Treatment Goal For Patients Research Articles

Ultra-high Magnification Endocytoscopy and Molecular Markers for Defining Endoscopic and Histologic Remission in Ulcerative Colitis-An Exploratory Study to Define Deep Remission.

BackgroundEndoscopic and histological remission are both important treatment goals in patients with ulcerative colitis (UC). We aimed to define cellular architecture, expression of molecular markers, and their correlation with endoscopic scores assessed by ultra-high magnification endocytoscopy (ECS) and histological scores.MethodsPatients with UC (n = 29) were prospectively recruited. The correlation among ECS score (ECSS), Mayo endoscopic score (MES), and histological scores were determined. Area under curve were plotted to determine the best thresholds for ECSS that predicted histological remission by Robarts (RHI) and Nancy Histological Index (NHI).Soluble analytes relevant to inflammation were measured in serum and mucosal culture supernatants using ProcartaPlex Luminex assays and studied by partial least square discriminant analysis and logistic model. Mucosal RNA sequencing and bioinformatics analysis were performed to define differentially expressed genes/pathways.ResultsEndocytoscope scoring system correlated strongly with RHI (r = 0.89; 95% CI, 0.51–0.98) and NHI (r = 0.86; 95% CI, 0.42–0.98) but correlated poorly with MES (r = 0.28; 95% CI, 0.27–0.70). We identified soluble brain-derived neurotrophic factors (BDNF), macrophage inflammatory proteins (MIP-1 α) and soluble vascular cell adhesion molecule 1 (sVCAM-1) predicted histological remission. Mucosal biopsy cultures also identified sVCAM-1 associated with healed mucosa. RNA-seq analysis identified gene expressions shared between ECSS, RHI, or NHI defined healing. A number of gene expressions and pathways were identified including inflammation and metabolic and tumor suppressors that discriminated healed from nonhealed mucosa.ConclusionsEndocytoscopy represents an interesting tool that may sit between endoscopy and histology—but closer to the latter—identifying gene expression markers and pathways that are also identified by histology.

AB0114 INVESTIGATION OF THE EFFECTS OF EXERCISE ON MIRNA EXPRESSIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background:The goal of treatment for patients with RA is achieve to remission, or at least a state of low disease activity. Exercise is recommended for patients with RA in addition to drug therapy. It has been found to be effective in greatly improving functionality and reducing cardiovascular risk without exacerbating disease activity. Therefore, it is recommended that all RA patients should be encouraged to include aerobic and resistant exercise training as part of their routine treatment (1).miRNAs(miRNA) are known to protect the pathophysiological process specific to RA. miRNA-146a is one of the miRNAs extensively studied in RA, its expression was found to be higher in the synovial fluid and synovial tissue of RA patients compared to healthy individuals (2).Many studies have found that miRNA-146a, along with miRNA-16 and miRNA155 may be related to disease pathology. It has also been found that high levels of miRNA-16 expression correlate with active disease and low levels of expression with inactive disease. It has been found that the increased level of miRNA-155 causes a problem in the modulation of arthritis It has been found that the expression level of miRNA-145 is increased in peripheral blood mononuclear cells of RA patients and synovium supporting osteoclastogenesis (3,4,5).Objectives:It is aimed to investigate the effect of exercise on microRNA expressions in patients with rheumatoid arthritis (RA).Methods:30 patients and 30 healthy controls aged 18-60 years who met the 2010 ACR / EULAR RA criteria were included in the study. A program consisting of strengthening and stretching exercises 2 days a week was applied to the study group for 8 weeks. One day a week, 30 minutes of mild moderate walking was requested. Of the cases at the beginning and at the end of the treatment; 5-10 cc peripheral blood samples were taken into one EDTA tube. Then Numeric Rating Scale (NRS) was used for pain, 28-joint Disease Activity Score (DAS28) was used to calculate disease activity, Health Assessment Questionnaire (HAQ) was used to assess general health and Short Form-36 (SF-36) was used to evaluate quality of life. 5-10 cc peripheral blood samples were taken to only 1 EDTA tube of the control group. In the samples taken, gene expressions of miRNA-146a, miRNA-155, miRNA-16, miRNA-145 were determined by real-time PZR method.Results:There was a significant difference in DAS28, SF-36, NRS, HAQ scales before and after treatment in the RA group of patients (p 0.05). The expression level of MiRNA-146a does not differ significantly before and after treatment (p> 0.05). However, these two groups differ significantly with the control group (p 0.05). No significant difference was observed in the miRNA-155 and miRNA-16 expression levels in the pretreatment, posttreatment, and control groups (p> 0.05).Conclusion:Exercise therapy has a good effect on pain, disease activity, quality of life and general health in patients with RA. It has been found that exercise can affect vii some of the miRNAs involved in disease pathogenesis. However, more comprehensive studies are needed.

Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

Improving symptoms is a primary treatment goal in patients with obstructive hypertrophic cardiomyopathy. Currently available pharmacological options for hypertrophic cardiomyopathy are not disease-specific and are often inadequate or poorly tolerated. We aimed to assess the effect of mavacamten, a first-in-class cardiac myosin inhibitor, on patients' health status-ie, symptoms, physical and social function, and quality of life. We did a health status analysis of EXPLORER-HCM, a phase 3, double-blind, randomised, placebo-controlled trial. The study took place at 68 clinical cardiovascular centres in 13 countries. Adult patients (≥18 years) with symptomatic obstructive hypertrophic cardiomyopathy (gradient ≥50 mm Hg and New York Heart Association class II-III) were randomly assigned (1:1) to mavacamten or placebo for 30 weeks, followed by an 8-week washout period. Both patients and staff were masked to study treatment. The primary outcome for this secondary analysis was the Kansas City Cardiomyopathy Questionnaire (KCCQ), a well validated disease-specific measure of patients' health status. It was administered at baseline and weeks 6, 12, 18, 30 (end of treatment), and 38 (end of study). Changes from baseline to week 30 in KCCQ overall summary (OS) score and all subscales were analysed using mixed model repeated measures. This study is registered with ClinicalTrials.gov, NCT03470545. Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned. Of 123 patients randomly assigned to mavacamten, 92 (75%) completed the KCCQ at baseline and week 30 and of the 128 patients randomly assigned to placebo 88 (69%) completed the KCCQ at baseline and week 30. At 30 weeks, the change in KCCQ-OS score was greater with mavacamten than placebo (mean score 14·9 [SD 15·8] vs 5·4 [13·7]; difference +9·1 [95% CI 5·5-12·8]; p<0·0001), with similar benefits across all KCCQ subscales. The proportion of patients with a very large change (KCCQ-OS ≥20 points) was 36% (33 of 92) in the mavacamten group versus 15% (13 of 88) in the placebo group, with an estimated absolute difference of 21% (95% CI 8·8-33·4) and number needed to treat of five (95% CI 3-11). These gains returned to baseline after treatment was stopped. Mavacamten markedly improved the health status of patients with symptomatic obstructive hypertrophic cardiomyopathy compared with placebo, with a low number needed to treat for marked improvement. Given that the primary goals of treatment are to improve symptoms, physical and social function, and quality of life, mavacamten represents a new potential strategy for achieving these goals. MyoKardia, a Bristol Myers Squibb company.

A preliminary single-center investigation of percutaneous biliary stenting in malignant hilar biliary obstruction: what impacts the clinical success and the long-term outcomes?

