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1.
Diagnostics (Basel) ; 14(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-39001249

RESUMO

Hyperparathyroidism (HPT) with hypercalcemia, often deemed irreversible and detrimental to graft survival post-kidney transplantation (KT), prompts pre-transplant parathyroidectomy in hypercalcemic patients. In this retrospective analysis of 1212 kidney transplant recipients (KTRs) between 2006 and 2019, the incidence and effect of persistent HPT and hypercalcemia on graft and patient survival, and risk factors for persistence were analyzed until 60 months of follow up (FU). At KT, 5.7% (n = 69) had no HPT, 32.7% (n = 396) had HPT without hypercalcemia and 37.0% (n = 448) had HPT with hypercalcemia. At 2 years FU, 26.4% (n = 320) of patients had no HPT and 6% (n = 73) had HPT with hypercalcemia. Dialysis and dialysis duration were linked to HPT development, while dialysis, KT waiting time and donor type correlated with persisting hypercalcemia after KT. KTRs with normalized PTH and recovered hypercalcemia had improved death-censored graft survival (p < 0.001) and overall patient survival (p < 0.001). HPT with hypercalcemia is frequent at time of KT with normalization of PTH and calcium in a substantial proportion of patients after a KT. These findings question the routine pre-KT parathyroidectomy for suspected parathyroid autonomy. Persisting HPT, especially with hypercalcemia, adversely affects graft and patient survival, suggesting the need for more aggressive treatment of HPT, especially in cases of persisting hypercalcemia.

2.
Front Surg ; 11: 1415010, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826811

RESUMO

Introduction: In recent years advances have been made in the microsurgical treatment of congenital or acquired central lymphatic lesions. While acquired lesions can result from any surgery or trauma of the central lymphatic system, congenital lymphatic lesions can have a variety of manifestations, ranging from singular thoracic duct abnormalities to complex multifocal malformations. Both conditions may cause recurrent chylous effusions and downstream lymphatic congestion depending on the anatomical location of the thoracic duct lesion and are associated with an increased mortality due to the permanent loss of protein and fluid. Methods: We present a case series of eleven patients undergoing central lymphatic reconstruction, consisting of one patient with a cervical iatrogenic thoracic duct lesion and eleven patients with different congenital thoracic duct lesions or thrombotic occlusions. Results: Anastomosis of the thoracic duct and a nearby vein was performed on different anatomical levels depending on the underlying central lymphatic pathology. Cervical (n = 4), thoracic (n = 1) or abdominal access (n = 5) was used for central lymphatic reconstruction with promising results. In 9 patients a postoperative benefit with varying degrees of symptom regression was reported. Conclusion: The presented case series illustrates the current rapid advances in the field of central microsurgical reconstruction of lymphatic lesions alongside the relevant literature.

3.
J Vasc Surg Venous Lymphat Disord ; : 101934, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925528

RESUMO

OBJECTIVE: Vascularized lymph node transfer (VLNT) has become an important surgical technique in the treatment of lymphedema. Considering the different available regions available for flap harvest, we aimed to analyze different donor sites for VLNT with respect to donor-site morbidity, impact on limb volume and patient-reported outcome measurements (PROMs). METHODS: A single-center prospective study on all patients receiving VLNT at the Department of Plastic Surgery and Hand Surgery of the University Hospital Zurich between September 2016 and 2023 was conducted. Lymph nodes were harvested either from the omentum (GE-VLNT), the lateral thoracic wall (LTW) or the superficial inguinal region (SI-VLNT). Volume measurements and PROMs were assessed preoperatively and at different postoperative intervals. RESULTS: Overall, 70 patients with upper limb lymphedema (21%) or lower limb lymphedema (79%) with different lymphedema stages were included. 49 patients received GE-VLNT, followed by LTW-VLNT (n = 16) and SI-VLNT (n = 5). Lymph node harvest from the superficial inguinal region was associated with a significantly higher frequency of seroma development. Average percentage volume loss related in comparison to the preoperative volume of the affected limb was 9% after GE-VLNT, 10% after LTW-VLNT and 5% after SI-VLNT without a significant difference between the groups. PROMs revealed significant improvements for physical functioning, symptoms and psychological well-being, with no difference between VLNT techniques. CONCLUSIONS: VLNT leads to a significant improvement of quality of life and can effectively reduce limb volume, regardless of the selection of donor-site. GE-VLNT has become our flap of choice due to its low donor-site morbidity and its properties that allow a double transplantation while avoiding a second donor-site.

