First-line Management Strategy Research Articles

Role of Routine Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infections.

The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny. We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis. The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI, .79-2.39; P = .27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI, .11-1.15; P = .09), which also had the highest risk of treatment failure. The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.

Comparison between beta-blockers and calcium channel blockers in patients with atrial fibrillation according to renal function.

Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.

Beyond a vestigial organ: effects of the appendix on gut microbiome and colorectal cancer.

The role of appendectomy in the pathogenesis of colorectal cancer (CRC) is a recent topic of contention. Given that appendectomy remains one of the most commonly performed operations and a first-line management strategy of acute appendicitis, it is inherently crucial to elucidate the association between prior appendectomy and subsequent development of CRC, as there may be long-term health repercussions. In this review, we summarize the data behind the relationship of CRC in post-appendectomy patients, discuss the role of the microbiome in relation to appendectomy and CRC pathogenesis, and provide an appraisal of our current understanding of the function of the appendix. We seek to piece together the current landscape surrounding the microbiome and immunological changes in the colon post-appendectomy and suggest a direction for future research involving molecular, transcriptomic, and immunologic analysis to complement our current understanding of the alterations in gut microbiome.

Bronchial Artery Embolization: IS NBCA/LIPIODOL Better Than PVA?

Introduction: Bronchial artery embolization (BAE) is a minimally invasive interventional procedure, which is now considered the first-line management strategy and an alternative to surgery for massive and recurrent haemoptysis. The advances in embolic agents have led to a significant improvement in the success rates of the procedure, however, there has been no significant change in the recurrence rate of haemoptysis. Methods: This retrospective study was conducted at a tertiary care center from January 2012 to December 2020. The final analysis was performed on 123 patients [NBCA(n= 37) and PVA(n= 86)]. Technical and clinical success rates, complications and recurrence rates were compared between the two groups. Results: A total of 248 arteries were embolized. In the PVA group, clinical success was achieved in 84 out of 86 cases (97.6%) and with NBCA in 36 out of 37 patients (97.3%) (p &gt;0.05). Of the 120 patients in whom BAE was clinically successful, recurrence was observed in 43 patients within the 12-month follow-up period. The study showed a statistically significant association between the embolizing agent used for BAE and the recurrence of hemoptysis (χ2 = 4.80, df = 1, p = 0.028). The use of PVA particles for BAE was found to have2.62 times higher odds (95% CI 1.10 - 6.81) of recurrence of hemoptysis as compared to the use of NBCA glue. Conclusions: BAE with NBCA provided higher hemoptysis-free survival rates compared with PVA particles without increasing complication rates.

Partner Alliance to Enhance Efficacy and Adherence of CBT-I.

Cognitive behavioral therapy for insomnia (CBT-I) is now widely recognized as the first-line management strategy for insomnia, both for insomnia in its "pure" form, and when comorbid with a physical or psychological illness. However, there is a definite need to develop and test both alternative and adjunct interventions to CBT-I, before implementing them into routine practice. The aim of this article is to provide a narrative review of the literature with regard to what is known about the influence of partners on sleep, insomnia, and its management.

Myths and misconceptions about childhood constipation.

Many widely held beliefs and assumptions concerning childhood constipation continue to interfere with rational management of childhood constipation. Although many still believe that constipation is not a common disease, about 9.5% of the world's children suffer from chronic constipation. Most of these children live in non-Western countries. There are major misconceptions about the etiology of constipation as a significant proportion of clinicians still believe that constipation is caused by some form an organic pathology, whereas in reality, the majority have functional constipation. Contrary to a commonly held belief that children outgrow constipation without long-term problems, there is evidence that constipation leads to significant bowel and psychological consequences and has a major impact on the quality of life which detrimentally affects future health and education. Finally, ineffective management strategies such as increasing fiber and water in the diet, and short duration of treatment owing to the fear that long-term laxative treatment leads to colonic dysfunction, interfere with effective therapeutic strategies. Conclusions: It is apparent that myths and misconception often lead to wrong assumptions regarding the distribution of the disease, its etiology, pathophysiology, and management leading to ordering incorrect investigations and ineffective therapeutic strategies while spending large sums of public funds unnecessarily. Poorly treated constipation leads to deleterious psychological consequences predisposing children to develop significant psychological damage and bowel dysfunctions. This review aims to challenge these myths about various elements of constipation by exploring the existing literature and encouraging clinicians to have a fresh look at old concepts that could interfere with the well-being of children with constipation. What is Known: • Childhood constipation is a growing problem in the world leading to significant suffering and high healthcare expenditure • Myths and misconceptions lead to poor management strategies causing psychological and bowel damage What is New: • Organic, systemic, and bowel disorders leading to constipation are uncommon, and in the majority, it arises due to deliberate fecal withholding and most investigations ordered by clinicians are not very helpful in the management • Most non-pharmacological interventions are not effective in the day-to-day management of childhood constipation. The use of laxatives is considered to be the first-line management strategy.

