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INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the 2-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite 2-dose vaccination. METHODS: Adults with IBD who had received 2-dose Heplisav-B vaccination between 2018 and 2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L measured at ≥4 weeks after vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data were compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted after 2-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1,000 IU/L) despite a median intervaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did vs did not seroconvert after third-dose vaccination. DISCUSSION: In patients with IBD lacking HBV immunity despite 2-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary 2-dose vaccination.
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BACKGROUND AND AIMS: The management of dual anti-platelet therapy after percutaneous coronary intervention (PCI) and GI bleeding (GIB) remains a clinical dilemma. We sought to identify predictors of GIB and recurrent bleeding and to determine whether recurrent bleeding increases the risk of major adverse cardiovascular events (MACEs). METHODS: In this single-center retrospective study, patients undergoing PCI were identified. The primary and secondary endpoints were GIB at 180 days and recurrent bleeding or MACE at 365 days. Logistic regression was used to identify predictors of GIB and recurrent bleeding. Cox proportional hazards modeling was used to determine whether recurrent bleeding can predict a MACE. RESULTS: Five hundred thirty-six patients were included. On multivariable analysis, PCI for acute coronary syndrome was associated with a 95% increased odds of GIB (P < .001). The P2Y12 inhibitor was continued in >90% of patients, which trended toward significance for recurrent bleeding (P < .10). The HAS-BLED score (Hypertension, Abnormal renal and liver function, Stroke, Bleeding tendency or predisposition, Labile INRs, Elderly, Drugs), including a labile international normalized ratio and prior major bleeding, was strongly associated with recurrent bleeding (P ≤ .009). Recurrent bleeding was associated with a 115% increased risk of MACEs (P = .02). We derived a novel risk score, named the SIGE score ([S]TEMI at PCI, having a labile [I]NR at PCI, index [G]IB within 180 days of PCI, and previous precatheterization [E]ndoscopy within 6 months), to predict recurrent bleeding at 365 days with a high predictive accuracy (area under the curve, .773; 95% confidence interval, .702-.845). CONCLUSIONS: The SIGE score may help to predict recurrent bleeding, which was shown to be associated with an increased risk of MACEs. Further external validation is needed.
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Intervenção Coronária Percutânea , Humanos , Idoso , Intervenção Coronária Percutânea/efeitos adversos , Terapia Antiplaquetária Dupla/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/tratamento farmacológico , Fatores de Risco , Inibidores da Agregação Plaquetária/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. STUDY: Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. RESULTS: Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. CONCLUSIONS: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.
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Doença de Crohn , Sistema Renina-Angiotensina , Humanos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Doença de Crohn/tratamento farmacológico , Estudos Retrospectivos , Progressão da Doença , Corticosteroides/efeitos adversosRESUMO
OBJECTIVE: Patients with inflammatory bowel disease (IBD) are at increased risk of vaccine-preventable diseases (VPDs). Despite the increasing prevalence of IBD in non-white populations, little is known regarding racial disparities in VPD burden. METHODS: Retrospectively analyzing the 2016 to 2020 National Inpatient Sample, we identified adults with IBD hospitalized for a principal diagnosis of VPD. The primary outcome investigated was hospitalization for VPD stratified by patient-reported race. Secondary outcomes were in-hospital morbidity, mortality, length of stay, and health care utilization. Multivariable regression analysis was performed to adjust for patient and hospital characteristics. RESULTS: The search identified 554,114 hospitalizations for VPD, including 4170 hospitalizations in patients with IBD. Patients with IBD had significantly greater odds of hospitalization from herpes zoster virus (adjusted odds ratio [aOR]: 1.73) and varicella zoster virus (aOR: 2.31). Comparing white and non-white patients with IBD, significant racial disparities were noted. Non-white patients were at greater odds of hospitalization from influenza (aOR: 1.74), herpes zoster virus (aOR: 1.77), and varicella zoster virus (aOR: 1.62). In-hospital morbidity was greater in non-white patients, including greater odds of requiring intensive care unit stay (aOR: 1.18). Morbidity was elevated in African Americans, with greater odds of acute kidney injury (aOR: 1.25), venous thromboembolism (aOR: 1.17), respiratory failure (aOR: 1.16), and intensive care unit stay (aOR: 1.18). No differences were found in mortality, length of stay, and health care utilization. CONCLUSIONS: Significant racial disparities in VPD hospitalization and in-hospital morbidity were found among adults with IBD in the United States. With the increasing prevalence of IBD in non-white populations, targeted efforts are needed to improve health equity.
