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Using big data and artificial intelligence to establish a multi-point monitoring, early warning, and disposal system to achieve early warning and intervention of infectious disease outbreaks is an important means of controlling the spread of the epidemic. Taking Xiaoshan district as an example, this study analyzes the monitoring contents, warning methods, and application effectiveness of the infectious disease monitoring, early warning and disposal system. Based on Xiaoshan's health big data resources, the system starts with syndrome, disease diagnosis and etiology. Through advanced technologies such as artificial intelligence and block chain, it realizes early identification of infectious disease outbreaks, data fusion, multi-cross collaboration, and closed-loop management. It has improved the sensitivity of clustered outbreaks monitoring and the effectiveness of epidemic disposal and provided a reference for grassroots disease prevention and control departments to establish an infectious disease monitoring and early warning system.
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Inteligência Artificial , Doenças Transmissíveis , Surtos de Doenças , Humanos , Surtos de Doenças/prevenção & controle , Doenças Transmissíveis/epidemiologia , Big Data , Controle de Doenças Transmissíveis/métodosRESUMO
BACKGROUND: Treatment response evaluated by tumour size change is an important indicator for outcome prediction. Advanced nasopharyngeal carcinoma (adNPC) grows irregularly, and so the unidimensional measurement may not be accurately applied to adNPC for outcome prediction. This study aimed to evaluate values of unidimensional and volumetric measurements for treatment response to induction chemotherapy (IC) for outcome prediction in adNPC and compared the values with that of RECIST 1.1 guideline. MATERIALS AND METHODS: Pre-treatment and post-IC magnetic resonance images (MRIs) from 124 patients with stage III-IVA NPC were retrospectively reviewed. Sums of the maximum unidimensional diameters (D) and volumes of the targeted tumours (primary tumour and two largest metastatic lymph nodes) on the pre- (Dpre and Vpre) and post-IC MRIs (Dpost-IC and Vpost-IC) and percentage changes in D (Δ D%) and V (ΔV%) between two scans were calculated and correlated with disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastases-free survival (DMFS) using Cox regression analysis. Area under the curves (AUCs) of independent measurements and RECIST groups (RECIST response and non-response groups) for predicting disease recurrence, locoregional recurrence, and distant metastases, respectively, were calculated and compared using the DeLong test. RESULTS: Univariable analysis showed correlations between high Dpost-IC with poor DFS and DMFS (P < 0.05), but not with LRRFS (P = 0.07); high Vpost-IC and low ΔV% (less decrease in volume on post-IC) with poor DFS, LRRFS, and DMFS (P < 0.05); and no correlations between Dpre, ΔD%, and Vpre and the outcomes (P > 0.05). Multivariable analysis showed that ΔV% was the only independent measurement for outcomes (P < 0.05). Compared with RECIST groups, ΔV% of 47.9% (median value) showed a higher AUC for disease recurrence (0.682 versus 0.526, P < 0.01) and for locoregional recurrence (0.782 versus 0.585, P < 0.01), but not for distant metastases (0.593 versus 0.518, P = 0.26). CONCLUSIONS: Volumetric measurement to evaluate treatment response to IC outperformed unidimensional measurement and RECIST guideline in outcome prediction in adNPC.
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Quimioterapia de Indução , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Critérios de Avaliação de Resposta em Tumores Sólidos , Humanos , Masculino , Quimioterapia de Indução/métodos , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Adulto , Idoso , Resultado do Tratamento , Estadiamento de Neoplasias , Adulto Jovem , Carga TumoralRESUMO
Objective: To summarize and analyze the diagnostic and therapeutic characteristics of asymptomatic primary hyperparathyroidism (aPHPT). Methods: A retrospective analysis was conducted on the clinical data of 103 patients with aPHPT admitted to the Chinese PLA General Hospital from January 2012 to September 2023. The clinical characteristics, treatment modes, and prognoses of the patients were analyzed. GraphPad Prism 8.0 software was used for statistical analysis. Results: Among the 103 cases, there were 37 males and 66 females, aged from 25 to 78 years, with an average age of (53.81±11.34) years. Ninety-eight cases (95.15%) visited due to abnormal findings during physical examination and 5 cases (4.85%) due to hypertension, diabetes or other diseases. All patients underwent minimally invasive parathyroidectomy with small incision, with 96 cases (93.20%) pathologically diagnosed as adenomas and 7 cases as hyperplasia (6.80%). Postoperative mean serum calcium, parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels were respectively significantly lower than preoperative levels, while postoperative serum phosphorus level was significantly higher than preoperative level (P<0.05). The mean lesion volume was (3.32±6.72)cm3 (range 0.05-49.50 cm3). Patients with different lesion volumes had significant differences in preoperative serum calcium, PTH and ALP levels. Lesion volume was positively correlated to preoperative serum calcium(ρ=0.36, P<0.01), PTH(ρ=0.50, P<0.01) and ALP(ρ=0.39, P<0.01). Among 103 patients, 94 cases were followed up (91.26%), 9 cases were lost (8.74%), and the mean follow-up period was (60.15±29.23) months. The followed-up patients were alive and had no recurrence of lesions or complications, and their blood calcium levels were normal. Conclusion: aPHPT can be preliminarily diagnosed through blood biochemistry and imaging examination, and minimally invasive surgery can offer good prognosis without serious complications.
