Antral Inflammatory Cells,Gastric Emptying,and Electrogastrography in Pediatric Functional Dyspepsia

The aims of the current study were to determine the activation states of antral eosinophils and mast cells and to evaluate the interactions of antral inflammatory cells with gastric emptying and electrogastrography (EGG) in 30 pediatric patients with functional dyspepsia. Eosinophil degranulation was moderate in 42% and extensive in 54% of patients. Mast cell degranulation was >50% in 81% of patients. Elevated mast cell density was associated with slower one hour gastric emptying and increased preprandial dysrhythmia. Mast cell density correlated with the preprandial percentage tachygastria. CD3+ cell density correlated with the preprandial percentage tachygastria also, but only in patients with increased eosinophil density. In conclusion, antral eosinophils and mast cells are significantly activated in pediatric functional dyspepsia. Mast cell density is associated with delayed gastric emptying and preprandial dysrhythmia, suggesting that there may be an interaction between antral inflammation and gastric electromechanical dysfunction in the pathophysiology of pediatric functional dyspepsia.     

Anti-vascular endothelial growth factor treatment normalizes tuberculosis granuloma vasculature and improves small molecule delivery

Tuberculosis (TB) causes almost 2 million deaths annually, and an increasing number of patients are resistant to existing therapies. Patients who have TB require lengthy chemotherapy, possibly because of poor penetration of antibiotics into granulomas where the bacilli reside. Granulomas are morphologically similar to solid cancerous tumors in that they contain hypoxic microenvironments and can be highly fibrotic. Here, we show that TB-infected rabbits have impaired small molecule distribution into these disease sites due to a functionally abnormal vasculature, with a low-molecular-weight tracer accumulating only in peripheral regions of granulomatous lesions. Granuloma-associated vessels are morphologically and spatially heterogeneous, with poor vessel pericyte coverage in both human and experimental rabbit TB granulomas. Moreover, we found enhanced VEGF expression in both species. In tumors, antiangiogenic, specifically anti-VEGF, treatments can “normalize” their vasculature, reducing hypoxia and creating a window of opportunity for concurrent chemotherapy; thus, we investigated vessel normalization in rabbit TB granulomas. Treatment of TB-infected rabbits with the anti-VEGF antibody bevacizumab significantly decreased the total number of vessels while normalizing those vessels that remained. As a result, hypoxic fractions of these granulomas were reduced and small molecule tracer delivery was increased. These findings demonstrate that bevacizumab treatment promotes vascular normalization, improves small molecule delivery, and decreases hypoxia in TB granulomas, thereby providing a potential avenue to improve delivery and efficacy of current treatment regimens.As one of the most prevalent infectious diseases in the world today, Mycobacterium tuberculosis (MTB) infects roughly one-third of the global population, resulting in 2 million deaths annually (1). Although current treatment regimens are largely successful in curing the disease (2), they require 6–8 mo of treatment with up to four agents (3), and multidrug-resistant bacterial strains have emerged and proliferated (4). Resistance to front-line therapies necessitates treatment with up to five or six second-line agents that are poorly tolerated, and treatment success is only achieved in 40–70% of patients (5). Failure to cure drug-resistant disease leads to acquisition of further resistance with a progressively poorer prognosis for these patients, thus fueling an emerging epidemic of drug-resistant disease that threatens to overwhelm fragile health care systems in developing countries (6).When infected with the tuberculosis (TB) bacilli, the body triggers an immune response that walls off the bacteria in dense cellular masses known as granulomas, or tubercular lesions (7). These abnormal tissue structures, which can vary in size within the same host, are surrounded by fibrous cuffs that serve to contain the MTB bacilli (7, 8). Recent studies have demonstrated a wide variation in the spatial distribution of drugs within TB granulomas, with very few agents able to penetrate the central regions (9). This differential ability of drugs to penetrate TB granulomas has been incorporated into modern TB drug development programs as a criterion for optimizing lead molecules and selecting efficacious combinations (10). However, the mechanisms that contribute to this differential penetration of drugs are not fully understood, and novel strategies to improve TB drug delivery and efficacy are urgently needed.Following infection with MTB, pulmonary granulomas form in humans and develop heterogeneous microenvironments, often featuring hypoxia (i.e., low levels of oxygen) and central necrosis, which are recapitulated in nonhuman primate and rabbit models of the disease (11). Large lesions appear to develop their own vasculature, presumably allowing them to continue to grow (7). However, the morphological and functional characteristics of granuloma-associated vessels are largely unknown. In solid tumors, cancer cells can form similar dense tissue masses with abnormal associated vasculature. The physiological abnormalities that characterize tumor vessels have been investigated extensively (12, 13). For example, hypoxia, a common feature in solid tumors, stimulates the overproduction of proangiogenic factors, such as VEGF. Proangiogenic factors enhance the formation of new immature, tortuous, and hyperpermeable vessels (12, 14), often with excess endothelial cells, a lack of associated pericytes (i.e., perivascular cells), and uneven basement membranes (15–17). These atypical features result in an impaired blood flow that further compromises delivery of drugs and oxygen (13). Hypoxia also causes immunosuppression, inflammation, and fibrosis, and it can also confer resistance to many drugs (18). Here, we propose that TB granulomas share many characteristics with solid tumors, namely, that they are associated with abnormal and dysfunctional vasculature that can impair the delivery of small molecules, such as oxygen and antibiotics.Because VEGF is a critical growth factor required for new blood vessel formation (16), anti-VEGF agents were originally developed to block tumor growth by inhibiting blood vessel formation (19). However, bevacizumab, a humanized monoclonal antibody developed to neutralize human VEGF, failed to improve survival benefit as a monotherapy but conferred survival benefit only in combination with chemotherapy or immunotherapy (18). A potential explanation for the success of combined therapies is that bevacizumab “normalizes” the abnormal vasculature of tumors, resulting in improved delivery of concurrently administered anticancer drugs, as well as alleviation of hypoxia (13, 15, 18, 20, 21). However, this strategy has not been tested in a TB disease model. In this study we show, for the first time to our knowledge, in a rabbit model of TB that treatment with bevacizumab normalizes granuloma vasculature, reduces hypoxia, and enhances small molecule delivery during a “window of normalization,” a transient effect observed in tumors (15, 20). Because anti-VEGF drugs have been approved for both malignant and nonmalignant diseases (18), our findings could be rapidly tested in the clinic to enhance TB treatment, shorten treatment duration, and avert the development of treatment resistance.     

