Percutaneous cryoablation for desmoid fibromatosis: initial experience at a UK centre.

AIM: To report the first UK experience of cryoablation in desmoid fibromatosis (DF) with particular focus on technique, safety, and efficacy. MATERIALS AND METHODS: Patients were selected at multidisciplinary tumour board meetings at a specialist cancer hospital. Radiation dose, procedure duration, and number of cryoprobes were compared for small versus large tumours (>10 cm long axis). Response at magnetic resonance imaging (MRI) was evaluated using different criteria, and percentage agreement with clinical response as assessed in oncology clinic calculated. RESULTS: Thirteen procedures were performed in 10 patients (eight women, median age 51 years, IQR 42-69 years) between February 2019 and August 2021. Procedures for large tumours had higher radiation dose (2,012 ± 1,012 versus 1,076 ± 519 mGy·cm, p=0.048) used more cryoprobes (13 ± 7 versus 4 ± 2, p=0.009), and were more likely to have residual unablated tumour (38 ± 37% versus 7.5 ± 10%, p=0.045). Adverse events were minor apart from one transient radial nerve palsy. Eight of 10 patients had symptomatic benefit at clinical follow-up (median 353 days, IQR 86-796 days), and three started systemic therapy mean 393 days later. All patients who had complete ablation demonstrated symptomatic response, with no instances of repeat treatment, recurrence, or need for systemic therapy during the study period. All progression occurred outside ablation zones. CONCLUSION: Cryoablation for symptomatic DF is a reproducible technique with low, transient toxicity, where one or two treatments can achieve a meaningful response. Where possible, the ablation ice ball should fully cover DF tumours.

Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK.

INTRODUCTION: Desmoid-type fibromatosis (DF) are locally infiltrative, non-metastasizing tumours associated with significant morbidity and mortality if located intra-abdominally, retroperitoneally or in head and neck localisation. They are mostly sporadic, due to somatic CTNNB1 mutations. Alternatively, they can be associated with germline pathogenic variants in APC causing Familial Adenomatous Polyposis (FAP). Germline APC variants and somatic CTNNB1 mutations are mutually exclusive. AIMS AND METHODS: We conducted a retrospective descriptive analysis of patients with DF seen at the Royal Marsden NHS Foundation Trust Sarcoma Unit in London. We aimed to describe the methods of screening for FAP in patients with DF from a specialist unit. Patients diagnosed between 1992 and 2020 were selected from the prospectively maintained Sarcoma Unit database. RESULTS: 226 patients were identified and 67% (n = 152) were female. Median age at diagnosis was 37.5 (range 2-81) years. Tumour localisation was limbs/pelvis in 30.9% (N = 70), intra-abdominal 16.8% (N = 38), abdominal wall 23.5% (N = 53), thorax 18.6% (N = 42), head and neck 3.1% (N = 7) and vertebral/paravertebral 7.1% (N = 16). Colonoscopy was requested in 65 patients (28.8% of all cases) and was completed in forty-six (20.4%). Molecular testing of CTNNB1 testing was requested in 35 cases (15.5%). APC germline test was requested in 12 cases. Four patients in our cohort had an FAP-associated DF. CONCLUSIONS: CTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF. CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. Negative CTNNB1 results, alongside clinical assessment, should prompt APC testing and/or colonoscopy.

Phase 2 study of anastrozole in rare cohorts of patients with estrogen receptor/progesterone receptor positive leiomyosarcomas and carcinosarcomas of the uterine corpus: The PARAGON trial (ANZGOG 0903).

BACKGROUND: Aromatase inhibitors have been used empirically to treat a subset of patients with hormone receptor positive uterine leiomyosarcomas(LMS) and carcinosarcomas (UCS) mainly supported by retrospective data. We evaluated the activity of anastrozole in two rare cohorts; patients with recurrent/metastatic LMS and UCS enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER+)/progesterone receptor positive (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER &/or PR + ve LMS or UCS with measurable disease, treated until progression or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 39 eligible patients were enrolled, 32 with LMS and 7 with UCS. For the LMS cohort CBR at 3 months was 35% (95% CI: 21-53%) with a median duration of clinical benefit of 5.8 months. Best response was a partial response in one patient. Two patients remained on treatment for more than one year. The median progression-free survival was 2.8 months (95% CI: 2.6-4.9). For the UCS cohort CBR at 3 months was 43% (95% CI: 16-75%) with a median duration of clinical benefit of 5.6 months. Stable disease was seen in 3 patients but no objective responses were seen. The median progression-free survival was 2.7 months (95% CI, 1.1-8.2). Safety was acceptable with 5/39 evaluable patients showing grade 3 toxicities. CONCLUSION: Whilst objective response rates with anastrozole are low, the clinical benefit rate and good tolerance suggests that aromatase inhibitor therapy may have a role in a subset of patients with metastatic LMS and UCS.

