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The vertebrate appendage comprises three primary segments, the stylopod, zeugopod and autopod, each separated by joints. The molecular mechanisms governing the specification of joint sites, which define segment lengths and thereby limb architecture, remain largely unknown. Existing literature suggests that reciprocal gradients of retinoic acid (RA) and fibroblast growth factor (FGF) signaling define the expression domains of the putative segment markers Meis1, Hoxa11 and Hoxa13. Barx1 is expressed in the presumptive joint sites. Our data demonstrate that RA-FGF signaling gradients define the expression domain of Barx1 in the first presumptive joint site. When misexpressed, Barx1 induces ectopic interzone-like structures, and its loss of function partially blocks interzone development. Simultaneous perturbations of RA-FGF signaling gradients result in predictable shifts of Barx1 expression domains along the proximo-distal axis and, consequently, in the formation of repositioned joints. Our data suggest that during early limb bud development in chick, Meis1 and Hoxa11 expression domains are overlapping, whereas the Barx1 expression domain resides within the Hoxa11 expression domain. However, once the interzone is formed, the expression domains are refined and the Barx1 expression domain becomes congruent with the border of these two putative segment markers.
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Articulações , Fatores de Transcrição , Animais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Articulações/metabolismo , Proteína Meis1/genética , Proteína Meis1/metabolismo , Vertebrados/genética , Vertebrados/metabolismo , Extremidades , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
Discovery and optimization of a biotherapeutic monoclonal antibody requires a careful balance of target engagement and physicochemical developability properties. To take full advantage of the sequence diversity provided by different antibody discovery platforms, a rapid and reliable process for humanization of antibodies from nonhuman sources is required. Canonically, maximizing homology of the human variable region (V-region) to the original germline was believed to result in preservation of binding, often without much consideration for inherent molecular properties. We expand on this approach by grafting the complementary determining regions (CDRs) of a mouse anti-LAG3 antibody into an extensive matrix of human variable heavy chain (VH) and variable light chain (VL) framework regions with substantially broader sequence homology to assess the impact on complementary determining region-framework compatibility through progressive evaluation of expression, affinity, biophysical developability, and function. Specific VH and VL framework sequences were associated with major expression and purification phenotypes. Greater VL sequence conservation was correlated with retained or improved affinity. Analysis of grafts that bound the target demonstrated that initial developability criteria were significantly impacted by VH, but not VL. In contrast, cell binding and functional characteristics were significantly impacted by VL, but not VH. Principal component analysis of all factors identified multiple grafts that exhibited more favorable antibody properties, notably with nonoptimal sequence conservation. Overall, this study demonstrates that modern throughput systems enable a more thorough, customizable, and systematic analysis of graft-framework combinations, resulting in humanized antibodies with improved global properties that may progress through development more quickly and with a greater probability of success.
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Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Animais , Humanos , Camundongos , Anticorpos Monoclonais Humanizados/química , Afinidade de Anticorpos , Regiões Determinantes de Complementaridade/químicaRESUMO
BACKGROUND: Although both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used for analgesia in acute pancreatitis (AP), the analgesic of choice is not known. We compared buprenorphine, an opioid, and diclofenac, an NSAID, for analgesia in AP. METHODS: In a double-blind randomized controlled trial, AP patients were randomized to receive intravenous diclofenac or intravenous buprenorphine. Fentanyl was used as rescue analgesia, delivered through a patient-controlled analgesia pump. Primary outcome was the difference in the dose of rescue fentanyl required. Secondary outcomes were the number of effective and ineffective demands of rescue fentanyl, pain-free interval, reduction in visual analogue scale (VAS) score, adverse events, and organ failure development. RESULTS: Twenty-four patients were randomized to diclofenac and 24 to buprenorphine. The 2 groups were matched at baseline. The total amount of rescue fentanyl required was significantly lower in the buprenorphine group:130 µg, interquartile range (IQR), 80-255 vs 520 µg, IQR, 380-1065 (P < .001). The number of total demands was 32 (IQR, 21-69) in the diclofenac arm vs 8 (IQR, 4-15) in the buprenorphine arm (P < .001). The buprenorphine group had more prolonged pain-free interval (20 vs 4 hours; P < .001), with greater reduction in the VAS score at 24, 48, and 72 hours compared with the diclofenac group. These findings were confirmed in the subgroup of moderately severe/severe pancreatitis. Adverse events profile was similar in the 2 groups. CONCLUSIONS: Compared with diclofenac, buprenorphine appears to be more effective and equally safe for pain management in AP patients, even in the subcohort of moderately severe or severe pancreatitis (Trial Registration number: CTRI/2020/07/026914).
