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1.
Urol Int ; : 1-7, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39084190

RESUMEN

INTRODUCTION: Studies comparing refluxing versus non-refluxing ureteric implantation in continent cutaneous urinary diversion (CCUD) are scarce and often characterized by heterogeneous study populations. This work therefore aimed at comparing both techniques regarding long-term outcomes in a propensity-scored approach. METHODS: We identified n = 19 patients, totaling n = 38 renal units (RU), who underwent CCUD surgery at our hospital out of a pool of 120 patients. Of these 38 RU, 27 RU were implanted via refluxing ureteric implantation utilizing various procedures due to special intraoperative circumstances (short ureters, damage due to radiation). In terms of preoperative renal function, a comorbidity index (Age-Adjusted Charlson Comorbidity Index [ACCI]), and gender, we compared them to n = 38 patients with a total of 76 RU with non-refluxing ureteric implantation in all RU (1:2 matching). The mean follow-up was 56 (IQR: 23-112) months. RESULTS: Long-term renal function was comparable in CCUD patients receiving refluxing versus non-refluxing ureteric implantation (estimated glomerular filtration rate: 63.11 mL/min vs. 71.7 mL/min, p = 0.22) with an average decline of 17.4 mL/min and 13.69 mL/min during the follow-up period, respectively. Also, the rate of new-onset chronic kidney disease (CKD) (both 15%, p = 1), the need for alkalizing medication, or the number of pyelonephritis episodes did not significantly differ between the groups. In Cox regression analysis, ACCI was the single most predictive parameter for the development of new-onset CKD (HR: 1.71 [1.10-2.66], p = 0.0167). None of the RU in the refluxing group needed revisional surgery concerning the ureterointestinal anastomosis, whereas 7 RU of the non-refluxing group did. CONCLUSIONS: Our study confirms that refluxing ureteric implantation in CCUDs is a valid and safe procedure regarding long-term renal, metabolic and functional outcomes. Our data also suggest that patients should be counseled according to their comorbidities regarding long-term renal function.

2.
Urol Int ; : 1-8, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39154646

RESUMEN

INTRODUCTION: Continent cutaneous urinary diversion post-cystectomy is an established approach addressing both oncological and functional indications. However, there is a noticeable gap of evidence when it comes to comparing outcomes between these indications, especially concerning the technique of Mainz pouch I (MPI). This study aimed to close the gap by analyzing the long-term functional and renal outcomes of patients with MPI after cystectomy due to both benign and malign bladder pathologies. METHODS: In this retrospective study, we examined 173 patients, who underwent MPI surgery between 2000 and 2022. Patients were categorized into a study group (benign conditions, n = 26) and a control group (bladder cancer, n = 52) using propensity score matching. Clinical demographics, surgical outcomes, and functional/renal parameters were analyzed using unpaired t tests and χ2 tests. RESULTS: Patients undergoing cystectomy with MPI due to benign bladder pathologies were significantly younger and had a lower comorbidity burden compared to those with bladder cancer. In contrast to a significantly higher incidence of chemotherapy in the oncological cohort, the long-term renal function was comparable between both populations. Surgical outcomes, revisions, and postoperative complications did not differ significantly between both groups. Nearly 90% of patients in both groups showed full continence. CONCLUSION: This study demonstrates the efficacy and safety of MPI surgery in both benign and malignant conditions, proving favorable long-term renal and functional outcomes.

3.
Urol Int ; 108(1): 49-59, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38035560

RESUMEN

INTRODUCTION: Metformin (MF) intake could be associated with a favorable outcome in sunitinib (SUT)- and axitinib (AX)-treated clear cell renal cell carcinoma (ccRCC) patients. Functionally, MF induces miR-205, a microRNA serving as a tumor suppressor in several cancers. METHODS: Real-time quantitative PCR, viability assays, and Western blotting analyzed MF and SUT/AX effects in RCC4 and 786-O cells. A tetracycline-inducible overexpression model was used to study the role of miR-205 and its known target gene, VEGFA. We analyzed miR-205 and VEGFA within a public and an in-house ccRCC cohort. Human umbilical vein endothelial cell (HUVEC) sprouting assays examined miR-205 effects on angiogenesis initiation. To determine the influence of the von Hippel-Lindau tumor suppressor (VHL), we examined VHLwt reexpressing RCC4 and 786-O cells. RESULTS: Viability assays confirmed a sensitizing effect of MF toward SUT/AX in RCC4 and 786-O cells. Overexpression of miR-205 diminished VEGFA expression - as did treatment with MF. Tumor tissue displayed a downregulation of miR-205 and an upregulation of VEGFA. Accordingly, miR-205 caused less and shorter vessel sprouts in HUVEC assays. Finally, VHLwt-expressing RCC4 and 786-O cells displayed higher miR-205 and lower VEGFA levels. CONCLUSION: Our results support the protective role of MF in ccRCC and offer functional insights into the clinical synergism with tyrosine kinase inhibitors.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Metformina , MicroARNs , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Metformina/farmacología , Línea Celular Tumoral , MicroARNs/genética , Sunitinib/farmacología , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo
4.
J Adv Nurs ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38323730