4.
Am J Otolaryngol ; 45(4): 104315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701728

RESUMO

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.


Assuntos
Colina , Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Colina/análogos & derivados , Idoso , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/complicações , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Valor Preditivo dos Testes , Ultrassonografia/métodos , Sensibilidade e Especificidade , Radioisótopos de Flúor , Compostos Radiofarmacêuticos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38605427

RESUMO

CONTEXT: Treatment options for advanced neuroendocrine tumors (NETs), pheochromocytomas and paragangliomas (together PPGLs) are still limited. In recent years, anti-tumor effects of cannabinoids have been reported; however, there are only very limited data available in NETs or PPGLs. OBJECTIVE: Investigation of the effects of cannabidiol (CBD) on patient-derived human NET/PPGL primary cultures and on NET/PPGL cell lines. METHODS: We established primary cultures derived from 46 different patients with PPGLs (n = 35) or NETs (n = 11) who underwent tumor resection at two centers. Treatment of patient primary cultures with clinically relevant doses (5 µM) and slightly higher doses (10 µM) of CBD was performed. RESULTS: We found opposing effects of 5 µM CBD: significant anti-tumor effects in 5/35 (14%) and significant tumor-promoting effects in 6/35 (17%) of PPGL primary cultures. In terms of anti-tumor effects, cluster 2-related PPGLs showed significantly stronger responsivity to CBD compared to cluster 1-related PPGLs (p = 0.042). Of the cluster 2-related tumors, NF1 PPGLs showed strongest responsivity (4/5 PPGL primary cultures with a significant decrease in cell viability were NF1-mutated). We also found opposing effects of 10 µM CBD in PPGLs and NETs: significant anti-tumor effects in 9/33 of PPGL (27%) and 3/11 of NET (27%) primary cultures, significant tumor-promoting effects in 6/33 of PPGL (18%) and 2/11 of NET (18%) primary cultures. CONCLUSIONS: We suggest a potential novel treatment option for some NETs/PPGLs, but also provide evidence for caution when applying cannabinoids as supportive therapy for pain or appetite management to cancer patients, and possibly as health supplements.

6.
J Affect Disord ; 356: 385-393, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38615844

RESUMO

Bipolar disorder (BD) is a leading cause of disability worldwide, as it can lead to cognitive and functional impairment and premature mortality. The first episode of BD is usually a depressive episode and is often misdiagnosed as major depressive disorder (MDD). Growing evidence indicates that peripheral immune activation and inflammation are involved in the pathophysiology of BD and MDD. Recently, by developing a panel of RNA editing-based blood biomarkers able to discriminate MDD from depressive BD, we have provided clinicians a new tool to reduce the misdiagnosis delay observed in patients suffering from BD. The present study aimed at validating the diagnostic value of this panel in an external independent multicentric Switzerland-based cohort of 143 patients suffering from moderate to major depression. The RNA-editing based blood biomarker (BMK) algorithm developped allowed to accurately discriminate MDD from depressive BD in an external cohort, with high accuracy, sensitivity and specificity values (82.5 %, 86.4 % and 80.8 %, respectively). These findings further confirm the important role of RNA editing in the physiopathology of mental disorders and emphasize the possible clinical usefulness of the biomarker panel for optimization treatment delay in patients suffering from BD.


