Clinical Improvement Research Articles

Endoscopic incisional balloon dilation combined with anti‐scarring agents for postoperative esophageal anastomotic strictures

AbstractThe management of locally advanced esophageal cancer typically involves esophagectomy; however, postoperative complications, particularly anastomotic stricture, remain prevalent. Anastomotic stricture can severely compromise patients' quality of life by leading to difficulties in food intake. Although endoscopic balloon dilation has become a standard treatment for gastrointestinal strictures, its efficacy is often limited due to the risk of perforation and the potential for recurrent stricture, necessitating multiple interventions. Recent advancements have introduced endoscopic radial incision and cutting methods, which aim to enhance patency by excising scar tissue. We experienced a case resistant to the radial incision and cutting therapy, necessitating further intervention strategies. This report details our experience utilizing a novel technique, endoscopic incisional balloon dilation, which combines endoscopic incisional technique and balloon dilation therapy with anti‐scarring medications, in cases of refractory anastomotic strictures following esophageal cancer resection. We present three challenging cases in which endoscopic incisional balloon dilation yielded significant clinical improvements, alongside supportive literature. Our findings suggest that endoscopic incisional balloon dilation is an effective and safer alternative to conventional methods, capable of addressing complex stricture scenarios while potentially enhancing patient outcomes and quality of life.

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI. We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.S. PICUs from October through December 2022. We assigned CPS-Ped (0=discharged home at respiratory baseline to 8=death) at admission, days 2-7,10, and 14. We identified predictors of clinical improvement (CPS-Ped≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS). Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV). Of the 49 (8.4%) infants whose CPS-Ped score worsened by 2 points after admission, one died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age <3 months, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2,031 for hospital LOS. CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV.

Case report: Selpercatinib in the treatment of RET fusion-positive advanced lung adenocarcinoma: a challenging clinical case

BackgroundRearranged during transfection (RET) fusions represent a distinct molecular subset of non-small cell lung cancer (NSCLC) with targeted therapeutic potential. Selpercatinib, a highly selective RET inhibitor, has demonstrated efficacy in various solid tumors harboring RET alterations. Here, we present a case highlighting the use and clinical outcomes of selpercatinib in a patient diagnosed with advanced lung adenocarcinoma harboring a RET fusion.Case presentationA 59-year-old woman with a history of stage IV lung adenocarcinoma harboring a KIF5B-RET fusion presented with disease progression following first-line chemo-immunotherapy. Selpercatinib was initiated as a targeted therapy, leading to a notable radiographic response and clinical improvement. The patient experienced a significant reduction in tumor burden and reported improved symptom control, with no significant adverse effects during the 21-month follow-up period.ConclusionsThis case highlights the efficacy and tolerability of selpercatinib in treating advanced lung adenocarcinoma with a RET fusion. The observed clinical response supports the early use of selpercatinib as a targeted therapy for RET fusion-positive NSCLC, including in patients with compromised general and respiratory conditions, especially in cases refractory to conventional treatments. Long-term follow-up studies are warranted to validate these findings and assess the durability of responses.

Evolution of a patient safety program in an academic medical center

Background The Academic Medical Center earned a 1-Star CMS designation and received an F on the Leapfrog Safety Grade in 2015, which led to leadership setting Clinical Quality Improvement as the #1 Strategic Priority. This paper presents the evolution of a structured patient safety program as a component of this plan to direct and motivate employees to succeed in reducing patient harm. Methods Data-driven quality improvement using simple, timely, actionable data drillable scorecards available to all employees was the cornerstone of the above strategic priority. A comprehensive patient safety program was developed utilizing three phases: Error Prevention Training, Improved Event Reporting, and the Chasing Zero Harm initiative. Results Improvement was achieved in Culture of Safety Survey domains of overall safety, event reporting, nonpunitive response to errors, and hand-off communication. Patient safety indicators and hospital-acquired infections improved on the Medical Center's internal scorecard and public reported data by &gt;60%. These resulted in improvement in Leapfrog Safety Score from an F in 2015 to a B in 2023, and increase from CMS 1-Star to 2-Star rank in 2023. Adverse event reports and review with follow up increased by 45% between 2018 and 2023. A Chasing Zero harm program was initiated following establishment of these steps. Discussion A successful patient safety program, predicated on high reliability, can successfully be built with leadership commitment, development of safety culture, and performance improvement.

