Curable Disease Research Articles

Successful "on-demand" plerixafor for autologous peripheral blood stem-cells transplantation for relapsed/refractory germ cell tumors.

BackgroundGerm cell tumors represent, among solid cancers, a potentially curable disease even if up to 20% to 30% of patients (pts) relapse after first‐line treatment especially considering intermediate and poor prognosis groups. In this scenario, patients are candidates for high‐dose chemotherapy and autologous stem‐cells transplantation as second‐line treatment even though stem‐cells mobilization potential can be affected by several cycles and regimens of chemotherapy. To date, plerixafor is authorized in poor mobilizer adult pts diagnosed with lymphoma or multiple myeloma and in pediatric solid tumors or lymphoma. Therefore, the use of plerixafor in adult pts with relapsing/refractory GCT is still off label.Materials and methodsIn our study, we describe mobilization and collection of peripheral blood stem cells for 10 pts with germ cell tumors. Six patients underwent plerixafor administration since classified as poor mobilizers based on WBC count (>5.000/μL) and CD34+ cell count (<15/μL) the day before apheresis procedure.ResultsOn the first day of apheresis, plerixafor administration in poor mobilizers made possible a remarkable boost of CD34+ cells in such a way to overlap that of good mobilizers' (32/μL vs 35/μL, respectively, P > .05).ConclusionTherefore, in our experience, plerixafor made a good fraction of poor mobilizer patients eligible for mobilization and collection and able to undergo the predicted autologous stem‐cells transplantation; thus, the lack of access to the use of plerixafor in this setting of patients risks jeopardizing an effective treatment, especially in case of poor prognosis.

Chronic deep recurrent pyoderma in the outpatient practice of the surgeon

Introduction. Chronic deep pyoderma occurs relatively rare in the surgeon practice and, due to the poor knowledge of this pathology, its diagnosis is difficult by surgeons. Misdiagnosis leads to erroneous treatment tactics. Chronic deep recurrent pyoderma includes: abscessing and disrupting perifolliculitis of the head (Hoffmann) (ADPH), axillary and inguinal-perineal suppurative hydradenitis, pilonidal cyst of the sacrococcygeal area. The diseases listed follow the same pathogenesis.The purpose of the publication: to acquaint surgeons with the diagnosis and treatment of a particular type of chronic deep recurrent pyoderma – abscessing and disrupting head perifolliculitis (Hoffmann) in the conditions of the surgery room, since this problem is purely issued in the literature of the subject.Material and methods. Since 2007 until to 2020, we had observed 20 cases of deep chronic recurrent pyoderma (15 men and 5 women), but only two cases were correctly detected before treatment, in other cases – retrospectively. Research method: analyzing of clinical observation data and laboratory tests.Results. In our practice, nine men suffered from abscessing and disrupting perifolliculitis of the head. We had described and classificated the features of this disease, focused on three clinical cases.Conclusions. Abscessing and disrupting perifolliculitis of the head is still purely diagnosable and curable disease, the treatment as follows: regimen and hygienic measures, surgical treatment, conservative treatment. Surgical treatment should be as radical as possible.

Update on optimal management for pancreatic cancer: expert perspectives from members of the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty

ABSTRACT Introduction Pancreatic cancer remains a challenging malignancy due to the high proportion of patients diagnosed at advanced stages and the limited treatment options. This article discusses recent evidence in the management of both localized and advanced pancreatic cancer and offers an expert opinion on current best practice. Areas covered For patients with localized disease, the evidence for adjuvant chemotherapy is discussed as well as emerging neoadjuvant approaches for resectable, borderline resectable, and locally advanced disease. Advances in metastatic disease are discussed including cytotoxic chemotherapy, targeted therapies, and the role of genomic testing to identify patients with molecular alterations. Reviewed literature included journal publications, abstracts presented at major international oncology meetings, and ongoing clinical trials databases. Expert opinion Pancreatic cancer is a devastating diagnosis and despite recent advances has a very poor prognosis. Only a minority of patients, 20%, are diagnosed with potentially curable disease. The shifting paradigm toward neoadjuvant therapy may improve resectability and survival rates; however, robust evidence is required. Thus far, there has only been limited progress in advanced stage disease. Genomic testing may potentially identify more treatment targets although limited to small subgroups.

Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia.

