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1.
Stroke ; 55(10): 2502-2509, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39234742

RESUMO

BACKGROUND: Functional activation of the focal ischemic brain has been reported to improve outcomes by augmenting collateral blood flow. However, functional activation also increases metabolic demand and might thereby worsen outcomes. Indeed, preclinical and clinical reports have been conflicting. Here, we tested the effect of functional activation during acute ischemic stroke using distal middle cerebral artery occlusion in anesthetized mice. METHODS: Using transgenic mice expressing channelrhodopsin-2 in neurons, we delivered functional activation using physiological levels of transcranial optogenetic stimulation of the moderately ischemic cortex (ie, penumbra), identified using real-time full-field laser speckle perfusion imaging during a 1-hour distal microvascular clip of the middle cerebral artery. Neuronal activation was confirmed using evoked field potentials, and infarct volumes were measured in tissue slices 48 hours later. RESULTS: Optogenetic stimulation of the penumbra was associated with more than 2-fold larger infarcts than stimulation of the contralateral homotopic region and the sham stimulation group (n=10, 7, and 9; 11.0±5.6 versus 5.1±4.3 versus 4.1±3.7 mm3; P=0.008, 1-way ANOVA). Identical stimulation in wild-type mice that do not express channelrhodopsin-2 did not have an effect. Optogenetic stimulation was associated with a small increase in penumbral perfusion that did not explain enlarged infarcts. CONCLUSIONS: Our data suggest that increased neuronal activity during acute focal arterial occlusions can be detrimental, presumably due to increased metabolic demand, and may have implications for the clinical management of hyperacute stroke patients.


Assuntos
AVC Isquêmico , Camundongos Transgênicos , Optogenética , Animais , Camundongos , AVC Isquêmico/fisiopatologia , Infarto da Artéria Cerebral Média/fisiopatologia , Masculino , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Isquemia Encefálica/fisiopatologia , Neurônios/metabolismo , Circulação Cerebrovascular/fisiologia , Camundongos Endogâmicos C57BL
3.
medRxiv ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39314927

RESUMO

Background and Purpose: Animal studies have suggested that valproic acid (VPA) is neuroprotective in aneurysmal subarachnoid hemorrhage (SAH). Potential mechanisms include an effect on cortical spreading depolarizations (CSD), apoptosis, blood-brain barrier integrity, and inflammatory pathways. However, the effect of VPA on SAH outcomes in humans has not been investigated. Methods: We conducted a retrospective analysis of 123 patients with nontraumatic SAH. Eighty-seven patients had an aneurysmal source and 36 patients did not have a culprit lesion identified. We used stepwise logistic regression to determine the association between VPA and the following: delayed cerebral ischemia (DCI), radiographic vasospasm, and discharge modified Rankin Scale (mRS) score > 3. Results: All 18 patients who received VPA underwent coil embolization of their aneurysm. VPA use did not have a significant association with DCI on adjusted analysis (Odds Ratio, OR = 1.07, 95% CI: 0.20 - 5.80). The association between VPA use and vasospasm was OR = 0.64 (0.19 - 1.98) and discharge mRS > 3 was OR = 0.45 (0.10 - 1.64). Increased age (OR = 1.04, 1.01 - 1.07) and Hunt and Hess (HH) grade > 3 (OR = 14.5, 4.31 - 48.6) were associated with an increased likelihood for poor discharge outcome (mRS > 3). Younger age (OR = 0.96, 0.93 - 0.99), mFS score = 4 (OR = 4.14, 1.81 - 9.45), and HH grade > 3 (OR = 2.92, 1.11 - 7.69) were all associated with subsequent development of radiographic vasospasm. There were no complications associated with VPA administration. Conclusion: We did not observe an association between VPA and the rate of DCI. There may have been a protective association on discharge outcome and radiographic vasospasm that did not reach statistical significance. We found that VPA use was safe and is plausible to be used in a population of SAH patients who have undergone endovascular treatment of their aneurysm. Larger, prospective studies are needed to determine the effect of VPA on outcome after SAH.