Priorities and preferences of advanced soft tissue sarcoma patients starting palliative chemotherapy: baseline results from the HOLISTIC study.

INTRODUCTION: Palliative chemotherapy is the principal treatment of patients with advanced soft tissue sarcomas (STS); however prognosis is limited (median overall survival 12-19 months). In this setting, patient values and priorities are central to personalised treatment decisions. PATIENTS AND METHODS: The prospective HOLISTIC study was conducted in the UK and the Netherlands assessing health-related quality of life in STS patients receiving palliative chemotherapy. Participants completed a questionnaire before starting chemotherapy, including attitudes towards quality of life (QoL) versus length of life (LoL), decisional control preferences, and decisional conflict. Chi-square and Fisher's exact tests were used to evaluate associations between patient characteristics and preferences. RESULTS: One hundred and thirty-seven patients with advanced STS participated (UK: n = 72, the Netherlands: n = 65). Median age was 62 (27-79) years. Preference for extended LoL (n = 66, 48%) was slightly more common than preference for QoL (n = 56, 41%); 12 patients (9%) valued LoL and QoL equally (missing: n = 3). Younger patients (age <40 years) prioritised LoL, whereas two-thirds of older patients (aged ≥65 years) felt that QoL was equally or more important than LoL (P = 0.020). Decisional conflict was most common in patients who prioritised QoL (P = 0.024). Most patients preferred an active (n = 45, 33%) or collaborative (n = 59, 44%) role in treatment decisions. Gender, performance status, and country were significantly associated with preferred role. Concordance between preferred and actual role in chemotherapy decision was high (n = 104, 76%). CONCLUSIONS: Heterogeneous priorities and preferences among advanced STS patients support personalised decisions about palliative treatment. Considering individual differences during treatment discussions may enhance communication and optimise patient-centred care.

Immunomodulatory and Mechanistic Considerations of Hibiscus sabdariffa (HS) in Dysfunctional Immune Responses: A Systematic Review.

Hibiscus sabdariffa calyx (HS) water decoction extract is a commonly consumed beverage with various pharmacological properties. This systematic review examines the possible effect of HS intake on immune mediators. The Scopus and PUBMED databases were searched for all human and animal studies that investigated the effect of HS administration on immune related biomarkers. For each of the immune biomarkers, the mean, standard deviation and number of subjects were extracted for both the HS treated and untreated group. These values were used in the computation of standardized mean difference (SMD). Statistical analysis and forest plot were done with R statistical software (version 3.6.1). Twenty seven (27) studies met the eligibility criteria. Twenty two (22) of the studies were used for the meta-analysis which included a total of 1211 subjects. The meta-analysis showed that HS administration significantly lowered the levels of TNF-α (n=10; pooled SMD: -1.55; 95% CI: -2.43, -0.67; P < 0.01), IL-6 (n=11; pooled SMD:-1.09; 95% CI: -1.77, -0.40; P < 0.01), IL-1ß (n=7; pooled SMD:-0.62; 95% CI: -1.25, 0.00; P = 0.05), Edema formation (n=4; pooled SMD: -2.29; 95% CI: -4.47, -0.11; P = 0.04), Monocyte Chemoattractant Protein -1 (n=4; pooled SMD: -1.17; 95% CI: -1.78, -0.57; P < 0.01) and Angiotensin converting enzyme cascade (n=6; pooled SMD: -0.91; 95% CI: -1.57, -0.25; P < 0.01). The levels of IL-10 (n=4; pooled SMD: -0.38; 95% CI: -1.67, 0.91; P = 0.56), Interleukin 8 (n=2; pooled SMD:-0.12; 95% CI: -0.76, 0.51; P = 0.71), iNOS (n=2; pooled SMD:-0.69; 95% CI: -1.60, 0.23 P = 0.14) and C- Reactive Protein (n=4; pooled SMD: 0.05; 95% CI: -0.26, 0.36; P = 0.75), were not significantly changed by HS administration. Some of the results had high statistical heterogeneity. HS may be promising in the management of disorders involving hyperactive immune system or chronic inflammation.