RESUMEN

AIM: To understand nurses' personal and professional experiences with the heat dome, drought and forest fires of 2021 and how those events impacted their perspectives on climate action. DESIGN: A naturalistic inquiry using qualitative description. METHOD: Twelve nurses from the interior of British Columbia, Canada, were interviewed using a semi-structured interview guide. Thematic analysis was employed. No patient or public involvement. RESULTS: Data analysis yielded three themes to describe nurses' perspective on climate change: health impacts; climate action and system influences. These experiences contributed to nurses' beliefs about climate change, how to take climate action in their personal lives and their challenges enacting climate action in their workplace settings. CONCLUSIONS: Nurses' challenges with enacting environmentally responsible practices in their workplace highlight the need for engagement throughout institutions in supporting environmentally friendly initiatives. IMPACT: The importance of system-level changes in healthcare institutions for planetary health.

5.
Qual Health Res ; 34(8-9): 717-731, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38305270

RESUMEN

Cannabis has long been stigmatized as an illicit drug. Since legalization in Canada for both medical and recreational purposes, older adults' cannabis consumption has increased more than any other age group. Yet, it is unclear how the normalization of cannabis has impacted perceptions of stigma for older adults consuming cannabis medicinally. Qualitative description was used to elucidate the experiences of older Canadians aged 60+ related to stigma and their consumption of cannabis for medicinal purposes. Data collection involved semi-structured interviews. Data analysis examined how participants managed stigma related to cannabis use. Perceived stigma was evident in many participants' descriptions of their perceptions of cannabis in the past and present, and influenced how they accessed and consumed cannabis and their comfort in discussing its use with their healthcare providers. Participants employed several distinct strategies for managing stigma-concealing, re-framing, re-focusing, and proselytizing. Findings suggest that while medical cannabis consumption is becoming increasingly normalized among older adults, stigma related to cannabis persists and continues to shape older adults' experiences. A culture shift needs to occur among healthcare providers so that they are educated about cannabis and willing to discuss the possibilities of medicinal cannabis consumption with older adults. Otherwise, older adults may seek advice from recreational or other non-medical sources. Healthcare providers require education about the use of medical cannabis, so they can better advise older adults regarding its consumption for medicinal purposes.


Asunto(s)
Marihuana Medicinal , Estigma Social , Humanos , Marihuana Medicinal/uso terapéutico , Femenino , Anciano , Masculino , Persona de Mediana Edad , Canadá , Investigación Cualitativa , Entrevistas como Asunto , Anciano de 80 o más Años , Estereotipo
6.
Int J Mol Sci ; 25(4)2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38396916