The purpose of this study is to investigate the influencing factors that may impact the clinical success, jaundice-free time, and overall survival in patients of malignant hilar biliary obstruction (MHBO) treated with a self-expanding metallic stent (SEMS). Patients diagnosed with MHBO and treated with SEMS through percutaneous access from 1 Jul. 2013 to 1 Jul. 2018 were enrolled in this monocentric study. Demographic information, disease baseline measurements, and interventional strategies were collected and examined. Bilirubin was measured 1-3days before and 3-7days after stenting using the unit of "μmol/L." The bilirubin reduction ratio was compared between different study groups, which were separated by specific characteristics. Univariate and multivariate analyses were performed to evaluate each characteristic's impact on jaundice-free time (JF) and overall survival time (OS). Statistical analyses were conducted using SPSS 14.0, p < 0.05 indicated significance. Eighty patients were enrolled. Direct bilirubin (DB) and indirect bilirubin (IB) both significantly decreased after stenting (U = 1575.0, p < 0.001; U = 1541.0, p < 0.001). The DB reduction ratio of the "nearby lymph metastases" group was significantly higher (U = 566.0, p = 0.037). The IB reduction ratio in the "single stent" group was significantly higher (U = 554.0, p = 0.018). Sixty-six cases reached jaundice recurrence, the median JF was 6months, and the 95% confidence interval was 4.411 ~ 7.589months. Fifty-eight cases ended in death, the median OS was 7months, and the 95% confidence interval was 5.759 ~ 8.241months. "Nearby lymph metastases" and "distant metastases" independently impacted OS (OR = 2.344, p = 0.013; OR = 3.239, p = 0.042). "IB reduction ratio" independently impacted both JF and OS (OR = 0.422, p = 0.021; OR = 0.315, p = 0.001). The goal of treatment in patients with MHBO is to recover liver function. However, the overall survival is greatly impacted by the presence of metastases. Managing to obtain adequate liver function recovery may improve the long-term outcomes in affected patients.

Pediatric Pleomorphic Xanthoastrocytoma: A National Database Inquiry on Current Treatment Approaches in the United States.

BackgroundPleomorphic xanthoastrocytomas (PXAs) account for <1% of primary brain tumors, occurring predominantly in children and young adults. Surgical resection serves as the primary treatment for PXAs, while radiotherapy (RT) and chemotherapy protocols remain poorly defined.AimThis study aims to determine current care patterns utilized for pediatric patients (≤ 18 years) diagnosed with PXAs and their effect on overall survival.MethodsThe United States National Cancer Database (NCDB) was queried between 2004 and 2015 for pediatric patients (≤18 years) diagnosed with PXAs.ResultsFrom the 224 qualifying patients, most patients proceeded with surgery only (78.1%), while 11.6% of patients received both adjuvant RT and chemotherapy. In the 2010‐2015 cohort, patients with subtotal resection were associated with poorer prognosis than those with gross‐total resection (hazard ratio = 17.44, 95% confidence interval = 2.10‐144.90, p < .001). RT and chemotherapy recipients were similarly associated with poorer survival than those treated with surgery only, with p‐values of <.001 and respective hazard ratios of 3.82 (95% confidence interval = 1.85‐7.90) and 6.68 (95% confidence interval = 3.21‐13.89). The key factors impacting the probability of RT delivery involved WHO grade (p < .001) and chemotherapy administration (p < .001). However, WHO grade alone did not significantly impact survival (p‐value = .088).ConclusionMaximally safe resection is the current treatment goal for patients with PXAs. RT and chemotherapy are poorly utilized but had a greater role in managing more aggressive cases of PXAs. Additional research focusing on the impact of adjuvant therapies on tumor progression is needed to better guide treatment decisions.

Oligometastases: history of a hypothesis.

