e o vírus do mosaico do tomateiro (ToMV) são as principais doenças/vírus. Um conjunto de 40 acessos (incluindo linhagens indígenas do Paquistão e germoplasma exótico da Europa, dos Estados Unidos e da Ásia) foi avaliado quanto à resistência/resposta à infecção ao ToMV com inoculação artificial em casa de vegetação. A resposta à infecção foi quantificada por meio de pontuação da doença e de teste DAS-ELISA (para ToMV). Um subconjunto de 24 linhas foi posteriormente rastreado para TYLCV usando pontuação de doença e TAS-ELISA. As linhas testadas apresentaram variabilidade significativa para resistência ao ToMV. Apenas um acesso (Acc-17878) foi resistente ao ToMV, enquanto sete acessos (Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352 e CLN-362) expressaram resistência ao TYLCV. A correlação entre a avaliação fenotípica foi confirmada pelos resultados do ELISA nas duas doenças, embora ambas as ferramentas tenham se complementado para avaliar o estado da infecção viral. No futuro, os programas de melhoramento de tomate devem considerar aperfeiçoamentos para resistência ao ToMV e TYLCV (usando germoplasma identificado em nosso estudo) de modo a fornecer variedades de tomate resistentes a vírus.

Phylo-geographic analysis of whitefly on the basis of mitochondrial cytochrome oxidase 1 gene

Abstract Bemisia tabaci is a species complex that causes damage to its broad range of plant hosts through serious feeding. It transmits plant viruses of different groups to important agricultural crops. Some important cash crops of Pakistan are sugar cane, rice, tobacco and seed oil. It shows high genetic variability and is differentiated as races or biotypes. Biotypes are, biotype Q, biotype B, biotype B2, biotype M, biotype L, biotype A, biotype H, biotype C, biotype K, biotype N, biotype R, biotype E, biotype P, biotype J, biotype S, biotype AN. Although the current report based on the Bayesian study of mitochondrial cytohrome oxidase gene1 (CO1) DNA sequences has classified the different populations of whiteflies into twelve genetic groups which are Mediterranean, Sub-Saharan Africa silverleafing, Indian Ocean, Asia II, Asia I, Australia, New World, Italy, China, Sub-Saharan Africa non-silverleafing, Mediterranean/Asia Minor/Africa and Uganda sweet potato. Begomoviruses is largest group of viruses transmitted by B. tabaci and cause major diseases of crops such as tomato and chili leaf curl disease, cassava mosaic disease; yellow mosaic disease of legumes and cotton leaf curl disease. The main objective of current study is to inculpate knowledge regarding genetic diversity of whitefly in cotton fields across Pakistan via analysis of partial DNA sequence of mitochondrial gene Cytochrom Oxidase I (mtCO1).

Resumo Bemisia tabaci é um complexo de espécies que causa danos a uma ampla gama de hospedeiros vegetais por meio de alimentação séria. Ele transmite vírus de plantas de diferentes grupos para importantes safras agrícolas. Algumas safras comerciais importantes do Paquistão são cana-de-açúcar, arroz, tabaco e óleo de semente. Apresenta alta variabilidade genética e é diferenciado em raças ou biótipos. Os biótipos são: biótipo Q, biótipo B, biótipo B2, biótipo M, biótipo L, biótipo A, biótipo H, biótipo C, biótipo K, biótipo N, biótipo R, biótipo E, biótipo P, biótipo J, biótipo S, biótipo AN . Embora o relatório atual baseado no estudo bayesiano das sequências de DNA do gene 1 da oxidase do citocromo mitocondrial (CO1) tenha classificado as diferentes populações de moscas-brancas em doze grupos genéticos, que são Mediterrâneo, África Subsaariana com folha de prata, Oceano Índico, Ásia II, Ásia I, Austrália, Novo Mundo, Itália, China, África Subsaariana sem folha prateada, Batata-doce Mediterrâneo / Ásia Menor / África e Uganda. Os begomovírus são o maior grupo de vírus transmitidos por B. tabaci e causam as principais doenças de culturas, como a doença do cacho do tomate e da pimenta-malagueta, doença do mosaico da mandioca, doença do mosaico amarelo de leguminosas e doença do enrolamento da folha do algodão. O principal objetivo do presente estudo é inculpar conhecimento sobre a diversidade genética da mosca-branca em campos de algodão em todo o Paquistão por meio da análise da sequência parcial de DNA do gene mitocondrial Citocromo Oxidase I (mtCO1).

