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Reinduction therapy with everolimus in combination with dexamethasone, high-dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD-R3i)

Br J Haematol. 2021 Nov 14. doi: 10.1111/bjh.17878. Online ahead of print.

ABSTRACT

Reinduction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second-line standard of care for transplant-eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high-dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant-eligible patients aged 18-60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase-I-part) was administered on day 0-13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end-point of computed tomography (CT)-based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT-based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end-point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.

PMID:34775591 | DOI:10.1111/bjh.17878

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Occurrence of heavy metals and their removal in Perna viridis mussels using chemical methods: a review

Environ Sci Pollut Res Int. 2021 Nov 13. doi: 10.1007/s11356-021-17343-3. Online ahead of print.

ABSTRACT

Despite the nutritional benefits, bivalves like mussels are also an excellent aquatic heavy metal biomonitoring agent due to their high tolerance to varying levels of temperature, salinity and oxygen, as well as pollutants. Although the accumulated toxic heavy metals may not exert direct negative impacts on the mussels, such toxicants in mussel tissues can give harmful effects on human body when consumed in toxic quantities and/or over prolonged period. The booming of urban and industrial activities, and consequently the increment of runoffs, as well as wastewater effluents and leaching, further exacerbated the magnitude of this issue. Hence, continuous monitoring of heavy metal contents in mussels is vital to ensure its compliance with food safety regulations, protecting consumers at large. This review paper discusses the occurrence of heavy metals in mussels especially that of Perna viridis in Malaysia and other parts of the world since year 2000 until 2021. Heavy metal concentration data and patterns from various coastal and/or estuaries were compared. Where applicable, statistical data that indicate variations between sampling sites, sampling months or years and chemical treatments for heavy metal removal were critically reviewed. Health risk assessment findings were also discussed. More importantly, related chemical-based interventions to minimize and/or eliminate toxic heavy metals from mussels are also reviewed.

PMID:34775561 | DOI:10.1007/s11356-021-17343-3

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Telomere length variation does not correspond with the growth disturbances in the rainbow trout (Oncorhynchus mykiss)

J Appl Genet. 2021 Nov 13. doi: 10.1007/s13353-021-00669-6. Online ahead of print.

ABSTRACT

Somatic growth is considered to affect pace of the telomere attrition in vertebrates. As normally developed and dwarf fish differ in the body size we have decided to compare telomere length in the rainbow trout (Oncorhynchus mykiss) with normal growth and with growth reduced due to the dwarf condition. Examined 1-year-old fish with normal and dwarf appearance were siblings originated from androgenetic fully homozygous doubled haploid (DH) line of rainbow trout. Particular dwarf individuals had body deformities such as humpback, kyphosis, and lordosis. Somatic cells of examined rainbow trout had an average telomere length between 17 and 20 kb, comparable in females and males. Dwarf rainbow trout exhibited significantly lower body length and weight than their normally developed siblings even though no differences in the telomere length were found between these fishes. Statistical analysis did not exhibit any correlation between body size and the telomere length. Equal length of telomeres observed in the studied normal and dwarf rainbow trout suggests morphological and physiological differences in fish with different growth rates do not affect dynamics of telomeric DNA. Or any variation in the telomere length might have been levelled by telomerase that in rainbow trout is active in all tissues irrespective of the individual developmental stage.

PMID:34775545 | DOI:10.1007/s13353-021-00669-6

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Concentration, source identification, and potential human health risk assessment of heavy metals in chicken meat and egg in Bangladesh

Environ Sci Pollut Res Int. 2021 Nov 13. doi: 10.1007/s11356-021-17342-4. Online ahead of print.