The term oligometastases represents a clinical state of metastatic disease that is limited in the number of metastatic sites and extent of disease, and amenable to metastasis-directed surgical or ablative therapy. While metastasis-directed approaches are used for palliation, the primary goal of such treatment for patients with oligometastases is to prolong survival and the duration of cancer control. Metastasis-directed therapy, for patients with limited number of metastatic sites, has been practiced for decades, dating back to the era before chemotherapy was widely used. Systemic therapy has become the accepted standard of care for metastatic disease. And while not curative for most solid cancers, systemic therapy can delay cancer progression, prolong life, and maintain or improve quality of life, albeit often at the expense of toxicities which can adversely impact quality of life. From the 1960s to 1980s, prominent physicians questioned whether metastasis-directed resection or radiotherapy could potentially be curative treatment approaches. In 1995, Drs. Hellman and Weichselbaum wrote an editorial that coined the term "oligometastases" and refined the hypothesis of metastasis-directed surgical and radiotherapeutic treatments as potentially curative for select patients. Their article was the first to explicitly describe the clinical state of metastases existing along a spectrum, with a spectrum of behaviors (ranging from indolent disease confined to limited sites to widespread disease) and, therefore, a spectrum of potential treatments. In the ensuing decades, there were rapid technologic advancements in radiotherapy, including stereotactic body radiation therapy (SBRT), which facilitated delivery of ablative doses of radiation to precisely and accurately targeted tumors. SBRT has been considered an optimal non-surgical approach to treat oligometastases, allowing for definitive-dose delivery and for targeting accuracy that minimizes normal tissue radiation exposure. In the early 2000s, many institutions began publishing prospective studies demonstrating favorable outcomes in patients with oligometastases treated with SBRT. Not answered in these single-arm studies was whether patients generally fared better than expected due to selection of patients with relatively indolent disease, or from metastasis-directed treatment. There is also a potential for immortal time bias with non-randomized comparisons. However, recent randomized phase II studies have suggested that SBRT for oligometastases is associated with improved survival outcomes. Phase III studies, many specific for certain cancers (i.e., breast, prostate or lung cancers) are accruing. Future work will be needed to identify which patients are most apt to benefit from metastasis-directed therapy; in addition to clinical factors, host and/or tumor genomics may prove to be prognostic. Metastasis-directed therapy may become more important with improvements in systemic therapy in controlling micrometastatic disease. Incorporating immunotherapy with SBRT may also be a promising approach, with SBRT perhaps augmenting the immune response. As personalized medicine evolves, patients with oligometastases will be better served. The history of oligometastases will continue to unfold.

Evolution of systemic therapy for stages I-III non-metastatic non-small-cell lung cancer.

The treatment goal for patients with early-stage lung cancer is cure. Multidisciplinary discussions of surgical resectability and medical operability determine the modality of definitive local treatment (surgery or radiotherapy) and the associated systemic therapies to further improve the likelihood of cure. Trial evidence supports cisplatin-based adjuvant therapy either after surgical resection or concurrently with radiotherapy. Consensus guidelines support neoadjuvant chemotherapy in lieu of adjuvant chemotherapy and carboplatin-based regimens for patients who are ineligible for cisplatin. The incorporation of newer agents, now standard forpatients with stage IV lung cancer, into the curative therapy paradigm has lagged owing to inefficient trial designs, the lengthy follow-up needed to assess survival end points and a developmental focus on the advanced-stage disease setting. Surrogate end points, such as pathological response, are being studied and might shorten trial durations. In 2018, the anti-PD-L1 antibody durvalumab was approved for patients with stage III lung cancer after concurrent chemoradiotherapy. Since then, the study of targeted therapies and immunotherapies in patients with early-stage lung cancer has rapidly expanded. In this Review, we present the current considerations in the treatment of patients with early-stage lung cancer and explore the current and future state of clinical research to develop systemic therapies for non-metastatic lung cancer.

Adult female urinary incontinence guidelines: a systematic review of evaluation guidelines across clinical specialties.

To systematically review evaluation guidelines of uncomplicated urinary incontinence (UI) in community-dwelling adult women to assess guidance available to the full range of providers treating UI. Systematic literature search of eight bibliographic databases. We included UI evaluation guidelines written for medical providers in English after January 1, 2008. guidelines for children, men, institutionalized women, peripartum- and neurologic-related UI. A quantitative scoring system included assessed components and associated recommendation level and clarity. Twenty-two guidelines met the criteria. All guidelines included: history taking, UI characterization, physical examination (PE) performance, urinalysis, and post-void residual volume assessment. At least 75% included medical and surgical history assessment, other disease process exclusion, medication review, impact on quality of life ascertainment, observing stress UI, mental status assessment, performing a pelvic examination, urine culture, bladder diary, and limiting more invasive diagnostics procedures. Fifty to 75% included other important evaluation components (i.e., assessing obstetric history, bowel symptoms, fluid intake, patient expectations/preferences/values, obesity, physical functioning/mobility, other PE [abdominal, rectal, pelvic muscle, and neurologic], urethral hypermobility, and pad testing. Less than 50% of guidelines included discussing patient treatment goals. Guidelines varied in level of detail and clarity, with several instances of unclear or inconsistent recommendations within the same guideline and evaluation components identified only by inference from treatment recommendations. Non-specialty guidelines reported fewer components with a lesser degree of clarity, but this difference was not statistically significant (p= 0.20). UI evaluation guidelines varied in level of comprehensiveness, detail, and clarity. This variability may lead to inconsistent evaluations in the work-up of UI, contributing to missed opportunities for individualized care.