Endovascular therapy versus medical treatment for spontaneous isolated dissection of the superior mesenteric artery.

Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) occurs when a tear in the inner layer of the superior mesenteric artery (SMA) allows blood to flow between the layers of the SMA, forcing the layers apart, and creating two lumens. Abdominal pain is the most prevalent clinical manifestation. Other people may have no symptoms or experience nausea, vomiting, diarrhea, or blood in their stools. For people with SIDSMA who are not suspected of intestinal necrosis or intra-abdominal bleeding, medical treatment and endovascular therapy are the main treatment options. There is no consensus on the optimum first-line management strategy. To evaluate the benefits and harms of endovascular therapy versus medical treatment for spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). We used standard, extensive Cochrane search methods. The latest search date was 3 August 2021. We planned to include all randomized controlled trials (RCTs) which compared endovascular therapy and medical treatments for SIDSMA. We planned to exclude studies where participants were treated with open surgery. We used standard Cochrane methods. Our primary outcomes were endovascular intervention rate and recurrent abdominal pain. Our secondary outcomes were open surgery rate, remodeling rate of SMA, new aneurysm formation of SMA, SMA occlusion, new dissection of SMA, death, symptom relief rate and complications of endovascular therapy. We planned to use GRADE to assess certainty of evidence for each outcome. We did not identify any RCTs to include in any analysis. We were not able to include any RCTs that compared endovascular therapy versus medical treatment in people with SIDSMA. High-quality RCTs that evaluate the benefits and harms of these interventions are needed to help determine the optimal strategy for managing SIDSMA.

Trends in Percutaneous Balloon Mitral Valvuloplasty Complications for Mitral Stenosis in the United States (the National Inpatient Sample [2008 to 2018

The epidemiology of mitral stenosis (MS) continues to evolve in the United States. Although the incidence of rheumatic MS has decreased in high-income countries, there is a paucity of data surrounding trends in percutaneous balloon mitral valvuloplasty (PBMV), the current first-line management strategy. This study aimed to identify contemporary trends in PBMV in the United States. Hospitalizations for adults (≥18years) with MS who underwent PBMV were identified from the National Inpatient Sample from 2008 to 2018. Baseline co-morbidities and outcomes over the study period were determined using Poisson regression. There were 3,980 weighted PBMV cases, 70% of which were women. PBMV hospitalizations decreased from 603 in 2008 to 210 in 2018 (p&lt;0.001). From 2008 to 2018, the age at hospitalization was unchanged in both female and male patients. In contrast, the Charlson Co-morbidity Index increased in both. Baseline heart failure (39% to 64%), hypertension (38% to 43%), and diabetes mellitus (17% to 26%) all substantially increased over the study period. In-hospital mortality occurred in 2% of female and 5% of male patients and was unchanged from 2008 to 2018. Vascular complications (12%) and acute kidney injury (10%) were the most frequent postprocedural complications during the 11-year study period. A composite of mortality or any postprocedural complication did not vary by gender (odds ratio 1.23, 95% confidence interval 0.88 to 1.72). In conclusion, the use of PBMV significantly decreased from 2008 to 2018, and patients with MS who underwent PBMV over this period had an increased burden of co-morbidities, elevated postprocedural complication rate, and no change in in-hospital mortality.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Development of 'Core Outcome Sets' for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings.