4.
J Surg Oncol ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39315466

RESUMO

BACKGROUND: Lymphatic drainage from the arm may be altered after axillary lymph node dissection (ALND). Understanding these alterations is important as they may change standard surgical and radiation treatment in recurrent breast cancer or upper extremity skin cancers, including melanoma. METHODS: Utilizing a single-institution planar and single photon emission computed tomography/computed tomography lymphoscintigraphy database, we identified patients with a diagnosis of upper extremity cutaneous melanoma from 2008 to 2023 who previously underwent ALND for cancer treatment and did not develop upper extremity cancer-related lymphedema. ALND patients were matched to control patients presenting with cutaneous melanomas at the same anatomic sites. Sentinel lymph nodes (SLNs) were compared between both groups. RESULTS: Of 3628 upper extremity melanoma cutaneous patients, 934 met inclusion criteria, including 22 ALND and 912 control patients. Level I axillary SLN drainage was observed in 98% of controls and 27% of ALND patients (p < 0.001). Level II axillary SLN drainage was observed in 3% of controls and 27% of ALND patients (p < 0.001). Level III axillary SLN drainage was observed in 1% of controls and 32% of ALND patients (p < 0.001). Epitrochlear SLN drainage was observed in 9% of controls and 32% of ALND patients, respectively (p < 0.046). Brachial SLN drainage was observed in 4% of controls and 23% of ALND patients (p < 0.001). CONCLUSIONS: Distinct changes in functional lymphatic drainage were seen between the arms of patients who previously underwent ALND versus control patients. Levels II and III axillary, epitrochlear, and brachial nodes are possible sites of metastatic disease that should be considered in patients with a prior ALND.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39277550

RESUMO

PURPOSE: Sentinel node biopsy (SNB) is a common staging tool for breast cancer. Initially, peritumoral (PT) injections were used, however subareolar (SA) injections were later introduced to simplify the technique. Controversy remains regarding whether PT and SA injections map the same sentinel lymph nodes (SLNs). This study aimed to determine whether the regional location of breast SLNs differs when using PT versus SA injections using a large dataset from a single institution. METHODS: A total of 1035 patients who underwent breast SNB (PT injections: n = 858 and SA injections: n = 177) with lymphoscintigraphy and SPECT/CT were included. The identified SLN locations using SA injections were compared with those using PT injections. Differences in drainage proportions and odds ratios (ORs) for each clockface breast region and the whole breast were calculated using a two-proportion z-test and Fisher's Exact Test. RESULTS: A higher proportion of internal mammary SLNs were identified using PT injections for the whole breast (0.30 versus 0.09) and for all breast regions, with all regions showing statistical significance except the upper outer quadrant. Similarly, ORs showed identification of internal mammary SLNs was significantly higher when using PT injections (4.35, 95% CI 2.53 to 7.95). There were no significant differences in identifying axillary SLNs between injection sites. CONCLUSION: This is the largest cohort study to compare the regional location of breast SLNs identified using PT injections versus SA injections. Discordance was shown in the SLNs identified between injection techniques, with PT injections more frequently identifying internal mammary SLNs.

6.
J Surg Oncol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138920

RESUMO

BACKGROUND: Variations of hand and forearm lymphatic drainage to upper-arm lymphatic pathways may impact the route of melanoma metastasis. This study compared rates of lymphatic drainage to epitrochlear nodes between anatomic divisions of the hand and forearm to determine whether the anatomic distribution of hand and forearm melanomas affects the likelihood of drainage to epitrochlear lymph nodes. METHODS: Using a single-institution lymphoscintigraphy database, we identified all patients with cutaneous melanoma on the hand and forearm. A body-map two-dimensional coordinate system was used to classify cutaneous melanoma sites between radial-ulnar and dorsal-volar divisions. Sentinel lymph nodes (SLNs) visualized on lymphoscintigraphy were recorded. Proportions of patients with epitrochlear SLNs were compared between anatomic divisions using χ2 analysis. RESULTS: Of 3628 upper extremity cutaneous melanoma patients who underwent lymphatic mapping with lymphoscintigraphy, 1400 met inclusion criteria. Twenty-one percent of patients demonstrated epitrochlear SLNs. Epitrochlear SLNs were observed in 27% of dorsal forearm melanomas and 15% of volar forearm melanomas (p < 0.001). Epitrochlear SLNs were observed in 31% of ulnar forearm melanomas and 17% of radial forearm melanomas (p < 0.001). CONCLUSIONS: Higher proportions of dorsal and ulnar forearm melanomas have epitrochlear SLNs. Metastasis to epitrochlear SLNs may be more likely from melanomas in these respective forearm regions.