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BACKGROUND: The diagnosis of isolated small bowel Crohn's disease (CD) can be challenging. Symptoms are non-specific and both imaging and capsule endoscopy (CE) may be misleading as several diseases may mimic CD. Double balloon enteroscopy (DBE) allows a more extensive endoscopic and histologic evaluation of the small bowel. Our aim was to describe the diagnostic utility and impact of DBE on management of patients with known CD and in patients with suspected/rule-out CD. METHODS: Retrospective review of our institution's DBE database from February 2009 to May 2013. Adult patients referred for DBE for further evaluation of known or suspected CD (due to symptoms, abnormal imaging and/or CE) were included. Patient demographics, clinical characteristics, imaging and CE results, prior DBE, indication for DBE, DBE findings, DBE adverse events, pathology findings, final diagnosis, treatment prior and post DBE and follow-up DBE were abstracted from the electronic medical record. RESULTS: A total of 108 patients were included, 61 (56%) females, mean age 52 years (range 20-83). Indications for DBE included: disease activity assessment/therapeutic in 10 patients with established diagnosis of CD and for diagnostic purposes in 98 patients with suspected CD (31 patients due to abnormal imaging, 29 due to abnormal CE and 26 due to both abnormal imaging and CE). Upper, lower, bidirectional upper and lower, and stomal DBE were performed in 21, 24, 62 and 1 patients, respectively. DBE revealed active disease in 8/10 patients with known CD with one patient undergoing dilation of a stricture. Changes in management were recommended for all patients with active disease - start thiopurine (2), optimize thiopurine dose (1), start biologics (3) change biologics (1), systemic steroids (1) and budesonide (1). The patient who underwent stricture dilation ultimately required surgery. A definitive diagnosis of CD (both endoscopic and histologic) was reached in only 39/98 (40%) patients who were referred for suspected CD. Changes in management were recommended in 32/39 (82%) patients. Interestingly, 24/98 patients had been diagnosed with CD at outside institutions and were recommended to initiate therapy for CD. Of these, CD was confirmed in only 15/24 (63%) patients. Adverse events included perforation in 1 patient (1%) who required surgical management and mouth swelling/abrasion in 3 patients (3%). Follow-up DBE to re-assess disease activity was performed in 10/49 (20%) patients with definitive diagnosis of CD, average time between procedures 4.5 years (range 0.7-11.6). One patient with CD was diagnosed with lymphoma 2.4 years after initial DBE. Changes in management were recommended in 6 patients: de-escalation of therapy (3, two underwent surgery), start thiopurine and/or biologic (2) and switch biologics (1). No complications were seen at follow-up DBE. CONCLUSION: DBE is a useful technique to confirm a diagnosis in patients who have suspected CD and can help establish a diagnosis of several diseases that may mimic CD on CT scan or CE. Additionally, DBE in patients with established diagnosis of small bowel CD is an effective tool to assess disease activity and guide therapy. Serious complications are infrequent.
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Nintedanib is a medication that has been increasingly used for treatment of idiopathic and progressive pulmonary fibrosis. In this case series, we describe 3 patients with colitis symptoms associated with nintedanib use. Nintedanib discontinuation resulted in symptomatic resolution in all patients. Budesonide decreased symptoms in 1 patient. Clinicians should be vigilant in taking a thorough medication history and include nintedanib as a cause for gastrointestinal symptoms including colitis.