Machine learning-based risk assessment of gene editing: degeneration during gene editing possibility of target effect

CRISPI-Cas 9 technology is currently the most popular gene editing tool, which has been used in biomedical research and clinical treatment, but it also has the problem of off-target effects that cause unexpected gene mutations, which limits its safety and efficacy. Now, various machine learning models have been trained to predict off-target events in order to: Gene editing is more precise. In terms of both accuracy and interpretability there are still issues in the existing models. This paper has focused on reviewing Machine learning archery Off Target Prediction models and their performance. The results of this study show that the deep learning model has high accuracy and interpretability in the prediction of off-target events, which provides a reference for the optimization of gene editing strategies. The results reveal that there is a lot of room for development of deep learning technology in improving the safety of gene editing, which provides an in-depth reference for the sustainable development of gene editing technology. The application of this study to this paper also has its limitations, including the inadequacy of the applicability of the model in multiple gene editing contexts. In the future research of gene editing, more attention can be paid to the study of new biological indicators, the establishment of more accurate prediction models, and the improvement of models with more explanatory interpretation, so as to more safely apply gene editing technology in clinical and agricultural treatment and improvement.

Understanding tinnitus symptom dynamics and clinical improvement through intensive longitudinal data

Intensive longitudinal sampling enhances subjective data collection by capturing real-time, dynamic inputs in natural settings, complementing traditional methods. This study evaluates the feasibility of using daily self-reported app data to assess clinical improvement among tinnitus patients undergoing treatment. App data from a multi-center randomized clinical trial were analysed using time-series feature extraction and nested cross-validated ordinal regression with elastic net regulation to predict clinical improvement based on the Clinical Global Impression—Improvement scale (CGI-I). With 50% app compliance (N = 129, 8480 entries), the model demonstrated good fit to the test data (McFadden R2 = 0.82) suggesting its generalizability. Clinical improvement was associated with linear declines in tinnitus-related thoughts, jaw tension, tinnitus loudness, increases in happiness, and variability changes in tinnitus loudness and distress. These findings suggest that daily self-reported data on tinnitus symptoms is sensitive to treatment response and provides insights into specific symptom changes that occur during treatment.

Rapid Clinical and Imaging Improvement in Features of Spontaneous Intracranial Hypotension in 48 hours After CSF-Venous Fistula Embolization.

Rapid Clinical and Imaging Improvement in Features of Spontaneous Intracranial Hypotension in 48 hours After CSF-Venous Fistula Embolization.

Blood from septic patients with necrotising soft tissue infection treated with hyperbaric oxygen reveal different gene expression patterns compared to standard treatment

BackgroundSepsis and shock are common complications of necrotising soft tissue infections (NSTI). Sepsis encompasses different endotypes that are associated with specific immune responses. Hyperbaric oxygen (HBO2) treatment activates the cells oxygen sensing mechanisms that are interlinked with inflammatory pathways. We aimed to identify gene expression patterns associated with effects of HBO2 treatment in patients with sepsis caused by NSTI, and to explore sepsis-NSTI profiles that are more receptive to HBO2 treatment.MethodsAn observational cohort study examining 83 NSTI patients treated with HBO2 in the acute phase of NSTI, fourteen of whom had received two sessions of HBO2 (HBOx2 group), and another ten patients (non-HBO group) who had not been exposed to HBO2. Whole blood RNA sequencing and clinical data were collected at baseline and after the intervention, and at equivalent time points in the non-HBO group. Gene expression profiles were analysed using machine learning techniques to identify sepsis endotypes, treatment response endotypes and clinically relevant transcriptomic signatures of response to treatment.ResultsWe identified differences in gene expression profiles at follow-up between HBO2-treated patients and patients not treated with HBO2. Moreover, we identified two patient endotypes before and after treatment that represented an immuno-suppressive and an immune-adaptive endotype respectively, and we characterized the genetic profile of the patients that transition from the immuno-suppressive to the immune-adaptive endotype after treatment. We discovered one gene MTCO2P12 that distinguished individuals who altered their endotype in response to treatment from non-responders.ConclusionThe global gene expression pattern in blood changed in response to HBO2 treatment in a direction associated with clinical biochemistry improvement, and the study provides potential novel biomarkers and pathways for monitoring HBO2 treatment effects and predicting an HBO2 responsive NSTI-sepsis profile.Trial registrationBiological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698) 04/02/2013.

