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Is adjuvant chemotherapy necessary in older patients with breast cancer?

Breast Cancer. 2022 Jan 15. doi: 10.1007/s12282-021-01329-7. Online ahead of print.

ABSTRACT

BACKGROUND: Due to the lack of clinical trials on the efficacy of chemotherapy in older patients, an optimal treatment strategy has not been developed. We investigated whether adjuvant chemotherapy could improve the survival of older patients with breast cancer in Japan.

METHODS: We retrospectively analyzed data of patients with breast cancer aged ≥ 70 years who underwent breast cancer surgery in eight hospitals between 2008 and 2013. Clinical treatment and follow-up data were obtained from the patients’ medical electric records.

RESULTS: A total of 1095 patients were enrolled, of which 905 were included in the initial non-matched analysis. The median age and follow-up period were 75 (range 70-93) and 6.3 years, respectively. Of these patients, 127 (14%) received adjuvant chemotherapy (Chemo group) while the remaining 778 (86%) did not (Control group). The Chemo group was younger (mean age in years 73 vs 76; P < 0.0001), had a larger pathological tumor size (mean mm 25.9 vs 19.9; P < 0.0001), and more metastatic axillary lymph nodes (mean numbers 2.7 vs 0.7; P < 0.0001) than the Control group. The disease-free survival (DFS) and overall survival (OS) did not differ significantly between the two groups (P = 0.783 and P = 0.558). After matched analyses, DFS was found to be significantly prolonged with adjuvant chemotherapy (P = 0.037); however, OS difference in the matched cohort was not statistically significant (P = 0.333).

CONCLUSION: The results showed that adjuvant chemotherapy was associated with a reduced risk of recurrence, but survival benefits were limited.

PMID:35032302 | DOI:10.1007/s12282-021-01329-7

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Individual differences in the effects of the ACTION-PAC intervention: an application of personalized medicine in the prevention and treatment of obesity

J Behav Med. 2022 Jan 15. doi: 10.1007/s10865-021-00274-2. Online ahead of print.

ABSTRACT

There is an increased interest in the use of personalized medicine approaches in the prevention or treatment of obesity, however, few studies have used these approaches to identify individual differences in treatment effects. The current study demonstrates the use of the predicted individual treatment effects framework to test for individual differences in the effects of the ACTION-PAC intervention, which targeted the treatment and prevention of obesity in a high school setting. We show how methods for personalized medicine can be used to test for significant individual differences in responses to an intervention and we discuss the potential and limitations of these methods. In our example, 25% of students in the preventive intervention, were predicted to have their BMI z-score reduced by 0.39 or greater, while at other end of the spectrum, 25% were predicted to have their BMI z-score increased by 0.09 or more. In this paper, we demonstrate and discuss the process of using methods for personalized medicine with interventions targeting adiposity and discuss the lessons learned from this application. Ultimately, these methods have the potential to be useful for clinicians and clients in choosing between treatment options, however they are limited in their ability to help researchers understand the mechanisms underlying these predictions.

PMID:35032253 | DOI:10.1007/s10865-021-00274-2

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A meta-analysis of genome-wide association studies using Japanese and Taiwanese has revealed novel loci associated with gout susceptibility

Hum Cell. 2022 Jan 15. doi: 10.1007/s13577-021-00665-2. Online ahead of print.

NO ABSTRACT

PMID:35032298 | DOI:10.1007/s13577-021-00665-2

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Investigation of the causes of BCG refractory in patients treated with intracavitary BCG as secondary treatment in superficial bladder tumors with transurethral resection

Int Urol Nephrol. 2022 Jan 15. doi: 10.1007/s11255-022-03104-9. Online ahead of print.

ABSTRACT

BACKGROUND: Non-muscle invasive bladder cancers (NMIBC) tend to recur and progress over time. Bacillus Calmette-Guerin (BCG) is an effective therapy for the treatment of NMIBC in that it reduces both recurrence and progression rates. The present study investigates the causes of BCG failure, with emphasis on those attributable to application errors by the practitioner and/or patient.

METHODS: The demographic and histopathological characteristics of 115 patients who underwent TUR-B for primary bladder tumors and who underwent intracavitary BCG in the postoperative period in the Urology Clinic of the İzmir Katip Çelebi University Atatürk Training and Research Hospital between January 2014 and January 2019, were analyzed retrospectively. BCG-refractory patients were compared with non-BCG refractory patients after BCG administration.

RESULTS: The extent of the tumor, and the involvement of the tumor in the bladder trigone and/or the bladder neck were found to increase significantly the likelihood of BCG refractory. When the micturition times of both groups were compared after instillation, the differences between the groups were found to be statistically significant. In the BCG-refractory patient group, the micturition time after instillation was shorter due to the tumor involvement in the trigone/bladder neck.