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Buprenorfina , Pancreatite , Humanos , Diclofenaco/efeitos adversos , Buprenorfina/efeitos adversos , Manejo da Dor , Doença Aguda , Pancreatite/complicações , Pancreatite/tratamento farmacológico , Pancreatite/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Dor/etiologia , Dor/induzido quimicamente , Fentanila/efeitos adversos , Método Duplo-CegoRESUMO
We developed a three-dimensional (3D) synthetic animated mouse based on computed tomography scans that is actuated using animation and semirandom, joint-constrained movements to generate synthetic behavioral data with ground-truth label locations. Image-domain translation produced realistic synthetic videos used to train two-dimensional (2D) and 3D pose estimation models with accuracy similar to typical manual training datasets. The outputs from the 3D model-based pose estimation yielded better definition of behavioral clusters than 2D videos and may facilitate automated ethological classification.
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Comportamento Animal , Imageamento Tridimensional/métodos , Animais , Feminino , Aprendizado de Máquina , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Unraveling the intriguing aspects of the intramolecular charge transfer (ICT) phenomenon of multi-modular donor-acceptor-based push-pull systems are of paramount importance considering their promising applications, particularly in solar energy harvesting and light-emitting devices. Herein, a series of symmetrical and unsymmetrical donor-acceptor chromophores 1-6, are designed and synthesized by the Corey-Fuchs reaction via Evano's condition followed by [2+2] cycloaddition retroelectrocyclic ring-opening reaction with strong electron acceptors TCNE and TCNQ in good yields (~60-85 %). The photophysical, electrochemical, and computational studies are investigated to explore the effect of incorporation of strong electron acceptors 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) and dicyanoquinodimethane (DCNQ) with phenothiazine (PTZ) donor. An additional low-lying broad absorption band extended towards the near-infrared (NIR) region suggests charge polarization after the introduction of the electron acceptors in both symmetrical and asymmetrical systems, leading to such strong ICT bands. The electrochemical properties reveal that reduction potentials of 3 and 6 are lower than those of 2 and 5, suggesting DCNQ imparts more on the electronic properties and hence largely contributes to the stabilization of LUMO energy levels than TCBD, in line with theoretical observations. Relative positions of the frontier orbitals on geometry-optimized structures further support accessing donor-acceptor sites responsible for the ICT transitions. Eventually, ultrafast carrier dynamics of the photoinduced species are investigated by femtosecond transient absorption studies to identify their spectral characteristics and target analysis further provides information about different excited states photophysical events including ICT and their associated time profiles. The key findings obtained here related to excited state dynamical processes of these newly synthesized systems are believed to be significant in advancing their prospect of utilization in solar energy conversion and related photonic applications.