ABSTRACT

Chicken meat and hen egg are very popular foodstuffs around the world and highly consumed as curry, fast food, processed food, etc. assuming a promising source of protein. In the present study, the concentrations of Pb, Cd, Cr, As, Hg, Mn, Fe, and Zn in nationally representative samples of chicken meat and hen egg were determined and found in the range of 0.03-2.73, 0.01-0.015, 0.025-0.67, 0.04-0.06, 0.01-0.015, 0.15-0.63, 2.50-38.6, and 1.02-19.4 mg/kg-fw, respectively. The results demonstrated that only Pb exceeded the maximum allowable concentration (MAC) for dietary food. Multivariate statistical analyses depicted that anthropogenic activities were the major source of heavy metals in the investigated foodstuffs. Human health risks associated with the dietary intake of these metals through the consumption of chicken meat and hen egg were evaluated in terms of estimated daily intake (EDI), non-carcinogenic risk of individual heavy metal by target hazard quotient (THQ), total target hazard quotient (TTHQ) for combined metals, and carcinogenic risk (CR) for lifetime exposure. The calculated values of EDI, THQ, TTHQ, and CR were below their respective permissible benchmarks indicating the safe consumption of the investigated foodstuffs with respect to heavy metal contamination.

PMID:34775560 | DOI:10.1007/s11356-021-17342-4

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Single pharmacy governed denosumab home administration: optimal adherence by means of a fracture liaison service (FLS) and home care collaboration

Osteoporos Int. 2021 Nov 13. doi: 10.1007/s00198-021-06234-5. Online ahead of print.

ABSTRACT

Low adherence for denosumab (Dmab, Prolia®) is of major concern. Dutch pharmacies deliveries were calculated recently being 76.5% for a total of 3 injections.

INTRODUCTION: Comparing a model where the prescriber maintains responsibility for adherence (model HC1) (Dmab is purchased and dispensed by patient’s own community pharmacy and administered through a home care service (HC)) or an all-in-one model where the pharmacist maintains responsibility for the adherence (Dmab is purchased, dispensed, and administered by a pharmacist’s HC) (HC2).

METHODS: We counted the number of Dmab injections, follow-up appointments on time, Dmab administrations delayed to a maximum of 60 days, the number of Dmab discontinuations, and all causes legally traceable under EU privacy act (EDPR).

RESULTS: Home care started by 2014 (study closure in 2021) and included 711 Dmab injections to 256 unique patients: HC1: 536 and HC2: 175 orders. The whole group received on average 2.8 Dmab injections by consistent intervals of about 182 days. Average administration after the latest Dmab injection: 272.8 days (HC1: 362.0 and HC2: 124.0 days). Administration of a subsequent injection > 60 days occurred in 26.6% (HC1: 38.8% and HC2: 6.2%; OR = 9.49). After adjustment for no more than three Dmab injections administered per patient, it occurred in 27.3% (HC1: 51.8% and HC2 4.4%; OR = 23.34).

CONCLUSION: It was possible to achieve 94% adherence for Dmab injections treatment just by transferring the complete supply chain to one pharmacy-initiated home care provider after treatment initiation by either a physician or FLS health care professional.

PMID:34775527 | DOI:10.1007/s00198-021-06234-5

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Night-shift work, breast cancer incidence, and all-cause mortality: an updated meta-analysis of prospective cohort studies

Sleep Breath. 2021 Nov 13. doi: 10.1007/s11325-021-02523-9. Online ahead of print.

ABSTRACT

OBJECTIVES: Night-shift work exposure is proposed to link to a wide range of health issues, especially cancer incidence, cancer-specific death, and all-cause death. However, the epidemiological associations among night-shift work exposure, breast cancer, breast cancer-specific death, and all-cause mortality remain inconclusive.

METHODS: We performed an updated systematic review and meta-analysis to confirm potential associations among night-shift work exposure, breast cancer, and all-cause mortality.

RESULTS: A total of 31 prospective cohort studies, involving 9.3 million participants, 31,244 incident breast cancer cases, 12,728 cancer-related deaths, 7882 cardiovascular deaths, and 30,807 all-cause mortalities were included. Overall, the summary RR of incident breast cancer in females for an increase of night-shift work was 1.029 (95% CI 1.003-1.055). Compared with standard day workers, night-shift workers had a statistically significantly increased RR (1.086, 95% CI 1.032-1.142) for breast cancer incidence in the subgroup of > 10 years exposure. Furthermore, a positive association was revealed in subgroup studies of rotating night-shift work (RR = 1.053, 95% CI 1.018-1.090). A significant increased risk of cardiovascular mortality was demonstrated in the night-shift work group (RR = 1.031; 95% CI 1.006-1.057).