Simple SummaryChronic myeloid leukemia is a type of blood cancer that is regarded as a success story in determining the exact biological origin, pathogenesis and development of a molecularly targeted (mutation-specific) therapy that has led to successful treatment of this fatal cancer. It is caused by the BCR-ABL fusion gene, which is formed from the translocation between chromosomes 9 and 22. Anti-BCR-ABL drugs, known as tyrosine kinase inhibitors (TKIs), have led to long-term remissions in more than 80% of CML patients and even cure in about one-third of patients. Nevertheless, many patients face drug resistance, and disease progression occurs in about 30% of CML patients, leading to morbidities and mortality. Unfortunately, no biomarkers of CML progression are available due to a poor understanding of the mechanism of progression. Therefore, finding reliable molecular biomarkers of CML progression is one of the most attractive research areas in 21st-century cancer research. In this study, we report novel genomic variants exclusively found in all our advanced-phase CML patients. This study will help in identifying CML patients at risk of disease progression and timely therapeutic interventions to avoid or at least delay fatal disease progression in this cancer.Background: Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, the mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find novel biomarkers of CML progression by employing whole-exome sequencing (WES). Materials and Methods: WES of accelerated phase (AP) and blast crisis (BC) CML patients was carried out, with chronic-phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing were carried out using Illumina platforms. Statistical analysis was carried out using SAS/STAT software version 9.4, and R package was employed to find mutations shared exclusively by all AP-/BC-CML patients. Confirmation of mutations was carried out using Sanger sequencing and protein structure modeling using I-TASSER followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modeling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in humans. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in the biology and progression of CML.

Knowledge, Attitude and Preventive Practice towards Breast Cancer among Women Visiting Public Health Facility, Saudi Arabia

Background: Breast cancer is the highest burden of disease in high and low income countries and it is the leading cause of disability and death. Knowledge is important predictor of breast cancer. The objective of this study is to determine the knowledge, attitude and practice regarding breast cancer among women visiting public health facilities in Hail, Saudi Arabia.&#x0D; Method: It’s was a cross-sectional study in the leading public sector hospital and 127 study participants were selected through stratified random sampling technique. Validated and structured questionnaire used. Study participants who scored greater than or equal to mean valued were considered good knowledge, positive attitude and safe practice. Chi square test was used to cross tabulation between socio-demographic characteristics and knowledge, attitude and practice score.&#x0D; Results: Over all 18.1%, 47.2% and 52% of study participants had good knowledge, positive attitude and safe practice for prevention of breast cancer respectively. More than two third (89%) of participants were stated that breast cancer was not curable disease, more than half (67.7%) of were heard about mammogram. Only 10.2% were belief that screening was essential to breast cancer for early diagnosis. More than two third (69,9%) were not practice self breast examination and 69% were stated that fear of disease was major barrier to mammogram test.&#x0D; Conclusion: The knowledge level among communities member of female regarding breast cancer was in-appropriate. Majority of them were not practicing self breast examination. Health education programme through workshops and seminars will be needed to increase the awareness toward breast cancer among females.

Survival and predictors of death in tuberculosis/HIV coinfection cases in Porto Alegre, Brazil: A historical cohort from 2009 to 2013.

Tuberculosis is a curable disease, which remains the leading cause of death among infectious diseases worldwide, and it is the leading cause of death in people living with HIV. The purpose is to examine survival and predictors of death in Tuberculosis/HIV coinfection cases from 2009 to 2013. We estimated the survival of 2,417 TB/HIV coinfection cases in Porto Alegre, from diagnosis up to 85 months of follow-up. We estimated hazard ratios and survival curves. The adjusted risk ratio (aRR) for death, by age, hospitalization, and Directly Observed Treatment was 4.58 for new cases (95% CI: 1.14-18.4), 4.51 for recurrence (95% CI: 1.11-18.4) and 4.53 for return after abandonment (95% CI: 1.12-18.4). The average survival time was 72.56 ± 1.57 months for those who underwent Directly Observed Treatment and 62.61 ± 0.77 for those who did not. Case classification, age, and hospitalization are predictors of death. The occurrence of Directly Observed Treatment was a protective factor that increased the probability of survival. Policies aimed at reducing the mortality of patients with TB/HIV coinfection are needed.