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Cálcio , Hiperparatireoidismo Primário , Hormônio Paratireóideo , Paratireoidectomia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/sangue , Adulto , Idoso , Cálcio/sangue , Hormônio Paratireóideo/sangue , Prognóstico , Fosfatase Alcalina/sangueRESUMO
Intestinal tuberculosis commonly affects the ileocecal area and the terminal ileum, and is extremely rare in the rectum, with isolated rectal involvement being even rarer. This paper described a case of an isolated rectal tuberculoma in a female patient of 44 years old, Yi ethnicity, who was admitted to the hospital with abdominal distension and constipation. She had a history of hepatitis B virus infection. A colonoscopy revealed a rectal mass, and an endoscopic resection was performed. Post-operative pathological examination confirmed rectal tuberculosis, with no evidence of extra-rectal tuberculosis infection found. The final diagnosis was an isolated rectal tuberculoma. In cases where endoscopic examination suggests a rectal tumor, especially in patients with immunosuppressive conditions such as HIV or diabetes, the possibility of tuberculoma should be considered.
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Tuberculoma , Tuberculose Gastrointestinal , Humanos , Feminino , Adulto , Tuberculoma/diagnóstico , Tuberculose Gastrointestinal/diagnóstico , Doenças Retais/diagnóstico , Doenças Retais/cirurgia , ColonoscopiaRESUMO
Objective: To investigate the efficacy of Da Vinci robotic transanal minimally invasive surgery (R-TAMIS) for rectal neoplasms. Methods: The patients of rectal neoplasms who underwent R-TAMIS and were regularly followed up at the First Medical Center of Chinese PLA General Hospital from January 2021 to January 2024 were retropectively selected. Follow-up visits were conducted at 1, 2, and 4 weeks postoperatively, and then every 3 months until January 20, 2024. The perioperative situation, postoperative histopathological results, and follow-up status of the patients were observed. Results: A total of 17 patients were included, including 10 males and 7 females, aged 35-80 (59±13) years. Eleven patients underwent surgery using the da Vinci® Si robot, while 6 patients underwent surgery using the da Vinci® Xi robot. The height of the resected tumor from the anal verge [M (Q1, Q3)] was 3.5 (3.0, 3.8) cm. The total operative time was 55.0 (50.0, 55.0) minutes, the platform installation time was 32.5 (30.0, 35.0) minutes. The actual surgical operation time was 22.5 (20.0, 27.5) minutes. Intraoperative blood loss was 9.2 (5.0, 10.0) ml. The postoperative hospital stay was 3.2 (3.0, 3.8) days. The total treatment cost was (29 447±4 765) yuan. Two patients who achieved clinical complete remission after neoadjuvant chemoradiotherapy experienced incision dehiscence one week postoperatively, which was resolved after four weeks of rectal irrigation therapy. All surgical specimens were intact, and all resection margins were negative. A total of 44(31,73) weeks were followed up, without local recurrence or distant metastasis. Conclusion: Da Vinci robotic transanal minimally invasive local resection may be a safe and feasible treatment option for rectal neoplasms.