A Comprehensive Approach to Reducing Patient Safety Indicators (PSI-90).

PSI-90, a composite measure comprising ten indicators, reflects the quality of care during hospital stays. The Hospital-Acquired Condition Reduction Program (HACRP), a Centers for Medicare and Medical Services (CMS) program, assesses hospital performance based on quality measures, including PSI-90, with financial implications for poor performers. To evaluate PSI events, establish workflows for accurate documentation, and foster collaboration across clinical and administrative teams, with the ultimate objective of reducing PSI events. Essential actions involved designating a PSI nurse reviewer and a quality physician advisor, securing the involvement of executive leadership, adopting computer-assisted coding technology, and promoting teamwork among Clinical Documentation Improvement (CDI), coding, and Health Information Management (HIM) teams. The collaborative efforts yielded a 45% reduction in PSI events, leading to estimated cost avoidance of $1.4 million, and exemption from HACRP penalties. Lessons learned encompassed the importance of executive leadership support, data-driven decision-making, and ongoing education. This study shows the significance of collaboration, leadership support, and data utilization in PSI reduction efforts. Furthermore, it shows benefit of a surgical quality officer in advancing patient safety, aligning with ACS recommendations.

Services and payments associated with the medicare new technology add-on payment program

Lay Summary In 2001, the Centers for Medicare and Medicaid Services (CMS) established the New Technology Add-On Payment (NTAP) program to help Medicare patients access costly new technologies. These technologies, approved by the Food and Drug Administration (FDA) must show “substantial clinical improvement” when compared to existing technologies. Recently, the FDA introduced two fast-track approval pathways allowing technologies to skip the “substantial clinical improvement” requirement. In this study, we describe the technologies and payments associated with NTAPs after this policy change.

Gonokokkenartritis bij een 69-jarige man

Gonococcal arthritis in a 69-year-old male A 69-year-old man presented with fever and a painful and swollen left wrist and right ankle joint. Aspiration of the left wrist showed purulent fluid and culture was positive for Neisseria gonorrhoeae. The diagnosis of gonococcal arthritis, a manifestation of disseminated gonococcal infection, was made. History revealed he had unprotected sexual contacts with men. Treatment with intravenous ceftriaxon for 7 days and surgical lavage of the joints led to clinical improvement. Gonorrhea has an increasing incidence in Belgium and is now the most diagnosed sexually transmitted disease (STDs) in men. If untreated, infection with N. gonorrhoeae can lead to a disseminated gonococcal infection, sometimes resulting in serious complications such as arthritis, osteomyelitis, and meningitis. A thorough sexual history is essential in cases of acute monoarthritis or oligoarthritis. Joint aspiration with gram stain, culture and/or polymerase chain reaction (PCR) is diagnostic. Treatment of disseminated gonococcal infection consists of intravenous ceftriaxon. Surgical drainage may be necessary in case of purulent arthritis. Notification and testing of sexual partners is crucial to prevent further spread of N. gonorrhoeae. This case illustrates the importance of considering N. gonorrhoeae as a cause of septic arthritis in sexually active individuals. Early recognition and adequate treatment can prevent complications and further transmission of infections. Physicians should be alert to the increasing incidence of gonorrhoea and its potential complications.