7.
Science ; 385(6709): eadp2065, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39116219

RESUMO

Hematopoietic stem cells (HSCs) are routinely mobilized from the bone marrow (BM) to the blood circulation for clinical transplantation. However, the precise mechanisms by which individual stem cells exit the marrow are not understood. This study identified cell-extrinsic and molecular determinants of a mobilizable pool of blood-forming stem cells. We found that a subset of HSCs displays macrophage-associated markers on their cell surface. Although fully functional, these HSCs are selectively niche-retained as opposed to stem cells lacking macrophage markers, which exit the BM upon forced mobilization. Macrophage markers on HSCs could be acquired through direct transfer by trogocytosis, regulated by receptor tyrosine-protein kinase C-Kit (CD117), from BM-resident macrophages in mouse and human settings. Our study provides proof of concept that adult stem cells utilize trogocytosis to rapidly establish and activate function-modulating molecular mechanisms.


Assuntos
Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas , Proteínas Proto-Oncogênicas c-kit , Trogocitose , Animais , Humanos , Camundongos , Células-Tronco Adultas/fisiologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Nicho de Células-Tronco , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Antígenos de Diferenciação
8.
Can Urol Assoc J ; 18(8): 234-238, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39151158

RESUMO

INTRODUCTION: Previous studies have demonstrated the feasibility of bedside placement of ureteric stents; however, they have traditionally required two skilled operators and were associated with some stent malposition especially for proximal ureteric obstruction. We sought to investigate the efficacy and safety of a modified technique for ultrasound-assisted bedside ureteric stent insertion without the presence of a skilled assist. METHODS: A single institution prospective study was performed from April-August 2023. Indications for stenting included infection, renal insufficiency, or intractable colic. Exclusion criteria included age <18 years, hemodynamic instability, and patients with history of chronic pain. Point-of-care ultrasound (POCUS) was used to confirm wire placement in the kidney and presence of a hydronephrotic drip from a 5 French ureteric catheter was used to confirm placement beyond the level of obstruction. RESULTS: Of 28 patients, all patients underwent successful bedside ureteric stent placement. Mean age was 64.9 years and mean body mass index (BMI) was 33.2. Proximal ureter obstruction was present in 52% of patients and mid/distal obstruction in 48%. In cases with obstructing stones, the mean stone size was 8.1 mm with a range of 4-15 mm. Infection was the indication for stent placement in most patients (71%), followed by pain (4%) and acute kidney injury (AKI) (4%). All patients who underwent successful stent placement had presence of hydronephrotic drip from the ureteric catheter. CONCLUSIONS: Ultrasound-assisted bedside ureteric stent insertion without a skilled assist is a safe and feasible option for management of acute ureteral obstruction. Presence of hydronephrotic drip can indicate successful access beyond the level of obstruction as an alternative to POCUS.