Clinical prediction model for postoperative ambulatory ability outcomes in patients with trochanteric fractures

IntroductionRegaining independent ambulatory ability is one of the primary goals of treatment in patients with trochanteric fractures. This study aimed to develop and evaluate the discriminative accuracy of a clinical prediction model for ambulatory ability outcomes 3 months after surgery for trochanteric fractures. MethodsThis retrospective cohort study included 346 patients treated with intramedullary nailing for trochanteric fractures who had independent ambulatory ability before their injury. Multiple regression models with preoperative and postoperative factors were used to predict ambulatory ability outcomes at 3 months. A clinical prediction model (CPM) was created based on a decision tree developed using a chi-square automatic interaction detector technique. ResultsThree months after surgery, 263 (76.0%) and 83 (24.0%) patients regained and lost independent ambulatory ability, respectively. Univariate analysis showed that the Barthel index (BI) total score at 2 weeks predicted the ambulatory ability outcome at 3 months with good discriminative accuracy (area under the receiver operating characteristic curve [AUROC]: 0.819; 95% confidence interval [CI]: [0.769, 0.868], cut-off value: 22.5; sensitivity: 69.5%; specificity: 82.3%). Multiple logistic regression analysis showed that preoperative factors (residence before injury, diagnosis of dementia, and serum albumin at admission) and postoperative factors (BI total score at 2 weeks) predicted ambulatory ability outcomes at 3 months (AUROC: 0.710; 95%CI: [0.636, 0.783]; sensitivity: 91.3%; specificity: 41.8%). The CPM with the BI total score at 2 weeks (≤10; 10<, ≤50; >50 points) and dementia status (present; absent) had a moderate discriminative accuracy (AUROC: 0.676; 95%CI: [0.600, 0.752]; sensitivity: 94.7%; specificity: 40.5%). ConclusionsWe developed a CPM with moderate accuracy to predict ambulatory ability outcomes in patients 3 months after surgery for trochanteric fractures. Our results demonstrate the importance of the BI score measured soon after surgery and dementia status for the prediction of postoperative ambulation.

Maintenance of Acute Stroke Care Service During the COVID-19 Pandemic Lockdown.

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Exploration and practice of post-marketing survival benefit evaluation of Chinese patent medicine for cancer

Traditional Chinese medicine(TCM) is an important feature of cancer treatment in China. The methods to tap the advantages of TCM, reasonably evaluate and accurately apply Chinese patent medicines have become current research hotspots and difficulties. TCM takes syndrome differentiation and treatment as the core, with the characteristics of overall regulation and multi-targets efficacy. Therefore, the post-marketing survival benefit evaluation of Chinese patent medicines for cancer is different from that in modern medicine. The primary treatment goals in cancer patients include to improve the disease control rate and prolong their survival time. At present, Chinese patent medicines for cancer patients are lacking indepth studies on survival benefit at the post-marketing stage. In addition, the characteristics of individualized treatment with TCM have also increased the complexity of clinical research on TCM. Therefore, it is of certain practical significance and necessity to evaluate the survival benefit of Chinese patent medicines for cancer after marketing. Based on this, in this paper, we first summarized the technical methodological means of survival benefit evaluation at this stage, and then explored the post-marketing survival benefit evaluation of Chinese patent medicines for cancer from three aspects: the evaluation of cancer treatment effect based on survival time and quality of life, treatment-related toxicity and the auxiliary effect of TCM, and the improvement effect for tumor-related symptoms. Based on the practices of early clinical researches, and according to the insufficient efficacy evaluation of current clinical research on Chinese patent medicines, this paper proposed to improve the evaluation system for clinical researches on Chinese patent medicines, establish the evaluation method with TCM characteristics, clarify the dominant population, lay a theoretical foundation for the evaluation of post-marketing survival benefits of Chinese patent medicines for cancer in the future, and promote the modernization process of TCM.