Phylo-geographic analysis of whitefly on the basis of mitochondrial cytochrome oxidase 1 gene / Análise filogeográfica da mosca-branca com base no gene citocromo oxidase 1 mitocondrial

Bemisia tabaci is a species complex that causes damage to its broad range of plant hosts through serious feeding. It transmits plant viruses of different groups to important agricultural crops. Some important cash crops of Pakistan are sugar cane, rice, tobacco and seed oil. It shows high genetic variability and is differentiated as races or biotypes. Biotypes are, biotype Q, biotype B, biotype B2, biotype M, biotype L, biotype A, biotype H, biotype C, biotype K, biotype N, biotype R, biotype E, biotype P, biotype J, biotype S, biotype AN. Although the current report based on the Bayesian study of mitochondrial cytohrome oxidase gene1 (CO1) DNA sequences has classified the different populations of whiteflies into twelve genetic groups which are Mediterranean, Sub-Saharan Africa silverleafing, Indian Ocean, Asia II, Asia I, Australia, New World, Italy, China, Sub-Saharan Africa non-silverleafing, Mediterranean/Asia Minor/Africa and Uganda sweet potato. Begomoviruses is largest group of viruses transmitted by B. tabaci and cause major diseases of crops such as tomato and chili leaf curl disease, cassava mosaic disease; yellow mosaic disease of legumes and cotton leaf curl disease. The main objective of current study is to inculpate knowledge regarding genetic diversity of whitefly in cotton fields across Pakistan via analysis of partial DNA sequence of mitochondrial gene Cytochrom Oxidase I (mtCO1).

Bemisia tabaci é um complexo de espécies que causa danos a uma ampla gama de hospedeiros vegetais por meio de alimentação séria. Ele transmite vírus de plantas de diferentes grupos para importantes safras agrícolas. Algumas safras comerciais importantes do Paquistão são cana-de-açúcar, arroz, tabaco e óleo de semente. Apresenta alta variabilidade genética e é diferenciado em raças ou biótipos. Os biótipos são: biótipo Q, biótipo B, biótipo B2, biótipo M, biótipo L, biótipo A, biótipo H, biótipo C, biótipo K, biótipo N, biótipo R, biótipo E, biótipo P, biótipo J, biótipo S, biótipo AN . Embora o relatório atual baseado no estudo bayesiano das sequências de DNA do gene 1 da oxidase do citocromo mitocondrial (CO1) tenha classificado as diferentes populações de moscas-brancas em doze grupos genéticos, que são Mediterrâneo, África Subsaariana com folha de prata, Oceano Índico, Ásia II, Ásia I, Austrália, Novo Mundo, Itália, China, África Subsaariana sem folha prateada, Batata-doce Mediterrâneo / Ásia Menor / África e Uganda. Os begomovírus são o maior grupo de vírus transmitidos por B. tabaci e causam as principais doenças de culturas, como a doença do cacho do tomate e da pimenta-malagueta, doença do mosaico da mandioca, doença do mosaico amarelo de leguminosas e doença do enrolamento da folha do algodão. O principal objetivo do presente estudo é inculpar conhecimento sobre a diversidade genética da mosca-branca em campos de algodão em todo o Paquistão por meio da análise da sequência parcial de DNA do gene mitocondrial Citocromo Oxidase I (mtCO1).

Variability in indigenous Pakistani tomato lines and worldwide reference collection for Tomato Mosaic Virus (ToMV) and Tomato Yellow Leaf Curl Virus (TYLCV) infection / Variabilidade em linhagens indígenas de tomate do Paquistão e coleção de referência global para infecção por vírus do mosaico do tomateiro (ToMV) e vírus da folha amarela do tomate (TYLCV)

