Hasil untuk "Specialties of internal medicine"

Rocio Roldan-Testillano, Rafael Sanchez-Salas

Lan Li, Lan Li, Qingyuan Tan et al.

Coagulopathy is a critical pathophysiological mechanism of acute pancreatitis (AP), arising from the complex interplay between innate immune, endothelial cells and platelets. Although initially beneficial for the host, uncontrolled and systemic activation of coagulation cascade in AP can lead to thrombotic and hemorrhagic complications, ranging from subclinical abnormalities in coagulation tests to severe clinical manifestations, such as disseminated intravascular coagulation. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1. Finally, increased fibrin generation and impaired break down lead to deposition of (micro) vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. Despite the high burden of coagulopathy that have a negative impact on AP patients’ prognosis, there is no effective treatment yet. Although a variety of anticoagulants drugs have been evaluated in clinical trials, their beneficial effects are inconsistent, and they are also characterized by hemorrhagic complications. Future studies are called to unravel the pathophysiologic mechanisms involved in coagulopathy in AP, and to test novel therapeutics block coagulopathy in AP.

Satoshi Higa

David Collister, Mark Farrar, Lesha Farrar et al.

Rationale & Objective: We sought to elicit patient preferences regarding the use of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and its tradeoffs of risk of kidney failure and risk of serious infection. Study Design: Patient survey. Setting & Participants: The online survey was circulated to adults with AAV via kidney and vasculitis networks in Canada, the United Kingdom, and the United States. Outcomes: Respondents reviewed the estimated 1-year risks of kidney failure and serious infection in AAV with and without plasma exchange across 5 serum creatinine categories (150, 250, 350, 450, and 600 μmol/L). For each scenario, participants indicated whether or not they would choose plasma exchange. Analytical Approach: Responses were assessed with multilevel multivariable logistic regression models to identify predictors of respondent choice regarding treatment with plasma exchange. Results: The 470 respondents from the 13 countries (United States 61.7%, United Kingdom 20.0%, Canada 13.8%, and other countries 4.5%) had a mean age of 58.6 (SD 14.3) years, 70.2% women. Respondents were more likely to choose plasma exchange in scenarios at high risk of kidney failure and serious infection (creatinine level of 350 or 450 μmol/L) compared with lower risk scenarios or the highest risk scenario. However, 145 (30.9%) chose plasma exchange across all scenarios, whereas 80 (17.0%) declined plasma exchange across all scenarios. Respondents from the United Kingdom (OR, 2.61; 95% CI, 1.09-6.22) who received previous dialysis (OR, 2.70; 95% CI, 1.12-6.52) or received previous plasma exchange (OR, 5.62; 95% CI, 2.72-11.61) were more likely to choose plasma exchange, whereas older respondents (OR, 0.98; 95% CI, 0.96-0.99 per 1 year increase) were less likely. Limitations: Unclear generalizability to non–English-speaking, older, and less health literate adults, possible responder bias, survivor bias, lack of individualized risk assessments for kidney failure, and serious infection. Conclusions: Patients with AAV do not express a consistent choice for plasma exchange, which highlights the need for shared decision making.

Muneto Izuhara, Muneto Izuhara, Kentaro Matsui et al.

IntroductionSleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully understood.MethodsIn this prospective observational study, we investigated the influence of sleep habits on immune acquisition induced by mRNA vaccines against SARS-CoV-2 in 48 healthy adults (BNT-162b2, n=34; mRNA-1273, n=14; female, n=30, 62.5%; male, n=18, 37.5%; median age, 39.5 years; interquartile range, 33.0–44.0 years) from June 2021 to January 2022. The study measured sleep duration using actigraphy and sleep diaries, which covered the periods of the initial and booster vaccinations.ResultsMultivariable linear regression analysis showed that actigraphy-measured objective sleep duration 3 and 7 days after the booster vaccination was independently and significantly correlated with higher antibody titers (B=0.003; 95% confidence interval, 0.000–0.005; Beta=0.337; p=0.02), even after controlling for covariates, including age, sex, the type of vaccine, and reactogenicity to the vaccination. Associations between acquired antibody titer and average objective sleep duration before vaccination, and any period of subjective sleep duration measured by sleep diary were negligible.DiscussionLonger objective, but not subjective, sleep duration after booster vaccination enhances antibody response. Hence, encouraging citizens to sleep longer after mRNA vaccination, especially after a booster dose, may increase protection against SARS-CoV-2.Study registrationThis study is registered at the University Hospital Medical Information Network Center (UMIN: https://www.umin.ac.jp) on July 30, 2021, #UMIN000045009.