Mental Health Among Patients with Non-Hodgkin Lymphoma: A Danish Nationwide Study of Psychotropic Drug Use in 7,201 Patients and 36,005 Matched Comparators

Introduction: A cancer diagnosis is associated with profound psychological distress that potentially can lead to mental health problems such as depression and anxiety. Non-Hodgkin lymphomas (NHLs) are a heterogenous group of indolent and aggressive cancer diseases with high variability in treatment selections and patient outcomes. Some patients are chronically ill with recurrent need for mild chemotherapy whereas others face immediately life-threatening, yet curable disease. To gain valuable insights into the psychological distress associated with NHLs, the present study investigated the incident psychotropic drug (PD - antidepressants, anxiolytics, and antipsychotics) use, contact patterns to psychiatric departments, and intentional self-harm (including suicide) in Danish NHL patients relative to sex- and age matched individuals from the background population.Methods: The study was carried out as a nationwide population-based matched cohort study based on prospectively collected data from several Danish registries. All adult NHL patients (≥18 years) diagnosed between 2005 and 2015 were identified in the Danish Lymphoma Registry and included if they had not been treated with any kind of PD within the last 10 years prior to date of NHL diagnosis (index date). NHL patients were matched on age and sex with five random comparators from the Danish background population on the index date. Comparators had to be alive and without PD use 10 years prior to the index date. Incident PD use was defined as first redeemed prescription of PD after index date. Prescriptions were captured in the National Prescription Registry and described by cumulative incidences using the Aalen-Johansen estimator with death and NHL relapse as competing risk. Contacts with psychiatric departments and registration of intentional self-harm or completed suicide were captured in the Danish National Patient Registry. Patients were subcategorized according to type of lymphoma (Table 1).Results: In total, 7,201 NHL patients and 36,005 matched comparators were included (median follow-up 7.1 years). Follicular lymphoma (FL, 44.4%) and diffuse large B-cell lymphoma (DLBCL, 41.0%) were the most common subtypes (Table 2). Two-year cumulative incidence of PD use was higher in NHL patients overall (16.2%, 95%CI 15.4-17.0%) compared to matched comparators (5.7%, 95%CI 5.5-5.9%). Patients with aggressive NHL subtypes tended to have the highest incidence of PD use (Figure 1). Antidepressants (two-year cumulative incidence, 9.0%, 95%CI 8.4-9.6) and anxiolytics (8.2%, 95%CI 7.6-8.8) were the most used PDs in all NHL subtypes. The risk of PD use was higher in the first years following diagnosis, but except for patients with indolent NHL subtypes, the risk of PD use normalized over time to that of the background population. As for the risk of any psychiatric department contacts, there was no difference in two-year cumulative incidences between NHL patients (range 0.6-0.9%) and the matched comparators (range 0.6%-0.9%), whereas the two-year cumulative incidence of intentional self-harm and suicide was slightly higher for NHL patients (0.3%) compared to the matched comparators (0.2%, p=0.01).Conclusion: This study suggests that NHL patients have a significantly higher risk of mental health problems compared to the Danish background population, (when) using PD prescriptions as a proxy measure. The risk of intentional self-harm and completed suicide was also higher, but numerical differences were very small. Overall, the results emphasize the need for directing clinical attention on mental health in newly diagnosed NHL patients and screening for relevant symptoms during follow-up to provide best possible support to patients suffering from anxiety and depression. [Display omitted] DisclosuresØvlisen: Abbvie: Other: Travel expenses. Kragholm: Novartis: Honoraria. Nielsen: Lundbeck: Honoraria, Other: Investigator, Research Funding; Otsuka Pharmaceuticals: Honoraria, Other: Prior Advisor, Research Funding; Bristol-Myers Squibb: Honoraria; Astra Zeneca: Honoraria, Other: Prior advisor; Janssen & Cilag: Honoraria, Other: Investigator; Servier: Honoraria; Teva A/S: Honoraria; Eli Lilly: Honoraria, Other: Prior Advisor; Takeda: Other: Prior advisor; Medivir: Other; Boehringer: Other: Investigator. Brown: BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Novartys: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Dahl-Soerensen: Takeda: Other: Travel grant. Frederiksen: Novartis: Research Funding; Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding. Mannering: Novartis: Research Funding; Swedish Orphan Biovitrum (SOBI): Membership on an entity's Board of Directors or advisory committees. Jørgensen: Gilead: Consultancy; Roche: Consultancy; Novartis: Consultancy; Celgene: Consultancy. Clausen: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expences ASH 2019; Gilead: Consultancy, Other: Travel expences 15th ICML . El-Galaly: ROCHE Ltd: Ended employment in the past 24 months; Abbvie: Other: Speakers fee.