10.
Urology ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39208947

RESUMO

OBJECTIVE: To prospectively assess surgical outcomes, complications, and patient-reported tolerability of invasive scrotal surgeries under local anesthesia (LA) alone, without sedation, compared to tolerability of penile procedures commonly performed in this manner. METHODS: Adult patients undergoing penile and scrotal surgeries under LA only were enrolled from August 2022 to June 2023 (NCT05617261). Demographics, surgeon-perceived and patient-reported pain, and surgical variables were collected. Tolerability to the procedures and future anesthetic choice for a repeat procedure was assessed on follow-up. Complication data were collected, including recurrence, infection, excessive pain, and emergency room and family physician visits. RESULTS: Hundred and seven patients were enrolled with a mean age ± SD of 42.2 ± 16.4 years. There was a 100% procedural success rate and no cases of perioperative complications or escalation of anesthetic. Around 92.4% (n = 97) of patients indicated they would opt for LA only for a hypothetical repeat procedure. Of the minority opting for general anesthetic, most indicated discomfort or preferring an element of amnesia. No differences between intraoperative pain or tolerability scores of invasive scrotal procedures compared to penile procedures were observed. On univariate analysis, longer procedure duration (P = .003), cannabis use (P = .01), and higher intra-operative pain (P = .005) was associated with lower tolerability. CONCLUSION: LA alone in an office-based setting is promising for scrotal surgeries. It offers similarly high patient tolerability compared to procedures that are routinely performed under LA, with the preservation of outcomes. Adopting this method has the potential for substantial cost savings, reduced wait times, enhanced accessibility, and improved surgical efficiency.

11.
J Invertebr Pathol ; 206: 108166, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39004164

RESUMO

Peptidoglycan recognition proteins (PGRPs) and Toll-like receptors (TLRs) are highly conserved pattern recognition receptors (PRRs). Earthworms possess genes encoding TLRs that specifically respond to Gram-positive bacteria. In addition, several PGRPs have been recently identified, which are predicted to exhibit amidase activity but lack receptor function. In lophotrochozoans, a membrane-bound PRR responsible for detecting Gram-negative bacteria remains unidentified. This study reveals several novel transmembrane peptidoglycan recognition proteins (Ean-PGRPLs) in earthworms, whose mRNA expression increases in response to Gram-negative but not Gram-positive bacteria. This indicates that Ean-PGRPLs may serve as a PRR associated with intracellular signaling for Gram-negative bacteria.


Assuntos
Proteínas de Transporte , Oligoquetos , Animais , Oligoquetos/microbiologia , Oligoquetos/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Bactérias Gram-Negativas , Bactérias Gram-Positivas
12.
Urology ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972394

RESUMO

OBJECTIVE: To evaluate the effectiveness of Eutectic Mixture of Local Anesthetic (EMLA), a topical anesthetic cream, in office-based invasive andrological procedures such as hydrocelectomy, spermatocelectomy, and others, aimed at minimizing pain perception and enhancing the overall patient experience. METHODS: A double-blinded randomized controlled trial was conducted for patients undergoing scrotal andrology surgeries under LA. Power calculation was performed with an estimated sample size of 72. Participants were randomly assigned in a 1:1 ratio to topical EMLA + LA versus LA alone. In the post-operative recovery area, patient will be asked to complete a VAS questionnaire rating pain with LA administration and pain with procedure. Analysis comparing VAS pain scores of both groups was performed using the independent sample t-test method. RESULTS: Seventy-two patients were included in our analysis, with 36 in the control and 36 in the intervention arm. For patient pain with administration of LA, the control arm reported an average VAS pain score of 4.31, compared to 3.72 in the intervention arm (P = .319). For patient pain with procedure, patients in the control arm reported a median VAS pain score of 3.47 compared to 3.03 (P = .432) in the intervention arm. Overall, 86% (62/72) of patients reported that they would either be "very likely" (4/5) or "highly likely" (5/5) to undergo future procedures under local anesthetic. CONCLUSION: While performing scrotal surgeries under LA appears to be well tolerated and a feasible option, the application of EMLA cream does not appear to significantly alter patient-reported outcomes.