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two ‘Core Outcome Sets’ (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508

A retrospective real-world study of the current treatment pathways for myelofibrosis in the United Kingdom: the REALISM UK study.

Background:Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom.Methods:The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF. The primary endpoint was the time from diagnosis to active treatment.Discussion:Two hundred patients were included (63% [n = 126/200] with primary MF; 37% [n = 74/200] with secondary MF). Symptoms and prognostic scores at diagnosis were poorly documented, with infrequent use of patient reported outcome measures. ‘Watch and wait’ was the first management strategy for 53.5% (n = 107/200) of patients, while the most commonly used active treatments were hydroxycarbamide and ruxolitinib. Only 5% of patients proceeded to allogeneic transplant. The median (IQR) time to first active treatment was 46 days (0–350); patients with higher risk disease were prescribed active treatment sooner.Conclusion:These results provide insight into real-world clinical practice for patients with MF in the United Kingdom. Despite the known high prevalence of disease-associated symptoms in MF, symptoms were poorly documented. Most patients were initially observed or received hydroxycarbamide, and ruxolitinib was used as first-line management strategy in only a minority of patients.Plain Language SummaryBackground: Myelofibrosis is a rare blood cancer associated with symptoms that can seriously affect a patient’s daily life, such as enlarged spleen and decreased white and red blood cells. Although several treatments are available for patients with myelofibrosis, it is not clear which ones clinicians use most frequently.Methods: We aimed to review which treatments are usually given to patients with myelofibrosis in the UK, by collecting information from the medical records of 200 patients with myelofibrosis treated in different centres across the UK.Results: The results showed that the symptoms patients experienced were not always written down in the medical records. Similarly, clinical scores based on patient characteristics (which clinicians use to try to predict if a patient will respond to treatment well or not) were also missing from the medical records. Clinicians also rarely asked patients to complete questionnaires that try to measure the impact of myelofibrosis and its treatment on their health. The most common approach for patients with myelofibrosis in the UK was ‘watch and wait’, which over half of patients received. The most common drugs used for treatment were hydroxycarbamide and ruxolitinib; only a very small proportion of patients received a bone marrow transplant. On average, patients waited for 46 days before receiving a treatment, although patients considered to have a more aggressive type of disease received treatment sooner.Conclusion: The results of this study suggest that medical records can be missing key information, which is needed to decide which is the best way to treat a patient with myelofibrosis. They also suggest that clinicians in the UK prefer observation to treatment for a large number of patients with myelofibrosis. This could mean that the approach used for many patients with myelofibrosis does not help them to control symptoms that have an impact on their daily lives.

Outcomes of Initial Management Strategies in Patients With Autoimmune Lymphocytic Hypophysitis: A Systematic Review and Meta-analysis.

Lymphocytic hypophysitis (LyHy) is characterized by inflammation of the pituitary and or neuroinfundibulum and is uncommon. Treatment options include observation, high-dose glucocorticoids (HD-GCs) or surgery. Optimal first-line management strategy, however, remains unknown. This work aimed to assess response to first-line treatment options (observation, HD-GCs, or surgery) of clinically relevant outcomes (symptomatic, hormonal, and radiographic improvement) among patients with LyHy. A systematic review was conducted in 6 databases through 2020. Meta-analysis was conducted when feasible using a random-effects model. We included 33 studies reporting on 591 patients (423 women, 72%) with LyHy. Improvement/resolution of anterior pituitary dysfunction was highest when HD-GCs was first-line treatment. Surgery was associated with the greatest proportion of patients who had regression on imaging. Subgroup analysis comparing HD-GCs to observation showed the odds of anterior pituitary hormone recovery (OR 3.41; 95% CI, 1.68-6.94) or radiographic regression (OR 3.13; 95% CI, 1.54-6.36) were higher with HD-GCs, but so was the need for additional forms of treatment (OR 4.37; 95% CI, 1.70-11.22). No statistically significant difference was seen in recovery of diabetes insipidus (OR 0.9; 95% CI, 0.26-3.10). Certainty in these estimates was very low. Observation and use of HD-GCs both are successful first-line management strategies in LyHy. Although use of HD-GCs was associated with increased recovery of anterior pituitary hormone deficit, it also was associated with greater likelihood of additional treatment after withdrawal. Optimal dosing and duration of HD-GCs remains unknown.