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OBJECTIVE: To evaluate the performance of dual-energy computed tomography (DECT) in differentiating non-acute benign from malignant gallbladder wall thickening (GBWT). METHODS: This prospective study comprised consecutive adults with GBWT who underwent late arterial phase (LAP) and portal venous phase (PVP) DECT between January 2022 and May 2023. The final diagnosis was based on histopathology or 3-6 months follow-up imaging. DECT images in LAP and PVP were assessed independently by two radiologists. The demographic, qualitative, and quantitative parameters were compared between two groups Multivariate logistic regression was performed to determine the association between the aforementioned factors and malignant GBWT. RESULTS: Seventy-five patients (mean age 56 ± 12.8 years, 46 females) were included. Forty-two patients had benign, and 33 had malignant GBWT. In the overall group, female gender (p = 0.018), lymphadenopathy (p = 0.011), and omental nodules (p = 0.044) were significantly associated with malignant GBWT. None of the DECT features differed significantly between benign and malignant GBWT in overall group. In the xanthogranulomatous cholecystitis (XGC, n = 9) vs. gallbladder cancer (GBC) (n = 33) subgroup, mean attenuation value at 140 keV LAP VMI was significantly associated with malignant GBWT [p = 0.023, area under curve 0.759 (95%CI 0.599-0.919)]. CONCLUSION: DECT-generated quantitative parameters do not add value in differentiating non-acute benign from malignant GBWT. However, DECT may have a role in differentiating XGC from GBC in a selected subgroup of patients. Further, larger studies may be necessary to confirm these findings. CLINICAL RELEVANCE STATEMENT: In patients with non-acute gallbladder wall thickening in whom there is suspicion of xanthogranulomatous cholecystitis (XGC), DECT findings may allow differentiation of XGC from wall thickening type of gallbladder cancer. KEY POINTS: Differentiation of benign and malignant gallbladder wall thickening (GBWT) at CT is challenging. Quantitative dual energy CT (DECT) features do not provide additional value in differentiating benign and malignant GBWT. DECT may be helpful in a subgroup of patients to differentiate xanthogranulomatous cholecystitis from gallbladder cancer.
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A one-pot, tandem reductive annulation of 2-nitrobenzenesulfonamides with aldehydes to the synthesis of substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxides in the presence of sodium dithionite (Na2S2O4) is reported under mild conditions. The method involves in situ reduction of the nitro group followed by condensation with aldehydes to form an imine, which upon subsequent intramolecular cyclization forms the product under one-pot conditions. The protocol features use of inexpensive Na2S2O4 as the exclusive reagent, appreciable functional group tolerance, broad substrate scope, high product yields, and scalability.
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A novel biomass-derived glucose-mediated one-pot multicomponent nitro-reductive cyclization method is presented for the direct synthesis of diverse pyrrole-fused heterocycles. The process involves two-component reactions of alkyl (NH)-pyrrole-2-carboxylates and 2-fluoronitroarenes, yielding pyrrolo[1,2-a]quinoxalin-4(5H)-ones, as well as three-component reactions utilizing (NH)-pyrroles, nitroarenes, and DMSO as carbon sources, resulting in various pyrrolo[1,2-a]quinoxaline derivatives. High yields were achieved with broad substrate scope and gram-scale synthesis capability, including pharmaceuticals featuring pyrroloquinoxaline scaffolds. The method's key innovation lies in enabling three or four reactions in a single-pot setup, previously unexplored in pyrrole chemistry. The simplicity of nitro group reduction by biomass-derived glucose ensures practical safety during scale-up, while mechanistic insights from control experiments reveal a new paradigm in pyrrole chemistry. The tandem process demonstrates low PMI values and high step and atom economies, aligning well with green chemistry principles.
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OBJECTIVES: Many reverse transcription polymerase chain reaction (RT-PCR) methods exist that can detect SARS-CoV-2 RNA in different matrices. RT-PCR is highly sensitive, although viral RNA may be detected long after active infection has taken place. SARS-CoV-2 proteins have shorter detection windows hence their detection might be more meaningful. Given salivary droplets represent a main source of transmission, we explored the detection of viral RNA and protein using four different detection platforms including SISCAPA peptide immunoaffinity liquid chromatography-mass spectrometry (SISCAPA-LC-MS) using polyclonal capture antibodies. METHODS: The SISCAPA-LC MS method was compared to RT-PCR, RT-loop-mediated isothermal amplification (RT-LAMP), and a lateral flow rapid antigen test (RAT) for the detection of virus material in the drool saliva of 102 patients hospitalised after infection with SARS-CoV-2. Cycle thresholds (Ct) of RT-PCR (E gene) were compared to RT-LAMP time-to-positive (TTP) (NE and Orf1a genes), RAT optical densitometry measurements (test line/control line ratio) and to SISCAPA-LC-MS for measurements of viral protein. RESULTS: SISCAPA-LC-MS showed low sensitivity (37.7â¯%) but high specificity (89.8â¯%). RAT showed lower sensitivity (24.5â¯%) and high specificity (100â¯%). RT-LAMP had high sensitivity (83.0â¯%) and specificity (100.0â¯%). At high initial viral RNA loads (<20 Ct), results obtained using SISCAPA-LC-MS correlated with RT-PCR (R2 0.57, p-value 0.002). CONCLUSIONS: Detection of SARS-CoV-2 nucleoprotein in saliva was less frequent than the detection of viral RNA. The SISCAPA-LC-MS method allowed processing of multiple samples in <150â¯min and was scalable, enabling high throughput.