RESUMEN

Ameloblastoma is a rare tumor but represents the most common odontogenic neoplasm. It is localized in the jaws and, although it is a benign, slow-growing tumor, it has an aggressive local behavior and high recurrence rate. Therefore, alternative treatment options or complementary to surgery have been evaluated, with the most promising one among them being a targeted therapy with the v-Raf murine sarcoma viral oncogene homologue B (BRAF), as in ameloblastoma the activating mutation V600E in BRAF is common. Studies in other tumors have shown that the synchronous inhibition of BRAF and human murine double minute 2 homologue (MDM2 or HDM2) protein is more effective than BRAF monotherapy, particularly in the presence of wild type p53 (WTp53). To investigate the MDM2 protein expression and gene amplification in ameloblastoma, in association with BRAFV600E and p53 expression. Forty-four cases of ameloblastoma fixed in 10% buffered formalin and embedded in paraffin were examined for MDM2 overexpression and BRAFV600E and p53 expression by immunohistochemistry, and for MDM2 ploidy with fluorescence in situ hybridization. Sixteen of forty-four (36.36%) cases of ameloblastoma showed MDM2 overexpression. Seven of sixteen MDM2-positive ameloblastomas (43.75%) were BRAFV600E positive and fifteen of sixteen MDM2-positive ameloblastomas (93.75%) were p53 negative. All MDM2 overexpressing tumors did not show copy number alterations for MDM2. Overexpression of MDM2 in ameloblastomas is not associated with MDM2 amplification, but most probably with MAPK activation and WTp53 expression. Further verification of those findings could form the basis for the use of MDM2 expression as a marker of MAPK activation in ameloblastomas and the trial of dual BRAF/MDM2 inhibition in the management of MDM2-overexpressing/BRAFV600E-positive/WTp53 ameloblastomas.


Asunto(s)
Ameloblastoma , Proteínas Proto-Oncogénicas B-raf , Proteínas Proto-Oncogénicas c-mdm2 , Animales , Humanos , Ratones , Ameloblastoma/genética , Ameloblastoma/metabolismo , Hibridación Fluorescente in Situ , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas B-raf/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteína p53 Supresora de Tumor/genética
7.
J Vasc Surg ; 77(3): 941-956.e1, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35948244

RESUMEN

OBJECTIVE: To provide an updated systematic literature review summarizing current evidence on aortic neck dilatation (AND) after endovascular aortic aneurysm repair (EVAR) in patients with infrarenal abdominal aortic aneurysm. METHODS: An extensive electronic search in major electronic databases was conducted between January 2000 and December 2021. Eligible for inclusion were observational studies that followed up with patients (n ≥ 20) undergoing EVAR with self-expanding endografts, for 12 or more months, evaluated AND with computed tomography angiography and provided data on relevant outcomes. The primary end point was the incidence of AND after EVAR, and the secondary end points were the occurrence of type Ia endoleak, stent graft migration, secondary rupture, and reintervention. RESULTS: We included 34 studies with a total sample of 12,038 patients (10,413 men; median age, 71 years). AND was defined clearly in 18 studies, but significant differences in AND definition were evidenced. The pooled incidence of AND based on quantitative analysis of 16 studies with a total of 9201 patients (7961 men; median age, 72 years) was calculated at 22.9% (95% confidence interval [CI], 14.4-34.4) over a follow-up period ranging from 12 months to 14 years. The risk of a type Ia endoleak was significantly higher in AND patients compared with those without AND (odds ratio, 2.95; 95% CI, 1.10-7.93; P = .030). Similarly, endograft migration was more common in the AND group compared with the non-AND group (odds ratio, 5.95; 95% CI, 1.80-19.69; P = .004). The combined incidence of secondary rupture and reintervention did not differ significantly between the two groups, even though the combined effect was in favor of the non-AND group. CONCLUSIONS: Proximal AND after EVAR is common and occurs in a large proportion of patients with infrarenal abdominal aortic aneurysm. AND can influence the long-term durability of proximal endograft fixation and is significantly related to adverse outcomes, often leading to reinterventions.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Masculino , Humanos , Anciano , Implantación de Prótesis Vascular/efectos adversos , Endofuga/etiología , Resultado del Tratamiento , Dilatación/efectos adversos , Factores de Riesgo , Procedimientos Endovasculares/efectos adversos , Estudios Retrospectivos , Aneurisma de la Aorta Abdominal/cirugía , Prótesis Vascular/efectos adversos
8.
Urol Int ; 107(1): 35-45, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-34515257