CONCLUSION: Our systematic review and meta-analysis provided convincing evidence supporting positive associations among night-shift work exposure, breast cancer incidence, and cardiovascular mortality. Taken together, night-shift work exposure significantly increased the risk of breast cancer morbidity by 2.9% for total, 8.6% for the subgroup of more than 10 years night-shift work, and 5.3% for rotating night-shift work. In addition, night-shift work increased the risk of cardiovascular mortality by 3.1%.

PMID:34775538 | DOI:10.1007/s11325-021-02523-9

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Oral bacterial decontamination using an innovative prototype for photocatalytic disinfection

Clin Oral Investig. 2021 Nov 13. doi: 10.1007/s00784-021-04282-z. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the effectiveness of a prototype photocatalytic device for bacterial decontaminations of the oral cavity.

METHODS: Sixty-four subjects (18-65) were selected and randomly assigned to eight groups (n = 8), according to oral disinfection protocol: (G1): distilled water (control); (G2): 1.5% hydrogen peroxide (HP); (G3): 3.0% HP; (G4): 0.12% chlorhexidine (CHX); (G5): Germinator; (G6): 1.5% HP + Germinator; (G7): 3.0%HP + Germinator; (G8): 0.12% CHX + Germinator. Stimulated saliva was collected before and after a 3-min mouthwash and/or Germinator application. The patients were kept relaxed and retained saliva 5-10 min, spitting out into the tube for 3 min. The percentage bacterial reduction was checked by counting the colony-forming units (CFUs) after culturing on blood agar plates. Data were subjected to one-way ANOVA followed by Tukey’s post hoc test (α = 5%) for statistical significance.

RESULTS: The highest bacterial reduction was observed in groups 3 (3.0% HP), 6 (1.5% HP + Germinator), and 7 (3.0% + Germinator), with no statistically significant difference between them (p > 0.05). Groups 6 (1.5% HP + Germinator) and 8 (0.12% CHX + Germinator) showed higher bacterial reduction than groups 2 (1.5% HP) and 4 (0.12% CHX) (p < 0.05). Finally, group 5 (Germinator) showed higher bacterial reduction than control group (DW) and group 4 (0.12% CHX) (p < 0.05).

CONCLUSIONS: The photocatalytic disinfection was effective against oral bacteria and improved the antimicrobial action of 1.5% HP and 0.12%.

CLINICAL SIGNIFICANCE: The photocatalytic disinfection can be an alternative protocol to provide the oral decontamination.

PMID:34775518 | DOI:10.1007/s00784-021-04282-z

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Neuroendoscopic lavage for the treatment of pyogenic ventriculitis in children: personal series and review of the literature

Childs Nerv Syst. 2021 Nov 13. doi: 10.1007/s00381-021-05413-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Pyogenic ventriculitis is a severe infection of the central nervous system with serious and often irreversible consequences in the quality of life of patients. Its treatment is difficult due to the impossibility of achieving sterility of cerebrospinal fluid (CSF) and the physiological characteristics promptly. Several treatment options have been described, from prolonged antibiotic treatments to placement of ventricular drains with continuous irrigation and puncture reservoirs. We propose an aggressive and minimally invasive treatment with neuroendoscopic lavage (NEL).

METHODS: Retrospective and descriptive study. We analyzed the NEL performed in our hospital for pyogenic ventriculitis between 2011 and 2020. A total of 16 patients were found; 2 of them lost follow-up, so they were not included. All patients had a diagnosis of pyogenic ventriculitis, either due to the macroscopic characteristics of the CSF or due to imaging criteria. Between 1 and 3 NEL were performed per patient until obtaining sterility and normalization of protein and cell counts of CSF.