Outcomes for Hispanic Patients with Acute Leukemia Treated at Academic Centers

▪Introduction: Health disparities for underrepresented U.S. minority populations with hematologic cancers contribute to differential treatment and higher death rates. The Hispanic population (including people of Mexican, South/Central American, Cuban, Puerto Rican, or other Spanish-speaking cultures, regardless of race) collectively constitutes the largest minority group in the United States. Hispanic patients have been reported to have an increased incidence of B-cell acute lymphoblastic lymphoma (B-ALL) and acute promyelocytic leukemia (APL). While APL is associated with favorable outcomes compared to other acute leukemias, registry data suggest poorer outcomes in Hispanic patients with both acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). The Hispanic paradox is an epidemiological paradox that refers to the finding that Hispanic patients have paradoxically comparable, or better, health outcomes compared to their U.S. non-Hispanic White counterparts despite barriers to care such as lower socioeconomic status. This paradox has also been reported in hematologic malignancies. Definitive data regarding differences in outcome between Hispanic and non-Hispanic patients with acute leukemias (AL) are lacking.We sought to compare outcomes of Hispanic patients and non- Hispanic patients with acute leukemia with access to care, and examine whether the Hispanic paradox reported in hematologic malignancies is attributable to enrichment of patients with highly curable disease such as APL.Methods: Using data from a Vizient Clinical Data Base, a healthcare claims database, we identified patients with leukemia using ICD 10 codes for acute leukemia. Adult patients with AL, ages 18-89 who were treated between January 2020 and June 2021 were evaluated. Data from 121 academic centers was included. We focused on academic centers to limit the impact of access to care . Demographic information was obtained from the registry, to which ethnicity was self-reported. Patients were stratified by age, and we compared complication rates, number of complications, number of deaths, percent deaths and mortality index between Hispanic and non-Hispanic patients. The key metric used to compare outcomes of Hispanic patients with non-Hispanic patients was the severity adjusted mortality index, which is the ratio of observed mortality over expected mortality for patients with the same diagnosis in this registry. Chi-squared test is used for to determine the statistical significance of differences in mortality (by age group) in Hispanics v. non-Hispanic patients. Initial analysis included all patients with acute leukemias, and the data was subsequently reanalyzed excluding patients with APL, as APL is known to portend a favorable prognosis.Results: A total of 29,967 patients were with acute leukemia were evaluated; of these patients, 2903 identified as Hispanic and 27,064 were non- Hispanic. As seen in table 1, patients of Hispanic origin generally had lower treatment related complication rates in all age groups compared to their age matched non-Hispanic counterparts. Except for the 51-64 and 80-84 age groups the mortality index was lower in Hispanic patients compared to non-Hispanic peers. Differences in mortality between Hispanic and non-Hispanic patients in all age groups were not statistically significant. Trends to a lower mortality index in Hispanic patients are highlighted in green in table 1. When patients with APL were excluded from the analysis, the trend lower mortality in Hispanic patients in most age groups persisted. Again, the mortality index was comparatively higher in hispanic patients in the 51-64 and 80-84 age groups, but differences in mortality between Hispanic and non- Hispanic patients were not statistically significant. Exclusion of APL patients did not have a significant impact on the complication rate or mortality supporting that the Hispanic paradox is independent of higher rates of very favorable risk myeloid malignacies in this population.Conclusions: Hispanic patients with access to academic cancer centers have the potential for non-inferior outcomes compared to non-Hispanic patients. Equivalent outcomes as assessed by mortality index were not attributable solely to the higher incidence of very favorable risk disease such as APL in the Hispanic population. [Display omitted] DisclosuresWatts: Takeda: Consultancy, Research Funding; Genentech: Consultancy; Rafael Pharma: Consultancy; Celgene/BMS: Consultancy. Bradley: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

A PROSPECTIVE STUDY ON CLINICAL PRESENTATION AND MANAGEMENT PROTOCOLS OF CARCINOMA PENIS IN TERTIARY CARE CENTRE

INTRODUCTION:Carcinoma of the penis is a malignancy with a wide range of clinical and pathological presentations. It constitutes a major substantial health concern in many developing countries including India. Proper evaluation of both the primary lesion and lymph nodes is critical because nodal involvement is the most important factor for survival. This study was undertaken to [1,2,3] determine incidence with age, religion, and socioeconomic status and to study risk factors and its management . METHODS:A descriptive study was conducted among 30 patients with proven carcinoma penis for a period of 2 years. RESULTS: In my study the maximum incidence was found to be in the age group of 50 to 70. All cases were Hindus and Muslims were free of disease may be due to early circumcision. In my study 86.6% of the patients associated with carcinoma penis were smokers. The commonest symptom at presentation was proliferative growth (76%). The most common site of origin was the Glans penis. The average time interval between onset of symptoms and seeking medical advice is 7 Months. The most common surgery performed was partial penectomy (73.3%) and a majority of the biopsy report showed SCC. Moderately and poorly differentiated tumors had a very strong association with nodal involvement. CONCLUSION: Carcinoma penis can be avoided by better penile hygiene and circumcision. It is a curable disease, if detected early and treated properly. The surgery is the mainstay of treatment. Creating awareness in public is the only way to reduce mortality and morbidity due to the carcinoma of the penis.