Circulating MicroRNAs in Patients with Psoriasis Treated with Anti-IL-23: A Cohort Study.

Psoriasis is characterized by aberrant keratinocyte activity and immune cell infiltration, driven by immune-mediated pathways. MicroRNAs (miRNAs) play crucial roles in regulating these processes, offering insights into disease mechanisms and therapeutic targets. This study aimed to investigate changes in circulating miRNAs in psoriasis patients undergoing risankizumab therapy, an anti-IL-23 monoclonal antibody, to understand its impact on disease pathogenesis and treatment response. Plasma samples from 12 psoriasis patients were collected before (T0) and after 1year (T1) of risankizumab treatment and analyzed using small RNA sequencing. Findings were validated in a separate cohort of 23 patients using quantitative real-time PCR (qRT-PCR). T-regulatory cell (Treg) numbers and pro-inflammatory cytokine levels were also assessed. Significant clinical improvement was observed in all patients after 1year of treatment, accompanied by increased Treg counts and reduced levels of pro-inflammatory cytokines. Twenty-four miRNAs exhibited differential expression post-treatment; 9 were downregulated and 15 upregulated. Notably, miR-200a-3p showed a significant correlation with baseline Psoriasis Area Severity Index (PASI), indicating its potential as a severity marker. Risankizumab therapy also decreased peripheral blood levels of IL-23, IL-1β, and IL-8. This study identifies specific circulating miRNAs, including miR-200a-3p, as potential biomarkers for monitoring treatment responses in psoriasis patients. The findings underscore the therapeutic efficacy of risankizumab in modulating miRNA profiles and immune pathways associated with psoriasis pathogenesis. Overall, these results provide new insights into the mechanisms of risankizumab action and highlight miRNAs as promising candidates for personalized medicine approaches in psoriasis management.

Differential effects of tibia varus deformity on clinical outcomes following high tibial osteotomy and unicompartmental knee arthroplasty for moderate medial compartment osteoarthritis with moderate varus alignment.

There is a lack of clinical evidence supporting the decision-making process between high tibial osteotomy (HTO) and unicomparmental knee arthroplasty (UKA) in gray zone indication, such as moderate medial osteoarthritis with moderate varus alignment. This study compared the outcomes between HTO and UKA in such cases and assessed the risk factor for not maintaining clinical improvements. We retrospectively reviewed 65 opening-wedge HTOs and 55 UKAs with moderate medial osteoarthritis (Kellgren-Lawrence grade ≥ 3 and Ahlback grade < 3) and moderate varus alignment (5°< Hip-Knee-Ankle angle < 10°) over 3 years follow-up. Confounding factors including patient demographics, postoperative lower limb alignment was assessed. Dummy variable was used to categorize the HTO and UKA according to presence of tibia varus deformity (medial proximal tibial angle of 85°). Clinical outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score preoperatively, 1 year postoperatively, and at the last follow-up. Cox regression analysis identified risk factors for not achieving minimal clinically important differences (MCID) in WOMAC scores. The WOMAC score at 1-postoperative year significantly improved beyond MCID in all UKA and HTO. However, over a mean follow-up of 68.7 months (HTO) and 64.3 months (UKA), 16 patients (13.3%) experienced clinical deterioration. Notably, patients with suboptimal postoperative alignment, those undergoing HTO without tibial vara, and UKA with tibial vara had higher risks of clinical deterioration during the mid-term period. Tibial varus deformity differentially affects clinical outcomes after HTO and UKA in moderate medial compartment osteoarthritis with moderate varus alignment. Clinicians should consider the deformity's origin when selecting treatment for this patient, as certain combinations (HTO without tibia vara and UKA with tibia vara) are associated with increased risk of not maintaining mid-term clinical improvements.

Immunometabolic Changes Following Gastric Bypass and Sleeve Gastrectomy: A Comparative Study.