Assuntos
Algoritmos , Biomarcadores , Transtorno Bipolar , Transtorno Depressivo Maior , Edição de RNA , Humanos , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Biomarcadores/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Diagnóstico Diferencial , Estudos de Coortes , Sensibilidade e Especificidade , Suíça
7.
Diagnostics (Basel) ; 14(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38472977

RESUMO

BACKGROUND: Iatrogenic injury of the parathyroid glands is the most frequent complication after total thyroidectomy. OBJECTIVE: To determine the effectiveness of near-infrared autofluorescence (NIRAF) in reducing postoperative hypocalcemia following total thyroidectomy. METHODS: PubMed, Scopus, and Google Scholar databases were searched. Randomised trials reporting at least one hypocalcemia outcome following total thyroidectomy using NIRAF were included. RESULTS: The qualitative data synthesis comprised 1363 patients from nine randomised studies, NIRAF arm = 636 cases and non-NIRAF arm = 637 cases. There was a statistically significant difference in the overall rate of hypocalcemia log(OR) = -0.7 [(-1.01, -0.40), M-H, REM, CI = 95%] and temporary hypocalcemia log(OR) = -0.8 [(-1.01, -0.59), M-H, REM, CI = 95%] favouring the NIRAF. The difference in the rate of permanent hypocalcemia log(OR) = -1.09 [(-2.34, 0.17), M-H, REM, CI = 95%] between the two arms was lower in the NIRAF arm but was not statistically significant. CONCLUSIONS: NIRAF during total thyroidectomy helps in reducing postoperative hypocalcemia. Level of evidence-1.

8.
Cancers (Basel) ; 15(23)2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38067274

RESUMO

Transthoracic esophagectomy results in a radical change in foregut anatomy with multiple consequences for digestive physiology. The aim of this study was to identify factors associated with poor functional outcomes by assessing multiple dimensions of digestive performance and health-related quality of life (HRQL). Patients with cancer-free survival after Ivor Lewis esophagectomy were included. Four functional syndromes (dysphagia, gastroesophageal reflux disease (GERD), delayed gastric conduit emptying (DGCE), and dumping syndrome (DS)) and HRQL were assessed using specifically designed questionnaires. Patient outcomes were compared with healthy controls. Independent factors associated with poor digestive performance were identified through multivariable analysis. Sixty-five postoperative patients and 50 healthy volunteers participated in this study. Compared with controls, patients had worse outcomes for dysphagia, GERD, DS, and HRQL, but not for DGCE. A multivariate analysis showed a significant correlation of reduced digestive performance with ASA score, squamous cell carcinoma, open or hybrid surgical approach, and (neo)adjuvant therapy. In contrast, no individual patient factor was found to be associated with dumping syndrome. Digestive function and HRQL are substantially impaired after Ivor Lewis esophagectomy for cancer. Comorbid patients undergoing multimodal treatment and open access surgery for squamous cell carcinoma have the highest risk of poor functional outcome.

9.
Cancers (Basel) ; 15(21)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37958373

RESUMO

Hypoxia activates pathways associated with tumor progression, metastatic spread, and alterations in the immune microenvironment leading to an immunosuppressive phenotype. In particular, the upregulation of PD-L1, a target for therapy with checkpoint inhibitors, is well-studied in several tumors. However, the relationship between hypoxia and PD-L1 regulation in pheochromocytomas and paragangliomas (PPGL), and especially in paragangliomas treated with embolization, is still largely unexplored. We investigated the expression of the hypoxia-marker HIF-2α and of PD-L1 in a PPGL-cohort with and without embolization as potential biomarkers that may predict the response to treatment with HIF-2α and checkpoint inhibitors. A total of 29 tumor samples from 25 patients who were operated at a single center were included and analyzed utilizing immunohistochemistry (IHC) for PD-L1 and HIF-2α. Embolization prior to surgery was performed in seven (24%) tumors. PD-L1 expression in tumor cells of head and neck paragangliomas (HNPGLs) receiving prior embolization (median PD-L1 positivity: 15%) was significantly higher as compared to PD-L1 expression in HNPGLs without prior embolization (median PD-L1 positivity: 0%) (p = 0.008). Consistently, significantly more HNPGLs with prior embolization were positive for HIF-2α (median nuclear HIF-2α positivity: 40%) as compared to HNPGLs without prior embolization (median nuclear HIF-2α positivity: 0%) (p = 0.016). Our results support the hypothesis that embolization with subsequent hypoxia leads to the upregulation of both PD-L1 and HIF-2α in HNPGLs, and could thus facilitate targeted treatment with HIF-2α and checkpoint inhibitors in the case of inoperable, locally advanced, or metastatic disease.