Local and exotic germplasm of tomato remains a major source for genetic improvement. Assessment of such lines for biotic stresses particularly viral diseases are the most important criteria for selection in Pakistan, where Tomato Yellow Leaf Curl Virus (TYLCV) and Tomato Mosaic Virus (ToMV) are the major diseases/viruses. A set of 40 accessions (including indigenous Pakistani lines and exotic germplasm from Europe, the United States, and Asia) were evaluated for their resistance/infection response to ToMV with artificial inoculation under greenhouse conditions. Infection response was quantified through disease scoring and DAS-ELISA test (for ToMV). A subset of 24 lines, was further screened for TYLCV using disease scoring and TAS-ELISA. The tested lines showed significant variability for resistance to ToMV. Only one accession (Acc-17878) was resistant to the ToMV whereas seven accessions i.e. Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352, and CLN-362 expressed resistance to TYLCV. Correlation between phenotypic evaluation was confirmed by the ELISA results in both diseases, although both tools complemented to assess the viral infection status. In future, tomato breeding programs must consider breeding for ToMV and TYLCV resistance (using identified germplasm in our study) so as to deliver virus resistant tomato varieties.

O germoplasma local e exótico do tomate continua sendo uma importante fonte de melhoramento genético. A avaliação de linhagens para estresses bióticos, particularmente as doenças virais, é o critério mais importantes para seleção no Paquistão, onde o vírus da folha amarela do tomate (TYLCV) e o vírus do mosaico do tomateiro (ToMV) são as principais doenças/vírus. Um conjunto de 40 acessos (incluindo linhagens indígenas do Paquistão e germoplasma exótico da Europa, dos Estados Unidos e da Ásia) foi avaliado quanto à resistência/resposta à infecção ao ToMV com inoculação artificial em casa de vegetação. A resposta à infecção foi quantificada por meio de pontuação da doença e de teste DAS-ELISA (para ToMV). Um subconjunto de 24 linhas foi posteriormente rastreado para TYLCV usando pontuação de doença e TAS-ELISA. As linhas testadas apresentaram variabilidade significativa para resistência ao ToMV. Apenas um acesso (Acc-17878) foi resistente ao ToMV, enquanto sete acessos (Acc-17890, AVR-261, CLN-312, AVR-321, EUR-333, CLN-352 e CLN-362) expressaram resistência ao TYLCV. A correlação entre a avaliação fenotípica foi confirmada pelos resultados do ELISA nas duas doenças, embora ambas as ferramentas tenham se complementado para avaliar o estado da infecção viral. No futuro, os programas de melhoramento de tomate devem considerar aperfeiçoamentos para resistência ao ToMV e TYLCV (usando germoplasma identificado em nosso estudo) de modo a fornecer variedades de tomate resistentes a vírus.

Screening, biochemical characterization and antibiotics resistance/susceptibility of bacteria isolated from native soil and water samples / Triagem, caracterização bioquímica e resistência/suscetibilidade a antibióticos de bactérias isoladas de amostras nativas de solo e água

The present study was conducted to isolate and characterize bacteria from water and soil sample taken from the Lahore Canal at different sites i.e. Mall Road, Mohlanwal and Khera site. Isolated bacterial strains were identified on the basis of morphological and biochemical tests. Identification was confirmed by culturing bacteria on selective media. Antibiotic resistance test was also performed to observe the resistance of bacteria against different antibiotics. Blood agar test was performed for identification of different pathogenic bacteria. The result revealed that water and soil samples of Lahore Canal Lahore from different sites were contaminated with Escherichia coli, Salmonella sp., Vibrio sp., Bacillus spp., Enterococcus sp. and Staphylococcus spp. Due to presence of these pathogens, this water is not suitable for any domestic and irrigation use. Study also revealed that water of the Lahore Canal is harmful for human health as it is contaminated with bacteria that can cause severe disease e.g., Escherichia coli can cause gastroenteritis, Bacillus spp. can cause nausea and vomiting, Enterococcus may infect urinary tract, Salmonella sp. is responsible for Bacteremia, Staphylococcus spp. can cause mild fever and Vibrio sp. can be the reason of cholera. Thus it is rendered unfit for any kind of human use even other than drinking like swimming, bathing, washing etc., until and unless some remedial measures are employed to eradicate pathogenic microorganisms by WASA and LWMS according to standards of WHO. Similarly, it is quite harmful, when and where ever it is used for irrigation without proper treatment.