The effect of iron deficiency and anaemia on women's health.

Iron deficiency and anaemia are global health problems and major causes of morbidity in women. Current definitions of anaemia in women are historic and have been challenged by recent data from observational studies. Menstrual loss, abnormal uterine bleeding and pregnancy put women at risk of developing iron deficiency which can result in severe fatigue, reduced exercise capacity and poor work performance. Iron deficiency and anaemia during pregnancy are associated with adverse maternal and fetal outcomes, including neurocognitive deficits in children born to iron-deficient mothers. Both iron deficiency and anaemia are common in women undergoing surgery but their association with poor outcomes remains uncertain. The enduring burden of iron deficiency and anaemia in women suggests that current strategies for recognition, prevention and treatment are limited in their utility. Improvements in our understanding of iron homeostasis and the development of new iron preparations, which are better absorbed with fewer side-effects, may improve therapeutic effectiveness of oral iron. Intravenous iron is efficacious for correcting anaemia rapidly but high-quality data on patient-centred outcomes and cost-effectiveness are currently lacking. Many recommendations for the treatment of iron deficiency and anaemia in national guidelines are not supported by high-quality evidence. There is a need for robust epidemiological data and well-designed clinical trials. The latter will require collaborative working between researchers and patients to design studies in ways that incorporate patients' perspectives on the research process and target outcomes that matter to them.

Phase 2 study of anastrozole in patients with estrogen receptor/progesterone receptor positive recurrent low-grade endometrial stromal sarcomas: The PARAGON trial (ANZGOG 0903).

BACKGROUND: Aromatase inhibitors are standard of care for low-grade endometrial stromal sarcomas (LGESS), based on very high response rates reported in retrospective studies. We evaluated the activity of anastrozole in recurrent/metastatic LGESS patients enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER±)/progesterone receptor (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER ± PR + ve LGESS with measurable disease, treated until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 15 eligible patients were enrolled. CBR at 3 months was 73% (95% CI: 48-89.1%); unchanged at 6 months. Best response was 26.7%, including complete response in one (6.7%; 95% CI 1.2-29.8%), partial response in three (20%, 95% CI 7.1-45.2%) and stable disease in seven (46.7%). Four patients ceased treatment by 3 months due to progression. Median PFS was not reached (25th percentile: 2.9 months (95% CI: 1.2-NR)). PFS was 73.3%, 73.3% and 66% at 6, 12, and 18 months, respectively. Six patients remained on treatment for an average of 44.2 months (range 34.5-63.6) up until data cut. Toxicity was as expected, with 3 patients stopping due to adverse effects. CONCLUSION: The 26.7% objective response rate with anastrozole is lower than reported in retrospective series, but the CBR was high and durable. The results underscore the importance of prospective trials in rare cancers.

Plant-Derived Food Grade Substances (PDFGS) Active Against Respiratory Viruses: A Systematic Review of Non-clinical Studies.

Human diet comprises several classes of phytochemicals some of which are potentially active against human pathogenic viruses. This study examined available evidence that identifies existing food plants or constituents of edible foods that have been reported to inhibit viral pathogenesis of the human respiratory tract. SCOPUS and PUBMED databases were searched with keywords designed to retrieve articles that investigated the effect of plant-derived food grade substances (PDFGS) on the activities of human pathogenic viruses. Eligible studies for this review were those done on viruses that infect the human respiratory tract. Forty six (46) studies met the specified inclusion criteria from the initial 5,734 hits. The selected studies investigated the effects of different PDFGS on the infectivity, proliferation and cytotoxicity of different respiratory viruses including influenza A virus (IAV), influenza B virus (IBV), Respiratory syncytial virus (RSV), human parainfluenza virus (hPIV), Human coronavirus NL63 (HCoV-NL63), and rhinovirus (RV) in cell lines and mouse models. This review reveals that PDFGS inhibits different stages of the pathological pathways of respiratory viruses including cell entry, replication, viral release and viral-induced dysregulation of cellular homeostasis and functions. These alterations eventually lead to the reduction of virus titer, viral-induced cellular damages and improved survival of host cells. Major food constituents active against respiratory viruses include flavonoids, phenolic acids, tannins, lectins, vitamin D, curcumin, and plant glycosides such as glycyrrhizin, acteoside, geniposide, and iridoid glycosides. Herbal teas such as guava tea, green and black tea, adlay tea, cistanche tea, kuding tea, licorice extracts, and edible bird nest extracts were also effective against respiratory viruses in vitro. The authors of this review recommend an increased consumption of foods rich in these PDFGS including legumes, fruits (e.g berries, citrus), tea, fatty fish and curcumin amongst human populations with high prevalence of respiratory viral infections in order to prevent, manage and/or reduce the severity of respiratory virus infections.