Micronutrient Deficiency in Pulmonary Tuberculosis - Perspective on Hepatic Drug Metabolism and Pharmacokinetic Variability of First-line Anti- Tuberculosis Drugs: Special Reference to Fat-soluble Vitamins A, D, &amp; E and Nutri-epigenetics

The liver plays a crucial role in endogenous metabolic activity and homeostasis of macro and micronutrients. Further, it acts as a metabolic hub in mammals, where the ingested food-derived nutrients and xenobiotics or drugs are metabolized for utilization and/or excretion through its enzymatic and non-enzymatic machinery. Nutritional deficiency, one of the major public health problems, is associated with global disease burden, including pulmonary tuberculosis (PTB) caused by Mycobacterium tuberculosis (Mtb) infection. Though it is a curable and preventable infectious disease, millions of people succumb to death, and people in numbers larger than this are still suffering. This scenario is further complicated by the addition of new cases, disease recurrence, and the emergence of drug-resistant, all of which contribute to the spread of this epidemic. Though the manifestation of TB disease has multiple aetiologies, poor nutritional status and sub-optimal therapeutic concentrations of first-line anti-TB drugs are considered as potential contributors to its widespread prevalence. Among various factors, the pharmacokinetic variability of anti-TB drugs is one of the main causes for sub-optimal therapeutic drug concentration in TB patients, which is influenced by the host's genetic make-up and nutritional status, besides several others. However, the role of epigenetic changes in hepatic drug metabolic pathways and their transcript levels is largely unexplored. Therefore, in this review, an attempt has been made to understand the role of micronutrient deficiencies with special reference to fat-soluble vitamins, namely vitamin A, D, & E in pulmonary TB, their possible impact on epigenetic changes on the drug-metabolizing pathway genes, thus their expression levels and plausible influence on pharmacokinetic variability of anti-TB drugs, besides discussing the limitations and emerging potential opportunities. Eventually, this would help in developing the host-directed/personalized therapeutic strategies for the elimination of pulmonary tuberculosis (PTB).

Role of immunotherapy in stage IIIA non-small cell lung cancer: a narrative review

: Non-small cell lung cancer (NSCLC) is one of the main leading causes of death by cancer worldwide. Approximately one third of cases are diagnosed at stage III, whose therapeutic strategy based on multimodal treatment has reached a plateau of effectiveness. Treatment with anti-PD-1/PD-L1 [anti-PD-(L)1] antibodies have been stablished in advanced stages due to their improved clinical benefit and acceptable profile of related adverse events. Lately, numerous clinical trials have been designed with diverse approaches to introduce immunotherapy into stages IIIA. The objective of this review is to discuss the different strategies that are being taken in the ongoing clinical trials, taking into account the peculiarities of stage IIIA and the tumor microenvironment. PubMed, major international conferences and clinicaltrials.gov databases were searched from January 1, 1990, to May 11, 2020 using the terms NSCLC, stage III, resectable, unresectable, immunotherapy, checkpoint inhibition, neoadjuvant and adjuvant. In this review we describe, in the context of stage IIIA disease, the impact of anti-PD-(L)1 and conventional therapies on the tumor microenvironment. Moreover, we describe the role of immunotherapy, through the heterogeneous landscape of stage IIIA NSCLC, summarizing ongoing clinical trials in incidental, potentially resectable, and unresectable tumors. We finally discuss the potential of PD-L1, tumor mutation burden (TMB), and T-cell receptor (TCR) repertoire analysis as predictive biomarkers in stage IIIA NSCLC. Initial results seem to favor neoadjuvant over adjuvant treatment, with chemoimmunotherapy combination standing out. Ongoing trials will answer whether immunotherapy can transform stage IIIA from lethal to a curable disease. Additionally, higher pathological response rates observed, open the possibility to establishing it as survival surrogate, speeding up the potential immunotherapy implementation in stage IIIA NSCLC.