Barriers to Referral to Fellowship-trained Minimally Invasive Gynecologic Surgery Subspecialists

Study ObjectiveTo determine patterns and barriers for referral to fellowship-trained minimally invasive gynecologic surgeons.DesignQuestionnaire.SettingUnited States and its territories and Canada.ParticipantsActively practicing general obstetrician/gynecologists (OB/GYNs).InterventionsInternet-based survey.Measurements and Main ResultsOf 157 respondents, 144 (91.7%) general OB/GYNs were included. Subspecialty fellowship training resulted in the exclusion of 13 (8.3%) respondents. A total of 86 respondents (59.7%) considered referral to fellowship-trained minimally invasive gynecologic surgery (MIGS) subspecialists. The top 3 cited reasons for nonreferral were adequate residency training (n = 84, 58.3%), preference for continuity of care (n = 48, 33.3%), and preference for referral to other subspecialists (n = 46, 31.9%). The top 3 cited reasons for referral to MIGS subspecialists were complex pathology (n = 92, 63.9%), complex medical and/or surgical history (n = 76, 52.8%), and out of scope of practice (n = 53, 36.8%). If providers required intraoperative assistance, respondents consulted an OB/GYN colleague with comparable training (n = 50, 34.7%), gynecologic oncologist (n = 48, 33.3%), or non-OB/GYN surgical subspecialist (n = 33, 22.9%). Factors that were not associated with the decision to refer to MIGS subspecialists included years in practice (p = .13), additional training experiences beyond residency (p = .45), and number of hysterectomies performed by laparotomy (p = .69). Self-reported high-volume surgeons (p <.01) were less likely to refer. In contrast, providers who self-reported as low-volume surgeons (p = .02) and were aware of MIGS subspecialists in the community (p <.01) were more likely to consider referral. Respondents reported using a laparoscopic approach to hysterectomy most frequently (n = 79, 54.9%). In contrast, 36.8% preferred the laparoscopic route for themselves or their partner, whereas 48.6% preferred the vaginal approach.ConclusionMost of the general OB/GYNs would consider referral to fellowship-trained MIGS subspecialists. Providers who reported adequate residency training and those who preferred continuity of care or referral to other surgical subspecialists were less likely to refer to MIGS subspecialists.     

