Search

Introduction: Testicular germ cell tumors, particularly nonseminomatous germ cell tumors (NSGCT), comprise the most common solid malignancy in male children and younger adults. While these patients experience excellent survival outcomes, few studies have characterized their survival by age. Thus, we aimed to characterize the relative survival of NSGCT by age, stratifying patients by stage group., Methods: Using the Surveillance Epidemiology and End Results (SEER) database, we divided patients with NSGCT into pediatric patients and adolescents (<19 years), young adults (19-30 years), and older adults (>30 years). Survival analysis, using Cox proportional hazards models and Kaplan Meier curves, described overall and cancer-specific survival (CSS) of each age category for Stage I-III NSGCT by stage group., Results: A total of 14,786 patients met inclusion criteria and comprised the age groups <19 years (N=1,287), 19 to 30 years (N=7,729), and >30 years (N=5,770). Stage group distribution at presentation was similar between each group. Survival analysis demonstrated no differences in cancer-specific survival (CSS) among Stage I or II NSGCT. However, among Stage III tumors, multivariable models noted worse CSS in patients >30 years (HR=3.35 (95%CI: 1.45-7.73), P=0.005) and those 19-30 years (HR=2.28 (95%CI: 0.99-5.21), P=0.053) compared to pediatric and adolescent patients., Conclusions: Younger NSGCT patients experience excellent oncologic outcomes compared to their older counterparts. These survival differences by age group are largely driven by differential survival among Stage III neoplasms. Furthermore, our report lends additional evidence that age is an important prognostic factor in advanced NSGCT, including pediatric and adolescent patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Malaria, the most devastating parasitic disease, is currently treated with artemisinin-based combination therapies (ACTs). Unfortunately, some ACTs are unable to rapidly clear Plasmodium falciparum parasites from the blood stream and are failing to cure malaria patients; a problem, so far, largely confined to Southeast Asia. There is a fear of resistant Plasmodium falciparum emerging in other parts of the world including Sub-Saharan Africa. Strategies for alternative treatments, ideally non-artemisinin based, are needed., Areas Covered: This narrative review gives an overview of approved antimalarials and of some compounds in advanced drug development that could be used when an ACT is failing. The selection was based on a literature search in PubMed and WHO notes for malaria treatment., Expert Opinion: The ACT drug class can still cure malaria in malaria endemic regions. However, the appropriate ACT drug should be chosen considering the background resistance of the partner drug of the local parasite population. Artesunate-pyronaridine, the 'newest' recommended ACT, and atovaquone-proguanil are, so far, effective, and safe treatments for uncomplicated falciparum malaria. Therefore, all available ACTs should be safeguarded from parasite resistance and the development of new antimalarial drug classes needs to be accelerated.

Background: Schistosomiasis is highly prevalent in Africa. Praziquantel is effective against adult schistosomes but leaves prepatent stages unaffected-which is a limit to patient management and elimination. Given the large-scale use of praziquantel, development of drug resistance by Schistosoma is feared. Antimalarials are promising drugs for alternative treatment strategies of Schistosoma infections. Development of drugs with activity against both malaria and schistosomiasis is particularly appealing as schistosome infections often occur concomitantly with malaria parasites in sub-Saharan Africa. Therefore, antiplasmodial compounds were progressively tested against Schistosoma in vitro, in mice, and in a clinical study., Results: Amongst 16 drugs and 1 control tested, pyronaridine, methylene blue and 5 other antimalarials were highly active in vitro against larval stage schistosomula with a 50% inhibitory concentration below 10 μM. Both drugs were lethal to ex vivo adult worms tested at 30 μM with methylene blue also active at 10 μM. Pyronaridine treatment of mice infected with S. mansoni at the prepatent stage reduced worm burden by 82% and cured 7 