Global scenario and recent advances in molecular diagnosis and management of drug-resistant tuberculosis

Tuberculosis (TB) is one of the oldest communicable bacterial diseases, spreads predominantly by inhalation of infected respiratory droplets. It is a curable and preventable disease yet remains the leading infectious cause of human death worldwide. The TB burden is high among developing nations of Asia and Africa. Major obstacles in controlling TB are patient’s non-compliance to the anti-tubercular therapy, co-infection with Human immunodeficiency virus (HIV), low socioeconomic status, crowded living condition, inadequate rapid diagnostic testing facilities especially in resource-poor developing countries, delay in diagnosis and initiation of therapy, and the emergence of drug-resistant strains of Mycobacterium tuberculosis (MTB). Multidrug-resistant (MDR-TB), extensively drug-resistant (XDR-TB), and total drug-resistant (TDR-TB) MTB strains are difficult to treat and are associated with frequent treatment failures and high mortality. The recent advent of molecular techniques including nucleic acid amplification tests (NAATs) and whole-genome sequencing (WGS) have significantly ameliorated the rapid detection of TB cases and drug-resistant MTB. This, in turn, enabled the early initiation of therapy and development of novel treatment plans which is crucial for the global TB elimination target. The World Health Organization (WHO) 2020 guideline prioritizes the use of newer drugs as part of all-oral regimens for the treatment of MDR-TB. Apart from the use of newer drug delivery methods, host factors including immune functions and cytokine responses as well as mycobacterial enzymatic pathways are targeted in TB drug development. Adjuvant therapy employing host-directed approaches is increasingly studied through the time-tested pathogen-targeted approach remains the mainstay in the current treatment of MDR-TB.

TP10.1.2Evaluating the impact of the COVID-19 pandemic on the presentation and management of UGI cancer at a district general hospital

IntroductionIt has been predicted that the COVID-19 pandemic would disrupt the delivery of UK cancer treatment pathways. This study aims to assess the mode of presentation and type of management offered to oesophagogastric (OG) and hepatopancreaticobiliary (HPB) cancer patients at a busy district general hospital during the pandemic.MethodsConfirmed OG and HPB cancer patients were identified in the local MDT database. Patients were identified between 01/03/2020 - 30/09/2020 (pandemic), and 01/03/2019 - 30/09/2019 (pre-pandemic). Mode of presentation and management was identified and compared.ResultsIn 2019, 42 and 15 patients were diagnosed with OG and HPB cancers, compared to 25 and 19 patients in 2020, respectively. 26 (46%) patients were referred via 2ww pathway in 2019, compared to 29 (66%) in 2020. The number of cancers referred routinely or emergently were 28 (49%) and 2 (4%) in 2019, compared to 2 (5%) and 9 (20%) in 2020, respectively (p < 0.0001). Patients suitable for curative treatment were 16 (28%) and 7 (16%), in 2019 and 2020, respectively. Palliative or supportive treatment was offered to 26 (46%) and 14 (25%) patients in 2019, compared to 21 (48%) and 10 (23%) patients in 2020, respectively.Conclusion2ww referrals were similar to 2019, while routine referrals reduced significantly. A marked, but not significant, reduction in patients suitable for curative intent is noted, perhaps due to delay in presentation despite the continuation of cancer surgical services. Further work on creating “COVID-free” pathways and increasing awareness of service availability would improve detectability of curable disease.

SP4.1.10 Colorectal Cancer Services During the First Wave of the COVID-19 Pandemic

AimsDuring the first wave of the COVID-19 pandemic, UK health services ceased National Bowel Cancer Screening programme and non-emergency diagnostic services were halted. This retrospective study evaluated the colorectal cancer (CRC) service at a district general hospital during that period by comparing the CRC services from 31/03/2020 to 28/06/2020 to services offered during the same 3-month period of the previous year.Methods65 patients were included in the study (47 from 2019 and 18 from 2020). Demographics, referral modes, treatment aims and Dukes cancer staging at diagnosis were compared. À2 and Fisher’s exact tests were used.ResultsThere was a 61.7% decrease in the volume of patients managed and 65.7% reduction in operations relative to the previous year. The mean age(years) of 66.6 (S.D 14.1) during the pandemic was lower than the average during the non-COVID year (75.5(S.D 13)) but gender distribution was similar. COVID-year referrals originated from rapid access pathway (61%), emergency (28%), routine referrals (11%), screening (0%) compared to 56%, 21%, 21%, and 2% respectively during the non-COVID period. Dukes staging varied with Dukes D doubling (39% vs 17%) and no Dukes A (6% in 2019) during the pandemic. The treatment goal during the pandemic was palliative in 44% vs 32% in the other group.ConclusionCessation of non-emergency diagnostic pathways that support identification of early disease contributed to diagnostic delays with increased proportion of palliative/Dukes D disease. Normal CRC services should be sustained during future pandemics to avoid missing curable disease.