Efficacy of Different Modalities of Treatment in Management of Different Types of Fungal Sinusits

Abstract Background Fungal sinusitis is generally classified into invasive and non invasive fungal sinusitis based on histological features, invasive fungal sinusitis divided into acute, chronic and chronic granulomatous invasive fungal sinusitis. While non invasive fungal sinusitis include saprophytic fungal infestation, fungal ball, and fungus-related eosinophilic. Distinguishing invasive disease from noninvasive disease is important because the treatment and prognosis are different for each. AIM A systemic review of effective and safe method in management of different types of fungal sinusitis either by medical or surgical approaches or even combined. Be up to date with the different upcoming new modalities. Methodology A meta-analysis study is done to evaluate the medical and surgical outcomes of patients with invasive and noninvasive Fungal Sinusits. Results Finally, forty-five studies were included in the present systematic review and metaanalysis. Fifteen included studies (No = 539 patients) assessed different modalities for management of fungal ball, via classic endoscopic technique, Canine-fossa approach, gauze technique and osteoplastic approach for FB of the maxillary sinus. The results showed that functional endoscopic sinus surgery has led to success rate of 98.1%. Twenty included studies (No = 806 patients) have assessed the efficacy and safety of different modalities for the management of allergic fungal sinusitis via,Endoscopic Sinus Surgery, Post-ESS Systemic steroids, Antifungals and immunotherapy. The results showed that ESS represents the firstline management strategy of AFRS, followed by aggressive medical therapies, the recurrence rate after postoperative steroids was 20.6%, postoperative antifungals was 40% and after immunotherapy was 9.1%. Ten studies (No = 327 patients) for Invasive Fungal Sinusitis.the results showed that combination of systematic antifungal therapy and aggressive surgical debridement are the treatment of choice. Conclusion FESS is the treatment of choice of fungal ball via classic endoscopic technique, Canine-fossa approach, gauze technique and osteoplastic approach. AFS treatment consists of surgical extirpation of the allergic mucin and polyps with maintenance of adequate sinus drainage followed by medical therapy consists of topical steroids, anti fungal therapy, Immunotherapy, and systemic corticosteroids. Treatment of invasive fungal sinusitis includes surgical resection of necrotic tissues, systemic antifungal therapy and reversal of immune dysfunction.

Management of chronic subdural hematoma with the subdural evacuating port system: Systematic review and meta-analysis

The subdural evacuating port system (SEPS) is a minimally invasive option for treating chronic subdural hematoma (cSDH). Individual case series have shown it to be safe and effective, but outcomes have not been systematically reviewed. We sought to review the literature in order to determine the safety and efficacy of SEPS as a first line treatment for cSDH. A comprehensive literature search for outcomes following SEPS placement as a primary treatment for cSDH was performed. The primary outcome was treatment success, which was defined as a composite of improvement in presenting symptoms and no need for further treatment in the operating room. Additional outcomes included discharge disposition, length of stay (LOS), hematoma recurrence, and complications. A total of 12 studies comprising 953 patients who underwent SEPS placement met the inclusion criteria. The pooled rate of a successful outcome was 0.79 (95% CI 0.75–0.83). Frequency of delayed hematoma recurrence was 0.15 (95% CI 0.10–0.21). The pooled inpatient mortality rate was 0.02 (95% CI 0.01–0.03). Complications rates included 0.02 (95% CI 0.00–0.03) for any acute hemorrhage, 0.01 (95% CI 0.00–0.01) for acute hemorrhage requiring surgery, and 0.02 (95% CI 0.01–0.03) for seizure. SEPS placement is associated with a success rate of 79% and very low rates of acute hemorrhage and seizure. This data supports its use as a first-line management strategy, although prospective randomized studies are needed.