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COVID-19 , Espectrometria de Massas , Técnicas de Diagnóstico Molecular , RNA Viral , SARS-CoV-2 , Saliva , Humanos , Saliva/virologia , Saliva/química , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/diagnóstico , COVID-19/virologia , RNA Viral/análise , Espectrometria de Massas/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Masculino , Sensibilidade e Especificidade , Feminino , Pessoa de Meia-Idade , Fosfoproteínas/análise , Fosfoproteínas/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/análise , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Antígenos Virais/análise , Antígenos Virais/imunologia , Adulto , Cromatografia Líquida/métodosRESUMO
BACKGROUND AND AIM: Discrimination of gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) is difficult. Use of artificial intelligence (AI)-based technologies may help in discriminating these two entities. METHODS: We conducted a systematic review on the use of AI for discrimination of GITB and CD. Electronic databases (PubMed and Embase) were searched on June 6, 2022, to identify relevant studies. We included any study reporting the use of clinical, endoscopic, and radiological information (textual or images) to discriminate GITB and CD using any AI technique. Quality of studies was assessed with MI-CLAIM checklist. RESULTS: Out of 27 identified results, a total of 9 studies were included. All studies used retrospective databases. There were five studies of only endoscopy-based AI, one of radiology-based AI, and three of multiparameter-based AI. The AI models performed fairly well with high accuracy ranging from 69.6-100%. Text-based convolutional neural network was used in three studies and Classification and regression tree analysis used in two studies. Interestingly, irrespective of the AI method used, the performance of discriminating GITB and CD did not match in discriminating from other diseases (in studies where a third disease was also considered). CONCLUSION: The use of AI in differentiating GITB and CD seem to have acceptable accuracy but there were no direct comparisons with traditional multiparameter models. The use of multiple parameter-based AI models have the potential for further exploration in search of an ideal tool and improve on the accuracy of traditional models.
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Doença de Crohn , Tuberculose Gastrointestinal , Humanos , Inteligência Artificial , Doença de Crohn/diagnóstico por imagem , Redes Neurais de Computação , Estudos Retrospectivos , Tuberculose Gastrointestinal/diagnóstico , Diagnóstico por ComputadorRESUMO
Acute pancreatitis is an acute inflammatory condition of the pancreas that has not only local but systemic effects as well. Venous thrombosis is one such complication which can give rise to thrombosis of the peripheral vasculature in the form of deep vein thrombosis, pulmonary embolism, and splanchnic vein thrombosis. The prevalence of these complications increases with the severity of the disease and adds to the adverse outcomes profile. With better imaging and awareness, more cases are being detected, although many at times it can be an incidental finding. However, it remains understudied and strangely, most of the guidelines on the management of acute pancreatitis are silent on this aspect. This review offers an overview of the incidence, pathophysiology, symptomatology, diagnostic work-up, and management of venous thrombosis that develops in AP.
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Pancreatite , Trombose Venosa , Humanos , Trombose Venosa/etiologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/diagnóstico , Trombose Venosa/terapia , Pancreatite/complicações , Pancreatite/terapia , Doença AgudaRESUMO
BACKGROUND: Longitudinal incision is the commonly used incision for entry into the submucosal space during peroral endoscopic myotomy (POEM) for esophageal motility disorders. Transverse incision is another alternative for entry and retrospective data suggest it has less operative time and chance of gas-related events. METHODS: This was a single-center, randomized trial conducted at a tertiary care hospital. Patients undergoing POEM for esophageal motility disorders were randomized into group A (longitudinal incision) and group B (transverse incision). The primary objective was to compare the time needed for entry into the submucosal space. The secondary objectives were to compare the time needed to close the incision, number of clips required to close the incision, and development of gas-related events. The sample size was calculated as for a non-inferiority design using Kelsey method. RESULTS: Sixty patients were randomized (30 in each group). On comparing the 2 types of incisions, there was no difference in entry time [3 (2, 5) vs 2 (1.75, 5) min, p = 0.399], closure time [7 (4, 13.5) vs 9 (6.75, 19) min, p = 0.155], and number of clips needed for closure [4 (4, 6) vs 5 (4, 7), p = 0.156]. Additionally, the gas-related events were comparable between the 2 groups (capnoperitoneum needing aspiration-5 vs 2, p = 0.228, and development of subcutaneous emphysema-3 vs 1, p = 0.301). CONCLUSION: This randomized trial shows comparable entry time, closure time, number of clips needed to close the incision, and gas-related events between longitudinal and transverse incisions. REGISTRATION NUMBER: CTRI/2021/08/035829.