11.
Neuropharmacology ; 237: 109648, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37385435

RESUMO

The connection between dysbiosis of the gut microbiome and diseases and injuries of the brain has attracted considerable interest in recent years. Interestingly, antibiotic-induced microbial dysbiosis has been implicated in the pathogenesis of traumatic brain injury (TBI), while early administration of antibiotics associates with improved survival in TBI patients. In animal models of TBI, short- or long-term administration of antibiotics, both peri- or post-operatively, were shown to induce gut microbiome dysbiosis but also anti-inflammatory and neuroprotective effects. However, the acute consequences of microbial dysbiosis on TBI pathogenesis after discontinuation of antibiotic treatment are elusive. In this study, we tested whether pre-traumatic antibiotic-induced microbial depletion by vancomycin, amoxicillin, and clavulanic acid affects pathogenesis during the acute phase of TBI in adult male C57BL/6 mice. Pre-traumatic microbiome depletion did not affect neurological deficits over 72 h post injury (hpi) and brain histopathology, including numbers of activated astrocytes and microglia, at 72 hpi. However, astrocytes and microglia were smaller after pre-traumatic microbiome depletion compared to vehicle treatment at 72 hpi, indicating less inflammatory activation. Accordingly, TBI-induced gene expression of the inflammation markers Interleukin-1ß, complement component C3, translocator protein TSPO and the major histocompatibility complex MHC2 was attenuated in microbiome-depleted mice along with reduced Immunoglobulin G extravasation as a proxy of blood-brain barrier (BBB) impairment. These results suggest that the gut microbiome contributes to early neuroinflammatory responses to TBI but does not have a significant impact on brain histopathology and neurological deficits. This article is part of the Special Issue on "Microbiome & the Brain: Mechanisms & Maladies".


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Animais , Camundongos , Masculino , Doenças Neuroinflamatórias , Antibacterianos/farmacologia , Disbiose , Camundongos Endogâmicos C57BL , Lesões Encefálicas/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Inflamação/metabolismo , Modelos Animais de Doenças , Microglia
12.
J Clin Endocrinol Metab ; 108(10): 2676-2685, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-36946182

RESUMO

CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors. OBJECTIVE: Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs. METHODS: Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical-pathological features of PPGLs. RESULTS: Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P < .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx). CONCLUSION: SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.


Assuntos
Neoplasias das Glândulas Suprarrenais , Segunda Neoplasia Primária , Paraganglioma , Feocromocitoma , Humanos , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/terapia , Neoplasias das Glândulas Suprarrenais/metabolismo , Paraganglioma/genética , Paraganglioma/terapia , Paraganglioma/metabolismo , Feocromocitoma/genética , Feocromocitoma/terapia , Feocromocitoma/metabolismo , Receptores de Somatostatina/genética , Receptores de Somatostatina/metabolismo , Estudos Retrospectivos , Succinato Desidrogenase/genética , Succinato Desidrogenase/metabolismo
13.
Surg Obes Relat Dis ; 19(7): 707-715, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36990881