Nevirapine pharmacokinetics in HIV-infected persons receiving rifapentine and isoniazid for TB prevention.

BACKGROUND: The use of rifamycin antibiotics for TB prevention carries a risk of detrimental drug-drug interactions with concomitantly used ART. OBJECTIVES: To evaluate the interaction of the antiretroviral drug nevirapine in combination with 4 weeks of daily rifapentine and isoniazid for TB prevention in people living with HIV. METHODS: Participants were individuals enrolled in the BRIEF-TB study receiving nevirapine and randomized to the rifapentine/isoniazid arm of the study. Participants provided sparse pharmacokinetic (PK) sampling at baseline and weeks 2 and 4 for trough nevirapine determination. Nevirapine apparent oral clearance (CL/F) was estimated and the geometric mean ratio (GMR) of CL/F prior to and during rifapentine/isoniazid was calculated. RESULTS: Seventy-eight participants had evaluable PK data: 61 (78%) female, 51 (65%) black non-Hispanic and median (range) age of 40 (13-66) years. Median (IQR) nevirapine trough concentrations were: week 0, 7322 (5266-9302) ng/mL; week 2, 5537 (3552-8462) ng/mL; and week 4, 5388 (3516-8243) ng/mL. Sixty out of 78 participants (77%) had nevirapine concentrations ≥3000 ng/mL at both week 2 and 4. Median (IQR) nevirapine CL/F values were: week 0 pre-rifapentine/isoniazid, 2.03 (1.58-2.58) L/h; and during rifapentine/isoniazid, 2.62 (1.81-3.42) L/h. The GMR (90% CI) for nevirapine CL/F was 1.30 (1.26-1.33). CONCLUSIONS: The CL/F of nevirapine significantly increased with concomitant rifapentine/isoniazid. The decrease in nevirapine trough concentrations during rifapentine/isoniazid therapy suggests induction of nevirapine metabolism, consistent with known rifapentine effects. The magnitude of this drug-drug interaction suggests daily rifapentine/isoniazid for TB prevention should not be co-administered with nevirapine-containing ART.

Beta-Lactamase-Producing Escherichia coli Isolates Recovered from Pig Handlers in Retail Shops and Abattoirs in Selected Localities in Southern Nigeria: Implications for Public Health.

Antibiotic resistance evolution among pathogenic microorganisms has become a huge burden globally as it has increased the burden of diseases amongst humans and animals. The prevalence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and metallo beta-lactamase-producing Escherichia coli (MBL-Ec) isolated from pig abattoir and handlers in retail shops was studied. In addition, the relationship between the isolates' prevalence and the background characteristics of the butchers/retailers was also investigated. Samples from 32 hand swabs of pork sellers at retail shops and 8 butchers at abattoirs, as well as 272 swabs taken from knives, tables, floors, water troughs, and carcasses from both retail shops and abattoirs, were collected. Escherichia coli (E. coli) was isolated from hand swabs, fomites, and carcasses and were identified by standard microbiological procedures. The isolates susceptibility to nitrofurantoin (300 µg), ciprofloxacin (5 µg), ceftazidime (30 µg), cefuroxime (30 µg), gentamicin (10 µg), cefixime (5 µg), ofloxacin (5 µg), amoxicillin/clavulanic acid (30 µg), imipenem (10 µg), and meropenem (10 µg) and their ability to produce ESBL and MBL was determined by phenotypic methods. Demographic information of the handlers was retrieved by means of a structured questionnaire and, in some cases, via face to face interviews. Out of 104 E. coli isolates from both sources, 52 (50.0%) and 8 (7.7%) were ESBL and MBL producers, respectively. ESBL was more prevalent on the hands of the retailers (40.6%) and butchers (75.0%). The isolates were 100% resistant to ceftazidime, cefotaxime, and amoxicillin-clavulanic acid and 4.8% resistant to nitrofurantoin. Diverse resistance patterns were observed among ESBL-Ec and MBL-Ec. It was found that 90% of ESBL-Ec and 100% of MBL-Ec were multidrug-resistant. A possible epidemiological link between the two sources was observed. The prevalence of E. coli ESBL- and MBL-producing isolates was associated with the duty performed by handlers (p = 0.012) and gender (p = 0.012). Our results provide evidence that the handlers' hands and abattoir environment had a great role to play in the high prevalence and resistance profiles of the microorganisms.