Online Opioid Stewardship Training for Long-Term Care Staff

Opioids are often the first-line chronic pain management strategy for long-term care (LTC) residents who are also at increased risk for opioid-related adverse events. Therefore, there is a need to train LTC providers and staff about appropriate opioid use and alternative treatment strategies. Our interdisciplinary team worked with LTC partners to identify staff educational needs around opioid stewardship. Based on this need’s assessment, we developed eight modules about opioid use and risks for older adults, including those with dementia, recommendations for de-prescribing including other pharmacological and non-pharmacological alternatives, SBIRT, and motivational interviewing to determine “what matters”. Each 20-minute module contains didactic and video content that is appropriate for group staff training or individuals and provides rural LTC facilities access to needed training in their home communities. Within the first month of launching online, the program received over 1100 hits and LTC partners are incorporating modules into clinical staff training schedules.

Pseudoaneurysm associated haemosuccus pancreaticus - a rare and dangerous disease

BackgroundIn patients with upper gastrointestinal bleeding and hemorrhage originating from the major duodenal papilla pseudoaneurysm associated haemosuccus pancreaticus (HP) is a rare differential diagnosis which should be considered. Diagnosis may be challenging, as clinical presentation is often unspecific with only intermittent hemorrhage. Treatment of the causal pseudoaneurysm is mandatory and endovascular coil embolization is the suitable first-line management strategy.Until now there are only a very few studies about this clinical picture and its therapeutic options, especially data regarding whether additional fluid embolization is beneficial/necessary in HP is currently lacking.Case presentationWe report a case of a 59-year-old male patient with chronic pancreatitis and haemosuccus pancreaticus caused by a pancreatico-arterial fistula with an associated inflammatory pseudoaneurysm of the splenic artery. Initially we sought to embolize the pseudoaneurysm with microcoils. As only one coil could be safely deployed in the pseudoaneurysm we additionally employed tissue adhesive embolization in order to achieve complete occlusion of the pseudoaneurysm as well as the pancretico-arterial fistula. In the presented case inflammatory levels decreased following embolization, possibly linked to a decline in pathologic excretion of elastase and autodigestion. As not only the pseudoaneurysm but also the underlying fistula were occluded, the risk of recurrence may conceivably be reduced.ConclusionsDiagnosis of HP is difficult and treatment of the causal pseudoaneurysm is mandatory. Endovascular embolization is the suitable first-line management strategy, complete occlusion of the fistula should be considered when possible.

Diet and functional dyspepsia: Clinical correlates and therapeutic perspectives.

Hypervigilance and symptoms anticipation, visceral hypersensitivity and gastroduodenal sensorimotor abnormalities account for the varied clinical presentation of functional dyspepsia (FD) patients. Many patients recognize meals as the main triggering factor; thus, dietary manipulations often represent the first-line management strategy in this cohort of patients. Nonetheless, scarce quality evidence has been produced regarding the relationship between specific foods and/or macronutrients and the onset of FD symptoms, resulting in non-standardized nutritional approaches. Most dietary advises are indeed empirical and often lead to exclusion diets, reinforcing in patients the perception of “being intolerant” to food and self-perpetuating some of the very mechanisms underlying dyspepsia physiopathology (i.e., hypervigilance and symptom anticipation). Clinicians are often uncertain regarding the contribution of specific foods to dyspepsia physiopathology and dedicated professionals (i.e., dietitians) are only available in tertiary referral settings. This in turn, can result in nutritionally unbalanced diets and could even encourage restrictive eating behaviors in severe dyspepsia. In this review, we aim at evaluating the relationship between dietary habits, macronutrients and specific foods in determining FD symptoms. We will provide an overview of the evidence-based nutritional approach that should be pursued in these patients, providing clinicians with a valuable tool in standardizing nutritional advises and discouraging patients from engaging into indiscriminate food exclusions.

The Variability of Lumbar Facet Joint Synovial Cyst Recurrence Requiring Revision Surgery After Decompression-only and Decompression/Fusion.