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Pancreatic fistula is a highly morbid complication of pancreatitis. External pancreatic fistulas result when pancreatic secretions leak externally into the percutaneous drains or external wound (following surgery) due to the communication of the peripancreatic collection with the main pancreatic duct (MPD). Internal pancreatic fistulas include communication of the pancreatic duct (directly or via intervening collection) with the pleura, pericardium, mediastinum, peritoneal cavity, or gastrointestinal tract. Cross-sectional imaging plays an essential role in the management of pancreatic fistulas. With the help of multiplanar imaging, fistulous tracts can be delineated clearly. Thin computed tomography sections and magnetic resonance cholangiopancreatography images may demonstrate the communication between MPD and pancreatic fluid collections or body cavities. Endoscopic retrograde cholangiography (ERCP) is diagnostic as well as therapeutic. In this review, we discuss the imaging diagnosis and management of various types of pancreatic fistulas with the aim to sensitize radiologists to timely diagnosis of this critical complication of pancreatitis.
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Pancreatopatias , Pancreatite , Humanos , Fístula Pancreática/diagnóstico por imagem , Fístula Pancreática/etiologia , Fístula Pancreática/terapia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Pancreatite/complicações , Pancreatite/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Pancreatopatias/patologia , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/patologia , Imageamento por Ressonância MagnéticaRESUMO
Background: Camphora officinarum (CO) is a commonly used homeopathic remedy for treating colds, collapse, and recurrent eruptive illnesses. Objective: Due to the non-availability of safety data on CO, the current study intended to determine the oral toxicity of CO in its ethanol-potentized dilutions 6C, 30C, and 200C in Wistar albino rats as per OECD guidelines. Materials and methods: A single oral dose of CO-6C, 30C, and 200C (2000 µl/kg) was administered, and the animals were monitored for behavior and mortality for up to 14 days in an acute toxicity study. In the subacute study, the effects of daily oral administration of CO-6C, 30C, and 200C (200 µl/kg) for 28 days were observed for clinical signs, change in body weight, and mortality. Hematological, biochemical, and histopathological analyses were assessed and organ weights were determined. Results: Results indicate no mortality of CO in its potencies in the acute toxicity study and was found to be safe at 2000 µl/kg dosage in the subacute toxicity study. CO (200 µl/kg/day) did not show any signs of toxicity in the hematological, biochemical, and histopathological analyses, along with organ weights. Conclusion: In conclusion, the findings suggest that CO in potencies of 6C, 30C, and 200C is safe up to a single oral dose of 2000 µl/kg body weight, and the No Observed Adverse Effect Level (NOAEL) was determined to be greater than 200 µl/kg/day.
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Extratos Vegetais , Ratos Wistar , Animais , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Masculino , Testes de Toxicidade Aguda , Feminino , Homeopatia/métodos , Relação Dose-Resposta a DrogaRESUMO
This study aims to evaluate the feasibility and utility of virtual reality (VR) for baffle planning in congenital heart disease (CHD), specifically by creating patient-specific 3D heart models and assessing a user-friendly VR interface. Patient-specific 3D heart models were created using high-resolution imaging data and a VR interface was developed for baffle planning. The process of model creation and the VR interface were assessed for their feasibility, usability, and clinical relevance. Collaborative and interactive planning within the VR space were also explored. The study findings demonstrate the feasibility and usefulness of VR in baffle planning for CHD. Patient-specific 3D heart models generated from imaging data provided valuable insights into complex spatial relationships. The developed VR interface allowed clinicians to interact with the models, simulate different baffle configurations, and assess their impact on blood flow. The VR space's collaborative and interactive planning enhanced the baffle planning process. This study highlights the potential of VR as a valuable tool in baffle planning for CHD. The findings demonstrate the feasibility of using patient-specific 3D heart models and a user-friendly VR interface to enhance surgical planning and patient outcomes. Further research and development in this field are warranted to harness the full benefits of VR technology in CHD surgical management.