Antimicrobial Resistance Profiles of Diarrheagenic E. coli (DEC) and Salmonella Species Recovered from Diarrheal Patients in Selected Rural Communities of the Amathole District Municipality, Eastern Cape Province, South Africa.

PURPOSE: The emergence of multidrug-resistant bacteria remains as one of the major impediments towards the prevention and treatment of microbial infections and continues to be a serious threat to medicine. Henceforth, this study aimed at elucidating the antimicrobial resistance profiles of diarrheagenic E. coli (DEC) and Salmonella species recovered from diarrheal patients in selected rural communities of the Amathole District Municipality (ADM), Eastern Cape Province, South Africa (SA). METHODS: The antimicrobial resistance profiles of diarrheagenic E. coli (DEC) and Salmonella isolates were evaluated using antimicrobial susceptibility tests and the relevant antimicrobial resistance factors were elucidated by the Polymerase Chain Reaction technique. RESULTS: A sum of 324 diarrheagenic E. coli (DEC) and 62 Salmonella isolates were recovered from diarrheal stool specimens collected amongst diarrheal patients admitted in medical facilities/health-care centers within the ADM in the Eastern Cape Province, South Africa. Multiple antimicrobial resistance index mean values of 0.7 and 0.5 for DEC and Salmonella isolates, respectively, were observed in this study, indicating that these isolates were from sources where antimicrobials were frequently used. The antimicrobial resistance factors ampC, blaTEM, SulI and II, tet A and aadA were detected among antimicrobial-resistant DEC pathotypes and Salmonella isolates recovered in this study. CONCLUSION: The occurrence of the multiple antimicrobial-resistant DEC and Salmonella isolates with the relevant antimicrobial resistance factors in this study suggests a portentous human health threat associated with diarrhea and a major deterrent in medicine.

Analysis of SARS-CoV-2 genomes from across Africa reveals potentially clinically relevant mutations.

SARS-CoV-2 is a betacoronavirus, the etiologic agent of the novel Coronavirus disease 2019 (COVID-19). The World Health Organization officially declared COVID-19 as a pandemic in March 2020 after the outbreak in Wuhan, China, in late 2019. Across the continents and specifically in Africa, all index cases were travel-related. Understanding how the viruss transportation across continents and different climatic conditions affect the genetic composition and the consequent effects on transmissibility, infectivity, and virulence of the virus is critical. Thus, it is crucial to compare COVID-19 genome sequences from the African continent with sequences from selected COVID-19 hotspots/countries in Asia, Europe, North and South America and Oceania. To identify possible distinguishing mutations in the African SARS-CoV-2 genomes compared to those from these selected countries, we conducted in silico analyses and comparisons. Complete African SARS-CoV-2 genomes deposited in GISAID and NCBI databases as of June 2020 were downloaded and aligned with genomes from Wuhan, China and other SARS-CoV-2 hotspots. Using phylogenetic analysis and amino acid sequence alignments of the spike and replicase (NSP12) proteins, we searched for possible vaccine coverage targets or potential therapeutic agents. Identity plots for the alignments were created with BioEdit software and the phylogenetic analyses with the MEGA X software. Our results showed mutations in the spike and replicate proteins of the SARS-Cov-2 virus. Phylogenetic tree analyses demonstrated variability across the various regions/countries in Africa as there were different clades in the viral proteins. However, a substantial proportion of these mutations (90%) were similar to those described in all the other settings, including the Wuhan strain. There were, however, novel mutations in the genomes of the circulating strains of the virus in African. To the best of our knowledge, this is the first study reporting these findings from Africa. However, these findings implications on symptomatic or asymptomatic manifestations, progression to severe disease and case fatality for those affected, and the cross efficacy of vaccines developed from other settings when applied in Africa are unknown.

Antiretroviral Adherence, Drug Resistance, and the Impact of Social Determinants of Health in HIV-1 Patients in the US.