13.
Cancer Imaging ; 24(1): 97, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080795

RESUMO

BACKGROUND: The identification and assessment of sentinel lymph nodes (SLNs) in breast cancer is important for optimised patient management. The aim of this study was to develop an interactive 3D breast SLN atlas and to perform statistical analyses of lymphatic drainage patterns and tumour prevalence. METHODS: A total of 861 early-stage breast cancer patients who underwent preoperative lymphoscintigraphy and SPECT/CT were included. Lymphatic drainage and tumour prevalence statistics were computed using Bayesian inference, non-parametric bootstrapping, and regression techniques. Image registration of SPECT/CT to a reference patient CT was carried out on 350 patients, and SLN positions transformed relative to the reference CT. The reference CT was segmented to visualise bones and muscles, and SLN distributions compared with the European Society for Therapeutic Radiology and Oncology (ESTRO) clinical target volumes (CTVs). The SLN atlas and statistical analyses were integrated into a graphical user interface (GUI). RESULTS: Direct lymphatic drainage to the axilla level I (anterior) node field was most common (77.2%), followed by the internal mammary node field (30.4%). Tumour prevalence was highest in the upper outer breast quadrant (22.9%) followed by the retroareolar region (12.8%). The 3D atlas had 765 SLNs from 335 patients, with 33.3-66.7% of axillary SLNs and 25.4% of internal mammary SLNs covered by ESTRO CTVs. CONCLUSION: The interactive 3D atlas effectively displays breast SLN distribution and statistics for a large patient cohort. The atlas is freely available to download and is a valuable educational resource that could be used in future to guide treatment.


Assuntos
Neoplasias da Mama , Imageamento Tridimensional , Linfonodo Sentinela , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Imageamento Tridimensional/métodos , Idoso , Adulto , Linfocintigrafia/métodos , Biópsia de Linfonodo Sentinela/métodos , Idoso de 80 Anos ou mais , Metástase Linfática/diagnóstico por imagem
14.
Can Urol Assoc J ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39037505

RESUMO

INTRODUCTION: Accurate diagnostic staging of upper tract urothelial cancer (UTUC) is challenging. Endoscopic staging is limited by its ability to provide adequate sampling of deeper layers of the ureter and renal pelvis. Further ability to accurately predict invasive disease would aid in better selecting the appropriate treatment for patients. We aimed to analyze the ability of preoperative cross-sectional radiologic findings to predict pathologic outcomes, including tumor grade, muscle-invasive disease, and presence of lymphovascular invasion (LVI). METHODS: All patients diagnosed with localized UTUC (cN0M0) who underwent nephroureterectomy between February 2012 and December 2018 in Manitoba, Canada, were identified. Preoperative radiologic characteristics, including the presence and severity of hydronephrosis, as well as tumor location were recorded. Patients' and pathologic characteristics were also recorded. Logistic regression analysis was used to assess the association between radiologic variables and pathologic outcomes at radical surgery. RESULTS: A total of 112 pathology reports of patients with UTUC were obtained. The median age was 70 years (range 50-87), and 58.8% of patients were men. On univariate analysis, ureteric location on computed tomography (odds ratio [OR] 2.240, 95% confidence interval [CU] 1.049- 4.783, p=0.037) and presence of hydronephrosis (OR 2.455, 95% CI 1.094-5.506, p=0.0029) were each independently associated with locally invasive disease (>pT2). No radiologic variables were found to be a predictor of adverse pathology on multivariable analysis. Only the presence of hydronephrosis was associated with high-grade disease on univariate analysis (OR 2.533, 95% CI 1.083-5.931, p=0.032). CONCLUSIONS: Our findings suggest a limited role for cross-sectional imaging in predicting the presence of high-grade disease, LVI, or locally advanced disease in UTUC.