O presente estudo foi realizado para isolar e caracterizar bactérias de amostras de água e solo retiradas do Canal Lahore, em Lahore, em diferentes locais, ou seja, Mall Road, Mohlanwal e Khera. As cepas bacterianas isoladas foram identificadas com base em testes morfológicos e bioquímicos. A identificação foi confirmada por cultura de bactérias em testes de meios seletivos. O teste de resistência aos antibióticos também foi realizado para observar a resistência das bactérias a diferentes antibióticos. Foi realizado o teste de ágar sangue para identificar diferentes bactérias patogênicas. O resultado revelou que amostras de água e solo do Canal Lahore, Lahore, de diferentes localidades estavam contaminadas com Escherichia coli, Salmonella sp., Vibrio sp., Bacillus spp., Enterococcus sp. e Staphylococcus spp. Por causa da presença desses patógenos, essa água não é adequada para qualquer uso doméstico e de irrigação. O estudo revelou que a água do Canal Lahore é prejudicial à saúde humana, pois está contaminada com bactérias que podem causar doenças graves, por exemplo: Escherichia coli pode ocasionar gastroenterite; Bacillus spp. pode causar náuseas e vômitos; Enterococcus sp. pode infectar o trato urinário; Salmonella sp. é responsável pela bacteremia; Staphylococcus spp. pode causar febre leve; e Vibrio sp. pode ser a razão da cólera. Assim, torna-se imprópria para uso humano, como natação, banho, lavagem etc., até que algumas medidas corretivas sejam empregadas para erradicar microrganismos patogênicos por WASA e LWMS de acordo com os padrões da OMS. Da mesma forma, é bastante prejudicial, quando usada para irrigação sem tratamento adequado.

Hypoxia as a potential inducer of immune tolerance, tumor plasticity and a driver of tumor mutational burden: Impact on cancer immunotherapy.

In cancer patients, immune cells are often functionally compromised due to the immunosuppressive features of the tumor microenvironment (TME) which contribute to the failures in cancer therapies. Clinical and experimental evidence indicates that developing tumors adapt to the immunological environment and create a local microenvironment that impairs immune function by inducing immune tolerance and invasion. In this context, microenvironmental hypoxia, which is an established hallmark of solid tumors, significantly contributes to tumor aggressiveness and therapy resistance through the induction of tumor plasticity/heterogeneity and, more importantly, through the differentiation and expansion of immune-suppressive stromal cells. We and others have provided evidence indicating that hypoxia also drives genomic instability in cancer cells and interferes with DNA damage response and repair suggesting that hypoxia could be a potential driver of tumor mutational burden. Here, we reviewed the current knowledge on how hypoxic stress in the TME impacts tumor angiogenesis, heterogeneity, plasticity, and immune resistance, with a special interest in tumor immunogenicity and hypoxia targeting. An integrated understanding of the complexity of the effect of hypoxia on the immune and microenvironmental components could lead to the identification of better adapted and more effective combinational strategies in cancer immunotherapy. Clearly, the discovery and validation of therapeutic targets derived from the hypoxic tumor microenvironment is of major importance and the identification of critical hypoxia-associated pathways could generate targets that are undeniably attractive for combined cancer immunotherapy approaches.

The Prevalence of Hyperthyroidism Amongst Atrial Fibrillation Patients in the National Guard Hospital, Riyadh, Saudi Arabia: A Cross-Sectional Retrospective Study.

Introduction The thyroid gland is the largest pure endocrine gland. It is also responsible for the production of multiple important hormones that regulate heart function. Dysfunction of the thyroid gland could lead to hyperthyroidism, which in turn leads to many lipid and cardiovascular problems. One such cardiac condition that is highly associated with hyperthyroidism is atrial fibrillation. Atrial fibrillation is when abnormal electrical impulses suddenly start firing in the atria. With a prevalence of 16% to 60% of atrial fibrillation in hyperthyroid patients. To the best of our knowledge, no similar study was conducted in Saudi Arabia. Objectives Our study aims to investigate the percentage of people with atrial fibrillation that is caused by hyperthyroidism in the National Guard Hospital. Moreover, we hope that this study will improve the quality of life of these affected patients and add to their knowledge of medicine. Methods Since the population size has increased by approximately 4000 patients in the last five years, we estimated the sample size based on a confidence interval of 95% and a level of significance of 5%, which is 350 patients. We included all patients with atrial fibrillation due to hyperthyroidism in KAMC-R and patients' records from 2015 to 2020. Also, we excluded all patients with atrial fibrillation due to other causes. In addition, the sampling method we used was convenient sampling. Result Out of 1100 patients with hyperthyroidism or subclinical hyperthyroidism, 40 or 3.6% of the patients had atrial fibrillation, while the rest were distributed among dilated cardiomyopathy, diabetes mellitus, heart failure, and other risk factors for atrial fibrillation. Conclusion We conclude that hyperthyroidism is a risk factor for atrial fibrillation; 3.6% of hyperthyroidism patients have atrial fibrillation. Most of the patients are elderly, and more than half (58%) are female.