Immunometabolism is the interaction between immune system and nutrient metabolism. Severe obesity is considered a state of meta-inflammation associated with obesity that influences the development of chronic-degenerative diseases. We aimed to establish the immunometabolic differences in bariatric patients and to determine whether cellular immunity is associated with metabolic changes. We conducted an observational study in patients who underwent laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB). We explored the differences in the immunometabolic profile before and after surgery in the study group, by surgical technique, and we evaluated the changes in immunological variables as a function of metabolic variables with correlation analysis. The follow-up rate was 88.7%. After the intervention, there were changes in cellular immunity, with a decrease in effector T lymphocytes (CD8+CD28-) and an increase in B lymphocytes, memory helper T cells, and cytotoxic T lymphocytes. LSG resulted in a greater decrease in (CD4+CD62-) T lymphocytes compared with LRYGB. Patients who underwent surgery with LRYGB presented greater clinical and metabolic improvements, as well as improvement of obesity-associated medical problems. Women who underwent LRYGB showed a greater reduction in fat-free mass compared with women who underwent LSG. Bariatric surgery, mainly LRYGB, leads to immunometabolic changes and improves associated medical problems.

Case of Metastatic Canine Transmissible Venereal Tumor in a Dog: Clinical and Cytological Evaluation

Canine transmissible venereal tumor (TVT) is a naturally occurring, transmissible neoplasm primarily affecting the genitalia in dogs. Though generally benign, it can rarely metastasize to other body parts. This report describes a rare case of metastatic TVT in a 2-year-old female Boerboel, presenting with a large, ulcerated vulvar mass and metastases to the popliteal lymph node and mammary glands. Clinical findings included progressive mass growth, emaciation, and systemic symptoms. Hematological tests revealed non-regenerative anemia and elevated white blood cell count, while cytological examination identified neoplastic round cells with high nucleus-to-cytoplasm ratios and mitotic figures. The dog was treated with vincristine chemotherapy, metronidazole, vitamin C, and a diet supplemented with crude sap extract of Telfairia occidentalis at 120 mg/kg once daily. Significant tumor regression and clinical improvement were observed after four weeks, although persistent anemia and borderline hypoproteinemia were noted. By the fifth week, the mass had notably reduced, and the dog's condition continued to improve, though some hemorrhage remained. This case highlights the rare occurrence of metastatic TVT and underscores the effectiveness of vincristine in treatment, emphasizing the need for prompt diagnosis and management despite its generally low metastatic rate.

Personalized theta-burst stimulation enhances social skills in young minimally verbal children with autism: a double-blind randomized controlled trial.

Minimally verbal children with autism are understudied and lack effective treatment options. Personalized continuous theta-burst stimulation (cTBS) targeting the amygdala and its circuitry may be a potential therapeutic approach for this population. In a double-blind randomized controlled trial, minimally verbal children with autism (ages 2-8 years) received 4 weeks of cTBS. An amygdala-optimized functional connectivity (AOFC) group (N=23) received personalized stimulation targeting a left dorsolateral prefrontal cortex site functionally connected with the amygdala. A non-optimized (NO) control group (N=21) received stimulation at a standard prefrontal site. We assessed changes in Autism Diagnostic Observation Schedule scores, amygdala volume, spontaneous neural activity, and functional connectivity. Personalized AOFC-guided cTBS improved social and communication skills with an effect size twice that of the NO group (Cohen's d = 0.55 vs. 0.24). The AOFC group showed greater reductions in amygdala volume, spontaneous neural activity, and hyper-connectivity. Network-level amygdala connectivity changes with default mode, frontoparietal, and dorsal attention networks were correlated with clinical improvements. Field mapping analysis revealed that greater electric field overlap between standard and optimized targets predicted better treatment outcomes. Personalized AOFC-guided cTBS enhanced social skills and communication in minimally verbal children with autism by modulating amygdala structure and connectivity. Changes in amygdala network connectivity predicted clinical improvements, suggesting a mechanistic link between neural circuit plasticity and behavioral outcomes. These findings demonstrate the potential of precision-targeted neuromodulation in addressing a critical gap in autism treatment for this understudied population.