Surgical Decision Regret in Women Pursuing Surgery for Endometriosis or Chronic Pelvic Pain

Study ObjectiveTo identify incidence of decision regret associated with surgery for endometriosis or chronic pelvic pain (CPP).DesignSurvey study.SettingAcademic medical center.PatientsAll patients undergoing excisional surgery for endometriosis or CPP between January 2016 and June 2019.InterventionsThe women were contacted to complete 2 validated questionnaires: the Decision Regret and Patient Global Impression of Improvement scales.Measurements and Main ResultsA total of 253 patients were contacted, and 154 patients responded (60.8% response rate) to the survey. A total of 137 women (90%) agreed or strongly agreed that having excisional surgery was the right decision; 134 women (87%) indicated that they would choose to have surgery again.The survey responders did not differ from nonresponders in age (years, 33.9 vs 35; p = .25), robotic route of surgery (83.1% vs 78.8%; p = .66), or performance of hysterectomy (27.3% vs 26.3%; p = .85). The responders were more likely to have stage III/IV endometriosis (50.6% vs 29.3%; p <.01), more previous surgeries for endometriosis (median surgeries, 1 vs 0; p = .01), higher complication rate (8.4% vs 2.0%; p = .03), and pathology test results more frequently positive for endometriosis (87.7% vs 77.8%; p = .03).Overall, 25 patients (16.3%) reported some level of regret after excisional surgery for endometriosis or CPP. Regret was not associated with a lower Patient Global Impression of Improvement score (odds ratio [OR] 4.37; 95% confidence interval [CI], 0.81–23.7), age (OR 0.98; 95% CI, 0.93–1.04), time since surgery (OR 1; 95% CI, 0.97–1.04), number of previous surgeries (OR 1.08; 95% CI, 0.9–1.31), negative pathology test results (OR 2.82; 95% CI, 0.95–8.32), hysterectomy (OR 1.23; 95% CI, 0.45–3.32), or complications (OR 1.07; 95% CI, 0.22–5.16).ConclusionMost women who pursue excisional surgery for endometriosis or CPP are satisfied with their decision. Regret was not associated with patient-reported lack of improvement, negative pathology test results, hysterectomy, or complications. Gynecologic surgeons should engage in shared decision-making with patients and feel comfortable offering surgical evaluation and management to patients with endometriosis or CPP when clinically indicated.     

Angelman syndrome and prenatally diagnosed Prader-Willi syndrome in first cousins

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by loss of function of imprinted genes in the 15q11-13 critical region. Reports of PWS and AS in close relatives within the same family are rare. We report on the diagnosis of a familial unbalanced 10;15 translocation causing AS in a child that led to the prenatal diagnosis of an unbalanced 10;15 translocation with resultant deletion of the Prader-Willi critical region in her maternal uncle's offspring.     

Robotic LESS and Reduced-Port Hysterectomy Using the da Vinci SP Surgical System: A Single-Institution Case Series

Study ObjectiveTo present a series of robotic laparoendoscopic single-site surgery (LESS) and reduced-port hysterectomy cases and discuss the surgical technique required for successful use on this new platform.DesignRetrospective case series.SettingAcademic medical center.PatientsAll patients undergoing robotic LESS or reduced-port hysterectomy with the SP1098 da Vinci SP Surgical System (Intuitive Surgical, Sunnyvale, CA) from December 2019 to March 2020.InterventionsRobotic LESS or reduced-port hysterectomy.Measurements and Main ResultsA total of 8 cases of hysterectomy were performed successfully. Four cases included concomitant resection of endometriosis. Five cases required placement of an additional port. The average uterine weight was 136.1 g ± 61.5 g (range 87–246). The average estimated blood loss was 37.5 mL ± 27 mL (range 20–100). The average operative time was 86.5 minutes ± 27.1 minutes (range 60–132). The time required for vaginal cuff closure was available for patients 5 to 8, and ranged from 10 minutes to 13 minutes. All patients had same-day discharge. There were no conversions to alternative surgical modality, complications, or readmissions.ConclusionOur preliminary experience with the SP1098 da Vinci SP Surgical System demonstrated the technical feasibility and safety of this surgical modality for gynecologic surgery. Additional studies examining postoperative outcomes and prospective studies comparing this modality with traditional robotic surgery are indicated.     

Situational Assessment of Functional Elements,Practices Adopted & Concerns Related to Bio Medical Waste Management in City of Pune,India

Abstract

The study was conducted with the objective of leading a situational assessment of Pune city with regard to Bio medical waste management, exploring knowledge, attitude & practices (KAP) of healthcare workers, and identifying challenges of stakeholders. Results revealed 69.2% of the hospitals had a biomedical waste management facility. Facilities like incineration, shredder, sharp pit, encapsulation, deep burial, and chemical disinfection were non- existing in 60% to 90% of hospitals. Bivariate analysis on questions with the type of employees and (KAP) was calculated. The utilization of the existing services and noncompliance are the major findings from the study.     