Maines LW, Green CL, Keller SN et al.

Lynn W Maines, Cecelia L Green, Staci N Keller, Leo R Fitzpatrick, Charles D Smith Apogee Biotechnology Corporation, Hummelstown, PA, USACorrespondence: Charles D Smith, Apogee Biotechnology Corporation, 1214 Research Blvd, Suite 2015, Hummelstown, PA, 17036, USA, Email cdsmith@apogee-biotech.comIntroduction: Acute kidney injury (AKI) is a common multifactorial adverse effect of surgery, circulatory obstruction, sepsis or drug/toxin exposure that often results in morbidity and mortality. Sphingolipid metabolism is a critical regulator of cell survival and pathologic inflammation processes involved in AKI. Opaganib (also known as ABC294640) is a first-in-class experimental drug targeting sphingolipid metabolism that reduces the production and activity of inflammatory cytokines and, therefore, may be effective to prevent and treat AKI.Methods: Murine models of AKI were used to assess the in vivo efficacy of opaganib including ischemia-reperfusion (IR) injury induced by either transient bilateral occlusion of renal blood flow (a moderate model) or nephrectomy followed immediately by occlusion of the contralateral kidney (a severe model) and lipopolysaccharide (LPS)-induced sepsis. Biochemical and histologic assays were used to quantify the effects of oral opaganib treatment on renal damage in these models.Results: Opaganib suppressed the elevations of creatinine and blood urea nitrogen (BUN), as well as granulocyte infiltration into the kidneys, of mice that experienced moderate IR from transient bilateral ligation. Opaganib also markedly decreased these parameters and completely prevented mortality in the severe renal IR model. Additionally, opaganib blunted the elevations of BUN, creatinine and inflammatory cytokines following exposure to LPS.Conclusion: The data support the hypotheses that sphingolipid metabolism is a key mediator of renal inflammatory damage following IR injury and sepsis, and that this can be suppressed by opaganib. Because opaganib has already undergone clinical testing in other diseases (cancer and Covid-19), the present studies support conducting clinical trials with this drug with surgical or septic patients at risk for AKI.Keywords: opaganib, sphingosine kinase, sphingolipid, acute kidney injury, ischemia-reperfusion injury, lipopolysaccharide, sepsis

Naruhiro Kimura, Toru Setsu, Yoshihisa Arao et al.

Abstract Background and Aim Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan–Meier analysis with propensity score matching and logistic progression analysis. Results The cumulative risk of developing a new symptom after 10 and 20 years of follow‐up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033–1.165; P = 0.002), the serum D‐Bil level (HR, 6.262; 95% CI, 2.522–15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183–1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan–Meier analysis showed that the overall survival and liver‐related death were not significant between patients with and without a new symptom. Conclusion The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D‐Bil level, and Paris II criteria.

Cansu Önlen Güneri, Hamza Malik Okuyan, Gülay Gülbol Duran et al.