RESUMEN

INTRODUCTION: Guideline recommendations are meant to help minimize morbidity and to improve the care of nonmuscle invasive bladder cancer (NMIBC) patients but studies have suggested an underuse of guideline-recommended care. The aim of this study was to evaluate the level of adherence of German and Austrian urologists to German guideline recommendations. METHODS: A survey of 27 items evaluating diagnostic and therapeutic recommendations (15 cases of strong consensus and 6 cases of consensus) for NMIBC was administered among 14 urologic training courses. Survey construction and realization followed the checklist for reporting results of internet e-surveys and was approved by an internal review board. RESULTS: Between January 2018 and June 2019, a total of 307 urologists responded to the questionnaire, with a mean response rate of 71%. The data showed a weak role of urine cytology (54%) for initial diagnostics although it is strongly recommended by the guideline. The most frequently used supporting diagnostic tool during transurethral resection of the bladder was hexaminolevulinate (95%). Contrary to the guideline recommendation, 38% of the participants performed a second resection in the case of pTa low-grade NMIBC. Correct monitoring of Bacille Calmette-Guérin (BCG) response with cystoscopy and cytology was performed by only 34% of the urologists. CONCLUSIONS: We found a discrepancy between certain guideline recommendations and daily routine practice concerning the use of urine cytology for initial diagnostics, instillation therapy with a low monitoring rate of BCG response, and follow-up care with unnecessary second resection after pTa low-grade NMIBC in particular. Our survey showed a moderate overall adherence rate of 73%. These results demonstrate the need for sharpening awareness of German guideline recommendations by promoting more intense education of urologists to optimize NMIBC care thus decreasing morbidity and mortality rates.


Asunto(s)
Neoplasias de la Vejiga Urinaria , Urología , Humanos , Vacuna BCG/uso terapéutico , Neoplasias de la Vejiga Urinaria/cirugía , Vejiga Urinaria , Encuestas y Cuestionarios , Administración Intravesical , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico
9.
Molecules ; 28(7)2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37049953

RESUMEN

The 1,2,3-dithiazole is an underappreciated scaffold in medicinal chemistry despite possessing a wide variety of nascent pharmacological activities. The scaffold has a potential wealth of opportunities within these activities and further afield. The 1,2,3-dithiazole scaffold has already been reported as an antifungal, herbicide, antibacterial, anticancer agent, antiviral, antifibrotic, and is a melanin and Arabidopsis gibberellin 2-oxidase inhibitor. These structure activity relationships are discussed in detail, along with insights and future directions. The review also highlights selected synthetic strategies developed towards the 1,2,3-dithiazole scaffold, how these are integrated to accessibility of chemical space, and to the prism of current and future biological activities.


Asunto(s)
Antibacterianos , Antivirales , Relación Estructura-Actividad , Antibacterianos/farmacología , Antivirales/farmacología , Antifúngicos/farmacología , Antifúngicos/química , Melaninas
10.
World J Microbiol Biotechnol ; 39(6): 161, 2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37067621

RESUMEN

It is well acknowledged that microplastics are a major environmental problem and that the use of plastics, both petro- and bio- based, should be reduced. Nevertheless, it is also a necessity to reduce the amount of the already spread plastics. These cannot be easily degraded in the nature and accumulate in the food supply chain with major danger for animals and human life. It has been shown in the literature that advanced oxidation processes (AOPs) modify the surface of polylactic acid (PLA) materials in a way that bacteria more efficiently dock on their surface and eventually degrade them. In the present work we investigated the influence of different AOPs (ultrasounds, ultraviolet irradiation, and their combination) on the biodegradability of PLA films treated for different times between 1 and 6 h. The pre-treated samples have been degraded using a home model compost as well as a cocktail of commercial enzymes at mesophilic temperatures (37 °C and 42 °C, respectively). Degradation degree has been measured and degradation products have been identified. Excellent degradation of PLA films has been achieved with enzyme cocktail containing commercial alkaline proteases and lipases of up to 90% weight loss. For the first time, we also report valorization of PLA into bacterial nanocellulose after enzymatic hydrolysis of the samples.


Asunto(s)
Compostaje , Plásticos , Animales , Humanos , Poliésteres , Bacterias
11.
Pharmacogenomics J ; 22(4): 211-222, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35725816

RESUMEN

The heterogeneity of psychiatric disorders and the lack of reliable biomarkers for prediction and treatments follow-up pose difficulties towards recognition and understanding of the molecular basis of psychiatric diseases. However, several studies based on NGS approaches have shown that miRNAs could regulate gene expression during onset and disease progression and could serve as potential diagnostic and pharmacogenomics biomarkers during treatment. We provide herein a detailed overview of circulating miRNAs and their expression profiles as biomarkers in schizophrenia, bipolar disorder and major depressive disorder and their role in response to specific treatments. Bioinformatics analysis of miR-34a, miR-106, miR-134 and miR-132, which are common among SZ, BD and MDD patients, showed brain enrichment and involvement in the modulation of critical signaling pathways, which are often deregulated in psychiatric disorders. We propose that specific miRNAs support accurate diagnosis and effective precision treatment of psychiatric disorders.