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Niacin, an important component of a balanced diet, is central to lipid metabolism. Occasionally used to treat hyperlipidemia, niacin is widely available without a prescription, making its use often unknown to treating physicians. Severe hepatotoxicity has been reported with niacin use. In the following report, we describe a case of hospitalization for acute decompensated cirrhosis with cholestatic morphology in a patient taking self-initiated large quantities of extended-release niacin. Despite medical management and support, the patient unfortunately expired on day 16 of hospitalization. Given ease of access and unclear long-term benefit in hyperlipidemia, the current case serves to raise awareness of niacin's potential hepatotoxicity through highlighting a severe outcome. Although mode of liver injury remains unknown, the use of extended-release niacin formulations and prolonged high-dose supplementation is associated with enhanced hepatotoxicity. Careful review and counseling of commonly available supplements remains an important task of both hospital and primary care physicians.
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Doença Hepática Induzida por Substâncias e Drogas , Colestase , Hiperlipidemias , Niacina , Humanos , Hiperlipidemias/tratamento farmacológico , Niacina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Suplementos NutricionaisRESUMO
Introduction: Crohn's disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment option for these patients. We investigated clinical outcomes of CD-CIF patients with SBS treated with teduglutide. Methods: Adults with CD-CIF and SBS who received teduglutide were identified at a tertiary care academic center between 2012 and 2023. Data was collected retrospectively. Primary outcome measured was reduction in parenteral support (PS) by ≥20% volume, with PS defined as utilization of parenteral nutrition (PN) or intravenous fluids (IVF). Several secondary outcomes included immunosuppressive medication changes, subjective symptom improvement, and stool output. Results: We identified 32 patients with CD-CIF and SBS receiving teduglutide. Comparing clinical outcomes before and after teduglutide, 26 of 32 patients achieved the primary outcome of ≥20% PS reduction. A decrease was seen in patients requiring PNâ +â IVF, with corresponding increases in patients requiring PN only and IVF only. Among all 3 groups, a total of 23 patients received PN prior to teduglutide, which decreased to 14 following teduglutide. Weekly PN volume reduced from 7.00 to 3.55 L and weekly frequency decreased from 7.00 to 3.00 instances (Pâ <â .01). Reductions in weekly volume and frequency were observed among all patients receiving IVF support (25 vs 15). Secondary outcomes showed improvement in patient reported subjective symptoms (84.4%), stool output (90.6%), patients meeting criteria for diarrhea/high ostomy output (27 vs 14), and use of unique antidiarrheal medications (3.0 vs 2.0). Conclusions: This retrospective case series demonstrated improved clinical outcomes in patients with CD-CIF and SBS treated with teduglutide resulting in decreased PS requirements, antidiarrheal medications requirement, and stool output without significant effects on immunosuppressive therapy.
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Treatment options for patients with inflammatory bowel disease are constantly evolving; however, medication-refractory disease remains an issue. Pediatric case series show the potential benefit of sirolimus therapy in refractory Crohn's disease (CD); however, limited data exist in adult patients. As such, we retrospectively identified and report clinical outcomes for 4 patients prescribed sirolimus for treatment of refractory CD. Despite a median sirolimus therapy duration of 524 days and some therapeutic benefits, all patients discontinued therapy due to adverse effects. Our findings suggest that while sirolimus may have clinical utility, its role may be limited by treatment-derived adverse effects.