RESUMO

BACKGROUND: Gastroesophageal reflux disease seems more frequent after laparoscopic sleeve gastrectomy (LSG) than Roux-en-Y gastric bypass (LRYGB). Retrospective case series have raised concerns about a high incidence of Barrett esophagus (BE) after LSG. OBJECTIVE: This prospective clinical cohort study compared the incidence of BE ≥5 years after LSG and LRYGB. SETTING: St. Clara Hospital, Basel, and University Hospital, Zürich, Switzerland. METHODS: Patients were recruited from 2 bariatric centers where preoperative gastroscopy is standard practice and LRYGB is preferred for patients with preexisting gastroesophageal reflux disease. At follow-up ≥5 years after surgery, patients underwent gastroscopy with quadrantic biopsies from the squamocolumnar junction and metaplastic segment. Symptoms were assessed using validated questionnaires. Wireless pH measurement assessed esophageal acid exposure. RESULTS: A total of 169 patients were included, with a median 7.0 ± 1.5 years after surgery. In the LSG group (n = 83), 3 patients had endoscopically and histologically confirmed de novo BE; in the LRYGB group (n = 86), there were 2 patients with BE, 1 de novo and 1 preexisting (de novo BE, 3.6% versus 1.2%; P = .362). At follow-up, reflux symptoms were reported more frequently by the LSG group than by the LRYGB group (51.9% versus 10.5%). Similarly, moderate-to-severe reflux esophagitis (Los Angeles grade B-D) was more common (27.7% versus 5.8%) despite greater use of proton pump inhibitors (49.4% versus 19.7%), and pathologic acid exposure was more frequent in patients who underwent LSG than in patients who underwent LRYGB. CONCLUSIONS: After at least 5 years of follow-up, a higher incidence of reflux symptoms, reflux esophagitis, and pathologic esophageal acid exposure was found in patients who underwent LSG compared with patients who underwent LRYGB. However, the incidence of BE after LSG was low and not significantly different between the 2 groups.


Assuntos
Esôfago de Barrett , Esofagite Péptica , Derivação Gástrica , Refluxo Gastroesofágico , Laparoscopia , Obesidade Mórbida , Humanos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Seguimentos , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/etiologia , Esofagite Péptica/etiologia , Incidência , Estudos Prospectivos , Estudos Retrospectivos , Estudos de Coortes , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Redução de Peso , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Gastrectomia/efeitos adversos , Laparoscopia/efeitos adversos
14.
Surg Endosc ; 37(7): 5295-5302, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36976420

RESUMO

BACKGROUND: Mesh augmentation is a highly controversial adjunct of hiatus hernia (HH) surgery. The current scientific evidence remains unclear and even experts disagree on indications and surgical techniques. With an aim to avoid the downsides of both non-resorbable synthetic and biological materials, biosynthetic long-term resorbable meshes (BSM) have recently been developed and are becoming increasingly popular. In this context, we aimed at assessing outcomes after HH repair with this new generation of mesh at our institution. METHODS: From a prospective database, we identified all consecutive patients that underwent HH repair with BSM augmentation. Data was extracted from electronic patient charts of our hospital information system. Endpoints of this analysis included perioperative morbidity, functional results and recurrence rates at follow-up. RESULTS: Between December 2017 and July 2022, 97 patients (elective primary cases n = 76, redo cases n = 13, emergency cases n = 8) underwent HH with BSM augmentation. Indications in elective and emergency cases were paraesophageal (Type II-IV) HH in 83%, and large Type I HH in 4%. There was no perioperative mortality, and overall (Clavien-Dindo ≥ 2) and severe (Clavien-Dindo ≥ 3b) postoperative morbidity was 15% and 3%, respectively. An outcome without postoperative complications was achieved in 85% of cases (elective primary surgery 88%, redo cases 100%, emergencies cases 25%). After a median (IQR) postoperative follow-up of 12 months, 69 patients (74%) were asymptomatic, 15 (16%) reported improvement, and 9 (10%) had clinical failure, of which 2 patients (2%) required revisional surgery. CONCLUSION: Our data suggest that HH repair with BSM augmentation is feasible and safe with low perioperative morbidity and acceptable postoperative failure rates at early to mid-term follow-up. BSM may be a useful alternative to non-resorbable materials in HH surgery.


Assuntos
Hérnia Hiatal , Laparoscopia , Humanos , Telas Cirúrgicas , Herniorrafia/métodos , Laparoscopia/métodos , Recidiva , Hérnia Hiatal/cirurgia , Hérnia Hiatal/complicações , Resultado do Tratamento , Estudos Retrospectivos
15.
Transl Psychiatry ; 12(1): 182, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35504874

RESUMO

In clinical practice, differentiating Bipolar Disorder (BD) from unipolar depression is a challenge due to the depressive symptoms, which are the core presentations of both disorders. This misdiagnosis during depressive episodes results in a delay in proper treatment and a poor management of their condition. In a first step, using A-to-I RNA editome analysis, we discovered 646 variants (366 genes) differentially edited between depressed patients and healthy volunteers in a discovery cohort of 57 participants. After using stringent criteria and biological pathway analysis, candidate biomarkers from 8 genes were singled out and tested in a validation cohort of 410 participants. Combining the selected biomarkers with a machine learning approach achieved to discriminate depressed patients (n = 267) versus controls (n = 143) with an AUC of 0.930 (CI 95% [0.879-0.982]), a sensitivity of 84.0% and a specificity of 87.1%. In a second step by selecting among the depressed patients those with unipolar depression (n = 160) or BD (n = 95), we identified a combination of 6 biomarkers which allowed a differential diagnosis of bipolar disorder with an AUC of 0.935 and high specificity (Sp = 84.6%) and sensitivity (Se = 90.9%). The association of RNA editing variants modifications with depression subtypes and the use of artificial intelligence allowed developing a new tool to identify, among depressed patients, those suffering from BD. This test will help to reduce the misdiagnosis delay of bipolar patients, leading to an earlier implementation of a proper treatment.


Assuntos
Transtorno Bipolar , Transtorno Depressivo , Inteligência Artificial , Biomarcadores , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/genética , Humanos , Edição de RNA
16.
Endocr Relat Cancer ; 29(6): 285-306, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35324454

RESUMO

Aggressive pheochromocytomas and paragangliomas (PPGLs) are difficult to treat, and molecular targeting is being increasingly considered, but with variable results. This study investigates established and novel molecular-targeted drugs and chemotherapeutic agents for the treatment of PPGLs in human primary cultures and murine cell line spheroids. In PPGLs from 33 patients, including 7 metastatic PPGLs, we identified germline or somatic driver mutations in 79% of cases, allowing us to assess potential differences in drug responsivity between pseudohypoxia-associated cluster 1-related (n = 10) and kinase signaling-associated cluster 2-related (n = 14) PPGL primary cultures. Single anti-cancer drugs were either more effective in cluster 1 (cabozantinib, selpercatinib, and 5-FU) or similarly effective in both clusters (everolimus, sunitinib, alpelisib, trametinib, niraparib, entinostat, gemcitabine, AR-A014418, and high-dose zoledronic acid). High-dose estrogen and low-dose zoledronic acid were the only single substances more effective in cluster 2. Neither cluster 1- nor cluster 2-related patient primary cultures responded to HIF-2a inhibitors, temozolomide, dabrafenib, or octreotide. We showed particular efficacy of targeted combination treatments (cabozantinib/everolimus, alpelisib/everolimus, alpelisib/trametinib) in both clusters, with higher efficacy of some targeted combinations in cluster 2 and overall synergistic effects (cabozantinib/everolimus, alpelisib/trametinib) or synergistic effects in cluster 2 (alpelisib/everolimus). Cabozantinib/everolimus combination therapy, gemcitabine, and high-dose zoledronic acid appear to be promising treatment options with particularly high efficacy in SDHB-mutant and metastatic tumors. In conclusion, only minor differences regarding drug responsivity were found between cluster 1 and cluster 2: some single anti-cancer drugs were more effective in cluster 1 and some targeted combination treatments were more effective in cluster 2.


Assuntos
Neoplasias das Glândulas Suprarrenais , Antineoplásicos , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Everolimo/uso terapêutico , Humanos , Camundongos , Paraganglioma/tratamento farmacológico , Paraganglioma/genética , Paraganglioma/patologia , Feocromocitoma/tratamento farmacológico , Feocromocitoma/genética , Feocromocitoma/metabolismo , Ácido Zoledrônico/uso terapêutico
17.
Sci Rep ; 12(1): 2843, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181680

RESUMO

In the context of social events reopening and economic relaunch, sanitary surveillance of SARS-CoV-2 infection is still required. Here, we evaluated the diagnostic performances of a rapid, extraction-free and connected reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay on saliva. Nasopharyngeal (NP) swabs and saliva from 443 outpatients were collected simultaneously and tested by reverse-transcription quantitative PCR (RT-qPCR) as reference standard test. Seventy-one individuals (16.0%) were positive by NP and/or salivary RT-qPCR. Sensitivity and specificity of salivary RT-LAMP were 85.9% (95%CI 77.8-94.0%) and 99.5% (98.7-100%), respectively. Performances were similar for symptomatic and asymptomatic participants. Moreover, SARS-CoV-2 genetic variants were analyzed and no dominant mutation in RT-LAMP primer region was observed during the period of the study. We demonstrated that this RT-LAMP test on self-collected saliva is reliable for SARS-CoV-2 detection. This simple connected test with optional automatic results transfer to health authorities is unique and opens the way to secure professional and social events in actual context of economics restart.


Assuntos
Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Técnicas de Diagnóstico Molecular/estatística & dados numéricos , Técnicas de Amplificação de Ácido Nucleico/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Adulto , Infecções Assintomáticas , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Carga Viral , Adulto Jovem
18.
Langenbecks Arch Surg ; 407(3): 957-964, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35041047

RESUMO

BACKGROUND: Endoscopic vacuum therapy (EVT) has emerged as a novel treatment option for upper gastrointestinal wall defects. The basic principle of action of EVT entails evacuation of secretions, removal of wound debris, and containment of the defect. Furthermore, there is increasing evidence that EVT reduces interstitial edema, increases oxygen saturation, and promotes tissue granulation and microcirculation. Various devices, such as macroporous polyurethane sponge systems or open-pore film drains, have been developed for specific indications. Depending on the individual situation, EVT devices can be placed in- or outside the intestinal lumen, as a stand-alone procedure, or in combination with surgical, radiological, and other endoscopic interventions. PURPOSE: The aim of this narrative review is to describe the current spectrum of EVT in the upper gastrointestinal tract and to assess and summarize the related scientific literature. CONCLUSIONS: There is growing evidence that the efficacy of EVT for upper GI leakages exceeds that of other interventional treatment modalities such as self-expanding metal stents, clips, or simple drainages. Owing to the promising results and the excellent risk profile, EVT has become the therapy of choice for perforations and anastomotic leakages of the upper gastrointestinal tract in many centers of expertise. In addition, recent clinical research suggests that preemptive use of EVT after high-risk upper gastrointestinal resections may play an important role in reducing postoperative morbidity.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Trato Gastrointestinal Superior , Fístula Anastomótica/cirurgia , Endoscopia , Esofagectomia , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Trato Gastrointestinal Superior/cirurgia
19.
Swiss Med Wkly ; 151: w30052, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34908385