Investigation of the Anti-TB Potential of Selected Phytochemicals of Nigella Sativa using Molecular Docking Approach

Background: Tuberculosis (TB) is one of the foremost causes of human mortality across the world. In general, it is a curable disease and several drugs are available in market for its treatment, however, because of the drug resistance to the currently available anti-TB drugs, the development and/or discovery of new drugs with better efficacy against TB cannot be overlooked. In the present study, we performed virtual screening of the major phytochemicals of the plant Nigella sativa for investigating their potential to inhibit some novel drug targets of Mycobacterium tuberculosis, which included- pantothenate kinase, type 1 (MtPanK), β-ketoacyl ACP synthase I (MtKasA), and decaprenylphosphoryl-β-D-ribose 2′-epimerase 1 (MtDprE1).&#x0D; Methods: The screening of the phytochemicals was investigated through a molecular docking approach using Auto dock vina and the molecular interactions in the protein-ligand complexes were visualized and analysed through PyMol and BioVia Discovery Studio Visualizer.&#x0D; Results: Our in silico observations reveal that, out of the nine selected phytochemicals screened, five compounds, namely α-hederin, dithymoquinone, nigellidine, thymoquinone and thymol binded to one or more of the selected target enzymes with significant docking scores. α-hederin binded to MtDprE1 and MtKasA with a docking score of −8.5kcal/mol and −7.9kcal/mol, respectively, dithymoquinone binded to MtKasA, MtDprE1 and MtPanK with a docking score of −6.5kcal/mol, −8.2kcal/mol and −9.2kcal/mol, respectively and nigellidine binded to MtDprE1 and MtPanK with a docking score of −8.1kcal/mol and −8.2kcal/mol, respectively. Further, thymol as well as thymoquinone were observed to bind MtKasA with a docking score of −6.6kcal/mol.&#x0D; Conclusions: The results of our study indicate that the five phytochemicals of N. sativa, including α-hederin, dithymoquinone, nigellidine, thymoquinone and thymol, are worth studying further for their anti-TB activity, however, additional biological studies are warranted to validate these findings.

Associated screening for HCV and SARS-Cov2 infection in an urban area of Southern Italy: A cohort study.

The SARS-Cov2 pandemic led to reorganize the clinical activities in Italy, reducing the available resources to manage other diseases. In particular,important milestones achieved towards HCV elimination are now at risk of being nullified. Moreover, the burden of SARS-Cov2 asymptomatic carriers remains still an unresolved issue. To associate those two screenings, in order to respond to these clinical needs seems of actual interest. A prospective cohort study was set-up in an urban area of the Naples province, in which a contemporary screening for HCVAb and SARS-Cov-2-Ab rapid blood tests was performed. Of the 3556 eligible subjects,2740(77.05%) participated.Of them,1.4% resulted SARS-Cov2-positive, none resulting positive for SARS-Cov2-RNA, whereas 1.5% were HCVAb-positive and 0.18% HCVRNA-positive. Of those HCVAb positive,87.8% were already aware and treated in 88.8% of cases .Of the other 4 patients aware of their positivity,2(50%) were HCVRNA-positive. Of the 5 HCVAb-positive unaware of their positivity, 2 were HCVRNA-positive. HCVAb-positivity was only detected in patients of >41 years. The screening in an urban area of Southern Italy showed a seroprevalence of SARS-Cov2-Ab and HCV-Ab of 1.4% and 1.5%, respectively,whereas 0.18% had an active HCV infection. This demonstrates how the pandemic can be an opportunity to promote prevention activities for HCV.

Knowledge of Secondary School Students about Pulmonary Tuberculosis in Tikrit City

Background: Pulmonary tuberculosis is epidemic disease it is a one cause of death worldwide it caused by bacteria (Mycobacterium tuberculosis) that mostly infect the lungs. Tuberculosis is curable and preventable disease. Transmission of TB is through the air, when person with pulmonary tuberculosis spit, cough, or sneeze, the microorganisms spread in the air. Few germs can cause infection with tuberculosis. About 1/3 of the population has latent tuberculosis, latent means there is an infection with tuberculosis bacteria but a person still not ill and cannot transmit the disease. Main objective (aim): The study aimed to evaluate the knowledge of secondary school students about pulmonary tuberculosis. Subject and Methods: This is a cross-sectional study, done on the secondary school students in Tikrit city at the period of time from first of January to rst of April 2016. Cluster sampling chosen then students selected randomly from each cluster. Sample size was 98 students was collected by questionnaire, then summarized and presented in simple tables and figures. Result: The study found (57.14%) of students were having some information about pulmonary tuberculosis. By education, we were trying to improve their information about the disease and learn the others "who didn't have any information about the disease" By comparison the results were yield by questionnaire, the students respond very well to the awareness seminar. Conclusions: Students don't have enough information about the disease relation to its epidemiological spread in Iraq. Health education of the students improves their information. Recommendations: perform a program of health education in schools, universities, for patients and for the general population about tuberculosis.