This is a retrospective study. The objective of this study was to evaluate lumbar spine synovial cyst recurrence rates of decompression-alone versus decompression/fusion procedures. Improvements in imaging modalities allow for increased diagnosis and surgical treatment of symptomatic spinal juxtafacet synovial cysts. Conservative management may be used as a first-line management strategy, however rarely provides durable, effective relief of symptoms. Surgical treatment of spinal synovial cysts ranges from decompression and cyst excision to decompression with fusion procedures. Decompression procedures alone have a higher risk of recurrence of spinal synovial cysts. We retrospectively reviewed 87 patients undergoing surgical treatment of lumbar spinal juxtafacet synovial cysts as a single institution over 20 years. Surgical treatment consisted of either decompression versus decompression/fusion procedures. Preoperative symptoms included back pain, radiculopathy, motor deficits, or sensory deficits. The incidence of recurrence of spinal synovial cysts at the same-site or differing sites was compared between 2 categories of surgical treatment. Revision surgical procedure rates were also evaluated. A total of 55 (63%) patients were treated with an index decompression-only procedure for the lumbar spinal synovial cyst compared with 32 (37%) patients treated with an index decompression and fusion procedure. Fifty-eight (68%) of the lumbar spinal cysts occurred at the L4-L5 level. There were 10 (11.5%) spinal synovial cyst recurrences in the decompression-only group, and 0 recurrences in the decompression/fusion group. Revision decompression procedures were performed in 4 of the 10 (4.6%) recurrences, and 6 of 10 (6.9%) recurrences had subsequent decompression and fusion surgery. The mean time to recurrence was 23.9±17.3 months. The mean length of follow-up was 65.1±48.6 months. Both recurrence and nonrecurrence cohorts had significant symptomatic improvement using Odom criteria. Decompression and cyst excision was the more common surgical treatment of lumbar spinal synovial cysts compared with decompression/fusion procedure in our study. The rate of synovial cyst recurrence and revision surgery in patients undergoing index decompression was relatively low and comparable to current literature. Symptomatic improvement of patients undergoing decompression versus decompression/fusion was similar in our study. Although the fusion may be required for the extent of pathology or coexisting instability, decompression and excision of spinal synovial cysts provide durable, effective treatment with a known, appropriate risk of recurrence and subsequent revision surgery.

Significance of Soluble Interleukin-2 Receptor to Predict Prognosis and Support Decision-Making on Watchful Waiting for Stage II-IV Follicular Lymphoma Patients in the Rituximab Era