15.
Can Urol Assoc J ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39037507

RESUMO

INTRODUCTION: Amidst substantial surgical waitlists, novel methods are needed to improve the delivery of surgical care in Canada. One strategy involves shifting select surgeries from hospitals into community ambulatory centers, which expedite procedures and allow hospitals to prioritize critical and complex patients. We sought to evaluate surgical outcomes at a novel Canadian urologic clinic and surgical center. METHODS: A retrospective study was conducted at a novel accredited surgical facility and outpatient ambulatory clinic from August 2022 to August 2023. Procedures ranged from scrotal and transurethral surgeries to inflatable penile prosthesis insertion. Traditional outpatient procedures, including vasectomy and cystoscopy, were excluded. All patients were discharged the same day and seen 4-6 weeks post-procedure. Variables of interest included surgery type, anesthesia administered, additional clinic appointments, unplanned family physician appointments, visits to the emergency department (ED), and hospital admissions. RESULTS: In a 12-month period, 519 surgeries were performed. The mean patient age was 49.6±17.3 years, with most classified as American Society of Anesthesiologists (ASA) 1-2 (88.8%). Most (95.8%, n=497) patients did not require medical care outside the clinic before scheduled followup; 2.5% (n=13) visited the ED presenting for wound concerns, postoperative pain, query infection, or catheter-related concerns. Only 1.7% (n=9) required an unscheduled appointment with their family physician, with concerns being inadequate postoperative pain management (n=4) or suspected infection (n=4). No patient required hospital admission. CONCLUSIONS: Many urologic surgeries classically performed in hospital operating rooms can be safely performed in a non-hospital, outpatient surgical facility with preservation of good outcomes. This strategy can potentially improve the efficiency of urologic healthcare delivery in select patients.

16.
Exp Neurol ; 380: 114903, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39079623

RESUMO

Endovascular middle cerebral artery occlusion (MCAO) is a widely used experimental ischemic stroke model. However, the model carries high early mortality. Our aim was to investigate the factors that influence early mortality within 48 h of reperfusion after transient MCAO. Using C57BL/6 mice, we induced 1-hour endovascular filament MCAO. To introduce heterogeneity of infarct volumes, a subset of animals had additional tandem common carotid artery occlusion (MCAO+CCAO). Continuous video monitoring was used to gain insight into the cause of death. Mortality within 48 h was 25% in the pooled cohort. All animals with early mortality suffered from infarcts in the hippocampus, sometimes accompanied by infarcts in the thalamus and midbrain, which occurred exclusively in the MCAO+CCAO group. All animals with early mortality developed convulsive seizures captured on video monitoring. None of the animals that did not develop convulsive seizures died. Among the three regions, hippocampal infarction appeared necessary for convulsive seizures and early mortality. Our data highlight seizures as the primary cause of mortality within the first 48 h after endovascular filament MCAO, linked to hippocampal infarction. Since hippocampal blood supply is mainly from the posterior cerebral artery (PCA), avoiding concurrent PCA ischemia can decrease mortality in proximal MCAO models.


Assuntos
Hipocampo , Infarto da Artéria Cerebral Média , Camundongos Endogâmicos C57BL , Convulsões , Animais , Convulsões/etiologia , Convulsões/mortalidade , Camundongos , Hipocampo/patologia , Infarto da Artéria Cerebral Média/mortalidade , Infarto da Artéria Cerebral Média/patologia , Masculino , Modelos Animais de Doenças , Procedimentos Endovasculares , Infarto Encefálico/etiologia , Infarto Encefálico/patologia
17.
Res Sq ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38883739

RESUMO

Lenalidomide maintenance is associated with a significantly improved progression-free in patients with newly diagnosed multiple myeloma. Maintenance with lenalidomide is generally well tolerated; however, lenalidomide associated diarrhea is a common side effect and bile acid malabsorption has been suggested as an underlying mechanism. We conducted a single arm phase 2 trial of colesevelam, a bile acid binder, for lenalidomide-associated diarrhea in multiple myeloma. Patients were treated with colesevelam daily starting at 1250 mg (2 tablets 625 mg) for 12 weeks. The trial included 25 patients, 1 patient with grade 3 diarrhea, 14 with grade 2, and 10 with grade 1 diarrhea. All patients were on treatment with single agent lenalidomide maintenance and no patient progressed during the trial. Colesevelam treatment was highly effective for treatment of lenalidomide-associated diarrhea; 22 (88%) of the 25 patients responded where 17 patients (68%) had complete resolution of diarrhea, and 5 patients (20%) had improvement by 1 grade of diarrhea. The responses to colesevelam were seen within the first two weeks of treatment. These findings support the conclusion that lenalidomide-associated diarrhea is driven by bile acid malabsorption. Five patients reported mild gastrointestinal side effects including constipation. Importantly, the pharmacokinetics of lenalidomide were not affected by concomitant colesevelam treatment. The stool microbiome composition was not significantly different before and after colesevelam treatment. Patients reported improved diarrhea, fewer gastrointestinal symptoms, and less interference with their daily life after starting colesevelam. In summary, colesevelam was safe and highly effective for treatment of lenalidomide-associated diarrhea in multiple myeloma and does not reduce the clinical effect of lenalidomide.