<b>Aim: </b>Patients infected with the hepatitis B virus (HBV) are at a higher risk of cirrhosis and hepatocellular carcinoma. Despite the recent advancement of antiviral therapy, many patients still cannot respond to existing therapies. Hence, to detect the changes in liver function earlier, non-invasive methods are needed. Long non-coding RNAs (lncRNAs) play important roles in essential biological process as well as human cancer. LncRNAs may be used as biomarkers in human diseases. Thus, in this study, we purposed to analyze the expression levels of lncRNAs (HOX transcript antisense RNA (HOTAIR), maternally expressed 3 (MEG-3), highly upregulated in liver cancer&nbsp;(HULC)) in patients with hepatitis B virus and healthy volunteers.<br /> <b>Methods: </b>We selected three lncRNAs as candidate lncRNAs based on their association with liver disease.&nbsp;Whole blood samples were collected from 40 patients with HBV and 48 healthy volunteers. The expression levels of all the samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis was implemented using GraphPad Prism software. A p-value lower than 0.05 was statistically meaningful.<br /> <b>Results: </b>The expression levels of HOTAIR and HULC were remarkably upregulated in the plasma of the patients with HBV compared with healthy control (p&lt;0.05). In contrast, no significant difference in MEG-3 expression levels was observed between groups.<br /> <b>Conclusion: </b>Our findings showed that the expression of HOTAIR and HULC in plasma might be new promising&nbsp;diagnostic and/or prognostic biomarkers for HBV.

Ciro Romano, Olga Tortorella, Liliana Dalla Mora et al.

BackgroundChronic immune stimulation by hepatitis C virus (HCV) may cause occurrence of several autoantibodies in infected patients, with or without features of clinically overt autoimmune diseases. The recent introduction of direct-acting antivirals (DAAs) has dramatically changed the natural history of chronic HCV infection. The aim of this study was to assess the effects of DAA therapy on serum autoantibodies in chronic hepatitis C (CHC) patients.MethodsThe medical records of 113 CHC patients were reviewed to assess autoantibody behavior following DAA-directed HCV eradication. Statistical analysis was performed to assess correlations between DAA treatment and autoantibody titers, HCV genotypes, and viral loads.ResultsAnti-nuclear (ANA), anti-smooth muscle cell (ASMA) and anti-mitochondrial (AMA) antibody testing was available in 77 patients; 31 out of 77 patients (40%) had one or more serum autoantibodies prior to treatment. Measurement of autoantibody titers before and after HCV eradication was performed in 20 of 31 patients. DAA treatment significantly affected ANA and ASMA titers, leading to disappearance or reduction of autoantibody titers; conversely, AMA were not influenced by DAA treatment. No correlations were observed between autoantibody specificity and both HCV genotypes and viral loads at baseline. Likewise, serum autoantibody titers were independent of HCV genotypes.ConclusionsDAA-directed HCV clearance may interrupt chronic immune stimulation by removing the drive for autoantibody induction. The isolated persistence of autoantibodies in the small fraction of patients who did not show clearance following DAA treatment may require long-term vigilance.

Christopher L. Bennett, M. Yiadom, O. Baker et al.

K. Yin, Liu Yang, Rui Zhang et al.

Background: Gender plays a significant role in the selection of medical specialty. Few studies have been conducted to explore the impact of gender differences on specialty choosing among Chinese medical students. Methods: The specialty choices of 648 students from six consecutive classes in an 8-year MD program were collected and compared between male and female students. A total of 110 students from one graduating class were surveyed by a questionnaire covering 22 career influencing factors. Each factor has a scale of zero to three (zero = no influence, one = mild influence, two = moderate influence, and three = strong influence). Results: Statistically significant gender differences were observed in 10 out of 16 specialties. Most male students limited their specialty choices to surgery (64%), internal medicine (12%), and orthopedics (12%), compared with a relatively diversified pattern in female students. For male students, the top three influencing factors were personal interest, future job prospects for the chosen specialty, and job opportunity in academic medicine. The strongest influencing factors of females were personal interest, specialty-specific knowledge and skills, and the sense of achievement. The expected salary was ranked among the top 10 influencing factors in male but not in females, while the work-life balance was ranked among the top 10 factors in females but not in males. Conclusion: There is a significant gender difference regarding specialty choices among Chinese medical students. Career coaching is needed to help students in their specialty choosing process.

Amanda Davis, Jacqueline Ellison, Amal Trivedi et al.