Adherence to antiretroviral therapy (ART) is critical to achieving viral suppression. However, social determinants of health (SDoH) can undermine patient adherence to ART, resulting in drug resistance that compromises future treatment options. We assessed ART adherence and HIV-1 drug resistance at the national and state levels in the US and investigated their associations with SDoH and other HIV-related outcomes. Data were obtained from Symphony Health's Integrated Dataverse (IDV), Monogram/LabCorp Database, as well as national and publicly available databases, including Centers for Disease Control and Prevention (CDC), American Community Survey (ACS), and J. Kaiser Family Foundation (KFF). Inferential analyses were performed to investigate associations using patient-level data, and the results were reported by state and overall within the nation. Correlations between continuous variables were estimated by the Spearman's test, and that between continuous variable and categorical variable were estimated using one-way analysis of variance (ANOVA). State-level rates of poor adherence and resistance ranged from 26 to 55% and 20 to 54%, respectively. Female gender, non-white race, low education, poverty, and unemployment were associated with poor adherence; female gender was associated with drug resistance. Both adherence and resistance were correlated to HIV prevalence rates. Our findings suggest that US patients living with HIV face great challenges associated with poor ART adherence and HIV-1 drug resistance.

Rotavirus and Cryptosporidium pathogens as etiological proxies of gastroenteritis in some pastoral communities of the Amathole District Municipality, Eastern Cape, South Africa.

OBJECTIVE: Cryptosporidium and Rotavirus agents have been associated with severe diarrheal illnesses and remain as one of the worst human health burdens in most developing regions. In the present study, we evaluated the incidences of Cryptosporidium and Rotavirus in diarrheal stool specimens of patients in some rural settlements of the Amathole District Municipality in the Eastern Cape Province, South Africa. Stool specimens from diarrheal children and elderly individuals were collected from clinics and hospitals within the rural communities of the region over a period of 21 months (February 2017-November 2018). Commercial enzyme-immuno-assays were used for the detection of Rotavirus and Cryptosporidium pathogens from processed diarrheal stool specimens. RESULTS: A total of 53 fresh stool samples from diarrheal patients were screened and 36% of the diarrheagenic stool specimens tested positive for Group A Rotavirus antigens, while 5.7% tested positive for Cryptosporidium antigens. Our findings reveal Rotavirus and Cryptosporidium pathogens as important etiological agents associated with diarrheal illnesses in children, among the rural hinterlands of the Amathole District Municipality.

Embryonal and Alveolar Rhabdomyosarcoma in Adults: Real-Life Data From a Tertiary Sarcoma Centre.

AIMS: Embryonal and alveolar rhabdomyosarcoma (ERMS, ARMS) are subtypes of RMS that mainly occur in children, with relatively good outcomes. The incidence in adults is extremely low and survival is significantly worse compared with children. Data are scarce and literature generally combines all RMS subtypes, including pleomorphic RMS, which primarily occurs in adults and behaves more like undifferentiated pleomorphic sarcoma. The aim of this study was to evaluate patient and tumour characteristics, outcome and prognostic factors in adult patients with ERMS and ARMS. MATERIALS AND METHODS: All adult (18 years or older) ERMS and ARMS patients (presenting 1990-2016) were identified from a prospectively maintained database and were included in this analysis. RESULTS: Overall, 66 patients were included (42 men, 24 women). The median age at presentation was 28 years (range 18-71). The median overall survival for all ARMS (n = 42) and ERMS (n = 24) patients was 18 months, with a 5-year overall survival rate of 27%. Patients presenting with localised disease (n = 38, 58%) and metastatic disease (n = 25, 42%), had a 5-year overall survival rate of 36% and 11%, respectively. In univariate analysis we found alveolar subtype, fusion gene positivity, infiltrative tumour and metastatic presentation to be negative prognostic factors. CONCLUSION: Survival in adult ERMS and ARMS patients is poor and the current data may be useful in the design of trials with novel agents. Ideally, paediatric and adult oncologists should set up trials together to get a better understanding of biological, genetic and clinically relevant factors in this disease.

The activity of commercial antimicrobials, and essential oils and ethanolic extracts of Olea europaea on Streptococcus agalactiae isolated from pregnant women.