18.
Emerg Med J ; 41(10): 628-629, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-38825364

RESUMO

People experiencing the highest levels of social deprivation are more likely to present to emergency care across the spectrum of disease severity, and to have worse outcomes following acute illness. Emergency medicine in the UK and Europe has lagged behind other regions in incorporating social emergency medicine into practice. There is evidence that emergency clinicians have the potential to mitigate health inequalities, through advocacy and intervention supported by high-quality research, while also acknowledging the limitations intrinsic to the environment in which they work.


Assuntos
Medicina de Emergência , Humanos , Reino Unido , Medicina Social , Europa (Continente)
19.
Can Urol Assoc J ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38896478

RESUMO

INTRODUCTION: We aimed to investigate the surgical outcomes following inguinal and subinguinal urological procedures under deep intravenous sedation (DIVS) with multimodal local anesthesia (LA). METHODS: We conducted a retrospective cohort study from September 2022 to December 2023 including adult patients deemed eligible for day surgery (American Society of Anesthesiologist score 1-3) undergoing radical orchiectomy (RO), microscopic varicocelectomy (MV), or microscopic denervation of spermatic cords (MDSC). All procedures were performed at a single urologic ambulatory surgical center and outpatient clinic, and by a single surgeon (PP). Procedures were performed through a subinguinal or inguinal approach with DIVS and adjunctive multimodal LA. We evaluated intraoperative complications and relevant surgical outcomes and parameters. RESULTS: A total of 103 patients were included in the analysis with a mean age ± standard deviation of 37.3±9.6. This included 25 patients who underwent RO, 54 patients who underwent MV, and 24 patients who underwent MDSC. All procedures were completed successfully without intraoperative complications. Oncologic outcomes were preserved, fertility outcomes improved, and pain scores reduced similar to the expected rates in the literature. CONCLUSIONS: Our preliminary results demonstrate the safety, effectiveness, and feasibility of performing inguinal and subinguinal urologic procedures under DIVS with LA. These findings suggest that this technique preserves high-quality care while avoiding unnecessary risks of general or spinal anesthesia, representing an opportunity to transfer these cases outside of hospitals' operating rooms into outpatient ambulatory centers.

20.
Clin Nucl Med ; 49(9): e451-e452, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38861407

RESUMO

ABSTRACT: A 17-year-old boy with Von Hippel-Lindau syndrome presented with hypertension, raised plasma catecholamines, and MRI findings of a new pancreatic tail lesion and 2 stable right adrenal lesions concerning for functional neuroendocrine tumors. A 68 Ga-DOTATATE PET/CT demonstrated intense tracer avidity within the pancreatic lesion with minimal uptake in the adrenal lesions. Conversely, a 123 I-MIBG SPECT/CT study demonstrated high-grade tracer uptake within the adrenal lesions, with no significant uptake appreciated in the pancreatic lesion. The adrenal lesions were resected, and pathology was consistent with pheochromocytoma. Plasma catecholamines returned to within the normal range and hypertension resolved.


Assuntos
3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais , Compostos Organometálicos , Feocromocitoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Doença de von Hippel-Lindau , Humanos , Feocromocitoma/diagnóstico por imagem , Adolescente , Masculino , Doença de von Hippel-Lindau/diagnóstico por imagem , Doença de von Hippel-Lindau/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem
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