K P Suraj, Arjun Chandran

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. Even with advancement in understanding the pathophysiology and various monitoring tools and treatment measures, sepsis still remains a major cause of mortality and morbidity in critically ill patients. Over the last three decades, significant changes were seen regarding understanding the pathophysiology of sepsis. The management of sepsis has evolved over the last two decades by the advent of the Surviving Sepsis Campaign Guidelines which recommends early recognition and prompt treatment without delay.

Terezka S. Mollee, Pieter U. Dijkstra, Rienk Dekker et al.

Abstract Background Obesity is common in persons with a lower limb amputation, an amputation can also lead to further weight gain. Data regarding the prevalence of obesity in the Dutch population with a lower limb amputation are lacking. Furthermore, the impact of obesity on skin problems of the residual limb and the need of prosthetic repairs is unknown. The aim of this study was to determine the prevalence of obesity in Dutch persons with a lower limb amputation and to investigate the relationship between body weight, body mass index and skin problems of the residual limb and the frequency of prosthetic repairs. Methods A survey was performed among adults with a unilateral lower limb amputation due to any cause, and who are user of a prosthesis. The survey consisted of measurement of the subjects’ body height and weight, a questionnaire which assessed self-reported skin problems in the previous month and factors potentially associated with these skin problems, and assessment of the frequency of visits to the orthopedic workshop. Results In total, 413 persons were enrolled. Of them, 39% (95 % confidence interval 35;44) were overweight and 28% (95% confidence interval 24;33) were obese. A total of 77% (95% confidence interval 73;81) reported one or more skin problems in the past month. Body weight and body mass index were neither associated with the presence of skin problems in general nor with the number of prosthetic repairs. Persons with severe skin problems had a slightly lower body mass index (26.6 kg/m2 vs. 28.0 kg/m2, p = 0.012). Persons with skin problems were younger than those without (difference in means 6.0 years (95% confidence interval 3.0;8.9)). Conclusions Our findings show that obesity is common in the Dutch ambulant population with a lower limb amputation, with a prevalence being higher than in the general Dutch adult population. However, its negative impact on the presence of skin problems and the frequency of prosthetic repairs may be limited.

Mahbuba A. Tusty, Brenda Flores, R. Victor et al.

The number of health disparities disproportionately affecting minority communities continue to rise. Thus, it is imperative to assess whether equity within medical school enrollment and along the academic pipeline has mirrored this growth, especially among elite surgical specialties such as otolaryngology. Census and educational data from 2010 and 2018 were used to assess the current otolaryngology, surgery, and internal medicine physician and faculty workforce diversity across each stage of the academic medicine trajectory by race and ethnicity. We found that disparities exist in medical school enrollment for minority students such that Hispanic/Latinx representation was only 30% and Black representation only 50% of their respective proportions in the US population in 2018. Disparities in achieving full professorship were also observed across all 3 specialties but most prominently in otolaryngology, with 1% Black representation among otolaryngology professors in 2018. A collective strategy toward diversifying the otolaryngology workforce should be explored.

Sarah Sweigert, Petar Bajic, Alessa Aragao et al.

Renal cell carcinoma (RCC) with invasion into the renal vein is well described; however, invasion into the gonadal vein is a rare event with less than five cases reported in the literature. RCC occasionally presents with metastasis to the ovaries or the fallopian tubes, although this is also a rare occurrence. We present a case of locally advanced left RCC with direct extension into the ipsilateral gonadal vein with extension into the bilateral ovaries and uterus, which has not been previously described. Computed tomography (CT) in a 72-year-old female with a 35-pound weight loss indicated the presence of a 16-cm left renal mass with caudal tumor extension through the left gonadal vein and regional lymph-adenopathy. There was no evidence of distant metastasis, and she underwent an open left radical nephrectomy. Intraoperatively, she was found to have direct extension of the tumor through the left gonadal vein into the uterus, bilateral ovaries, and the left fallopian tube. All visible dis-ease was resected, and retroperitoneal and pelvic lymphadenectomy were performed. The patient had an uneventful hospital course. Pathology revealed clear cell RCC, Fuhrman grade 3. The final pathologic stage was pT4N1M1. The patient was ultimately noted to have pulmonary metastasis and was treated with immunotherapy with no evidence of disease progression.