out of 12 animals, however in mice adult stages remained viable. In contrast, methylene blue inhibited adult worms by 60% but cure was not achieved. In an observational pilot trial in Gabon in children, the antimalarial drug combination pyronaridine-artesunate (Pyramax) reduced S. haematobium egg excretion from 10/10 ml urine to 0/10 ml urine, and 3 out of 4 children were cured., Conclusion: Pyronaridine and methylene blue warrant further investigation as candidates for schistosomiasis treatment. Both compounds are approved for human use and evidence for their potential as antischistosomal compounds can be obtained directly from clinical testing. Particularly, pyronaridine-artesunate, already available as an antimalarial drug, calls for further clinical evaluation., Trial Registration: ClinicalTrials.gov Identifier NCT03201770., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Use of hydroxychloroquine in patients with coronavirus disease 2019 (COVID-19) was widespread and uncontrolled until recently. Patients vulnerable to severe COVID-19 are at risk of hydroxychloroquine interactions with co-morbidities and co-medications contributing to detrimental, including fatal, adverse treatment effects., Methods: A retrospective survey was undertaken of health conditions and co-medications of patients with COVID-19 who were pre-screened for enrolment in a randomized, double-blind, placebo-controlled hydroxychloroquine multi-centre trial., Results: The survey involved 305 patients [median age 71 (interquartile range 59-81) years]. The majority of patients (n = 279, 92%) considered for inclusion in the clinical trial were not eligible, mainly due to safety concerns caused by health conditions or co-medications. The most common were QT-prolonging drugs (n = 188, 62%) and haematologic/haemato-oncologic diseases (n = 39, 13%) which prohibited the administration of hydroxychloroquine. In addition, 165 (54%) patients had health conditions and 167 (55%) patients were on co-medications that did not prohibit the use of hydroxychloroquine but had a risk of adverse interactions with hydroxychloroquine. The most common were diabetes (n = 86, 28%), renal insufficiency (n = 69, 23%) and heart failure (n = 58, 19%)., Conclusion: The majority of hospitalized patients with COVID-19 had health conditions or took co-medications precluding safe treatment with hydroxychloroquine. Therefore, hydroxychloroquine should be administered with extreme caution in elderly patients with COVID-19, and only in clinical trials., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: We sought to compare re-treatment rates between shockwave lithotripsy and ureteroscopy to evaluate the effectiveness of these modalities. Additionally, we aimed to compare costs associated with re-treatment., Methods: The Healthcare Cost and Utilization Project State Ambulatory Surgery Database for Florida from 2009 to 2015 was used to identify patients who underwent shockwave lithotripsy or ureteroscopy. Patients were tracked for subsequent stone surgeries within 3 months, 6 months and 1 year. Costs of care were estimated and descriptive analyses were performed. A multivariable logistic regression model was used to determine predictors of a second procedure., Results: A total of 98,011 patients underwent initial shockwave lithotripsy or ureteroscopy. Of those who underwent initial shockwave lithotripsy 21.2% had a second surgery (shockwave lithotripsy or ureteroscopy) within 3 months compared to 10% of patients who underwent initial ureteroscopy (p <0.01). On multivariable analysis, patients who underwent initial shockwave lithotripsy were more than twice as likely (OR 2.4, 95% CI 2.3-2.5) to undergo a second procedure within 3 months. Older patients were also more likely to undergo a second surgery, while African Americans, Hispanics, uninsured patients and patients with more comorbidities had decreased odds of undergoing a second surgery (all p <0.05). The per patient cost of the initial procedure plus re-treatment at the 3-month mark was $6,239 for initial shockwave lithotripsy and $5,319 for initial ureteroscopy (p <0.01)., Conclusions: Patients undergoing shockwave lithotripsy are more likely than those undergoing ureteroscopy to have additional stone procedures, making shockwave lithotripsy a more expensive intervention.