Asunto(s)
Trastorno Depresivo Mayor , Trastornos Mentales , MicroARNs , Biomarcadores , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/genética , MicroARNs/genética , Farmacogenética
12.
J Oral Pathol Med ; 51(7): 649-658, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35665542

RESUMEN

BACKGROUND: Odontogenic keratocyst is characterized by local aggressive behavior and a high recurrence rate, as well as its potential to develop in association with the basal cell nevus syndrome. The aim of this study was to decode the gene expression program accompanying odontogenic keratocyst phenotype. METHODS: 150-bp paired-end RNA-sequencing was applied on six sporadic and six basal cell nevus syndrome-associated whole-tissue odontogenic keratocyst samples in comparison to six dental follicles, coupled with bioinformatics and complemented by immunohistochemistry. RESULTS: 2654 and 2427 differentially expressed genes were captured to characterize the transcriptome of sporadic and basal cell nevus syndrome-associated odontogenic keratocysts, respectively. Gene ontologies related to "epidermis/skin development" and "keratinocyte/epidermal cell differentiation" were enriched among the upregulated genes (KRT10, NCCRP1, TP63, GRHL3, SOX21), while "extracellular matrix organization" (ITGA5, LOXL2) and "odontogenesis" (MSX1, LHX8) gene ontologies were overrepresented among the downregulated genes in odontogenic keratocyst. Interestingly, upregulation of various embryonic stem cells markers (EPHA1, SCNN1A) and genes committed in cellular reprogramming (SOX2, KLF4, OVOL1, IRF6, TACSTD2, CDH1) was found in odontogenic keratocyst. These findings were highly shared between sporadic and basal cell nevus syndrome-associated odontogenic keratocysts. Immunohistochemistry verified SOX2, KLF4, OVOL1, IRF6, TACSTD2/TROP2, CDH1/E-cadherin, and p63 expression predominantly in the odontogenic keratocyst suprabasal epithelial layers. CONCLUSION: The odontogenic keratocyst transcriptomic profile is characterized by a prominent epidermal and dental epithelial fate, a repressed dental mesenchyme fate combined with deregulated extracellular matrix organization, and enhanced stemness gene signatures. Thus, we propose a developed epidermis-like phenotype in the odontogenic keratocyst suprabasal epithelial cells, established in parallel to a significant upregulation of marker genes related to embryonic stem cells and cellular reprogramming.


Asunto(s)
Síndrome del Nevo Basocelular , Quistes Odontogénicos , Tumores Odontogénicos , Síndrome del Nevo Basocelular/genética , Expresión Génica , Humanos , Factores Reguladores del Interferón/genética , Recurrencia Local de Neoplasia , Quistes Odontogénicos/genética , Quistes Odontogénicos/patología , Tumores Odontogénicos/genética , Tumores Odontogénicos/patología , Fenotipo
13.
Urol Int ; 106(11): 1150-1157, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35158357

RESUMEN

INTRODUCTION: The aim of this study was to test for differences in overall (OS) and progression-free survival (PFS) rates and toxicity in first-line immune checkpoint inhibition (IO) combination therapy in metastatic renal-cell carcinoma (mRCC) patients. METHODS: Between November 2017 and April 2021, 104 patients with histologically confirmed mRCC from 6 tertiary referral centers with either IO + IO (nivolumab + ipilimumab, n = 68) or IO + tyrosine kinase inhibitor (TKI) (pembrolizumab + axitinib, n = 36) were included. Kaplan-Meier and Cox regression analyses tested for OS and PFS differences. RESULTS: Of 104 mRCC patients, 68 received IO + IO (65.4%) and 36 IO + TKI (34.6%) therapy, respectively. Median age was 67 years (interquartile range: 57-70.3). Patients receiving IO + TKI were less likely to be poor risk according to the International Metastatic Renal-Cell Carcinoma Database Consortium score (16.7 vs. 30.9%) and presented with lower T-stage, compared to IO + IO treated patients. Median PFS was 9.8 months (CI: 5.3-17.6) versus 12.3 months (CI: 7.7 - not reached) for IO + IO versus IO + TKI treatment, respectively (p = 0.22). Median OS was not reached, survival rates at 12 months being 73.9 versus 90.0% for IO + IO versus IO + TKI patients (p = 0.089). In subgroup analyses of elderly patients (≥70 years, n = 38), IO + TKI treatment resulted in better OS rates at 12 months compared to IO + IO (91.0 vs. 57.0%; p = 0.042). CONCLUSION: IO + IO and IO + TKI as first-line therapies in mRCC patients were both comparable as for the oncological outcome and toxicity.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Anciano , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Supervivencia sin Progresión
14.
J Comput Chem ; 42(1): 6-18, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33009851