Prions and Oral Cavity: The Oblivious Single Handed Protein Machinery

BACKGROUND: The world today is facing an unprecedented situation with the spread of novel COVID-19. Covid era has brought the whole world to its knees. Oral health care professionals are at the risk of acquiring numerous diseases which amounts to occupational hazards. Now is the time to widen our horizons and look at different spectrum of diseases, prions being one of them. The short clinician course and long incubation period poses many challenges to this group of neurodegenerative diseases. AIM: The aim of this review is to highlight uncharted aspects of prions and oral health. REVIEW DETAILS: It sheds light on the spectrum of prion diseases. Since there is no known cure of this dreaded disease and it is ineffective with normal sterilization and disinfection procedures, prevention is the only way ahead. This review highlights the colliding world of prions and human body. This also keeps in mind the precautions and guidelines which will help health care professionals in combating this non curable fatal disease. CONCLUSION: Ensuing endeavors should be undertaken to help find plausible detection techniques, treatment options (if any), precaution and guidelines to be kept in mind to fight off this protein entity.&#x0D;

Barriers to Access of Healthcare Services for Rural Women-Applying Gender Lens on TB in a Rural District of Sindh, Pakistan.

Background: Women in the rural districts of Pakistan face numerous barriers to healthcare, rendering gender-responsive health programming important, including for the disease of tuberculosis (TB). This study was conducted to assess the general understanding of TB and for women’s access to healthcare, as a first step towards implementation of a gender responsive TB program in Tando Allahyar, a rural district of Pakistan. Methods: A total of 36 participants were interviewed for the study. The focus group discussion guide comprised of questions on: (1) family/household dynamics, (2) community norms, (3) healthcare systems, (4) women’s access to healthcare, (5) TB Awareness, and (6) women’s access to TB Care. Results: Limited autonomy in household financial decision-making, disapproval of unassisted travel, long travel time, lack of prioritization of spending on women’s health and inadequate presence of female health providers, were identified as barriers to access healthcare for women, which is even higher in younger women. Facilitators to access of TB care included a reported lack of TB-related stigma, moderate knowledge about TB disease, and broad understanding of tuberculosis as a curable disease. Other suggested facilitators include health facilities closer to the villages and the availability of higher quality services. Conclusion: Significant barriers are faced by women in accessing TB care in rural districts of Pakistan. Program implementers in high burden countries should shift towards improved gender-responsive TB programming.

The impact of COVID-19 pandemic on the rate of newly diagnosed gynecological and breast cancers: a tertiary center perspective

PurposeThe aim of the present study was to assess the impact of postponed screening examinations and lockdown measures on gynecological and breast cancer diagnoses throughout the year 2020 in a gynecological oncological center in Austria.MethodsData of 889 patients with either newly diagnosed gynecological or breast cancer between January 2019 and December 2020 were collected. Clinical parameters including symptoms, performance status, comorbidities and referral status were compared in patients, who were newly diagnosed with cancer in the period of the first lockdown from March 2020 to April 2020 and the second lockdown from November 2020 to December 2020 and compared to the same period in 2019.ResultsOur results showed a strong decline in newly diagnosed cancers during the lockdown periods: −45% in gynecological cancer and -52% in breast cancer compared to the same period in 2019. Compared to the analogue period of 2019, breast cancer patients reported significantly more tumor-associated symptoms (55% vs. 31%, p = 0.013) during and in between (48% vs. 32%, p = 0.022) the lockdowns. During the lockdown, periods in the group of breast cancer patients’ tumor stage varied significantly compared to 2019 (T2–T4; p = 0.047).ConclusionBoth lockdowns led to a strong decrease in newly diagnosed gynecological and breast cancers. Treatment delays in potentially curable disease could lead to inferior clinical outcomes, with the risk of missing the optimal treatment window. As the COVID-19 pandemic will be a challenge for some time to come, new strategies in patient care are needed to optimize cancer screening and management during the pandemic.