The prevalence and clinical characteristics of restless legs syndrome in patients with iron deficiency anemia in Korea.

While the prevalence and clinical characteristics of restless legs syndrome (RLS) are known to vary according to ethnicity, a detailed evaluation of this condition among patients with iron deficiency anemia (IDA) has not yet been reported in an Asian population. We investigated the prevalence and clinical characteristics of RLS in patients with IDA in Korea compared with age- and sex-matched patients diagnosed with idiopathic RLS. This prospective single-center study was performed at a regional university hospital. Consecutive patients with IDA were enrolled over a 4-year period. Clinical interviews and laboratory tests were conducted at the first visit. RLS diagnosis was confirmed through face-to-face interviews. We randomly selected patients with idiopathic RLS without comorbid medical disorders from our sleep center dataset as control patients. The clinical characteristics of both groups were compared. We enrolled 124 patients with IDA. Fifty (40.3%) patients were diagnosed with RLS, with 82% exhibiting severe to very severe symptoms. Patients with IDA and RLS were older and reported more sleep deterioration than patients with IDA without RLS. Patients with IDA and RLS also had a more depressed mood and higher periodic limb movement index scores than patients with idiopathic RLS. The prevalence of RLS among patients with IDA in Korea was high, with the majority having severe to very severe symptoms. Patients with IDA and RLS had poorer sleep quality and more emotional problems than patients with IDA without RLS. Therefore, patients with IDA should be screened for RLS to prevent adverse effects on the quality of sleep and life.

Socially conscious surgical care must prioritize older adults

TopicA commentary on social justice issues in geriatric surgery Future directionsRecognizing social determinants of health and racism as a contributing mechanism for inequities in the care of older adult surgical patients Knowledge gapsIdentifying the role of the surgeon in achieving health equity for older adults PurposeIncrease recognition of opportunities for antiracist care in everyday surgical practice, including shared decision-making and palliative care State of the artPatient treatment goals documented in their own words. Social needs screening in older adult surgical patients Technology gapsPlatform for clear documentation of surgical treatments offered and patient treatment goals, social determinants of health and social risk factors, and collaborative treatment and discharge plans discussed across multidisciplinary, elder-friendly teams

Understanding Treatment Strategies and Preferences in Nonmetastatic Castration-Resistant Prostate Cancer From the Japanese Physician Perspective.

PURPOSESixteen percent (16%) of patients with castration-resistant prostate cancer (CRPC) show no bone metastasis at diagnosis. However, 33% will become metastatic within 2 years. The goal of treatment in patients with nonmetastatic CRPC (nmCRPC), therefore, is to delay symptomatic metastases without undue toxicity. With novel antiandrogen treatments of different strengths and limitations available, physician preferences for nmCRPC treatment in Japan should be understood.METHODSA discrete choice experiment was conducted. Physicians chose between two hypothetical treatments in nmCRPC defined by six attributes: risk of fatigue, falls or fracture, cognitive impairment, hypertension, rashes as side effects of treatment, and extension of time until cancer-related pain occurs. Relative preference weights and relative importance were estimated by hierarchical Bayesian logistic regression. Physicians were also asked to make treatment decisions based on four hypothetical patient profiles to understand the most important factors driving decision making.RESULTSA total of 151 physicians completed the survey. Extension of time until cancer-related pain occurs was the most important attribute (relative importance, 32.3%; CI, 31.3% to 33.3%). Based on summed preference weights across all attributes, preferences for hypothetical treatment profiles I, II, and III were compared. A hypothetical treatment profile with better safety though shorter extension time was preferred (I: mean [standard deviation] = 1.7 [1.6 to 2.1]) over treatment profiles with lower safety but longer extension time (II: −2.7 [−2.8 to −2.6] and III: −0.2 [−0.3 to −0.1]). Treatment characteristics were more important factors for physicians' decision making than patient characteristics in prescribing treatment.CONCLUSIONPhysicians preferred a treatment with better safety profile, and treatment characteristics were the most important factors for decision making. This might have implications in physicians' decision making for nmCRPC treatment in the future in Japan.

Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management.

Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra-cutaneous organs. The major criterion is presence of multifocal clusters of spindled MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. Establishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). Identification of poor-risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical-molecular risk models have been developed to more accurately assign prognosis in SM patients. Treatment goals for ISM patients are primarily directed towards anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease-related organ dysfunction. High response rates have been seen with small-molecule inhibitors that target mutant-KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon-α, although head-to-head comparisons are lacking. Treatment of SM-AHN primarily targets the AHN component, particularly if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib-sensitive KIT mutations.

Network meta-analysis of biologic treatments for psoriasis using absolute Psoriasis Area and Severity Index values ≤1, 2, 3 or 5 derived from a statistical conversion method.

BackgroundIn practice, the goal of treatment for patients with psoriasis is to achieve almost clear or clear skin and maintain disease control, regardless of baseline disease severity. However, identifying absolute Psoriasis Area and Severity Index (PASI) values for new treatment goals is challenging, as most clinical trials report relative PASI 50, 75, 90 or 100 improvements but rarely absolute PASI values achieved.ObjectiveOur objective was to illustrate a statistical conversion method that was developed to derive absolute PASI values from available clinical trial data on relative PASI improvements. The results of network meta‐analyses (NMAs) based on these derived data were then compared with those of NMAs based on the corresponding relative PASI improvement data for selected biologics for moderate‐to‐severe psoriasis.MethodsThe PASI statistical conversion method was applied to relative PASI improvement data for 11 biologic treatment regimens and placebo at 12 weeks using data from 50 published studies. The respective proportions of patients reaching absolute PASI values ≤1, 2, 3 or 5 were then calculated. Frequentist NMAs (Rücker method) were subsequently used to compare efficacy results across relative and absolute PASI data.ResultsThe ranking of included treatment regimens for patients achieving absolute PASI 0 to 8 was aligned with results for relative PASI scores (from 100 to 60) at end of induction therapy. Across the range of PASI scores considered, the most effective treatment regimens based on both absolute and relative PASI NMAs were brodalumab 210 mg every 2 weeks and ixekizumab 80 mg every 2 weeks, followed by guselkumab 100 mg every 8 weeks and risankizumab 150 mg every 12 weeks.ConclusionData generated using this mathematical model will be useful to inform ongoing scientific discussions on treatment goals in the absence of primary absolute PASI data for all available treatments for moderate‐to‐severe plaque psoriasis.

Clinician prescription of lipid-lowering drugs and achievement of treatment goals in patients with newly diagnosed type 2 diabetes mellitus

IntroductionLipid control is essential in type 2 diabetes mellitus (T2DM). The aim of this study is to investigate factors associated with lipid therapy adherence and achievement of goals in real-life...

Dynamics of hepatic steatosis resolution and changes in gut microbiome with weight loss in nonalcoholic fatty liver disease.