RESUMEN

In hybrid particle-field (hPF) simulations (J. Chem. Phys., 2009 130, 214106), the entangled dynamics of polymer melts is lost due to chain crossability. Chains cross, because the field-treatment of the nonbonded interactions makes them effectively soft-core. We introduce a multi-chain slip-spring model (J. Chem. Phys., 2013 138, 104907) into the hPF scheme to mimic the topological constraints of entanglements. The structure of the polymer chains is consistent with that of regular molecular dynamics simulations and is not affected by the introduction of slip-springs. Although slight deviations are seen at short times, dynamical properties such as mean-square displacements and reorientational relaxation times are in good agreement with traditional molecular dynamics simulations and theoretical predictions at long times.

15.
Clin Endocrinol (Oxf) ; 94(3): 413-423, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33340135

RESUMEN

OBJECTIVE: To report the clinical presentation, management and outcomes of young patients with prolactinomas (<20 years) and conduct a systematic review and meta-analysis. PATIENTS AND DESIGN: Clinical, biochemical and radiological data (1996-2018) were collected from our centre. A systematic review and meta-analysis of published literature (1994-2019) on prolactinoma (age <20 years) were conducted. Both random and fixed effects meta-analysis were used to pool outcomes across studies. RESULTS 1 CASE SERIES: Twenty-two patients (14 females) were identified; median age at diagnosis 15.7 years (range 13-19); 12 patients (6 females) had a macroprolactinoma. Seven patients (macroprolactinoma-6) had associated pituitary hormone deficiencies at presentation. Five patients (4 males) underwent surgical resection due to poor response to cabergoline or apoplexy. Patients undergoing surgery had larger tumours (p < .02) and higher serum prolactin concentration (p < .005). All patients with macroprolactinoma >20 mm required surgical intervention. RESULTS 2 SYSTEMATIC REVIEW AND META-ANALYSIS: We selected 11 studies according to strict inclusion criteria describing 275 patients. Macroprolactinoma was more common in girls (78.7% [95% CI 70.5-85.9]) than boys and was more frequent than microprolactinoma (56.6% [95% CI 48.4-64.5]). In males, only 6/57 (10.5%) of tumours were microprolactinoma as compared to 102/198 (51.5%) microprolactinoma in females (risk difference -0.460; [95% CI -0.563 to -0.357]; p < .001). Surgery was first-line therapy in 18.9% patients, with another 15.4% requiring it as a second line (overall 31.3%). CONCLUSIONS: Macroprolactinoma, particularly if >20 mm, usually requires multimodal therapy including surgical intervention. While overall prolactinomas in <20 years age group are more common in females, the proportion of macroprolactinoma vs microprolactinoma is greater in males, particularly for large invasive tumours. Microprolactinoma is a rare diagnosis in adolescent males.


Asunto(s)
Neoplasias Hipofisarias , Prolactinoma , Adolescente , Adulto , Factores de Edad , Cabergolina , Agonistas de Dopamina , Femenino , Humanos , Masculino , Neoplasias Hipofisarias/patología , Neoplasias Hipofisarias/terapia , Prolactina , Prolactinoma/patología , Prolactinoma/terapia , Adulto Joven
16.
J Org Chem ; 86(8): 5702-5713, 2021 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-33818096

RESUMEN

2-[(3,5-Dichloro-4H-1,2,6-thiadiazin-4-ylidene)amino]benzamides are cyclized to benzo[e][1,2,6]thiadiazino[3,4-b][1,4]diazepin-10(11H)-ones via (i) treatment with NaH and via (ii) Pd-catalyzed C-N coupling. The behavior of the latter toward nucleophiles and thermal, oxidative, and reductive conditions revealed unexpected transformations to 3,5-dioxo-4,5-dihydro-3H-benzo[e][1,4]diazepine-2-carbonitrile and 2-(4-substituted-1,2,5-thiadiazol-3-yl)quinazolin-4(3H)-ones.