The Measurement of Bovine Pericardium Density and Its Implications on Leaflet Stress Distribution in Bioprosthetic Heart Valves.

PURPOSE: Bioprosthetic Heart Valves (BHVs) are widely used in clinical practice, showing promising outcomes. Computational modeling offers a valuable tool for quantitatively characterizing BHVs. To ensure the accuracy of computational models, it is crucial to consider precise leaflet properties, including mechanical properties and density. Bovine pericardium (BP) serves as a common material for BHV leaflets. Previous computational studies often assume BP density to approximate that of water or blood. Given that BP leaflets undergo various treatments, such as tissue fixation and anti-calcification, this study aims to measure the density of BP used in BHVs and assess its impact on leaflet stress distribution. METHODS: Eight square BP samples were laser cut from Edwards BP patches and their density was determined. Specimen weight was measured using an A&D Analytical Balance, while volume was assessed through high-resolution imaging. Additionally, finite element models resembling a BHV, like the Carpentier-Edwards PERIMOUNT Magna, were constructed in ABAQUS. RESULTS: The average density of the BP samples was found to be 1,410 kg/m3. During the acceleration phase of a cardiac cycle, the maximum stress reached 1.89 MPa for a density of 1,410 kg/m3 and 2.47 MPa for a density of 1,000 kg/m3 (a 30.7% difference). In the deceleration phase, the maximum stress reached 713 kPa and 669 kPa, respectively. CONCLUSION: Leaflet stress distribution and motion in BHVs are influenced by density variations. Establishing an accurate density value for BHV leaflets is imperative for enhancing the computational models, which can ultimately contribute to improved BHV design and outcomes.

The Use of Problem-Based Learning Curriculum to Increase Medical Student Exposure to Radiation Oncology.

PURPOSE/OBJECTIVE(S): In recent years, there has been a decline in the number of radiation oncology residency applicants. New techniques to recruit students to the field are necessary. Early exposure to oncology care in pre-clinical years may translate to increased student interest in oncology-related fields and improved understanding of oncologic treatment modalities. We propose that a cancer-specific problem-based learning (PBL) case will increase exposure to oncology during pre-clinical years. MATERIALS/METHODS: A PBL case regarding pancreatic cancer was created by a radiation oncology resident/faculty member and the gastrointestinal course director for first-year medical students (n = 140) at a single institution. The one-hour small group case focused on oncologic work up, multi-disciplinary care and radiotherapy concepts. Students were provided with a case prompt and resources to review prior to the PBL session. Volunteer radiation oncology facilitators then guided students through the case to achieve desired learning objectives. Following the PBL, students completed an optional nine-question survey regarding their experience. RESULTS: A total of 76 (54%) medical students completed the post-PBL survey. The majority (89%) of students reported that the case motivated them to learn more about oncology, and almost all (99%) noted improved understanding of the multidisciplinary nature of cancer care. 75 (99%) students reported increased understanding of how radiotherapy is delivered. 62 (82%) students reported increased motivation to learn about radiation oncology. 38 (50%) students reported that they plan to participate in an elective in oncology. 36 (47%) reported that they are considering pursuing an oncologic field. There was an increase in the number of subscribers to the Oncology Interest Group (43% increase from previous year) and positive feedback was noted from free-text responses from participants. CONCLUSION: Integrating a cancer-specific PBL case facilitated by radiation oncology educators into the pre-clinical curriculum is an effective avenue to introduce oncology concepts and stimulate interest in oncology amongst first-year medical students.

Risk Factors and Clinical Features of Fistula after Concurrent Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer.