BackgroundWeight loss is recommended as the primary treatment for nonalcoholic fatty liver disease (NAFLD). However, the magnitude and velocity of hepatic steatosis resolution with weight loss is unclear, making it difficult to counsel patients seeking weight loss for treatment of NAFLD. The aim of this study was to determine the rate of hepatic steatosis improvement and stool microbiome changes associated with rapid diet‐induced weight loss in NAFLD.MethodsFourteen NAFLD patients (mean ± standard deviation, body mass index [BMI] 36.4 ± 4 kg/m2) enrolled in a 12‐week meal replacement program underwent frequent measurement of Fibroscan‐controlled attenuation parameter (CAP). Magnetic resonance imaging (MRI‐Dixon method) for hepatic fat quantitation and stool microbiome analysis (16S rRNA gene sequencing) were completed in 11 subjects at baseline and Week 12.ResultsAt Week 12, mean (95% confidence interval) weight loss was −13.4 (−15.2, −11.5)% and CAP score −26.6 (−35.6, −17.6)% (both Ps < 0.001). CAP scores changed at a rate of −4.9 dB/m/kg (−30.1 dB/m per unit BMI) in Weeks 1–4 and −0.6 dB/m/kg (−2.4 dB/m per unit BMI) in Weeks 8–12. MRI‐determined hepatic fat fraction decreased by −74.1% (p < 0.001) at a rate of −0.51%/kg (−3.19% per unit BMI), with complete steatosis resolution in 90% patients. BMI change was associated with decreased stool microbial diversity (coefficient = 0.17; Shannon Index), increased abundance of Prevotella_9 (Bacteroidetes; coefficient = 0.96) and decreased abundance of Phascolarctobacterium (Firmicutes; coefficient = −0.42) (both Ps < 0.05).ConclusionsDiet‐induced intensive weight loss is associated with rapid improvement and complete resolution of hepatic steatosis and decreased stool microbial diversity. These findings highlight the dynamic nature of hepatic fat and may help clinicians to develop evidence‐based treatment goals for patients with NAFLD and obesity who undertake weight loss interventions. Further research is warranted to understand the effects of intensive weight loss and gut microbiome changes on long‐term NAFLD resolution.

Effectiveness of TENS and home exercises as an adjunct to drug therapy in the management of myogenous masticatory pain: a comparative study

Introduction: Pain relief is the primary goal of treatment in patients with myogenous temporomandibular disorder. This study evaluated the effectiveness of TENS and Home exercises as an adjunct to drugs in relieving myogenous masticatory pain. Materials and methods: This prospective clinical study was conducted on 60 patients with myogenous masticatory pain. Patients were randomly allocated into three groups of 20 patients each. Patients in Group A received TENS and drugs, while patients in Group B received home exercises and drugs and Group C received drugs only. The drugs prescribed were Diclofenac 50 mg and Orphenadrine 100 mg, to be taken twice daily for 5 days. All patients were followed up for three weeks. The severity of pain was recorded using the Visual Analog Scale. Inter and intragroup differences in the pain scores were analyzed using one-way ANOVA along with post hoc Tukey's test, and Paired t-test, respectively. p &lt; 0.05 was considered as statistically significant. Results: There was a significant reduction in the mean pain scores in all the three groups at 1st, 2nd, and 3rd post-treatment weeks as compared to the baseline scores with p &lt; 0.001. However, when the pain scores were compared across groups, maximum pain reduction was observed in group A (0.2 ± 0.04), followed by group B (0.5 ± 0.06), and the least reduction was noticed in group C (2.1 ± 0.8). This result was significant with p &lt; 0.001. Conclusion: Both TENS and Home exercises program were effective as adjuncts to drugs, in controlling myogenous masticatory pain, as compared to drugs alone.

Cardiac Rehabilitation in Heart Failure.

Heart failure (HF) is a complex clinical syndrome caused by a structural and/or functional cardiac abnormality, resulting in reduced organ perfusion. The goals of treatment in patients with HF are to improve functional capacity and quality of life, and to reduce mortality. Cardiac rehabilitation (CR) including exercise training is one of the treatment options, and current guidelines recommend CR as safe and effective for patients with HF. CR has been known to improve exercise capacity and quality of life, minimize HF progression, and lower mortality in patients with HF. Improvement of vascular endothelial function, activation of the neurohormonal system, increase of mitochondrial oxygen utilization in peripheral muscles, and increase of chronotropic responses are possible mechanisms of the beneficial effects of exercise-based CR in HF. Although CR has been shown to decrease morbidity and mortality, it is underutilized in clinical practice. Despite the existence of concrete evidence of clinical benefits, the CR participation rates of patients with HF range from only 14% to 43% worldwide, with high dropout rates after enrollment. These low participation rates have been attributed to several barriers, including patient factors, professional factors, and service factors. The motivation for participating in CR and for overcoming the patients' barriers for CR before discharge should be provided to each patient. Current guidelines strongly recommend applying a CR program to all eligible patients with HF.