17.
Int J Hyperthermia ; 38(1): 511-522, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33784924

RESUMEN

Objective: In magnetic particle hyperthermia, a promising least-invasive cancer treatment, malignant regions in proximity with magnetic nanoparticles undergo heat stress, while unavoidably surrounding healthy tissues may also suffer from heat either directly or indirectly by the induced eddy currents, due to the developed electric fields as well. Here, we propose a facile upgrade of a typical magnetic particle hyperthermia protocol, to selectively mitigate eddy currents' heating without compromising the beneficial role of heating in malignant regions.Method: The key idea is to apply the external magnetic field intermittently (in an ON/OFF pulse mode), instead of the continuous field mode typically applied. The parameters of the intermittent field mode, such as time intervals (ON time: 25-100 s, OFF time: 50-200 s, Duty Cycle:16-100%) and field amplitude (30-70 mT) are optimized based on evaluation on healthy tissue and cancer tissue phantoms. The goal is to sustain in cancer tissue phantom the maximum temperature increase (preferably within 4-8°C above body temperature of 37°C), while in the healthy tissue phantom temperature variation is suppressed far below the 4°C dictating the eddy current mitigation.Results: Optimum conditions of intermittent field (ON/OFF: 50/100 in s, Duty Cycle: 33%, magnetic field: 45mT) are then examined in ex-vivo samples verifying the successful suppression of eddy currents. Simultaneously, a well-elaborated theoretical approach provides a rapid calculation of temperature increase and, furthermore, the ability to quickly simulate a variety of duty cycle times and field controls may save experimental time.Conclusion: Eventually, the application of an intermittent field mode in a magnetic particle hyperthermia protocol, succeeds in eddy current mitigation in surrounding tissues and allows for the application of larger field amplitudes that may augment hyperthermia efficiency without objecting typical biomedical applicability field constraints such as Brezovich criterion.


Asunto(s)
Hipertermia Inducida , Humanos , Hipertermia , Campos Magnéticos , Magnetismo , Temperatura
18.
Ann Vasc Surg ; 72: 498-506, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32949740

RESUMEN

BACKGROUND: We aimed to investigate whether the transfusion of 2 units of fresh frozen plasma (FFP) immediately post aneurysm exclusion has any effect on the perioperative fibrinogen levels and the outcome of patients undergoing elective endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). METHODS: Consecutive infrarenal AAA patients undergoing elective EVAR with the bifurcated Endurant-II stent-graft (Medtronic) were recruited from 2 vascular units. The first unit has a routine policy of administering 2 units of FFP immediately upon aneurysm exclusion (FFP group), whereas the second unit has no such policy (control group). Serum fibrinogen levels were measured on admission and 24 hr post-EVAR and the perioperative change in fibrinogen (Δfib) was calculated (24-hr postoperative minus preoperative fibrinogen). The 2 groups were compared with regards to the perioperative fibrinogen levels (preoperative, 24-hr postoperative, and Δfib) and the outcome (endoleaks, reinterventions, major adverse cardiovascular events, death) during follow up. RESULTS: A total of 70 patients (41 in the FFP group, 29 controls) were examined. There were 68 men, the mean age was 70 ± 7 years and the maximum AAA diameter was 63.3 ± 13.8 mm. During the follow up (34 ± 19 months), a total of 6 endoleaks were recorded (2 type Ia, 2 type Ib and 1 type II). Mean preoperative fibrinogen, 24-hr postoperative fibrinogen and Δfib was 391.1 ± 92.8 mg/dL, 367.7 ± 97.8 mg/dL and -23.5 ± 51.02 mg/dL, respectively. There was a trend for the fibrinogen to fall 24 hr postprocedure, but this was not statistically significant (P = 0.07). There was a weak negative association between Δfib and endoleaks (P = 0.007, r = -0.29). Compared to controls, the FFP group had a higher 24-hr postoperative fibrinogen (401.8 ± 112.9 mg/dL vs. 319.3 ± 34.9 mg/dL, P < 0.0001) and a lower Δfib (-3.00 ± 56.01 mg/dL vs. -52.48 ± 21.15 mg/dL, P < 0.0001). No significant difference was observed between the 2 groups with regards to endoleaks, reinterventions, major adverse cardiovascular events, or deaths. CONCLUSIONS: Transfusion of 2 units of FFP postaneurysm exclusion prevents a significant drop in plasma fibrinogen 24 hr post-EVAR, but the impact on clinical outcome has yet to be defined.


Asunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Fibrinógeno/metabolismo , Intercambio Plasmático , Plasma , Anciano , Aneurisma de la Aorta Abdominal/sangre , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/mortalidad , Biomarcadores/sangre , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Procedimientos Quirúrgicos Electivos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Grecia , Humanos , Masculino , Persona de Mediana Edad , Intercambio Plasmático/efectos adversos , Intercambio Plasmático/mortalidad , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/cirugía , Reoperación , Factores de Tiempo , Resultado del Tratamiento
19.
Orthod Craniofac Res ; 24(2): 206-213, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32991769

RESUMEN

The role of thyroxine administration on orthodontically induced tooth movement and/or inflammatory root resorption remains unclear. The aim was to assess the influence of thyroxine administration on orthodontically induced tooth movement and/or inflammatory root resorption. The study protocol was registered in PROSPERO (CRD42020164151). An electronic search of indexed databases was conducted without time or language restrictions up to and including May 2020. The following eligibility criteria were imposed: (a) original prospective controlled clinical studies and/or experimental studies on animal models; (b) subjects undergoing orthodontic therapy with fixed appliances; (c) presence of a control group [orthodontic tooth movement without thyroxine administration]; and (d) intervention: orthodontic tooth movement with thyroxine administration. Review articles, commentaries, letters to the editor, case reports/series, studies with no control group, cross-sectional studies, retrospective studies and studies where thyroxine was administered along with other interventions such as calcitonin and prostaglandins were excluded. Quality of available evidence and risk of bias within studies were assessed. Any disagreements were resolved via consensus discussions. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 8 animal studies were included. Four studies reported that thyroxine administration increases the rate of orthodontic tooth movement; 3 studies did not show a significant difference. Three studies showed that thyroxine administration decreases orthodontically induced inflammatory root resorption; 2 studies found no significant difference. The risk of bias among studies was high. In conclusion, the influence of thyroxine administration on orthodontic tooth movement and/or orthodontically induced inflammatory root resorption in animal models remains unclear.


Asunto(s)
Resorción Radicular , Animales , Estudios Transversales , Suplementos Dietéticos , Estudios Prospectivos , Estudios Retrospectivos , Resorción Radicular/etiología , Resorción Radicular/prevención & control , Tiroxina , Técnicas de Movimiento Dental
20.
Urol Int ; 105(5-6): 477-482, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33535223

RESUMEN

BACKGROUND: Complex soft tissue defects involving the lower abdomen, perineum, and groin (LAPG) represent reconstructive challenges following urologic surgery. Consequently, these often require an interdisciplinary approach involving plastic surgery. While pedicled flaps from the lower abdomen are a reliable option, previous placement of colostomies and urinary urostomies renders these flap types unavailable. Here, the pedicled anterolateral thigh perforator (ALT) flap represents a reliable pedicled alternative which can harvest from the thigh. MATERIALS AND METHODS: A retrospective data analysis of pedicled perforator flaps harvested from the thigh to reconstruct soft tissue defects was conducted. Seven patients treated in the urology department with soft tissue defects following tumor resection, infection, and dehiscence were included. RESULTS: In all patients, the ALT flap was utilized successfully to reconstruct soft tissue defects up to 450 cm2 in size. All flaps survived. In 1 case, prolonged wound healing was observed. All defects were adequately addressed with no recurrence of dehiscence or fistula formation. CONCLUSIONS: Pedicled perforator flaps represent a valid option for the soft tissue reconstruction of the lower abdomen and perineum when a pedicled rectus abdominis flap is no longer available. This flap is, therefore, a good option in an interdisciplinary approach to soft tissue reconstruction, especially following urologic surgery, which is predominantly performed in the LAPG region.


Asunto(s)
Abdomen/cirugía , Ingle/cirugía , Colgajo Perforante , Procedimientos de Cirugía Plástica/métodos , Procedimientos Quirúrgicos Urológicos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Muslo/cirugía
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