CONCLUSION: Some modifiable factors originating from the patient and the tumoral characteristics were found to have an effect on BCG failure. It was further determined that the time until micturition after BCG administration is an important parameter to be considered in the prevention of application deficiencies. We believe these factors should be subjected to careful consideration during patient selection and follow-up.

PMID:35032249 | DOI:10.1007/s11255-022-03104-9

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Dysfunction of CD27+IgD+ B cells correlates with aggravated systemic lupus erythematosus

Clin Rheumatol. 2022 Jan 15. doi: 10.1007/s10067-022-06051-z. Online ahead of print.

ABSTRACT

OBJECTIVE: The apoptotic signaling pathway is obviously disordered in systemic lupus erythematosus (SLE). Natural IgM (nIgM) is important in clearing apoptotic cells and preventing them from triggering deleterious autoimmunity. B-1 and innate-like B (ILBs) cells are the main nIgM producers. Human CD27+IgD+ B cells (un-switched memory B cells) are considered ILBs. However, their functional properties in SLE remain undefined.

METHODS: Peripheral blood sample of 50 SLE patients and 50 healthy controls were collected, and twelve SLE patients were assessed in a follow-up study. The amount of CD27+IgD+ B cell in each population was analyzed by flow cytometry. The IgM and IL-10 levels of CD27+IgD+ B cell were assessed by ELISPOT and qRT-PCR, respectively. SPSS 17.0 (SPSS, USA) was employed for data analysis. P < 0.05 indicated statistical significance.

RESULT: The amounts of CD27+IgD+ B cell were significantly decreased in SLE patients than healthy control (P < 0.01). CD27+IgD+ B cell amounts were positively correlated with WBC (r = 0.337, P = 0.017), platelet count (r = 0.396, P = 0.004), and serum C3 levels (r = 0.415, P = 0.003) and negatively correlated with serum creatinine levels (r = – 0.285, P = 0.045), SLEDAI(r = – 0.724, P = 0.000), and anti-dsDNA(r = – 0.477, P = 0.000). The IgM and IL-10 levels of CD27+IgD+ B in active SLE were decreased than healthy control (P < 0.001). Moreover, CD27+IgD+ B cells are increased in SLE cases after treatment than before treatment (P < 0.001).

CONCLUSION: The amounts of CD27+IgD+ B cell were significantly decreased in SLE patients compared with the healthy population, and CD27+IgD+ B cell was verified to be correlated with clinical and immunological features in SLE patients. CD27+IgD+ B cells had impaired function associated with IgM and IL-10 production in active SLE. Moreover, the amounts of CD27+IgD+ B cells were recovered to the normal level in SLE cases with treatment-related disease remission. Key Points • CD27+IgD+ B cell amounts are significantly decreased in SLE patients than healthy control. • CD27+IgD+ B cells are functionally impaired in producing natural antibody-like IgM and IL-10 in SLE patients. • CD27+IgD+ B cell amounts are correlated with clinical and immunological features in SLE.

PMID:35032222 | DOI:10.1007/s10067-022-06051-z

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Monocytes and pyrophosphate promote mesenchymal stem cell viability and early osteogenic differentiation

J Mater Sci Mater Med. 2022 Jan 15;33(1):11. doi: 10.1007/s10856-021-06639-y.

ABSTRACT

Pyrophosphate-containing calcium phosphate implants promote osteoinduction and bone regeneration. The role of pyrophosphate for inflammatory cell-mesenchymal stem cell (MSC) cross-talk during osteogenesis is not known. In the present work, the effects of lipopolysaccharide (LPS) and pyrophosphate (PPi) on primary human monocytes and on osteogenic gene expression in human adipose-derived MSCs were evaluated in vitro, using conditioned media transfer as well as direct effect systems. Direct exposure to pyrophosphate increased nonadherent monocyte survival (by 120% without LPS and 235% with LPS) and MSC viability (LDH) (by 16-19% with and without LPS). Conditioned media from LPS-primed monocytes significantly upregulated osteogenic genes (ALP and RUNX2) and downregulated adipogenic (PPAR-γ) and chondrogenic (SOX9) genes in recipient MSCs. Moreover, the inclusion of PPi (250 μM) resulted in a 1.2- to 2-fold significant downregulation of SOX9 in the recipient MSCs, irrespective of LPS stimulation or culture media type. These results indicate that conditioned media from LPS-stimulated inflammatory monocytes potentiates the early MSCs commitment towards the osteogenic lineage and that direct pyrophosphate exposure to MSCs can promote their viability and reduce their chondrogenic gene expression. These results are the first to show that pyrophosphate can act as a survival factor for both human MSCs and primary monocytes and can influence the early MSC gene expression. Graphical abstract.