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Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Neoplasias Retais/cirurgia , Masculino , Pessoa de Meia-Idade , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Adulto , Idoso de 80 Anos ou mais , Canal Anal/cirurgia , Duração da Cirurgia , Cirurgia Endoscópica Transanal/métodos , Resultado do Tratamento , Tempo de InternaçãoRESUMO
1. This study evaluated the effects and mechanisms of action of the peptide gADP3 on hepatic inflammatory injury induced by lipopolysaccharide (LPS).2. Hepatic inflammatory injury was induced in geese by intraperitoneal injection of LPS and gADP3, and the adiponectin receptor agonist AdipoRon (positive control) was used for potential amelioration. Serum inflammatory factor levels, liver function-related biochemical indicators and oxidative stress-related biochemical parameters in the liver tissues were determined. The expression levels of adiponectin and its receptors, inflammation and oxidative stress-related genes and key signalling molecules involved in adiponectin, inflammation and oxidative stress signalling pathways in liver tissues were detected.3. The peptide gADP3 alleviated inflammatory cell infiltration and hepatic inflammatory changes, reversed the decrease in serum albumin (ALB), total protein (TP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content or activity induced by LPS and increased the activity of the antioxidant enzymes CAT (catalase), SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase).4. The peptide gADP3 upregulated the expression of antioxidant enzyme-related genes GCLC, HO-1 and NQO1 in liver tissues, decreased the levels of inflammatory factors like TNF-α, IL-1ß, IL-6, IFN-γ and TGF-ß and reduced mRNA expression levels of inflammatory-related genes TNF-α, IL-1ß, iNOS and TGF-ß. Additionally, it increased the mRNA and protein expression levels of adiponectin and its receptors, as well as key molecules in the adiponectin signalling pathway like AMPK and PPARα. In addition, gADP3 reversed the changes in mRNA or protein expression of inflammatory and oxidative stress signalling pathway-related genes P38MAPK, NF-κBP65, TLR4 and Nrf2 in liver tissues caused by LPS treatment.5. In conclusion, goose-derived adiponectin peptide gADP3, similar to the adiponectin receptor agonist AdipoRon, attenuated LPS-induced hepatic inflammatory injury in geese.
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With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.
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Antineoplásicos , Humanos , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a MedicamentosRESUMO
Objective: To investigate the clinical features of acute macular neuroretinopathy (AMN) following coronavirus disease 2019 (COVID-19). Methods: This retrospective case series study included 15 patients (28 eyes) diagnosed with AMN at the Department of Ophthalmology, Peking University Third Hospital, from November 2022 to January 2023. The AMN group comprised 4 males and 11 females, with a mean age of (31.36±8.08) years. A control group of 15 individuals [5 males, 10 females; mean age (33.20±5.10) years] who had COVID-19 but did not develop AMN was also included. Data collected for all patients included best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fluorescein fundus angiography (FFA), and optical coherence tomography (OCT) results. Serum cytokine levels, including interleukins (ILs), interferons (IFNs), and tumor necrosis factor-alpha (TNF-α), were measured for both groups. Results: Among the 28 eyes, severe vision loss (BCVA≤0.3) was observed in 3 eyes (10.7%), moderate vision loss (BCVA>0.3 and≤0.5) in 2 eyes (13.3%), and mild vision loss (BCVA>0.5 and≤1.0) in 23 eyes (82.1%). OCT findings in all 28 eyes revealed hyperreflectivity of the outer nuclear layer and disruption of outer retinal structure. Additionally, 3 eyes (10.7%) exhibited cotton wool spots in the posterior pole, 2 eyes (7.1%) showed mild cystoid macular edema with intraretinal hyperreflective dots, and 1 eye (3.6%) presented with paracentral acute middle maculopathy. FFA indicated retinal vasculitis in 2 cases (4 eyes, 14.3%). Serum levels of IL-4, IL-5, IFN-α, and IFN-γ were significantly higher in the AMN group compared to the control group: IL-4 [4.49 (3.66, 6.08) vs. 1.40 (0.62, 1.68) pg/ml], IL-5 [7.34 (5.04, 14.06) vs. 0.17 (0.11, 1.86) pg/ml], IFN-α [8.42 (6.31, 14.89) vs. 0.50 (0.30, 0.83) pg/ml], and IFN-γ [17.93 (12.75, 32.44) vs. 7.43 (0.00, 14.74) pg/ml], with all differences being statistically significant (all P<0.05). Conclusion: AMN following COVID-19 can present with wedge-shaped dark red lesions in the macular area, often accompanied by cotton wool spots and retinal vasculitis. Additionally, there is a significant elevation in various inflammatory cytokines in the serum.
