Some minimally invasive techniques have been introduced to decrease morbidity related to standard laparoscopic procedures. One such approach is laparoendoscopic single-site surgery (LESS), which can ...also be applied for transvesical surgery. The aim of the study was to present our initial clinical experience of using this technique for transvesical vesicovaginal fistula (VVF) repair. In August 2011, we carried out the LESS repair of a 3-mm in diameter vesicovaginal fistula on a 72-year-old woman, who failed the conservative treatment with Foley placement. The procedure was performed transvesically (percutaneous intraluminal approach) with a single-port device (4-channel, TriPort+, Olympus Winter&IBE GMBH) via a 1.5-cm incision made 2 cm above the pubic symphysis. A standard 10-mm optic and straight laparoscopic instruments were used. The fistulous tract was dissected and partially excised. The bladder and vaginal wall defects were closed in two layers with running absorbable V-Loc (Covidien, Norwalk, CT, USA) suture. Ureteral catheters were left for 5 days and the Foley catheter for 14 days. The operative time was 170 min. The blood loss was minimal. No complications were observed. The postoperative period was uneventful. During a 6-month follow-up the patient reported no involuntary discharge of urine into the vagina. Diagnostic scans revealed no presence of VVF and laboratory examination results were all within the normal range. Although substantial development of the instruments and skills is needed, the transvesical LESS vesicovaginal fistula repair appeared to be feasible and safe. Nevertheless, further experience and observations are necessary.
Aim
We wanted to investigate serum levels of ghrelin and leptin – appetite‐regulating hormones – and their correlation with the nutritional status of children with neurogenic bladder (NB) due to ...myelomeningocele (MMC) in comparison to healthy individuals.
Methods
This prospective analysis was conducted on 67 children with NB after MMC and 20 healthy children. Children's medical charts were analysed to determine age, gender, anthropometric measurements, body mass index (BMI), activity assessment using Hoffer's scale and renal function parameters. Serum total ghrelin and leptin levels were measured using the enzyme‐linked immunosorbent assay.
Results
There were no differences in the age, gender, weight and BMI between the studied groups. Median serum levels of ghrelin and leptin were higher compared with the reference group. A significant negative correlation between serum leptin concentration and Hoffer's scale was found in children with NB.
Conclusions
Elevated levels of leptin and ghrelin could be considered factors influencing nutritional status in children with NB due to MMC. Children with NB after MMC may have disturbed endocrine regulation of energy homeostasis. Physical activity may be the factor that affects serum leptin concentration.
Acute myeloid leukemia (AML) remains a therapeutic challenge, and a paucity of tumor-specific targets has significantly hampered the development of effective immune-based therapies. Recent ...paradigm-changing studies have shown that natural killer (NK) cells exhibit innate memory upon brief activation with IL-12 and IL-18, leading to cytokine-induced memory-like (CIML) NK cell differentiation. CIML NK cells have enhanced antitumor activity and have shown promising results in early phase clinical trials in patients with relapsed/refractory AML. Here, we show that arming CIML NK cells with a neoepitope-specific chimeric antigen receptor (CAR) significantly enhances their antitumor responses to nucleophosphmin-1 (NPM1)-mutated AML while avoiding off-target toxicity. CIML NK cells differentiated from peripheral blood NK cells were efficiently transduced to express a TCR-like CAR that specifically recognizes a neoepitope derived from the cytosolic oncogenic NPM1-mutated protein presented by HLA-A2. These CAR CIML NK cells displayed enhanced activity against NPM1-mutated AML cell lines and patient-derived leukemic blast cells. CAR CIML NK cells persisted in vivo and significantly improved AML outcomes in xenograft models. Single-cell RNA sequencing and mass cytometry analyses identified up-regulation of cell proliferation, protein folding, immune responses, and major metabolic pathways in CAR-transduced CIML NK cells, resulting in tumor-specific, CAR-dependent activation and function in response to AML target cells. Thus, efficient arming of CIML NK cells with an NPM1-mutation-specific TCR-like CAR substantially improves their innate antitumor responses against an otherwise intracellular mutant protein. These preclinical findings justify evaluating this approach in clinical trials in HLA-A2
AML patients with NPM1c mutations.
BackgroundResponses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell-based therapy is a ...promising modality to treat post-HCT relapse.MethodsWe initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. High-resolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion.ResultsIn the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires.ConclusionGiven their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies.Trial RegistrationClinicalTrials.gov NCT04024761.FundingDunkin' Donuts, NIH/National Cancer Institute, and the Leukemia and Lymphoma Society.
Objectives: To describe a modification of the index of clinical consequences of untreated dental caries pulpal involvement, ulceration, fistula and abscess (PUFA/pufa) index to pulpal ...involvement-roots-sepsis (PRS/prs) and to compare the two indices using the example of caries in primary molar teeth in children aged 6-8 years. Subjects andMethods: The study sample included 542 children aged 6-8 years, from five randomly selected schools in the Bialystok District, Poland. The occurrence of clinical consequences of untreated caries in deciduous molars using the pufa and prs indices was evaluated. Data were analysed to express the prevalence, the experience and the distribution of particular pufa and prs codes in the sample population. The differences in layout of the pufa and prs components were expressed. Results: The response rate was 77.6%. The prevalence of the clinical consequences of untreated caries was 40.77%, mean pufa and prs were the same (0.85 ± 1.33). According to the pufa index, the following mean values were obtained: p = 0.79, u = 0.01, f = 0.04 and a = 0.01. For the prs index, the mean values were as follows: p = 0.45, r = 0.35 and s = 0.05. Conclusion: The proposed prs index was a useful epidemiological instrument for the evaluation of the clinical consequences of untreated caries in the surveyed population. The PRS instrument could be a good alternative to the PUFA index.