PMID:35032239 | DOI:10.1007/s10856-021-06639-y

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De novo transcriptome sequencing of the northern fowl mite, Ornithonyssus sylviarum, shed light on parasitiform poultry mites evolution and its chemoreceptor repertoires

Parasitol Res. 2022 Jan 15. doi: 10.1007/s00436-022-07432-8. Online ahead of print.

ABSTRACT

The northern fowl mite (NFM), Ornithonyssus sylviarum, and the poultry red mite (PRM), Dermanyssus gallinae, are the most serious pests of poultry, both of which have an expanding global prevalence. Research on NFM has been constrained by a lack of genomic and transcriptomic data. Here, we report and analyze the first global transcriptome data across all mite live stages and sexes. A total of 28,999 unigenes were assembled, of which 19,750 (68.10%) were annotated using seven functional databases. The biological function of these unigenes was classified using the GO, KOG, and KEGG databases. To gain insight into the chemosensory receptor-based system of parasitiform mites, we furthermore assessed the gene repertoire of gustatory receptors (GRs) and ionotropic receptors (IRs), both of which encode putative ligand-gated ion channel proteins. While these receptors are well characterized in insect model species, our understanding of chemosensory detection in mites and ticks is in its infancy. To address this paucity of data, we identified 9 IR/iGluRs and 2 GRs genes by analyzing transcriptome data in the NFM, while 9 GRs and 41 IR/iGluRs genes were annotated in the PRM genome. Taken together, the transcriptomic and genomic annotation of these two species provide a valuable reference for studies of parasitiform mites and also help to understand how chemosensory gene family expansion/contraction events may have been reshaped by an obligate parasitic lifestyle compared with their free-living closest relatives. Future studies should include additional species to validate this observation and functional characterization of the identified proteins as a step forward in identifying tools for controlling these poultry pests.

PMID:35032220 | DOI:10.1007/s00436-022-07432-8

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Frequency reallocation based on cochlear place frequencies in cochlear implants: a pilot study

Eur Arch Otorhinolaryngol. 2022 Jan 15. doi: 10.1007/s00405-021-07245-y. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study is to evaluate speech perception outcomes after a frequency reallocation performed through the creation of an anatomically based map obtained with Otoplan®, a tablet-based software that allows the cochlear duct length to be calculated starting from CT images.

METHODS: Ten postlingually deafened patients who underwent cochlear implantation with MED-EL company devices from 2015 to 2019 in the Tertiary referral center University Hospital of Verona have been included in a retrospective study. The postoperative CT scans were evaluated with Otoplan®; the position of the intracochlear electrodes was obtained, an anatomical mapping was carried out and then it was submitted to the patients. All patients underwent pure tonal and speech audiometry before and after the reallocation and the audiological results were processed considering the Speech Recognition Threshold (SRT), the Speech Awareness Threshold (SAT) and the Pure Tone Average (PTA). The differences in the PTA, SAT and SRT values before and after the reallocation were determined. The results were statistically processed using the software Stata with a significance value of α < 0.05.

RESULTS: The mean values of SRT (61.25 dB versus 51.25 dB) and SAT (49 dB versus 41 dB) were significantly lower (p: 0.02 and p: 0.04, respectively) after the reallocation. No significant difference was found between PTA values (41.5 dB versus 39.25 dB; p: 0.18).

CONCLUSIONS: Our preliminary results demonstrate better speech discrimination and rapid adaptation in implanted postlingually deaf patients after anatomic mapping and subsequent frequency reallocation.

PMID:35032205 | DOI:10.1007/s00405-021-07245-y

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One in five, not one in 17, youth patients deteriorate during psychotherapy for depression

Eur Child Adolesc Psychiatry. 2022 Jan 15. doi: 10.1007/s00787-022-01941-8. Online ahead of print.

NO ABSTRACT

PMID:35032215 | DOI:10.1007/s00787-022-01941-8

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Dipeptidyl-peptidase IV inhibitor (DPP4i) confers increased odds of bullous pemphigoid even years after drug initiation

Arch Dermatol Res. 2022 Jan 15. doi: 10.1007/s00403-021-02317-9. Online ahead of print.

ABSTRACT

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case-control study was performed comparing diabetic patients with BP (n = 1458) with age-, sex- and ethnicity-matched diabetic control subjects (n = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46-2.08; P < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69-4.29; P < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33-1.84; P < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1-2 years after commencing the drug (OR, 2.66; 95% CI, 1.97-3.59; P < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09-1.91; P = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30-2.13; P < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.

PMID:35032198 | DOI:10.1007/s00403-021-02317-9