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Background: Colorectal surgery in patients with inflammatory bowel disease (IBD) and cirrhosis has increased morbidity, which may preclude surgery. Preoperative transjugular intrahepatic portosystemic shunt (TIPS) is postulated to reduce surgical risk. In this retrospective single-center study, we characterized perioperative outcomes in patients with IBD and cirrhosis who underwent preoperative TIPS. Methods: We identified patients with IBD and cirrhosis who had undergone preoperative TIPS for portal decompression between 2010 and 2023. All other indications for TIPS led to patient exclusion. Demographic and medical data were collected, including portal pressure measurements. Primary outcome of interest was perioperative outcomes. Results: Ten patients met the inclusion criteria. The most common surgical indications were dysplasia (50%) and refractory IBD (50%). TIPS was performed at a median of 47 days (IQR 34-80) before surgery, with reduction in portal pressures (22.5 vs. 18.5 mmHg, Pâ <â .01) and portosystemic gradient (12.5 vs. 5.5 mmHg, Pâ <â .01). Perioperative complications occurred in 80% of patients, including surgical site bleeding (30%), wound dehiscence (10%), systemic infection (30%), liver function elevation (50%), and coagulopathy (50%). No patients required re-operation, with median length of stay being 7 days (IQR 5.5-9.3). The 30-day readmission rate was 40%, most commonly for infection (75%), with 2 patients having intra-abdominal abscesses and 1 patient with concern for bowel ischemia. Ninety-day and one-year survival was 100% and 90%, respectively. Patients with primary sclerosing cholangitis (PSC)-cirrhosis were noted to have higher perioperative morbidity and a 30-day readmission rate. Conclusions: In patients with IBD and cirrhosis, preoperative TIPS facilitated successful surgical intervention despite heightened risk. Nevertheless, significant complications were noted, in particular for patients with PSC-cirrhosis.
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Background Gastrointestinal manifestations of coronavirus disease 2019 (COVID-19) are increasingly recognized. Through potentially overlapping pathophysiology, co-occurrence of COVID-19 and first-time acute diverticulitis has been reported. Our study aims to further characterize this association in COVID-19-positive patients within a large tertiary care academic center. Methodology Patients diagnosed with COVID-19 who subsequently developed acute diverticulitis within 30 days were identified between 2020 and 2022. COVID-19 and acute diverticulitis were diagnosed by polymerase chain reaction and computed tomography, respectively. Patients with prior history of acute diverticulitis were excluded. Patient characteristics and comorbid conditions were collected. Characterization of the COVID-19 course (treatment setting, medical/ventilatory therapy) and acute diverticulitis (treatment setting, medical/surgical therapy, complications) was performed retrospectively. Subanalysis was performed by COVID-19 vaccination status, the severity of COVID-19, and the timing of acute diverticulitis diagnosis. Results A total of 81 patients were identified, with a median duration between COVID-19 diagnosis and acute diverticulitis of 13 days (interquartile range = 2.5-21.0), with 44.4% of patients requiring hospitalization for COVID-19. The all-cause complication rate of acute diverticulitis was noted to be 59.3%, most commonly intestinal perforation (39.5%), abscess formation (37.0%), and peritonitis (14.8%). Although a trend toward increased all-cause complications (65.9%), intestinal perforation (43.9%), and peritonitis (19.5%) was noted in unvaccinated patients, this did not reach significance. Although all-cause complication rate did not differ in patients diagnosed with acute diverticulitis at the time of COVID-19 presentation, a significantly elevated incidence of intestinal perforation (55.9% vs. 27.7%, p = 0.01), peritonitis (29.4% vs. 4.3%, p < 0.01), and the need for emergent surgical intervention (38.2% vs. 10.6%, p < 0.01) was noted. Conclusions Our study indicates that patients diagnosed with first-time acute diverticulitis within 30 days of COVID-19 infection have a high complication rate, most commonly intestinal perforation. Additionally, patients diagnosed with acute diverticulitis at the same time as COVID-19 detection had a significantly elevated rate of complications and emergent surgical needs. Given the high complication rate, patients who develop diverticulitis within a short timeframe of COVID-19 infection may benefit from increased clinician vigilance and monitoring.
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INTRODUCTION: The Leukemia Inhibitory Factor (LIF) is a member of the interleukin-6 (IL-6) cytokine family. Known to induce differentiation of myeloid leukemia cells, evidence has accumulated supporting its role in cancer evolution through regulating cell differentiation, renewal, and survival. LIF has recently emerged as a biomarker and therapeutic target for pancreatic ductal adenocarcinoma (PDAC). The first in-human clinical trial has shown promising safety profile and has suggested a potential role for LIF inhibitor in combination regimen. AREAS COVERED: Herein, we summarize, discuss, and give an expert opinion on the role of LIF in PDAC promotion, and its potential role as a biomarker and target of anti-cancer therapy. We conducted an exhaustive PubMed search for English-language articles published from 1 January 1970, to 1 August 2022. EXPERT OPINION: PDAC carries a devastating prognosis for patients, highlighting the need for advancing drug development. The results of the phase 1 trial with MSC-1 demonstrated tolerability and safety but modest efficacy. Future research should focus on investigating LIF targets in combination with current standard-of-care chemotherapy, and immunotherapy can be a promising approach. Further, larger multicenter clinical trials are needed to define the use of LIF as a new biomarker in PDAC patients.