Background: Follicular lymphoma (FL) shows indolent clinical course and the optimal management strategy includes watchful waiting (WW). To define prognostic models for WW in clinical practice, we focused on serum soluble interleukin-2 receptor (sIL-2R) in the era of rituximab (R).Methods: To evaluate risk stratification of patients with FL, we employed the current retrospective study. The data and follow-up information of patients were collected from three medical centers. The diagnosis of FL is made by the WHO criteria. Eligible patients were aged 18-90 years, previously untreated, and diagnosed between 2004 and 2016. WW was considered as an initial approach for patients with asymptomatic, no organ damage by lymphoma, or lacking bulky disease. Progression-free survival from diagnosis (PFS1) was defined as the time from diagnosis to disease progression requiring therapy in WW, first progression after frontline active therapy, or death from any cause. Progression free survival after active therapy (PFSA) was defined as the time from anti-lymphoma therapy to progression or death, and PFS2 was defines as the time from diagnosis to secondary progression or death from any cause. This study was approved by the independent ethics committee or institutional review board at participating institutions.Results: Total 291 patients with newly diagnosed FL with stage II-IV and with grade 1-3a were included. Of these, 12.7% of patients were older than 75 years, 45% were men, 62.5% had stage IV disease, 18.9% were elevated LDH, 16.7% were beta 2-microglobulin (B2m) beyond 3 mg/L, 7.2% were grade3a, and 32.0% were FLIPI-high. The serum levels of B2m and sIL-2R were measured in each center, and the examination rates were 88.6% and 100%, respectively. In a simple linear regression, statistic correlation between serum B2m and sIL-2R of individual patients were confirmed with R-squared of 0.4 and P-value of <0.001. The sIL-2R of 1000 IU/mL was correlated with B2m of nearly 1.2 mg/L. The proportion of patients with sIL-2R ≤500, >500 ≤1000, and >1000 were 18.9%, 26.8%, and 54.3%, respectively. Total 89 patients (30.6%) had a first-line management strategy of WW, and during the median follow-up of 6.9 years, 52 patients required active therapy consisted of R-CHOP like (100%). The other 202 patients received frontline active therapy, included R-CHOP like (82.7%), R-CVP (12.9%), R-bendamustine (1%), or R-monotherapy (3.4%), and only 5 patients received R-maintenance. With a median follow-up of 5.5 years, there were 8 deaths in WW and 22 in frontline active therapy, demonstrating no difference in overall survival (P = 0.3). Based on multivariate analysis, factors associated with PFS1 are sIL-2R of ≤500, >500 ≤1000 IU/mL, and >1000 IU/mL (HR, 1.34; 95% CI 1.03-1.74) and stage IV (HR 1.71, 95% CI 1.11-2.63), while gender, age >75 years, B2m >3.0 mg/L, elevated LDH, and histological grade were not significant. When divided into three groups using sIL-2R, 6-year PFS1 were 74.2%, 51.4%, and 40.3%, respectively (P <0.001) in the entire patients, and were 65.2%, 41.4%, and 20.7%, respectively (P <0.001) among patients with WW. Overall, PFS1 of patients with WW was not so favorable as those with frontline active therapy (HR 1.43; 95% CI 1.01-2.02, P = 0.043), but PFS2 was equivalent (HR 1.57; 95% CI 0.76-3.27, P = 0.22). Among patients with sIL-2R ≤1000 IU/L, 6-year PFS1 was equally favorable in patients with WW compared to frontline active therapy (51.9% vs. 70.4%, P = 0.06; Figure 1), and 6-year PFSA was also equally favorable (80.6% vs. 67.7%, P = 0.75). On the contrary, among patients with sIL-2R >1000 IU/L, WW was associated with inferior PFS1 (HR 3.00; 95% CI 1.48-3.89; Figure 1) and PFS2 (HR 2.87; 95% CI 1.25-6.60) compared with frontline active therapy. The rate of histological transformation (HT) was similar: 5 in WW vs. 4 in frontline active therapy (P = 0.1). Median time to HT from diagnosis was 6.0 years (1.2-7.0) in WW, which was quite longer compared to 1.3 years (0.3-1.8) in frontline active therapy (P = 0.01). Secondary myeloid malignancies had developed in 4 patients at median 3.6 years (2.5-6.2) after frontline active therapy.Conclusion: For FL patients, the usefulness of sIL-2R is demonstrated for predicting intervals from starting WW until therapy requirements. In addition to general guidelines, the variable of sIL-2R ≤1000 IU/L at diagnosis was the simple indicator to recommend WW to postpone active therapy without impairing prognosis. DisclosuresNo relevant conflicts of interest to declare.

Cost-effectiveness analysis of first-line treatments for early-stage, low-grade follicular lymphoma.

6619 Background: Low-grade follicular lymphoma (FL) can present as localized stage I to II disease in up to one-third of patients. Upfront involved-site radiation therapy (RT) to 24-30Gy is the preferred first-line management strategy for these patients. However, the National LymphoCare Study found that less than one quarter of patients with early-stage, low-grade FL received upfront RT, while more than half received either chemoimmunotherapy or observation. Methods: We performed a cost-effectiveness analysis using a Markov state-transition model to simulate the progression of early-stage, low-grade FL in a cohort of 60-year-old men. The following first-line treatments were compared: RT, observation, rituximab induction (RI), rituximab and bendamustine (BR), and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Patients who relapsed received second-line therapies that were dependent on their first-line treatment: RT for RI and observation, RCHOP for RT and BR, and BR for RCHOP. Disease-progression probabilities and other model inputs were from published trials. Results: First-line RT followed by RCHOP for relapses had a quality-adjusted life expectancy (QALE) of 11.4 years, superior to first-line observation, RI, BR, and RCHOP strategies. First-line RT strongly dominated observation, BR, and RCHOP. Compared with RI, first-line RT resulted in an incremental cost-effectiveness ratio of $2,740 per quality-adjusted life year. The probability of dying from other causes, the probability of a complete response to RT, and the probability of relapse had the greatest impact on both cost and effectiveness expected values. Conclusions: In contrast to current practice patterns, first-line RT is the most effective upfront treatment for patients with early-stage, low-grade FL. Further, first-line RT paired with RCHOP for relapses is a cost-effective treatment paradigm, relative to other strategies. [Table: see text]