Recommendations for a Clinical Decision Support for the Management of Individuals with Chronic Kidney Disease

Background and objectives: Care for advanced CKD patients is suboptimal. CKD practice guidelines aim to close gaps in care, but making providers aware of guidelines is an ineffective implementation strategy. The Institute of Medicine has endorsed the use of clinical decision support (CDS) for implementing guidelines. The authors’ objective was to identify the requirements of an optimal CDS system for CKD management.Design, setting, participants, and measurements: The aims of this study expanded on those of previous work that used the facilitated process improvement (FPI) methodology. In FPI, an expert workgroup develops a set of quality improvement tools that can subsequently be utilized by practicing physicians. The authors conducted a discussion with a group of multidisciplinary experts to identify requirements for an optimal CDS system.Results: The panel considered the process of patient identification and management, associated barriers, and elements by which CDS could address these barriers. The panel also discussed specific knowledge needs in the context of a typical scenario in which CDS would be used. Finally, the group developed a set of core requirements that will likely facilitate the implementation of a CDS system aimed at improving the management of any chronic medical condition.Conclusions: Considering the growing burden of CKD and the potential healthcare and resource impact of guideline implementation through CDS, the relevance of this systematic process, consistent with Institute of Medicine recommendations, cannot be understated. The requirements described in this report could serve as a basis for the design of a CKD-specific CDS.Chronic kidney disease (CKD) is an increasingly common condition that can progress to end-stage renal disease (ESRD), resulting in large health and resource burdens (1,2). Early and appropriate care consistent with practice guidelines during the stages before ESRD can delay or limit progression, and improves outcomes even if ESRD develops (3).However, given poor adherence to these current CKD practice guidelines, care for advanced CKD patients is not optimal (4–6). These CKD practice guidelines aim to close gaps in care (7,8); however, simply making providers aware of guidelines has long proven to be an ineffective strategy for improving care. Several guideline implementation tools and implementation strategies have been used to promote adherence to clinical guidelines but have had limited success (9). The problem of guideline implementation has been attributed to several factors, including lack of awareness, inertia of previous practice, and lack of time required for implementing guidelines (10–12).In seeking to address the problem of implementing guidelines in clinical practice, groups including the Institute of Medicine (13) have endorsed the use of clinical decision support (CDS), defined as the “act of providing clinicians, patients and other health care stakeholders with pertinent knowledge and/or person-specific information, intelligently filtered or presented at appropriate times, to enhance health and health care” (14). Examples of CDS include providing reminders of required chronic disease management services to clinicians within an electronic health record system, providing cancer screening recommendations to patients within a web-based personal health record system, and delivering patient-specific recommendations to clinicians within a computerized provider order entry system.Practical guidance on the design, development, and deployment of CDS systems is available from an implementation workbook published by the Healthcare Information and Management Systems Society (15) This workbook organizes the process of CDS implementation into six concrete steps and provides worksheets and examples for accomplishing them. The steps are (1) identify stakeholders and determine goals and objectives; (2) catalog the available information systems infrastructure; (3) select CDS interventions to achieve the goals and objectives; (4) specify and validate the proposed interventions and implementation plan, then develop the implementations and logistics; (5) test and launch the CDS interventions; and (6) evaluate the intervention impact, then enhancing as needed.CDS systems have tremendous potential to facilitate improvements in the management of CKD; however, they are neither routinely used nor widely available. In kidney disease, they have been predominantly used for providing guidance regarding medication dosage (16). Individual CDS applications have also been developed for assisting with the management of several common comorbidities associated with CKD, including hypertension (17) and diabetes mellitus (18). However, there are few, if any, CDS systems available that optimally support the comprehensive care of patients with CKD.Given the need for CDS to improve CKD management and the lack of an existing solution to meet this need, our primary objective was to identify the requirements of an optimal CDS system for CKD management according to existing guidelines. In addition, our secondary goal was to develop a systematic strategy that could be used by other individuals interested in identifying the requirements of a CDS system for the management of other chronic medical conditions.     

Frequent EVI1 translocations in myeloid blast crisis CML that evolves through tyrosine kinase inhibitors

Clinical variables associated with ecotropic viral integration site 1 (EVI1) translocations were evaluated in 42 consecutive chronic myeloid leukemia (CML) patients in myeloid blast crisis (MBC). Translocations were confirmed with fluorescence in situ hybridization, and Western blot analysis demonstrated EVI1 expression. Translocations of EVI1 were present in 3 of 24 (12%) patients whose disease evolved MBC before tyrosine kinase inhibitor (TKI) exposure, and 7 of 18 (39%) patients who had received one or more TKIs. Univariate analysis showed that prior TKI therapy was the only clinical variable that was significantly associated with EVI1 translocation (P = 0.047). TKI-resistant BCR-ABL1 mutations were present in 71% of MBC patients with EVI1 translocations at the time of disease progression. These observations suggest that EVI1 overexpression collaborates with BCR-ABL1 in the evolution of TKI-resistant MBC. Inhibition of c-ABL kinase-mediated DNA double-strand repair by TKIs may predispose to EVI1 translocation in this setting.