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Adenocarcinoma , Antineoplásicos , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Fator Inibidor de Leucemia/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Antineoplásicos/farmacologia , Biomarcadores , Estudos Multicêntricos como Assunto , Neoplasias PancreáticasRESUMO
Hyponatraemia on hospital admission is associated with increased length of stay, healthcare expenditures and mortality. Urine studies collected before fluid or diuretic administration are essential to diagnose the underlying cause of hyponatraemia, thereby empowering admitting teams to employ the appropriate treatment. A multidisciplinary quality improvement (QI) team led by internal medicine residents performed a QI project from July 2020 through June 2021 to increase the rate of urine studies collected before fluid or diuretic administration in the emergency department (ED) in patients admitted with moderate to severe hyponatraemia. We implemented two plan-do-study-act (PDSA) cycles to address this goal. In PDSA Cycle #1, we displayed an educational poster in employee areas of the ED and met with nursing staff at their monthly meetings to communicate the project and answer questions. We also obtained agreement from ED attending physicians and nursing leaders to support the project. In PDSA Cycle #2, we implemented a structural change in the nursing triage process to issue every patient who qualified for bloodwork with a urine specimen container labelled with a medical record number on registration so that the patient could provide a sample at any point, including while in the waiting area. After PDSA Cycle #1, urine specimen collection increased from 34.5% to 57.5%. After PDSA Cycle #2, this increased further to 59%. We conclude that a combination of educational and structural changes led to a significant increase in urine specimen collection before fluid or diuretic administration among patients presenting with moderate-to-severe hyponatraemia in the ED.
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Hiponatremia , Humanos , Hiponatremia/diagnóstico , Hiponatremia/terapia , Serviço Hospitalar de Emergência , Instalações de Saúde , Hospitalização , DiuréticosRESUMO
Bleomycin, a cytotoxic antibiotic commonly used as part of combination chemotherapy regimes in the treatment of germ cell tumors, is well known among clinicians for its potential pulmonary toxicity. Less well known, although postulated to occur through a similar pathomechanism, are the wide spectrum of dermatologic adverse reactions associated with bleomycin therapy. The current case report describes the sudden and distressing appearance of a pruritic erythematous flagellate "whip-like" rash in a 30-year-old Caucasian male undergoing treatment for testicular embryonal carcinoma following the second infusion of bleomycin-containing chemotherapy. Diagnosed as bleomycin-induced flagellate dermatitis, the case describes the dermatologic sequela and therapeutic interventions utilized. While commonly used in testicular cancer, decreasing use of bleomycin-containing chemotherapy regimens has made the appearance of this increasingly rare, yet important and distressing, toxic adverse reaction a diagnostic challenge. Given that patients may present acutely to primary care providers, dermatologists, and nurse practitioners, awareness of this rare adverse reaction is important in order to alleviate patient anxiety, initiate appropriate therapy, set expectations of expected dermal sequela, and initiate an informed collaborative discussion regarding the continuation versus cessation of bleomycin-containing therapy.
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A man in his 60s presented to the emergency room with fever and fatigue after a 2.5-month course of corticosteroids. His medical history was significant for bioprosthetic aortic valve replacement and moderately severe ulcerative colitis treated with balsalazide and daily lactobacillus-containing probiotics. Initial investigations revealed Lactobacillus rhamnosus bacteraemia without complication. Four days after hospital discharge, the patient experienced acute-onset right-sided paraesthesia and lower-limb paresis. On return to the emergency room, MRI of the brain demonstrated innumerable ring-enhancing lesions with haemorrhagic transformation. Transoesophageal echocardiogram revealed a small mobile density on the bioprosthetic aortic valve, raising the suspicion for L. rhamnosus infective endocarditis with secondary septic emboli to the brain. The patient was subsequently treated with intravenous gentamycin and ampicillin, with transition to indefinite oral amoxicillin suppressive therapy. The current case highlights the potential risk of lactobacilli translocation in an immunosuppressed patient with ulcerative colitis taking probiotics.