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COVID-19 , Doenças Retinianas , SARS-CoV-2 , Tomografia de Coerência Óptica , Humanos , COVID-19/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , China/epidemiologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Angiofluoresceinografia/métodos , Macula Lutea/patologia , Macula Lutea/diagnóstico por imagem , Doença Aguda , Citocinas/sangueRESUMO
Hashtags on Instagram help users globally search for posts to their liking. This study aimed to determine who posts the most popular oral and maxillofacial surgery (OMS) hashtags on Instagram and to evaluate the impact of educational content. The posts were analyzed for the type of post and differences between content creators when posting OMS-related content. This cross-sectional study evaluated OMS content categorized by 36 hashtags. The top 9 posts with each hashtag were evaluated based on the type of content creator, if it was a video or picture, and if it was educational or for marketing purposes. 6 million posts existed among 36 hashtags. Regarding the categories of person/organization posting the content (US or non-US oral and maxillofacial surgeon, residency program, patient, and 'other'), the top posts (N = 295) were posted by 'other' and the least by 'residency program'. Among the posts by non-US oral and maxillofacial surgeons, there was 3.8-fold more marketing content, while among the posts by US oral and maxillofacial surgeons, there was 2-fold more educational content. Educational posts achieved the highest engagement in terms of 'likes'. This study highlights how oral and maxillofacial surgeons can educate the general population and expand their reach.
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Mídias Sociais , Cirurgia Bucal , Humanos , Estudos Transversais , Cirurgia Bucal/educaçãoRESUMO
BACKGROUND: Colorectal cancer (CRC) incidence and mortality rates have been increasing among young patients (YP), for uncertain reasons. It is unclear whether YP have a distinct tumor biology or merit a different treatment approach to older patients (OP). METHODS: We reviewed prospectively collected data from consecutive patients with metastatic CRC (MCRC) enrolled in the multi-site Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Australian registry. Clinicopathological features, treatment and survival outcomes were compared between YP (<50 years) and OP (≥50 years). RESULTS: Of 3692 patients diagnosed August 2009 - March 2023, 14 % (513) were YP. YP were more likely than OP to be female (52% vs. 40 %, P < 0.0001), have ECOG performance status 0-1 (94% vs. 81 %, P < 0.0001), to have a left-sided primary (72% vs. 63 %, P = 0.0008) and to have fewer comorbidities (90% vs. 60 % Charleston score 0, P < 0.0001). There were no differences in the available molecular status, which was more complete in YP. YP were more likely to have de novo metastatic disease (71% vs. 57 %, P < 0.0001). YP were more likely to undergo curative hepatic resection (27% vs. 17 %, P < 0.0001), to receive any chemotherapy (93% vs. 78 % (P < 0.0001), and to receive 3+ lines of chemotherapy (30% vs. 24 % (P < 0.0034)). Median first-line progression free survival (10.2 versus 10.6 months) was similar for YP vs OP, but overall survival (32.1 versus 25.4 months, HR = 0.745, P < 0.0001) was longer in YP. CONCLUSION: Known prognostic variables mostly favored YP versus OP with newly diagnosed mCRC, who were also more heavily treated. Consistent with this, overall survival outcomes were improved. This data does not support that CRC in YP represent a distinct subset of mCRC patients, or that a modified treatment approach is warranted.
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Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Feminino , Masculino , Austrália/epidemiologia , Pessoa de Meia-Idade , Idoso , Metástase Neoplásica , Adulto , Estudos Prospectivos , Idade de Início , Sistema de Registros/estatística & dados numéricos , Idoso de 80 Anos ou maisRESUMO
Problematic alcohol consumption is associated with deficits in decision-making and alterations in prefrontal cortex neural activity likely contribute. We hypothesized that the differences in cognitive control would be evident between male Wistars and a model of genetic risk: alcohol-preferring P rats. Cognitive control is split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus, whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol seeking whereas P rats would show reactive control over alcohol seeking. Neural activity was recorded from the prefrontal cortex during an alcohol seeking task with two session types. On congruent sessions, the conditioned stimulus (CS+) was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, made more incorrect approaches during incongruent sessions, suggesting that Wistars utilized the previously learned rule. This motivated the hypothesis that neural activity reflecting proactive control would be observable in Wistars but not P rats. While P rats showed differences in neural activity at times of alcohol access, Wistars showed differences prior to approaching the sipper. These results support our hypothesis that Wistars are more likely to engage in proactive cognitive control strategies whereas P rats are more likely to engage in reactive cognitive control strategies. Although P rats were bred to prefer alcohol, the differences in cognitive control may reflect a sequela of behaviors that mirror those in humans at risk for an AUD.