Umut C. Kucuksezer, Cevdet Ozdemir, Lacin Cevhertas et al.

Allergen-specific immunotherapy (AIT) is the mainstay treatment for the cure of allergic disorders, with depicted efficacy and safety by several trials and meta-analysis. AIT impressively contributes to the management of allergic rhinitis, asthma and venom allergies. Food allergy is a new arena for AIT with promising results, especially via novel administration routes. Cell subsets with regulatory capacities are induced during AIT. IL-10 and transforming growth factor (TGF)-β are the main suppressor cytokines, in addition to surface molecules such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) within the micro milieu. Modified T- and B-cell responses and antibody isotypes, increased activity thresholds for eosinophils, basophils and mast cells and consequent limitation of inflammatory cascades altogether induce and maintain a state of sustained allergen-specific unresponsiveness. Established tolerance is reflected into the clinical perspectives as improvement of allergy symptoms together with reduced medication requirements and evolved disease severity. Long treatment durations, costs, reduced patient compliance and risk of severe, even life-threatening adverse reactions during treatment stand as major limiting factors for AIT. By development of purified non-allergenic, highly-immunogenic modified allergen extracts, and combinational usage of them with novel adjuvant molecules via new routes may shorten treatment durations and possibly reduce these drawbacks. AIT is the best model for custom-tailored therapy of allergic disorders. Better characterization of disease endotypes, definition of specific biomarkers for diagnosis and therapy follow-up, as well as precision medicine approaches may further contribute to success of AIT in management of allergic disorders.

Rosanna Smart, Caroline K. Geiger, Christopher M. Jones et al.

K. E. Stige, I. O. Gjerde, G. Houge et al.

Beta‐propeller protein‐associated neurodegeneration (BPAN) is a rare disorder, which is increasingly recognized thanks to next‐generation sequencing. Due to a highly variable phenotype, patients may present to pediatrics, neurology, psychiatry, or internal medicine. It is therefore essential that physicians of different specialties are familiar with this severe and debilitating condition.

Jonatan Jacobsson, Christian Reitan, Jonas Carlson et al.

Abstract Background In patients with cardiac resynchronization therapy (CRT), atrial fibrillation (AF) is associated with an unfavorable outcome and may cause loss of biventricular pacing (BivP). An effective delivery of BivP of more than 98% of all ventricular beats has been shown to be a major determinant of CRT-success. Methods At a Swedish tertiary referral center, data was retrospectively obtained from patient registers, medical records and preoperative electrocardiograms. Data regarding AF and BivP during the first year of follow-up was assessed from CRT-device interrogations. No intra-cardiac electrograms were studied. Kaplan-Meier curves and Cox-regression analyses adjusted for age, etiology of heart failure, left ventricular ejection fraction, left bundle branch block and NYHA class were performed to assess the impact of AF and BivP on the risk of death or heart transplantation (HTx) at 10-years of follow-up. Results Preoperative AF-history was found in 54% of the 379 included patients and was associated with, but did not independently predict death or HTx. The one-year incidence of new device-detected AF was 22% but not associated with poorer prognosis. At one-year, AF-history and BivP≤98%, was associated with a higher risk of death or HTx compared to patients without AF (HR 1.9, 95%CI 1.2–3.0, p = 0.005) whereas AF and BivP> 98% was not (HR 1.4, 95%CI 0.9–2.3, p = 0.14). Conclusions In CRT-recipients, AF-history is common and associated with poor outcome. AF-history does not independently predict mortality and is probably only a marker of a more severe underlying disease. BivP≤98% during first-year of CRT-treatment independently predicts poor outcome thus further supporting the use of 98% threshold of BivP, which should be attained to maximize the benefits of CRT.