Concomitant Streptococcus Suis Septic Arthritis and Gouty Arthritis: A Case Report

Septic arthritis, when occurring together with crystal-induced arthritis such as gout, can make the diagnosis more difficult and increase the risk of complications compared with septic arthritis without concomitant gout. Streptococcus suis, a common pathogen in swine, can be transmitted from animals to humans. Human infections are rare. Patients often have a history of contact with or consumption of undercooked pork. Most patients present with meningitis, septicemia, endocarditis, and septic arthritis. A 71-year-old man presented with bilateral knee pain, swelling, and fever. Synovial fluid aspiration from the knee revealed intracellular urate crystals and Streptococcus suis on the culture. He was diagnosed with septic arthritis due to Streptococcus suis with concomitant gouty arthritis. The patient was treated with intravenous ceftriaxone and bilateral knee arthrotomy. After clinical improvement, he was switched to oral amoxicillin and completed a total of 4 months of antibiotics. At the 1-year follow-up, his function was near pre-infection levels. This is the first reported case of septic arthritis due to Streptococcus suis, an uncommon pathogen, in a patient with gouty arthritis. Concurrent septic arthritis and gouty arthritis can make the diagnosis more difficult. A high index of suspicion for septic arthritis with gouty arthritis is important for the accurate diagnosis and appropriate treatment in order to minimize complications.

Stent stoma: Endoscopic stent insertion for refractory small intestine fistulas.

The therapeutic management of fistulas presents significant challenges, often involving both conservative and surgical approaches. Despite these interventions, recurrence and postoperative mortality rates remain high. Endoscopic stent insertion into the fistula, along with the creation of a stent stoma, may offer a promising alternative for patients who fail surgical or conservative therapies. This study aimed to evaluate the feasibility, effectiveness, and safety of endoscopic stent insertion in the treatment of refractory small intestinal fistulas. Patients with refractory small intestine fistulas who underwent endoscopic stent insertion were included. The primary endpoint was defined as successful fistula treatment, which included an improvement in clinical symptoms related to the fistula, successful bridging to subsequent surgical revision, and the restoration of enteral nutrition. Secondary endpoints comprised the feasibility of the endoscopic procedure, complications, procedure-related complications, and in-hospital mortality. Eight patients were included, with a median follow-up period of 2.7 months. The implantation of a self-expanding metal stent was successfully performed in all patients (technical success rate, 100%; n = 8/8). The clinical success rate was 87.5% (n = 7/8), indicating clinical improvement in fistula-related symptoms, wound care, and enteral nutrition. Procedure-related complications occurred in one patient (12.5%; n = 1/8), involving stent dislocation leading to small intestine perforation, which was managed endoscopically. No procedure-related mortality was observed. Endoscopic stent insertion is a feasible, effective, and safe option for the management of therapy-refractory small intestinal fistulas. The creation of a stent stoma improves patient quality of life.

Prospective evaluation of opioid cessation in patients with suspected Opioid-induced esophageal dysfunction (OIED).

The causal relationship between chronic opioid use and esophageal motor dysfunction in symptomatic patients has not been established. A prospective before-and-after multicenter study, including chronic active opioid patients referred for esophageal motility tests due to non-obstructive dysphagia. 37 patients were evaluated, 27 (73%) had criteria of opioid-induced esophageal dysfunction (OIED). In 19 patients who discontinued opioids for at least 7 days, esophageal motor disorders resolved in 10 (52.6%), accompanied by a clinical success response (defined as Eckardt ≤3) in 64.3%. Discontinuation of opioids is associated with clinical and esophageal motility improvement in up to half of the patients.

C5 complement inhibition versus FcRn modulation in generalised myasthenia gravis

BackgroundMyasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity....