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1.
Artículo en Inglés | MEDLINE | ID: mdl-38977487

RESUMEN

PURPOSE: The study aimed to identify parameters that could predict oncological and functional outcomes in patients with pT4aN0 laryngeal squamous cell carcinoma (LSCC) who underwent open partial horizontal laryngectomy (OPHL). The role of paratracheal neck dissection (PTND) was analyzed as the primary outcome. Additionally, the study compared the outcomes of patients who underwent postoperative radio/chemotherapy (PORT/PORCT) with those who refused or did not adhere to adjuvant treatments. METHODS: Twenty-nine OPHL patients whose pathological exam was consistent with pT4aN0-x disease were enrolled and their clinical charts were retrospectively reviewed. The study analyzed oncological outcomes, such as local, regional, and distant recurrence rates (RR), overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). Additionally, functional results were analyzed, including decannulation rate, hospitalization time, and postoperative complication rate. RESULTS: The study revealed and overall recurrence rate of 27%. The final rates for OS and DSS were 68% and 79%, respectively. Based on the univariate analysis the PTND was significantly associated with longer DFS. No significant differences inoncological outcomes were observed between pT4a patients who underwent adjuvant radio/radiochemotherapy and those who did not, in terms of RR, DFS, DSS or OS. However, adjuvant treatment was found to significantly increase decannulation time. CONCLUSIONS: In a properly super-selected subgroup of patients with pT4aN0 LSCC, OPHL may beconsidered as a conservative surgical option even without adjuvant treatment. However, for optimal oncological outcomes, it is strongly recommended to consider a central compartment dissection in cases of hypoglottic and anterior extra-laryngeal tumor extension.

2.
Laryngorhinootologie ; 2024 Feb 26.
Artículo en Alemán | MEDLINE | ID: mdl-38408483

RESUMEN

BACKGROUND: Lacrimal sac localization of an Inverted Papilloma is extremely rare and no risk factors are reported in literature. HISTORY: A chemical trauma was followed by a painless, growing mass in the medial canthal area associated with epiphora. FINDINGS: Rhinoendoscopy, Computed Tomography and Magnetic Resonance showed a well-defined mass in left lacrimal fossa extended to the nasolacrimal duct. TREATMENT: An endoscopic resection and a dacryocystorhinostomy were performed. CONCLUSION: The aim of the present study is to show an atypical presentation of a well-known tumor along with a suspicious risk factor and to lead otolaryngologists to consider an inverted papilloma of the lacrimal system among lesions causing lateral nasal swelling.

3.
J Clin Med ; 12(20)2023 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-37892620

RESUMEN

BACKGROUND: Younger and physically active patients demand a return to sport after total hip arthroplasty (THA). However, because of the risk of implant wear and loosening, high-impact activities are often not recommended. The current study evaluates predictive factors and revision rates in patients with higher activity levels. METHODS: This retrospective study included 4152 hips in 3828 patients aged 45-75 that underwent primary THA for primary osteoarthritis between 2009 and 2019 with a minimum follow-up of 2 years. Pain and Lower Extremity Activity Scale (LEAS) were assessed before and 2 years after surgery. Activity was classified as low (LEAS 1-6), moderate (LEAS 7-13), or high (LEAS 14-18). RESULTS: Pain and LEAS improved from preoperative to 2-years postoperative (p < 0.001). The activity level was low in 6.2%, moderate in 52.9%, and high in 40.9% of the patients. Younger age, lower BMI, ASA, and CCI, male sex, and higher preoperative LEAS correlated with higher activity at 2 years (p < 0.001). The predicted revision-free survival rates between the activity groups were better for more highly active patients (p < 0.001). CONCLUSIONS: High physical activity 2 years following THA, with participating in sports like jogging several times a week, did not increase the risk of revision surgery. THA patients should not be prevented from a highly active lifestyle.

4.
BMC Musculoskelet Disord ; 24(1): 665, 2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37608323

RESUMEN

BACKGROUND: Intra-articular corticosteroid injections (ICSI) are an effective symptomatic treatment for osteoarthritis of the hip. However, the safety of ICSI has been questioned and a relatively high risk for septic arthritis, rapidly progressive osteoarthritis (RPIO) and periprosthetic joint infections (PJI) in patients undergoing subsequent total hip arthroplasty (THA) have been suggested. METHODS: This is a retrospective evaluation of 682 hips that underwent ICSI with 40 mg of Triamcinolone for primary osteoarthritis of the hip. All ICSI were performed using sterile techniques, the number of ICSI in each hip and the cumulative corticosteroid dosage were assessed. Pre- and post-injection radiographs were compared to identify cases with RPIO. Native joint septic arthritis, surgical site infections and PJI were identified by chart review. RESULTS: 4 hips (0.6%) developed RPIO 2-4 months following ICSI. The cumulative Triamcinolone dose was not associated with the development of RPIO (p = 0.281). 1 case was diagnosed with septic arthritis and treated with staged THA, there were no signs of infection at a 5 years follow-up. 483 hips (75.7%) underwent THA, including 199 hips with THA less than 3 months following ICSI and 181 hips with > 1 ICSI prior to THA. There were 3 superficial surgical site infections/wound dehiscence and no PJI. CONCLUSION: The rate of RPIO was 0.6%. The current findings suggest that if ICSI is performed under sterile conditions, the risk for septic arthritis or PJI following THA, even in patients with multiple ICSI or ICSI within 3 months prior to surgery, is minimal.


Asunto(s)
Artritis Infecciosa , Osteoartritis de la Cadera , Humanos , Infección de la Herida Quirúrgica , Osteoartritis de la Cadera/diagnóstico por imagen , Osteoartritis de la Cadera/tratamiento farmacológico , Osteoartritis de la Cadera/cirugía , Estudios Retrospectivos , Corticoesteroides/efectos adversos , Triamcinolona , Artritis Infecciosa/tratamiento farmacológico
5.
Liver Cancer ; 12(2): 129-144, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37325488

RESUMEN

Background: Checkpoint inhibitors act on exhausted CD8+ T cells and restore their effector function in chronic infections and cancer. The underlying mechanisms of action appear to differ between different types of cancer and are not yet fully understood. Methods: Here, we established a new orthotopic HCC model to study the effects of checkpoint blockade on exhausted CD8+ tumor-infiltrating lymphocytes (TILs). The tumors expressed endogenous levels of HA, which allowed the study of tumor-specific T cells. Results: The induced tumors developed an immune-resistant TME in which few T cells were found. The few recovered CD8+ TILs were mostly terminally exhausted and expressed high levels of PD-1. PD-1/CTLA-4 blockade resulted in a strong increase in the number of CD8+ TILs expressing intermediate amounts of PD-1, also called progenitor-exhausted CD8+ TILs, while terminally exhausted CD8+ TILs were almost absent in the tumors of treated mice. Although transferred naïve tumor-specific T cells did not expand in the tumors of untreated mice, they expanded strongly after treatment and generated progenitor-exhausted but not terminally exhausted CD8+ TILs. Unexpectedly, progenitor-exhausted CD8+ TILs mediated the antitumor response after treatment with minimal changes in their transcriptional profile. Conclusion: In our model, few doses of checkpoint inhibitors during the priming of transferred CD8+ tumor-specific T cells were sufficient to induce tumor remission. Therefore, PD-1/CTLA-4 blockade has an ameliorative effect on the expansion of recently primed CD8+ T cells while preventing their development into terminally exhausted CD8+ TILs in the TME. This finding could have important implications for future T-cell therapies.

6.
Cells ; 12(11)2023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37296574

RESUMEN

Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in the treatment of autoimmune diseases; however, the use of polyspecific Tregs has limited effects. However, obtaining a sufficient number of antigen-specific Tregs from patients with autoimmune disorders remains challenging. Chimeric antigen receptors (CARs) provide an alternative source of T cells for novel immunotherapies that redirect T cells independently of the MHC. In this study, we aimed to generate antibody-like single-chain variable fragments (scFv) and subsequent CARs against tetraspanin 7 (TSPAN7), a membrane protein highly expressed on the surface of pancreatic beta cells, using phage display technology. We established two methods for generating scFvs against TSPAN7 and other target structures. Moreover, we established novel assays to analyze and quantify their binding abilities. The resulting CARs were functional and activated specifically by the target structure, but could not recognize TSPAN7 on the surface of beta cells. Despite this, this study demonstrates that CAR technology is a powerful tool for generating antigen-specific T cells and provides new approaches for generating functional CARs.


Asunto(s)
Receptores Quiméricos de Antígenos , Humanos , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T Reguladores , Inmunoterapia , Tetraspaninas
7.
Eur Arch Otorhinolaryngol ; 280(11): 4869-4878, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37160464

RESUMEN

PURPOSE: To describe the surgical procedure of exclusive endoscopic ossiculoplasty (EEO) with autologous grafts and evaluate audiological results, focusing on the advantages or drawbacks compared to the corresponding microscopic technique. METHODS: A retrospective review of consecutive adult and pediatric patients affected by chronic otitis media (COM) with or without cholesteatoma who underwent EEO was conducted. Only autologous ossiculoplasty was included in the study. The procedure was performed by experienced surgeons of our institution between November 2014 and September 2019. Hearing outcomes were evaluated using postoperative air-bone gap (ABG) and success rates in different subgroups of patients and different types of ossiculoplasty (OPL) were analyzed. Our results were finally compared with the existing literature regarding both microscopic and endoscopic ossicular chain reconstruction. RESULTS: In total, 74 endoscopic ossicular chain repair procedures performed within the study period met the inclusion criteria. Of these, 21 were pediatric patients (28%) and 53 were adults (72%). Surgical reconstruction procedures included 43 partial ossicular reconstructions (POR) and 31 total ossicular reconstructions (TOR). The postoperative ABG improved significantly compared to preoperative measurements, and the mean ABG closure was 7.85 dB HL (p = 0.00064). No statistically significant differences in audiological outcomes between TOR/POR techniques and pediatric/adult groups were found in our study cohort, with p values of 0.10 and 0.88, respectively. CONCLUSIONS: At present, EEO can be considered a valid surgical option for re-establishing a functioning ossicular chain with acceptable hearing restoration in children and adults. Further reports in wider case series are required to confirm these results.


Asunto(s)
Prótesis Osicular , Reemplazo Osicular , Adulto , Humanos , Niño , Reemplazo Osicular/métodos , Resultado del Tratamiento , Timpanoplastia/métodos , Osículos del Oído/cirugía , Estudios Retrospectivos
8.
Oper Orthop Traumatol ; 35(3-4): 135-145, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37133809

RESUMEN

OBJECTIVE: Two-stage exchange with an antibiotic-loaded polymethylmethacrylate (PMMA) spacer is standard treatment for chronic periprosthetic joint infection of the shoulder. We present a safe and simple technique for patient-specific spacer implants. INDICATION: (Chronic) periprosthetic joint infection of the shoulder. RELATIVE CONTRAINDICATIONS: Known allergy against components of PMMA bone cements. Inadequate compliance for two-stage exchange. Patient is unfit to undergo two-stage exchange. SURGICAL TECHNIQUE: Hardware removal, histologic and microbiologic samples, and debridement. Preparation of targeted or calculated antibiotic-loaded PMMA. Tailoring of patient-specific spacer. Spacer implantation. POSTOPERATIVE MANAGEMENT: Rehabilitation protocol. Antibiotic treatment. Reimplantation after successful eradication of infection.


Asunto(s)
Artritis Infecciosa , Artroplastía de Reemplazo de Hombro , Infecciones Relacionadas con Prótesis , Humanos , Polimetil Metacrilato , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/cirugía , Resultado del Tratamiento , Antibacterianos/uso terapéutico , Artritis Infecciosa/cirugía , Reoperación/métodos , Estudios Retrospectivos
9.
Medicina (Kaunas) ; 59(2)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36837472

RESUMEN

Malpositioned implants in total hip arthroplasty are associated with impingement, increased wear, and dislocations, thus precise cup positioning is crucial. However, significant deviations between targeted and actually achieved cup positions have been found even in patients operated by experienced surgeons. When aiming for higher accuracy, various methods based on freehand positioning lead by anatomic landmarks, C-arm fluoroscopy, imageless navigation, or robotic-assisted-surgery have been described. There is a constant development of new products aiming to simplify and improve intraoperative guidance. Both the literature and expert opinions on this topic are often quite controversial. This article aims to give an overview of the different methods and systems with their specific advantages and potential pitfalls while also taking a look into the future of cup positioning in anterior hip replacements.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Cirugía Asistida por Computador , Humanos , Acetábulo/cirugía , Cirugía Asistida por Computador/métodos , Fluoroscopía
10.
Eur J Med Res ; 27(1): 284, 2022 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-36496477

RESUMEN

Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. It is known that AIH originates not from the spleen but from the liver itself. Nonetheless, most details of the etiology and pathophysiology are unknown. We induced experimental murine AIH (emAIH) in NOD/Ltj mice by single administration of a replication-deficient adenovirus and performed splenectomy during late-stage disease. Biochemical disease remission occurred, which was characterized by improvement in transaminase levels. The causes of this remission included a shift in the transcriptomic signature of serum proteins toward regeneration. At the cellular level, there was a marked decrease in activated CD8+ T cells and an increase in intrahepatic regulatory T cells (Tregs). Here, intrahepatic Treg numbers correlated with biochemical remission. Notably, an imbalance in the T-cell/B-cell ratio was observed, with a disproportionate increase in total B cells. In summary, intrahepatic increases in Tregs, biochemical remission, and regeneration could be induced by splenectomy in the late stage of emAIH.


Asunto(s)
Hepatitis Autoinmune , Ratones , Animales , Hepatitis Autoinmune/cirugía , Linfocitos T CD8-positivos , Ratones Endogámicos NOD , Linfocitos T Reguladores/metabolismo , Hígado/cirugía , Hígado/metabolismo
11.
BMC Musculoskelet Disord ; 23(1): 390, 2022 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-35473681

RESUMEN

BACKGROUND: Joint aspiration with analysis of synovial fluid white blood cell count (WBC) and microbiological culture is a widely established aspect in the diagnosis of shoulder joint infections (SJI). In case of a two stage revision for SJI, joint aspiration before re-/implantation of a total shoulder arthroplasty (TSA) was used to rule out persistent infection for years but its value is under debate. Shoulder specific data on all aspects is rare. The current study aims to answer the following research questions: Does joint aspiration have an insufficient predictive value in the diagnosis of SJI in (1) initial workup and (2) before definite arthroplasty with polymethylmethacrylate (PMMA)-Spacer in place? METHODS: This retrospective evaluation investigates 35 patients that were treated for SJI with a two staged implantation of a TSA after debridement and implantation of an PMMA-Spacer. Joint aspirations were performed preoperatively (PA) and before re-/implantation of the prosthesis while spacer was in place (interstage aspiration, IA). Samples were taken for microbiological culture and analysis of WBC. Sensitivity and specificity were calculated with reference to intraoperative microbiological samples. Receiver Operating Characteristic (ROC), Area-Under-Curve analysis (AUC) and calculation of the Youden index were performed to find optimum cut-off for WBC. RESULTS: The sensitivity of microbiological cultures from PA was 58.3% and the specificity was 88.9%. The mean WBC was 27,800 leucocytes/mm3 (range 400-96,300). The maximum Youden index (0.857) was a cut-off of 2600 leucocytes/mm3 with a sensitivity of 85.7% and a specificity of 100.0%. The sensitivity and specificity of IA were 0.0% and 88.5%, respectively. CONCLUSIONS: Preoperative aspiration is likely to miss Cutibacteria spp. and CoNS and cannot rule out infection for sure. However, we recommend it for its advantages of targeted antibiotic therapy in case of germ identification. Empiric antibiotic therapy should cover Cutibacteria and CoNS even if aspiration showed negative microbiological cultures. In contrast, the diagnostic value of interstage aspiration does not qualify for its routine use.


Asunto(s)
Infecciones Relacionadas con Prótesis , Articulación del Hombro , Antibacterianos , Humanos , Polimetil Metacrilato , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/cirugía , Reoperación/métodos , Estudios Retrospectivos , Líquido Sinovial/microbiología
12.
Eur Arch Otorhinolaryngol ; 279(8): 4085-4092, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35034188

RESUMEN

PURPOSE: Quality of Life (QoL) after extensive head and neck resections is of paramount importance, especially after pharyngolaryngectomy or pharyngolaryngoesophagectomy where complex digestive tract reconstruction is required (with gastric pull-up or colon transposition). Tracheodigestive puncture (TDP) is the only vocal restoration option in this group of patients. The aim of this study is to evaluate postoperative complications, vocal outcomes, voice-related and swallowing-related QoL after secondary TDP in this cohort of patients. METHODS: A retrospective study was conducted in the tertiary referral center of Verona Hospital between June 2014 and June 2020. Patient demographics, clinical and surgical data were assessed. Speech objective and subjective evaluation was performed. QoL was assessed with Voice Handicap Index-10 (VHI-10) and M.D. Anderson Dysphagia Inventory (MDADI) questionnaires. RESULTS: Seven patients met the inclusion criteria, but two had died before questionnaires were administered. No intraoperative complications were noted after TDP surgery. There were delayed complications in four cases (57.1%) and all were treated with restoration. Intelligible voice was restored in all patients. Maximum phonation time and maximal voice intensity recorded were 5.42 ± 3.27 s and 65.20 ± 5.45 dB, respectively. Acceptable average VHI-10 and MDADI scores were obtained in all patients. CONCLUSIONS: Secondary TDP performed after gastric pull-up or colon transposition reconstructions are feasible and effective procedures. An intelligible voice was restored in all patients, with satisfactory patient-perceived voice-related and dysphagia-related quality-of-life outcomes.


Asunto(s)
Trastornos de Deglución , Laringectomía , Trastornos de Deglución/etiología , Trastornos de Deglución/rehabilitación , Trastornos de Deglución/cirugía , Humanos , Laringectomía/rehabilitación , Calidad de Vida , Estudios Retrospectivos
13.
Eur Arch Otorhinolaryngol ; 279(6): 2777-2782, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34191113

RESUMEN

PURPOSE: The aim of this study is to evaluate the feasibility and the safety of a novel, alternative method for bone tissue management in facial nerve decompression by a middle cranial fossa approach. Several applications of Piezosurgery technology have been described, and the technique has recently been extended to otologic surgery. The piezoelectric device is a bone dissector which, using micro-vibration, preserves the anatomic integrity of soft tissue thanks to a selective action on mineralized tissue. METHODS: An anatomic dissection study was conducted on fresh-frozen adult cadaveric heads. Facial nerve decompression was performed by a middle cranial fossa approach in all specimens using the piezoelectric device under a surgical 3D exoscope visualization. After the procedures, the temporal bones were examined for evidence of any injury to the facial nerve or the cochleovestibular organs. RESULTS: In all cases, it was possible to perform a safe dissection of the greater petrosal superficial nerve, the geniculate ganglion, and the labyrinthine tract of the facial nerve. No cases of semicircular canal, cochlea, or nerve damage were observed. All of the dissections were carried out with the ultrasonic device without the necessity to replace it with an otological drill. CONCLUSION: From this preliminary study, surgical decompression of the facial nerve via the middle cranial fossa approach using Piezosurgery seems to be a safe and feasible procedure. Further cadaveric training is recommended before intraoperative use, and a wider case series is required to make a comparison with conventional devices.


Asunto(s)
Nervio Facial , Ganglio Geniculado , Adulto , Cadáver , Fosa Craneal Media/anatomía & histología , Fosa Craneal Media/cirugía , Descompresión Quirúrgica/métodos , Nervio Facial/anatomía & histología , Nervio Facial/cirugía , Ganglio Geniculado/anatomía & histología , Ganglio Geniculado/cirugía , Humanos , Canales Semicirculares/cirugía , Ultrasonido
14.
Biomed Res Int ; 2021: 8442435, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34840982

RESUMEN

PURPOSE: Contradicting definitions of periprosthetic joint infection (PJI) are in use. Joint aspiration is performed before total hip arthroplasty (THA) revision. This study investigated the influence of PJI definition on PJI prevalence at THA revision. Test quality of prerevision aspiration was evaluated for the different PJI definitions. METHODS: 256 THA revisions were retrospectively classified to be infected or not infected. Classification was performed according to the 4 different definitions proposed by the Musculoskeletal Infection Society (MSIS), the Infectious Diseases Society of America (IDSA), the International Consensus Meeting (ICM), and the European Bone and Joint Infection Society (EBJIS). Only chronic PJIs were included. RESULTS: PJI prevalence at revision significantly correlated with the applied PJI definition (p = 0.01, Cramer's V = 0.093). PJI prevalence was 20.7% for the MSIS, 25.4% for the ICM, 28.1% for the IDSA, and 32.0% for the EBJIS definition. For synovial fluid white blood cell count, the best ROC-AUC for predicting PJI was 0.953 in combination with the MSIS definition. CONCLUSION: PJI definition significantly influences the rate of diagnosed PJIs at THA revision. Synovial fluid white blood cell count is a reliable means to rule out PJI. In cases with a borderline high synovial white blood cell count before THA revision as the only sign of chronic PJI, an extended diagnostic work-up should be considered.


Asunto(s)
Artroplastia de Reemplazo de Cadera/efectos adversos , Infecciones Relacionadas con Prótesis/diagnóstico , Reoperación/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Artritis Infecciosa/diagnóstico , Artritis Infecciosa/epidemiología , Artritis Infecciosa/etiología , Enfermedad Crónica , Femenino , Alemania , Prótesis de Cadera/efectos adversos , Prótesis de Cadera/microbiología , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Paracentesis , Prevalencia , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/etiología , Estudios Retrospectivos , Líquido Sinovial/citología , Líquido Sinovial/microbiología , Adulto Joven
15.
Cells ; 10(6)2021 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-34208308

RESUMEN

BACKGROUND: Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of B cells can improve disease progression in the long term. METHODS: We tested a single administration of anti-CD20 antibodies to reduce B cells and the amount of IgG to induce intrahepatic immune tolerance. We used our experimental murine AIH (emAIH) model and treated the mice with anti-CD20 during the late stage of the disease. RESULTS: After treatment, the mice showed the expected reductions in B cells and serum IgGs, but no improvements in pathology. However, all treated animals showed a highly altered serum protein expression pattern, which was a balance between inflammation and regeneration. CONCLUSIONS: In conclusion, anti-CD20 therapy did not produce clinically measurable results because it triggered inflammation, as well as regeneration, at the proteomic level. This finding suggests that anti-CD20 is ineffective as a sole treatment for AIH or emAIH.


Asunto(s)
Anticuerpos Monoclonales/farmacología , Antígenos CD20/inmunología , Linfocitos B/inmunología , Hepatitis Autoinmune/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Proteoma/metabolismo , Regeneración , Animales , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Células Hep G2 , Hepatitis Autoinmune/inmunología , Hepatitis Autoinmune/metabolismo , Hepatitis Autoinmune/patología , Humanos , Terapia de Inmunosupresión , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Ratones , Ratones Endogámicos NOD , Proteoma/análisis , Proteoma/efectos de los fármacos
16.
Eur Arch Otorhinolaryngol ; 278(11): 4459-4467, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33582848

RESUMEN

PROPOSE: The aim of the present article is to propose an alternative technique to the traditional secondary tracheoesophageal puncture (TEP) for voice rehabilitation after total laryngectomy, describing the procedure step-by-step, analyzing the complications and long-term results. METHODS: A retrospective study was conducted on patients who underwent secondary TEP with the blind technique using a rigid hysterometer. The main steps in this technique are described and illustrated. Patient demographics and surgical outcomes were assessed. RESULTS: Thirty-two patients were enrolled in this study. In all but one case, risk factors that could hinder rigid esophagoscopy were identified (37.5% neopharyngeal/esophageal post-surgical issues, 81.3% prior radiotherapy, 21.9% cervical arthrosis, and 12.5% prior coloplasty or gastric transposition). No intra- or postoperative surgical complications were noted. CONCLUSION: The blind technique offers an alternative method to perform a secondary TEP safely and efficiently in patients with unfavorable anatomical or clinical conditions, lowering the risk of procedure-related complications.


Asunto(s)
Neoplasias Laríngeas , Laringe Artificial , Humanos , Neoplasias Laríngeas/cirugía , Laringectomía , Punciones , Estudios Retrospectivos , Tráquea/cirugía , Resultado del Tratamiento
17.
Biomedicines ; 9(1)2021 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-33435354

RESUMEN

Autoimmune hepatitis (AIH) is detected at a late stage in the course of the disease. Therefore, induction and etiology are largely unclear. It is controversial if the induction of autoimmunity occurs in the liver or in the spleen. In our experimental murine AIH model, the induction of autoimmunity did not occur in the spleen. Instead, a protective role of the spleen could be more likely. Therefore, we splenectomized mice followed by induction of experimental murine AIH. Splenectomized mice presented more severe portal inflammation. Furthermore, these mice had more IL-17, IL-23 receptor (IL-23R) and caspase 3 (casp3) and a decreased amount of erythropoietin in serum, while intrahepatic T cell compartments were unaffected. These results indicate that the spleen is not necessary for induction of AIH, and splenectomy disrupts the ability to immune regulate the intensity of hepatic inflammation, production of IL-17 and apoptosis.

18.
Cell Mol Gastroenterol Hepatol ; 11(5): 1387-1404, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33484913

RESUMEN

BACKGROUND & AIMS: A coordinated stress and regenerative response is important after hepatocyte damage. Here, we investigate the phenotypes that result from genetic abrogation of individual components of the checkpoint kinase 2/transformation-related protein 53 (p53)/cyclin-dependent kinase inhibitor 1A (p21) pathway in a murine model of metabolic liver injury. METHODS: Nitisinone was reduced or withdrawn in Fah-/- mice lacking Chk2, p53, or p21, and survival, tumor development, liver injury, and regeneration were analyzed. Partial hepatectomies were performed and mice were challenged with the Fas antibody Jo2. RESULTS: In a model of metabolic liver injury, loss of p53, but not Chk2, impairs the oxidative stress response and aggravates liver damage, indicative of a direct p53-dependent protective effect on hepatocytes. Cell-cycle control during chronic liver injury critically depends on the presence of both p53 and its downstream effector p21. In p53-deficient hepatocytes, unchecked proliferation occurs despite a strong induction of p21, showing a complex interdependency between p21 and p53. The increased regenerative potential in the absence of p53 cannot fully compensate the surplus injury and is not sufficient to promote survival. Despite the distinct phenotypes associated with the loss of individual components of the DNA damage response, gene expression patterns are dominated by the severity of liver injury, but reflect distinct effects of p53 on proliferation and the anti-oxidative stress response. CONCLUSIONS: Characteristic phenotypes result from the genetic abrogation of individual components of the DNA damage-response cascade in a liver injury model. The extent to which loss of gene function can be compensated, or affects injury and proliferation, is related to the level at which the cascade is interrupted. Accession numbers of repository for expression microarray data: GSE156983, GSE156263, GSE156852, and GSE156252.


Asunto(s)
Lesión Pulmonar Aguda/complicaciones , Carcinogénesis/patología , Quinasa de Punto de Control 2/fisiología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/fisiología , Neoplasias Hepáticas/patología , Regeneración Hepática , Proteína p53 Supresora de Tumor/fisiología , Animales , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
19.
JSES Int ; 4(4): 959-963, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33345240

RESUMEN

BACKGROUND: The treatment of septic arthritis, caused by either hematogenous seeding, injections, or surgery, can be challenging. Staged reverse shoulder arthroplasty (RSA) with temporary implantation of an antibiotic-loaded spacer is widely accepted but still discussed controversially. This study investigated the shoulder-specific bacterial spectrum, infection control rate, functional outcome, and infection-free survival rate after staged RSA in the mid- to long-term follow-up. It was hypothesized that staged RSA would show a high infection-free survival rate. METHODS: A total of 39 patients treated with staged RSA for primary septic arthritis (n = 8), secondary infection (n = 8), or periprosthetic infection (n = 23) were retrospectively included. The infection control rate was calculated based on cultures taken intraoperatively at spacer removal and RSA implantation. Infection-free survival was defined as no revision due to infection. The minimum follow-up period for functional outcome assessment was 2 years (n = 14; mean, 76 months; range, 31-128 months). RESULTS: Cutibacterium (26%) and coagulase-negative staphylococci (23%) were the predominant pathogens. The infection control rate was 90%. The cumulative infection-free survival rate was 91% after 128 months. Follow-up examinations showed a mean Constant score of 48 (range, 7-85), a mean QuickDASH (short version of Disabilities of the Arm, Shoulder and Hand questionnaire) score of 40.0 (range, 11.4-93.3), and a mean pain score of 1.6 (range, 0-7). CONCLUSION: Staged RSA implantation was confirmed to be a reliable treatment option for primary, secondary, and periprosthetic infections of the shoulder. The infection control rate and infection-free survival rate are satisfactory. However, patients and surgeons must be aware of functional impairment even after successful treatment of infections.

20.
Int J Mol Sci ; 21(21)2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33167328

RESUMEN

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming the most common liver disease worldwide. Within the NAFLD spectrum, patients with nonalcoholic steatohepatitis (NASH) are at the highest risk of developing cirrhosis and disease progression to hepatocellular carcinoma. To date, therapeutic options for NASH patients have been ineffective, and therefore, new options are urgently needed. Hence, a model system to develop new therapeutic interventions is needed. Here, we introduce two new in vitro models of steatosis induction in HepG2 cells and primary murine hepatocytes. We used a recently discovered novel class of bioactive anti-inflammatory lipids called branched fatty acid esters of hydroxyl fatty acids. Among these bioactive lipids, palmitic-acid-9-hydroxy-stearic-acid (9-PAHSA) is the most promising as a representative nondrug therapy based on dietary supplements or nutritional modifications. In this study, we show a therapeutic effect of 9-PAHSA on lipotoxicity in steatotic primary hepatocytes and HepG2 cells. This could be shown be increased viability and decreased steatosis. Furthermore, we could demonstrate a preventive effect in HepG2 cells. The outcome of 9-PAHSA administration is both preventative and therapeutically effective for hepatocytes with limited damage. In conclusion, bioactive lipids like 9-PAHSA offer new hope for prevention or treatment in patients with fatty liver and steatosis.


Asunto(s)
Hígado Graso/patología , Hepatocitos/efectos de los fármacos , Mitocondrias Hepáticas/efectos de los fármacos , Enfermedades Mitocondriales/prevención & control , Ácido Palmítico/farmacología , Ácidos Esteáricos/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citoprotección/efectos de los fármacos , Hígado Graso/metabolismo , Hígado Graso/fisiopatología , Células Hep G2 , Hepatocitos/patología , Hepatocitos/fisiología , Humanos , Hígado/efectos de los fármacos , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Mitocondrias Hepáticas/fisiología , Enfermedades Mitocondriales/etiología
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