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Colite Ulcerativa , Endocardite , Lacticaseibacillus rhamnosus , Probióticos , Sepse , Antibacterianos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Endocardite/tratamento farmacológico , Humanos , Masculino , Probióticos/efeitos adversos , Sepse/complicaçõesRESUMO
INTRODUCTION: Cancer immunotherapy has seen tremendous strides in the past 15 years, with the introduction of several novel immunotherapeutic agents. Nevertheless, as clinical practice has shown, significant challenges remain with a considerable number of patients responding sub-optimally to available therapeutic options. Research has demonstrated the important immunoregulatory role of the tumor microenvironment (TME), with the potential to either hinder or promote an effective anti-tumor immune response. As such, scientific efforts have focused on investigating novel candidate immunomodulatory agents with the potential to alter the TME toward a more immunopotentiating composition. AREAS COVERED: Herein, we discuss the novel investigational toll-like receptor 9 agonist tilsotolimod currently undergoing phase II and III clinical trials for advanced refractory cancer, highlighting its mode of action, efficacy, tolerability, and potential future applications in the treatment of cancer. To this effect, we conducted an exhaustive Web of Science and PubMed search to evaluate available research on tilsotolimod as of August 2021. EXPERT OPINION: With encouraging early clinical results demonstrating extensive TME immunomodulation and abscopal effects on distant tumor lesions, tilsotolimod has emerged as a potential candidate immunomodulatory agent with the possibility to augment currently available immunotherapy and provide novel avenues of treatment for patients with advanced refectory cancer.
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Melanoma , Receptor Toll-Like 9 , Humanos , Fatores Imunológicos/farmacologia , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Receptor Toll-Like 9/agonistas , Microambiente TumoralRESUMO
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy projected to be the 2nd leading cause of cancer related death in the USA by 2030. This manuscript discusses current and evolving treatment approaches in patients with pancreatic cancer. AREAS COVERED: PDAC is classified as: a) resectable, b) borderline resectable, c) unresectable (locally advanced and metastatic). The standard of care for patients who present with resectable pancreatic adenocarcinoma is six months of adjuvant modified (m) FOLFIRINOX, gemcitabine plus capecitabine, or single agent gemcitabine. For many reasons, there has been a paradigm shift to employing neoadjuvant chemotherapy. For resectable and borderline resectable patients, we generally start with systemic therapy and reevaluate resectability with subsequent scans specifically when the tumor is located in the head or body of the pancreas. Combined chemoradiation therapy can be employed in select patients. The standard of care for metastatic PDAC is FOLFIRINOX or gemcitabine and nab-paclitaxel. Germline and somatic genomic profiling should be obtained in all patients. Patients with a germline BRCA mutation can receive upfront gemcitabine and cisplatin. EXPERT OPINION: Thorough understanding of molecular pathogenesis in PDAC has opened various therapeutic avenues. We remain optimistic that future treatment modalities such as targeted therapies, cellular therapies and immunotherapy will further improve survival in PDAC.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias PancreáticasRESUMO
CASE PRESENTATION: A 49-year-old woman presented to the ED with sudden onset abdominal pain, nausea, and vomiting. Her medical history included an uncomplicated gastric lap band surgery 9 years ago and subsequent removal of lap band after 6 years. She had a Roux-en-Y gastric bypass and cholecystectomy 5 months prior to the current presentation. The patient had been diagnosed with asthma and was prescribed an inhaled corticosteroid that she used only as needed. The patient denied smoking and heavy alcohol consumption. She was currently employed as a scrub technician in a local surgical center.