PURPOSE/OBJECTIVE(S): The standard treatment for locally advanced cervical cancer (LACC) is concurrent chemoradiation and brachytherapy (CRT-B). Fistula formation is a serious complication of treatment; however, risk factors and clinical outcomes are not well described. We sought to identify the incidence, risk factors and prognosis of radiation-induced fistula in women who underwent CRT-B for LACC. MATERIALS/METHODS: A single institution retrospective review of patients treated with CRT-B for LACC from July 2013 to August 2022 across 3 centers was performed. Inclusion criteria were Stage IB-IVB cervical cancer treated with definitive intent. Patients with upfront or adjuvant surgery were excluded. Cox-proportional hazards model was performed to assess factors associated with fistula. Local control and fistula-free survival were estimated using the Kaplan-Meyer method. Clinical significance was defined as p < 0.05. RESULTS: A total of 105 patients met the inclusion criteria and were included in this analysis. Patients consisted of FIGO Stage I (n = 20, 19%), Stage II (n = 22, 21%), Stage III (n = 46, 43.8%) or Stage IV disease (n = 17, 16.2%). 12 (11.4%) patients developed fistula following CRT-B; 1/12 patients (8.3%) had fistula present at time of diagnosis. Median time to fistula development was 12 months. Fistula was characterized as vesicovaginal/urethrovaginal in 58.3% (n = 7) and rectovaginal/intestinovaginal in 83.3% (n = 10), including 8 patients (66.7%) who had more than one type of fistula. 4/12 (33.3%) of patients with fistula had concurrent local recurrence. Patients were treated with conservative management (41.7%), hyperbaric oxygen (16.7%) and/or surgery (83.3%). Complications included infection (50.0%), urinary/bowel diversion (83.3%), hospitalization (50.0%) and death (8.3%). Fistula was resolved in 7/12 patients (58.3%) at time of last follow up. Higher BMI (p = 0.04) and use of hybrid applicators (p = 0.02) were associated with decreased likelihood of fistula development. Disease extension into bladder was associated with increased likelihood of fistula development (p = 0.03). Compared to former and never smoking, current smoking was associated with a higher risk of developing fistula (p = 0.04, OR 4.42, CI:1.07-18.34). Compared to intracavitary and hybrid applicators, the use of a Syed applicator was associated with increased likelihood of fistula development (p = 0.02, OR 8.00, CI: 1.37-46.55). Two-year local control was 82.5% (CI: 64.5-91.9) for Stage I-II, 80.7% (CI: 62.8-90.6) for Stage III, and 62.2% (CI: 30.1-82.9) for Stage IV. Two-year fistula free survival was 89.9% (CI: 80.6 - 94.9). CONCLUSION: Women who undergo definitive chemoradiation for treatment of LACC have a 11.4% risk of fistula formation overall. The risk is higher amongst patients with current smoking, disease extension into bladder and Syed applicators. Overall two-year local control was 78.7% and fistula free survival was 89.9%.

Single Institution Experience of the Effect of Adjuvant Radiation on Outcomes for Patients with Uterine Carcinosarcoma.