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Cardiopatias Congênitas , Realidade Virtual , Humanos , Imageamento Tridimensional/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , CoraçãoRESUMO
BACKGROUND: Ferrum phosphoricum (FP) has been used by traditional medicine practitioners for various ailments since ancient times. However, scientific evidence on the safety of FP is still unavailable. Thus, the current study aimed to investigate the acute and sub-acute oral toxicity of homeopathic FP in experimental rats. METHODS: In an acute toxicity investigation, a single dose of 2,000 µL/kg of FP 6c, 30c and 200c was administered to female Wistar rats, which were monitored for up to 14 days according to the Organization for Economic Cooperation and Development (OECD) guideline 423. For a sub-acute toxicity study, FP 6c, 30c and 200c (200 µL/kg) were administered to male and female rats for 28 days as per the OECD guideline 407. All the animals were observed for mortality, clinical signs and body weight during the study. At the end of the experiment, hematological, biochemical and histopathological assessments were performed. RESULTS: During the acute toxicity study, no mortality was observed in rats administered with FP, and thus the median lethal dose (LD50) was identified as >2,000 µL/kg. In the sub-acute study, no mortality or adverse clinical signs were noticed with FP treatment. Moreover, weekly body weight gain was normal. Hematological and biochemical investigations revealed no abnormalities. Furthermore, histological analysis of FP-treated rats' vital organs revealed no pathological changes. CONCLUSION: Overall, our findings imply that FP 6c, 30c and 200c potencies are safe and do not cause toxicity when given orally to Wistar albino rats for an extended period at a dose of 200 µL/kg.
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Homeopatia , Ratos , Feminino , Masculino , Animais , Ratos Wistar , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica , Peso Corporal , Extratos VegetaisRESUMO
Historically, invasive procedures and surgeries were deferred in patients with haematological malignancies including advanced stage chronic lymphocytic leukaemia (CLL) because of limited life expectancy. However, novel, and often continuous, treatments have markedly improved outcomes in CLL. Some patients may expect years of treatment response and disease control, overcoming the short life expectancy that deters interventionalists. Such patients now often undergo various invasive procedures including major surgery. To inform peri-operative management, we summarize the relevant side effects and drug interactions of continuous CLL therapies, highlight potential surgical risks, and provide recommendations on withholding specific CLL drugs around invasive procedures.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/cirurgia , Leucemia Linfocítica Crônica de Células B/patologia , Antineoplásicos/uso terapêuticoRESUMO
INTRODUCTION: The role of prophylactic biliary stenting after clearance of choledocholithiasis in patients awaiting cholecystectomy for concomitant cholelithiasis is controversial. We planned a randomized controlled trial to study the effect of prophylactic biliary stenting after achieving biliary clearance in reducing recurrence of choledocholithiasis and biliary complications in patients awaiting cholecystectomy. METHODS: Patients with concomitant cholelithiasis and choledocholithiasis were included, and those who had evidence of clearance of choledocholithaisis (documented on occlusion cholangiogram during endoscopic retrograde cholangiography [ERC]) were randomized to prophylactic biliary stenting or no stenting. Choledocholithaisis recurrence rate (primary outcome), biliary complications and need for repeat/emergency ERC (secondary outcomes) were compared till 3 months after clearance. RESULTS: Between September 2021 and July 2022, 70 patients were randomized into group A, stenting (n = 35), and group B, no stenting (n = 35). Sixty-six patients were included in the final analysis. Baseline characteristics were comparable between the 2 groups. Ten (15.2%) patients had recurrence of choledocholithiasis, and it was comparable between the 2 groups (7/34 [20.6%] and 3/34 [9.4%], P = 0.306). Five patients (2 cholecystitis and 3 post-ERC pancreatitis) from the stent group while none from the no stent group developed complications, and this difference was statistically significant ( P = 0.024). None of the patients in both the groups needed emergency ERC during the follow-up. DISCUSSION: This randomized trial shows a higher complication rate with prophylactic stenting, while there is no benefit in preventing choledocholithiasis recurrence in patients waiting for cholecystectomy after biliary clearance (CTRI registration number: CTRI/2021/09/036538).