Objectives: Eravacycline is a novel synthetic halogenated tetracycline derivative with a broad antibacterial spectrum. Antibiotics, including tetracyclines, have been used for prophylaxis and, more rarely, for the treatment of malaria for several decades. The rise in drug-resistant malaria parasites renders the search for new treatment candidates urgent. We determined the in vitro potency of eravacycline against Plasmodium falciparum and investigated the apicoplast as a potential drug target., Methods: Four tetracyclines, including eravacycline, tetracycline, tigecycline, and doxycycline, and the lincosamide clindamycin, were tested in 3-day and 6-day in vitro susceptibility assays of P. falciparum laboratory strain 3D7 and/or of clinical isolates obtained from 33 P. falciparum infected individuals from Gabon in 2018. Assays with isopentenyl pyrophosphate substitution were performed to investigate whether apicoplast-encoded isoprenoid biosynthesis is inhibited by these antibiotics., Results: Eravacycline showed the highest activity of all tetracyclines tested in clinical isolates in the 3-day and 6-day assays. Substitution of isopentenyl pyrophosphate in vitro using the laboratory strain 3D7 reversed the activity of eravacycline and comparator antibiotics, indicating the apicoplast to be the main target organelle., Conclusions: These results demonstrate the potential of novel antibiotics, and eravacycline, as candidate antimalarial therapies., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: The objective is to describe our experience with robot-assisted laparoscopic diverticulectomy with extravesical ureteral reimplantation in a pediatric patient., Methods: A 7-year-old male presented with a symptomatic urinary tract infection secondary to Staphylococcus epidermidis. The patient was found to have a large congenital paraureteral bladder diverticulum on work-up. His options were discussed and he proceeded with robotic diverticulectomy. Intraoperatively, the diverticulum was found to obscure the left ureteral orifice, which necessitated synchronous dismembered extravesical ureteral reimplantation., Results: Robot-assisted laparoscopic diverticulectomy with extravesical ureteral reimplantation was performed. The procedure time was 283 min, and estimated blood loss was 3 mL. The patient was discharged home on post-operative day 1. He was last seen in clinic six months after surgery and was doing well without any recurrent urinary tract infections., Conclusion: This video demonstrates a robotic approach for the treatment of complex congenital bladder diverticula. Robotic surgery offers the benefits of good visualization in the pelvis, minimal blood loss, and quick convalescence. Key portions of the diverticulectomy and ureteral reimplantation are clearly illustrated in this video, which can help other surgeons adopt this technique., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon., Methods: A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS-AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti‑malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened., Results: Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86-100) and 95% (95% CI 84-99) for AL and AS-AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment., Conclusion: This study showed that AL and AS-AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True.

Background: Plasmodium falciparum deficient for hrp2 and hrp3 genes are a threat to malaria management and elimination, since they escape widely used HRP2-based rapid diagnostic tests and treatment. Hrp2/hrp3 deletions are increasingly reported from all malaria endemic regions but are currently only identified by laborious methodologies., Methods: We developed a novel hydrolysis probe-based, quantitative, real-time PCR (4plex qPCR) for detection and discrimination of P. falciparum infection (cytb) and hrp2 and hrp3 gene status, and to control assay validity (btub). A cross-sectional, diagnostic accuracy study was performed in Gabon for assay validation and deletion screening., Findings: In parallel to identification of P. falciparum infection in samples down to 0.05 parasites/µl, the 4plex qPCR enabled specific and valid interrogation of the parasites´s hrp2 and hrp3 genes in one go - even in low parasitemic samples. The assay was precise and robust also when performed in a routine healthcare setting in Gabon. The risk of falsely identifying hrp2 or hrp3 deletion was reduced by 100-fold compared to conventional PCR. Evaluation against microscopy was performed on 200 blood samples collected in Gabon: sensitivity and specificity of 4plex qPCR (cytb) were 100% and 80%, respectively. Stringent testing revealed hrp2 deletion in 2 of 95 P. falciparum positive and validated samples., Interpretation: The novel 4plex qPCR is sensitive, accurate and allows resource-efficient rapid screening. Monitoring and mapping of hrp2/hrp3 deletions is required to identify areas where control strategies may need to be adapted to ensure appropriate patient care and ultimately achieve malaria elimination., Funding: BMBF (03VP00402)., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)