PURPOSE/OBJECTIVE(S): Uterine carcinosarcoma (UCS) is a rare but aggressive malignancy with poor outcomes. Due to its low incidence, there is no well-established optimal treatment. Standard treatment involves surgery and chemotherapy (CT) +/- adjuvant radiation therapy (RT). Our primary aim was to determine if patients who underwent adjuvant RT had improved distant metastasis free survival (DMFS) and locoregional recurrence free survival (LRRFS). Our secondary aim was to determine the effect of adjuvant RT on overall survival (OS). MATERIALS/METHODS: We performed a single institutional retrospective review of all patients with UCS who underwent primary surgical resection +/- CT and +/- RT between 2007 to 2021. Patients without at least 3 months of documented follow-up were excluded. We assessed DMFS, LRRFS, and OS between patients who did and did not receive adjuvant RT, consisting of vaginal brachytherapy (VBT), external beam radiation therapy (EBRT), or EBRT + VBT. Statistical analysis was performed with spreadsheet and statistical software. RESULTS: Sixty-four patients underwent primary surgical resection for FIGO stage I-IV UCS. Sixty six percent (n = 42) had early stage, FIGO I-II disease and 34% (n = 22) had late stage, FIGO III-IV disease. Eleven percent (n = 7) underwent surgery alone, 28% (n = 18) underwent surgery + CT, 6% (n = 4) underwent surgery + adjuvant RT, and 55% (n = 35) underwent surgery + CT + RT. Most patients who underwent surgery + CT + EBRT + VBT (n = 9) had worse clinicopathologic features including late stage (56%), lymphovascular invasion positive (78%) disease with 50% or greater myometrial invasion (56%). EBRT doses ranged from 45-50.4 Gray (Gy) in 1.8 Gy per fraction. VBT doses ranged from 21-25 Gy in 3-5 fractions when delivered alone and 10-15 Gy in 2-3 fractions when delivered as a boost. Median DMFS was 20.3 months, median LRRFS was 22.6 months, median DFS was 19.4 months, and median OS was 24.7 months. Rate of distant metastasis appeared to drive rate of disease-free survival (Table 1). Patients who underwent adjuvant RT had improved median DMFS (71.5 vs. 11.3 months, p = .002), median LRRFS (71.5 vs 22.5 months, p = .002), and median OS (60.7 vs. 22.5 months, p = .002) compared to those who did not receive RT. CONCLUSION: Prognosis of patients with UCS remains poor; however, adjuvant RT delivered after CT may offer potential benefit in survival outcomes despite worse clinicopathologic features in these patients.

19†Unilateral lateral rectus resection as preferred procedure to treat patients with acquired distance esotropia.

To report the results of a series of patients with acquired distance esotropia (ET) who underwent lateral rectus resection.We retrospectively analysed data from 21 symptomatic patients with acquired esotropia who did not tolerate prisms. Twelve patients had myopic esotropia, 5 patients decompensated esophoria and 4 patients age-related distance esotropia. Patients were divided in two groups; myopic and non myopic. Two patients in each group had undergone surgery to medial recti muscles previously. Near and distance angles were measured over 2 visits. Data were analysed with t-test (paired and unpaired).Average age was 47 (myopes), 77 (distance ET) and 26 years (esophoria). Mean spherical equivalent was -4.00 DS (myopes) and + 1 SD (non myopes). Lateral rectus resection ranged between 6 and 8 mm with an average of 7 mm in the myopic group and between 4 and 8 mm with an average of 6 mm in the non-myopic group.The distance angle was reduced from 19 PD to 6 PD in myopes (mean difference 12 PD, p<0.0001) and from 19 PD to 8 PD in non myopes (mean difference 12 PD, p=0.0011). There was no difference in reduction of distance angle between myopes and non-myopes (p=0.771). All patients had complete resolution of diplopia after surgery without needing prisms. Near angle was also fully corrected in 19 patients. One patient with myopia and one patient with distance esotropia went on to have medial rectus recession.Unilateral lateral rectus resection is an effective procedure for acquired distance esotropia in myopic and non-myopic patients.

Recommendations for centers performing pediatric heart surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Remote ischaemic conditioning for fatigue after stroke (RICFAST): A pilot randomised controlled trial.

BACKGROUND: Post stroke fatigue (PSF) affects 50 % of stroke survivors, and can be disabling. Remote ischaemic conditioning (RIC), can preserve mitochondrial function, improve tissue perfusion and may mitigate PSF. This pilot randomised controlled trial evaluates the safety and feasibility of using RIC for PSF and evaluated measures of cellular bioenergetics. METHODS: 24 people with debilitating PSF (7 item Fatigue Severity Score, FSS-7 > 4) were randomised (1:1) in this single-centre phase 2 study to RIC (blood pressure cuff inflation around the upper arm 200 mmHg for 5 min followed by 5 min of deflation), or sham (inflation pressure 20 mmHg), repeated 4 cycles, 3 times per week for 6 weeks. Primary outcomes were safety, acceptability, and compliance. Secondary outcomes included FSS-7, 6 min walking test (6MWT), peak oxygen consumption (V̇O2peak), ventilatory anaerobic threshold (VAT), and muscle adenosine triphosphate (ATP) content measured using 31-phosphorous magnetic resonance spectroscopy of tibialis anterior. RESULTS: RIC was safe (no serious adverse events, adverse events mild) and adherence excellent (91 % sessions completed). Exploratory analysis revealed lower FSS-7 scores in the RIC group compared to sham at 6 weeks (between group difference FSS-7 -0.7, 95 %CI -2.0 to 0.6), 3 months (-1.0, 95 %CI -2.2 to 0.2) and 6 months (-0.9, 95 %CI -2.0 to 0.2). There were trends towards increased VAT, increased muscle ATP content and improved 6MWT in the RIC group. DISCUSSION: RIC is safe and acceptable for people with PSF and may result in clinically meaningful improvements in fatigue and muscle bioenergetics that require further investigation in larger studies.