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Consumo de Bebidas Alcoólicas , Córtex Pré-Frontal , Humanos , Ratos , Masculino , Animais , Ratos Wistar , Consumo de Bebidas Alcoólicas/genética , Etanol , MotivaçãoRESUMO
Pain is the fifth major vital sign, and chronic pain is a large category of diseases that affects health seriously. At present, the incidence of chronic pain is high, but the overall treatment satisfaction is low. It is necessary to continuously optimize pain diagnosis and treatment strategies and improve the connotation of pain management. Based on the clinical practice of our pain center, combined with relevant literature, the article proposes a diagnosis and treatment strategy of "whole field pain management" should be carried out from the four dimensions of feeling, emotion, cognition, and behavior. Innovative digital pain diagnosis and treatment technologies such as VR/MR and brain-computer interface are used to regulate emotional, cognitive, and behavioral regulation, and combined with lifestyle changes, rehabilitation physiotherapy, drugs, and minimally invasive interventional therapy to constitute a " whole field pain management strategy" to explore the new development direction of further improving the management of chronic pain.
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Dor Crônica , Manejo da Dor , Humanos , Manejo da Dor/métodos , Dor Crônica/diagnóstico , Dor Crônica/terapia , Modalidades de Fisioterapia , Emoções , CogniçãoRESUMO
Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.
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Tumor Glômico , Paraganglioma Extrassuprarrenal , Masculino , Feminino , Humanos , Criança , Tumor Glômico/cirurgia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Paraganglioma Extrassuprarrenal/metabolismo , Paraganglioma Extrassuprarrenal/patologia , Imuno-HistoquímicaRESUMO
Problematic alcohol consumption is associated with deficits in decision-making, and alterations in prefrontal cortex neural activity likely contributes. We hypothesized that differences in cognitive control would be evident between male Wistar rats and a model for genetic risk for alcohol use disorder (alcohol-preferring P rats). Cognitive control can be split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol-seeking whereas P rats would show reactive control over alcohol-seeking. Neural ensembles were recorded from prefrontal cortex during an alcohol seeking task that utilized two session types. On congruent sessions the CS+ was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, exhibited an increase in incorrect approaches during incongruent sessions, suggesting that Wistars utilized the previously learned task-rule. This motivated the hypothesis that ensemble activity reflecting proactive control would be observable in Wistars but not P rats. While P rats showed differences in neural activity at times relevant for alcohol delivery, Wistars showed differences prior to approaching the sipper. These results support our hypothesis that Wistars are more likely to engage proactive cognitive-control strategies whereas P rats are more likely to engage reactive cognitive control strategies. Although P rats were bred to prefer alcohol, differences in cognitive control may reflect a sequela of behaviors that mirror those in humans at risk for an AUD.
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BACKGROUND: Acquired resistance limits long-term epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) efficacy in patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) in whom anti-programmed death-ligand 1 (PD-L1) efficacy is also limited. We hypothesized that combining atezolizumab with erlotinib could enhance antitumor immunity and extend efficacy in these patients. PATIENTS AND METHODS: This open-label phase Ib trial was conducted in adults aged ≥18 years who had advanced, unresectable NSCLC. Stage 1 (safety evaluation) enrolled EGFR TKI-naive patients regardless of EGFR status. Stage 2 (expansion) enrolled patients with EGFR-mutant NSCLC treated with ≤1 prior non-EGFR TKI therapy. Patients received 150 mg erlotinib orally once daily. After a 7-day erlotinib run-in, atezolizumab 1200 mg was administered intravenously every 3 weeks. The primary endpoint was the safety and tolerability of the combination in all patients; secondary endpoints included antitumor activity per RECIST 1.1 in stage 2 patients. RESULTS: At the data cut-off on 7 May 2020, 28 patients (8 in stage 1, 20 in stage 2) were assessable for safety. No dose-limiting toxicities or grade 4 or 5 treatment-related adverse events occurred. Grade 3 treatment-related adverse events occurred in 46% of patients; the most common were increased alanine aminotransferase, diarrhea, pyrexia, and rash (each in 7% of patients). Serious adverse events occurred in 50% of patients. Pneumonitis (grade 1) was reported in a single patient (4%). The objective response rate was 75% [95% confidence interval (CI) 50.9% to 91.3%]), median response duration was 18.9 months (95% CI 9.5-40.5 months), median progression-free survival was 15.4 months (95% CI 8.4-39.0 months), and median overall survival was not estimable (NE) (95% CI 34.6-NE). CONCLUSIONS: Atezolizumab combined with erlotinib demonstrated a tolerable safety profile and encouraging, durable clinical activity in patients with advanced EGFR mutation-positive NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Humanos , Adolescente , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cloridrato de Erlotinib/efeitos adversos , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.