RESUMO

AIMS OF THE STUDY: Surgery for large hiatal hernias has greatly evolved over the last decade, but there is an ongoing controversy regarding many technical aspects, such as the use of meshes or the necessity to add a fundoplication. The purpose of this survey was to assess the current spectrum of surgical care for mixed axial and paraoesophageal hiatal hernias (type III hiatal hernia) in Switzerland. METHODS: In April 2020, we conducted a web-based survey comprising 25 questions on surgical management of type III hiatal hernia among members of the Swiss Society for Visceral Surgery. The survey focused exclusively on primary hernias in an elective setting. Responses were graded on a five-point Likert scale and analysed using descriptive statistics. Consensus was defined as agreement (agree or strongly agree) ≥75%. RESULTS: Forty-seven visceral surgeons with a median annual institutional caseload of 15 (interquartile range 10-30) type III hiatal hernia participated in the survey (response rate 15%). Agreement ≥75% was found for several basic technical steps (access via laparoscopy, hernia sac resection, preservation of vagus nerves, preservation of aberrant left hepatic artery, single-stitch posterior suture repair of hiatus with braided, non-resorbable material, complementary antireflux procedure). In contrast, consensus was not achieved for several important surgical details (mesh hiatoplasty, type of antireflux procedure, gastropexy, management of short oesophagus). A high percentage of participating surgeons experienced mesh related complications in their own or assigned patients: erosions (15% and 36%, respectively), stenoses (26% and 24%, respectively) and pericardial tamponades (9% and 15%, respectively). Nevertheless, hiatal reinforcement with mesh (in all or in selected cases) was reported by 91% of participants without consensus regarding mesh type, shape, placement and fixation technique. CONCLUSIONS: Apart from a few generally accepted technical steps, surgical management of type III hiatal hernia is highly variable amongst visceral surgeons in Switzerland. Although mesh-related complications appear to be common, most Swiss surgeons report routine mesh use for hiatal reinforcement.


Assuntos
Hérnia Hiatal , Laparoscopia , Fundoplicatura , Cirurgia Geral , Hérnia Hiatal/cirurgia , Humanos , Laparoscopia/métodos , Sociedades Médicas , Telas Cirúrgicas , Inquéritos e Questionários , Suíça
20.
Ann Surg ; 274(5): 751-757, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34334639

RESUMO

OBJECTIVE: Preemptive endoluminal vacuum therapy (pEVT) is a novel concept to reduce postoperative morbidity and has the potential to disrupt current treatment paradigms for patients undergoing esophagectomy. SUMMARY OF BACKGROUND DATA: Endoluminal vacuum therapy is an accepted treatment for AL after esophagectomy. METHODS: Retrospective analysis of patients undergoing minimally invasive Ivor Lewis esophagectomy with pEVT between 11/2017 and 10/2020. The sponge was removed endoscopically after 4-6 days, and anastomosis and gastric conduit were assessed according to a novel endoscopic grading system. Further management was customized according to endoscopic appearance and clinical course. Endpoints were postoperative morbidity and AL rate, defined according to the Clavien-Dindo (CD) and International Esodata Study Group classifications. RESULTS: PEVT was performed in 67 consecutive patients, 57 (85%) were high-risk patients with an ASA score >2, WHO/ECOG score >1, age >65 years, or BMI >29 kg/m2. Thirty patients experienced textbook outcome, and overall minor (≤CD IIIa) and major (≥CD IIIb) morbidity was 40.3% and 14.9% respectively. 30-day-mortality was 0%. Forty-nine patients (73%) had uneventful anastomotic healing after pEVT without further endoscopic treatment. The remaining 18 patients (27%) underwent prolonged EVT with uneventful anastomotic healing in 13 patients (19%), contained AL in 4 patients (6%), and 1 uncontained leakage (1.5%) in a case with proximal gastric conduit necrosis, resulting in an overall AL rate of 7.5%. CONCLUSIONS: PEVT is an innovative and safe procedure with a promising potential to reduce postoperative morbidity after minimally invasive Ivor Lewis esophagectomy and may be particularly valuable in highly comorbid cases.


Assuntos
Endoscopia do Sistema Digestório/métodos , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Anastomose Cirúrgica/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Suíça/epidemiologia , Vácuo
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