BACKGROUND: Streptococcus agalactiae also known as Group B Streptococcus (GBS) is a major cause of disease in pregnant women and new born babies where it causes early and late onset disease characterised by sepsis, pneumonia and meningitis. Ten to 37 % of pregnant women in the world are colonised with GBS while intrapartum antibiotic prophylaxis has led to significant reduction in early onset disease. The increase in drug resistant microorganisms has become a major threat. Development of vaccines is still in progress so there is need for new and safer alternatives to treatment. METHODS: Benzyl penicillin, Ampicillin, Cefotaxime, Ceftriaxone, Levofloxacin, Erythromycin, Clindamycin, Linezolid, Vancomycin, Tetracycline and Cotrimoxazole, Olea europaea leaf extracts and essential oil were tested against GBS isolates from South Africa and Namibia. RESULTS: The isolates showed 100% sensitivity to benzyl penicillin, ampicillin, ceftriaxone, levofloxacin, linezolid, vancomycin, O. europaea leaf extracts and essential oils. Only one isolate (0.6%) was resistant to cefotaxime and 23.4 and 10.4% were resistant to clindamycin and erythromycin respectively. CONCLUSION: GBS isolates showed sensitivity to O. europaea extracts at low minimum inhibitory concentrations. Β lactams are still the drugs of choice for treatment of GBS disease but O. europaea extracts potent as an alternative source of antimicrobials.

Prevalence and capsular type distribution of Streptococcus agalactiae isolated from pregnant women in Namibia and South Africa.

BACKGROUND: Streptococcus agalactiae or Group B Streptococcus (GBS) is the leading cause of neonatal morbidity and mortality resulting in septicaemia, bacteraemia and meningitis. Long term problems in children range from loss of hearing to mental retardation. While Intrapartum Antibiotic Prophylaxis (IAP) has reduced the incidence of S. agalactiae infection, it still remains the leading cause of disease in neonates. GBS has ten capsular types whose distribution varies across the world. Therefore, this study sought to determine the prevalence of GBS in Namibia and South Africa amongst pregnant women between 35 and 37 weeks gestation and elucidate the capsular types. METHODS: Lower vaginal and rectal swabs were collected from pregnant women between 35 and 37 weeks gestation. Five hundred and thirty pregnant women were recruited into the study in Windhoek, Namibia while one hundred pregnant women were recruited in the Eastern Cape, South Africa. The swabs were cultured on 5% sheep blood agar (Biomerieux, New Jersey, USA) for isolation of GBS. Presumptive isolates were confirmed using both the Vitek (2) and molecular techniques targeting the scpB gene. Capsular typing was performed in a multiplex PCR with capsular specific primer pairs. RESULTS: The prevalence of GBS in Namibia was 13.6 and 37% in South Africa respectively. In both countries most women were dually colonised with GBS. Capsular types II, III and V were the most prevalent. CONCLUSIONS: The prevalence of GBS in Namibia was lower than in South Africa in this study. The prevalence in both countries was not different from those reported in other African countries and around the world. The predominant capsular types in this study are the ones commonly associated with adverse maternal outcomes.

Corepressor SMRT is required to maintain Hox transcriptional memory during somitogenesis.

Nuclear hormone receptors (NRs), such as retinoic acid receptors (RARs), play critical roles in vertebrate development and homeostasis by regulating target gene transcription. Their activity is controlled by ligand-dependent release of corepressors and subsequent recruitment of coactivators, but how these individual receptor modes contribute to development are unknown. Here, we show that mice carrying targeted knockin mutations in the corepressor Silencing Mediator of Retinoid and Thyroid hormone receptor (SMRT) that specifically disable SMRT function in NR signaling (SMRTmRID), display defects in cranial neural crest cell-derived structures and posterior homeotic transformations of axial vertebrae. SMRTmRID embryos show enhanced transcription of RAR targets including Hox loci, resulting in respecification of vertebral identities. Up-regulated histone acetylation and decreased H3K27 methylation are evident in the Hox loci whose somitic expression boundaries are rostrally shifted. Furthermore, enhanced recruitment of super elongation complex is evident in rapidly induced non-Pol II-paused targets in SMRTmRID embryonic stem cells. These results demonstrate that SMRT-dependent repression of RAR is critical to establish and maintain the somitic Hox code and segmental identity during fetal development via epigenetic marking of target loci.

Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study.

Since the publication of this paper, the authors noticed an error in Fig. 1. The X-axis on all the figure panels should read 'Time (years)', not 'Time (months)'. The corrected Fig. 1 is shown below.