RESULTS: The average age was 38 months (2 months to 16 years). Ten patients were female and 4 were male. Sixty-four percent of germs in cultures corresponded to gram-negative and polymicrobial flora. The average number of days until the first sterile CSF post-NEL was 3.8 days (0 to 10 days). The NEL produced a significant improvement in the characteristics of the CSF compared to the pre-NEL. The mean pre-NEL of CSF protein levels was 907 mg/dl (123-4510 mg/dl) compared with the post-NEL of 292 mg/dl (38-892 mg/dl) with a p-value = 0.0076. Regarding cellularity, statistically significant results were also achieved (p-value = 0.0011) with a pre-surgical cellularity of 665 elements/mm3 (4-3090 elements/mm3) compared with 57 elements/mm3 (0-390 elements/mm3) post-NEL. Of the patients, 85.7% had a shunt prior to the onset of ventriculitis and the average number of days until the new shunt was 36.56 days (17-79 days), with a total hospitalization days ranging from 22 to 170.

CONCLUSIONS: NEL allows rapid sterilization of CSF, decreasing the deleterious effect of infection in the CNS more rapidly compared to other types of conventional treatment.

PMID:34775525 | DOI:10.1007/s00381-021-05413-3

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Dentinal tubule blockage using nanobioglass in the presence of diode (980 nm) and Nd:YAG lasers: an in vitro study

Clin Oral Investig. 2021 Nov 13. doi: 10.1007/s00784-021-04279-8. Online ahead of print.

ABSTRACT

OBJECTIVES: The main objective of this study was to enhance the blockage of dentinal tubules using nanobioglass in the presence of diode (980 nm) and Nd:YAG lasers in order to reduce permeability and dentin hypersensitivity.

MATERIALS AND METHODS: Thirty-six dentinal samples were randomly divided into 6 subgroups (n = 6): (A) control, (B) diode laser (980 nm, 3-W), (C) Nd:YAG laser (1064, 1.0-W), (D) nanobioglass, (E) nanobioglass + diode laser (980 nm), (F) nanobioglass + Nd:YAG laser. The average number of open dentinal tubules was qualitatively and quantitatively evaluated by scanning electron microscopy (SEM). Data were evaluated by SPSS software version 22, Kruskal-Wallis test, and Mann-Whitney tests with Bonferoni’s correction (α = 0.008).

RESULTS: Based on the results of Mann-Whitney test, there was a significant difference in the mean number of open dentinal tubules between the control group and the other groups (p < 0.008). However, the difference among the other groups was not statistically significant (p > 0.008).

CONCLUSIONS: Findings of this study showed that high-power laser radiation, such as Nd:YAG and diode (980 nm) alone or with nanobioglass, has a significant effect on the blockage of dentinal tubules.

CLINICAL RELEVANCE: Introduction of non-invasive methods with long-term and lasting effect on reducing pain and discomfort caused by dentin hypersensitivity.

PMID:34775517 | DOI:10.1007/s00784-021-04279-8

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PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors

Pharmacogenomics J. 2021 Nov 13. doi: 10.1038/s41397-021-00261-5. Online ahead of print.

ABSTRACT

No biomarkers are available to predict patients at risk of developing hypertension induced by VEGF-pathway inhibitors. This study aimed to identify predictive biomarkers of hypertension induced by these drugs using a discovery-replication approach. The discovery set included 140 sorafenib-treated patients (TARGET study) genotyped for 973 SNPs in 56 genes. The most statistically significant SNPs associated with grade ≥2 hypertension were tested for association with grade ≥2 hypertension in the replication set of a GWAS of 1039 bevacizumab-treated patients from four clinical trials (CALGB/Alliance). In the discovery set, rs444904 (G > A) in PIK3R5 was associated with an increased risk of sorafenib-induced hypertension (p = 0.006, OR = 3.88 95% CI 1.54-9.81). In the replication set, rs427554 (G > A) in PIK3R5 (in complete linkage disequilibrium with rs444904) was associated with an increased risk of bevacizumab-induced hypertension (p = 0.008, OR = 1.39, 95% CI 1.09-1.78). This study identified a predictive marker of drug-induced hypertension that should be evaluated for other VEGF-pathway inhibitors.ClinicalTrials.gov Identifier:NCT00073307 (TARGET).

PMID:34775477 | DOI:10.1038/s41397-021-00261-5