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OBJECTIVE: To investigate the diagnostic performance of a multiparametric magnetic resonance imaging (MRI) protocol comprising quantitative MRI (diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and dynamic contrast-enhanced (DCE) perfusion MRI) and conventional MRI in the characterization of gallbladder wall thickening (GWT). METHODS: This prospective study comprised consecutive adults with GWT who underwent multiparametric MRI between July 2020 and April 2022. Two radiologists evaluated the MRI independently. The final diagnosis was based on surgical histopathology. The association of MRI parameters with malignant GWT was evaluated. The area under the curve (AUC) for the quantitative MRI parameters and diagnostic performance of conventional, and multiparametric MRI were compared. The interobserver agreement between two radiologists was calculated. RESULTS: Thirty-five patients (mean age, 56 years, 23 females) with GWT (25 benign and ten malignant) were evaluated. The quantitative MRI parameters significantly associated with malignant GWT were apparent diffusion coefficient on DWI (p = 0.007) and mean diffusivity (MD) on DTI (p = 0.013), perfusion fraction (f) on IVIM (p = 0.033), time to peak enhancement (TTP, p = 0.008), and wash in rate (p = 0.049) on DCE-MRI. TTP had the highest AUC of 0.790, followed by MD (0.782) and f (0.742) (p = 0.213) for predicting malignant GWT. Multiparametric MRI had significantly higher sensitivity (90% vs. 80%, p = 0.045) than conventional MRI for diagnosing malignant GWT. The two radiologists' reading had substantial to near-perfect agreement (kappa = 0.639-1) and moderate to strong correlation (interclass correlation coefficient = 0.5-0.88). CONCLUSION: Multiparametric protocol incorporating advanced sequences improved the diagnostic performance of MRI for differentiating benign and malignant GWT. KEY POINTS: ⢠Multiparametric MRI had 90% sensitivity and 88% specificity for diagnosing malignant GWT, compared to 80% sensitivity and 88% specificity for conventional CE-MRI. ⢠Among the quantitative MRI parameters, TTP (perfusion-MRI) had the highest AUC of 0.790, followed by MD (0.782) and IVIM-f (0.742). ⢠For most quantitative MRI parameters, there was moderate to strong agreement (ICC = 0.5-0.88).
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Imagem de Tensor de Difusão , Vesícula Biliar , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Meios de Contraste/farmacologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Perfusão , Movimento (Física)RESUMO
A series of symmetrical and unsymmetrical donor-acceptor type phenothiazine derivatives 1-18 were designed and synthesized via Pd-catalyzed Sonogashira cross-coupling and [2 + 2] cycloaddition-retroelectrocyclization reactions. The incorporation of cyano-based acceptors 1,1,4,4-tetracyanobutadiene (TCBD) and dicyanoquinodimethane (DCNQ) in the phenothiazine derivatives resulted in systematic variation in the photophysical, thermal, and electrochemical properties. The electronic absorption spectra of the phenothiazine derivatives with strong acceptors 2, 3, 5, 6, 8, 9, 11, 12, 14, 15, 17, and 18 show red-shifted absorption as compared to phenothiazine derivatives 1, 4, 7, 10, 13, and 16 in the near-IR region due to a strong intramolecular charge transfer (ICT) transition. The electrochemical analysis of the phenothiazine derivatives 2, 3, 5, 6, 8, 9, 11, 12, 14, 15, 17, and 18 reveals two reduction waves at low potential due to the TCBD and DCNQ acceptors. The mono-TCBD-functionalized phenothiazine 2 shows higher thermal stability compared to other phenothiazine derivatives. The computational studies on phenothiazines 1-18 reveal the LUMO is substantially stabilized as acceptor strength increases, which lowers the HOMO-LUMO gap.