The crucial issue for defining successful natural killer (NK)-based anticancer therapy is the ability of tumor cells to activate resistance mechanisms leading to escape from NK-mediated killing. It ...is now well established that such mechanisms are likely evolved under hypoxia in the tumor microenvironment. Here, we show that hypoxia-induced autophagy impairs breast cancer cell susceptibility to NK-mediated lysis and that this impairment is reverted by targeting autophagy. We provide evidence that activation of autophagy in hypoxic cells is involved in selective degradation of the pro-apoptotic NK-derived serine protease GZMB/granzyme B, thereby blocking NK-mediated target cell apoptosis. Our in vivo data validate the concept that targeting autophagy in cancer cells promotes tumor regression by facilitating their elimination by NK cells. This study provides a cutting-edge advance in our understanding of how hypoxia-induced autophagy impairs NK-mediated lysis and might pave the way for formulating more effective NK-based antitumor therapy by combining autophagy inhibitors.
Background: Hepatocyte growth factor (HGF), endogenous cytokine with pleiotropic repairing and regeneration properties in relation to most tissues and organs, contributes to the progression of ...periodontal disease (PD). Furthermore, PD is a significant health problem in patients with chronic renal failure (CRF). The role of HGF in the development of PD in this specific population was not a subject of research so far. Material and methods: The following groups were enrolled in the study: (1) 26 chronic hemodialysis (HD) subjects, (2) 26 patients treated by continuous ambulatory peritoneal dialysis (CAPD), (3) 28 predialysis CRF patients, (4) 26 subjects with advanced PD (without coexisting diseases), and (5) 20 healthy subjects without PDs. HGF level in saliva was measured using the immunoenzymatic method. Gingival index, papillary bleeding index, plaque index, and the loss of clinical attachment level were evaluated. Results: The HGF level in saliva of HD patients was twice higher than in that of subjects with healthy periodontium. Direct relationships between proper HGF level in saliva and the indices GI, PBI, and PI in CAPD-treated patients and with more severe PD were shown. It was found that PD is most advanced in HD patients, moderately in CAPD-treated patients and to the smallest extent in predialysis CRF patients. Conclusions: The HGF level in mixed saliva is the index of PD progression in subjects without renal failure and in CAPD-treated patients. PD is common in renal failure patients and is a significant problem concerning general health status.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The aim of the study was to determine oral health-related quality of life (OHRQoL) using the measures Geriatric/General Oral Health Assessment (GOHAI) and Oral Health Impact Profile (OHIP-14) in ...relation to missing teeth in the Polish population aged 20-79. This was a cross-sectional study carried out among 1112 randomly selected participants. The mean age was 48.72 and mean number of teeth was 20.12. Altogether, in the GOHAI, the percentage that gave a positive response to each question ranged from 3.3% to 48.0%; in the OHIP-14, these answers ranged from 2.4% to 25.1%. The GOHAI measure was statistically significant, with more grouping variables than the OHIP-14 measure. Both measures showed significant associations with gender, age, dry mouth, education, professional status, number of teeth, and upper and lower total dentures. We detected a significant relationship between oral health-related quality of life and the factors influencing the presence or absence of dentition. Missing teeth were statistically associated with GOHAI, OHIP-14, advanced age, self-reported dry mouth, lower education, higher Body Mass Index (BMI), lower professional status, diabetes, myocardial infraction, and total dentures in upper or/and lower jaws. However, edentulous individuals had two times higher risk of having an OHIP-14 score above the median. This suggests that oral health practitioners should work to prevent oral diseases that lead to tooth loss in their patients, starting from an early age.
Periodontitis (PD), a widespread chronic infectious disease, compromises oral health and is associated with various systemic conditions and hematological alterations. Yet, to date, it is not clear ...whether serum protein profiling improves the assessment of PD. We collected general health data, performed dental examinations, and generated serum protein profiles using novel Proximity Extension Assay technology for 654 participants of the Bialystok PLUS study. To evaluate the incremental benefit of proteomics, we constructed two logistic regression models assessing the risk of having PD according to the CDC/AAP definition; the first one contained established PD predictors, and in addition, the second one was enhanced by extensive protein information. We then compared both models in terms of overall fit, discrimination, and calibration. For internal model validation, we performed bootstrap resampling (n = 2000). We identified 14 proteins, which improved the global fit and discrimination of a model of established PD risk factors, while maintaining reasonable calibration (area under the curve 0.82 vs 0.86; P < 0.001). Our results suggest that proteomic technologies offer an interesting advancement in the goal of finding easy-to-use and scalable diagnostic applications for PD that do not require direct examination of the periodontium.
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