A loop closure Audit on Quality of Handover for Patient care to the Post-Anaesthetic Care Unit.

Aim Effective handover of a patient's care in the recovery room is essential for the continuity, quality and safety of patient care. Each handover has the potential for poor communication that may jeopardize patient safety. Methods This audit was done in Post Anaesthesia Care Unit (PACU) of the main operation theatre complex of Letterkenny University Hospital. It was a Prospective Audit and was done over 4 weeks in April 2017. Data from 72 handovers was collected by PACU staff in the day time from 9am to 5pm excluding weekends. In the 2nd cycle of the audit, data from 52 handovers was collected by PACU staff over 4 weeks. Results In the 1st cycle of audit, quality of handover was poor. The information mostly lacking in handover in the 1st cycle of audit was ASA status: 71% Yes and 29% No; duration of anaesthesia 36% Yes and 64% No; allergy information 62.5% Yes and 37% No; past medical history 73.61% Yes and 26.39% No. In the 2nd cycle of audit after introduction of checklist of standard handover there was significant improvement in quality of handover. ASA status 80% Yes and 20% No; duration of anaesthesia 63% Yes and 37% No; allergy information 86% Yes and 14% No; past medical history 96% Yes and 4% No. Discussion There was a lack of information handed over to PACU staff. Most commonly missed information was ASA status, Duration of anaesthesia, Information about allergy. Patient's name and age. Overall 70% of information was provided and 30% was deficient. A loop closure re-audit was done after the introduction of checklist with standard handover was provided and there was significant improvement in quality of handover.

Recommendations for Centers Performing Pediatric Heart Surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Early Outcomes of Pulmonary Valve Replacement With the Edwards Inspiris Resilia Pericardial Bioprosthesis.

BACKGROUND: Controversy regarding the optimal pulmonary valve substitute remains, with no approved surgical valve for pulmonary valve replacement (PVR). Furthermore, unfavorable anatomy often precludes transcatheter PVR in patients with congenital heart disease. We therefore sought to evaluate the feasibility of the Edwards Inspiris pericardial aortic bioprosthesis in the pulmonary position in pediatric and adult patients requiring PVR. METHODS: Data from consecutive patients who underwent PVR from February 2019 to February 2021 at our institution were retrospectively reviewed. Postoperative adverse events included paravalvular or transvalvular leak, endocarditis, explant, thromboembolism, valve thrombosis, valve-related bleeding, hemolysis, and structural valve degeneration. Progression of valve gradients was assessed from discharge to 30 days and one year. RESULTS: Of 24 patients with median age of 26 years (interquartile range [IQR]: 17-33; range: 4-60 years), 22 (91.7%) patients had previously undergone tetralogy of Fallot repair and 2 (8.3%) patients had undergone double-outlet right ventricle repair in the neonatal period or infancy. All patients had at least mild right ventricular (RV) dilatation (median RV end-diastolic volume index 161.4, IQR: 152.3-183.5 mL/m2) and at least moderate pulmonary insufficiency (95.8%) or stenosis (8.3%). Median cardiopulmonary bypass and cross-clamp times were 71 (IQR: 63-101) min and 66 (IQR: 60-114) min, respectively. At a median postoperative follow-up of 2.5 years (IQR: 1.4-2.6; range: 1.0-3.0 years), there were no mortalities, valve-related reoperations, or adverse events. Postoperative valve gradients and the severity of pulmonary regurgitation did not change significantly over time. CONCLUSIONS: At short-term follow-up, the bioprosthesis in this study demonstrated excellent safety and effectiveness for PVR. Further studies with longer follow-up are warranted.

Recommendations for Centers Performing Pediatric Heart Surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.