Clinical Treatment Recommendations Research Articles

The Resurgent Threat of Highly Pathogenic Avian Influenza HPAI A (H5N1) Virus: A Zoonotic Infectious Disease and Public Health Concern

The highly pathogenic avian influenza (HPAI) A (H5N1) virus of clade 2.3.4.4b was identified among waterfowl (wild birds and geese) and domestic poultry across Southeast Asia, Europe, and Africa in 2021. By 2022, the HPAI virus was detected in North America, signifying further global dissemination. There is no human immunity to clade 2.3.4.4b A (H5N1). With the spread of the A (H5N1) virus throughout the United States and increasing viral infection in humans, resurgence of the A (H5N1) virus is of great public health concern that it could lead to the next infectious zoonotic pandemic after Covid-19. This paper describes the characteristics of HPAI A (H5N1) virus of clade 2.3.4.4b and recommendations for clinical treatment and prevention.

Development and pilot administration of the amputation-related pain and sensation assessment tool

Purpose To develop and administer an assessment tool for facilitating patient–clinician discussions regarding amputation-related pain and sensation. Materials and methods An assessment tool was developed to measure the impact of different types of amputation-related pain and sensation on a patient’s life. The tool first provides patients with written descriptions and images of three common types of amputation-related pain or sensations: residual limb pain, phantom limb sensation, and phantom limb pain. The tool then asks them to rate the frequency, intensity, and interference of each experience. Participants were also asked to provide qualitative descriptions of these experiences. Results Fifty Veterans with lower limb amputation participated in the study. In the past month, 74% reported experiencing residual limb pain, 76% reported phantom limb sensation, and 84% reported phantom limb pain, with 52% reporting all three. Participants’ descriptions of some experiences were distinct, while others (e.g., “tingling”) were common between experiences. Phantom limb pain had the most varied descriptions. Conclusions The amputation-related pain and sensation assessment tool can be used to identify and measure the effects of different experiences on patients’ lives, thereby improving the specificity of diagnosis and informing clinical treatment recommendations. Further development of this tool should include evaluating its psychometric properties.

Abstract PO1-08-04: Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making

Abstract Background: Prior work from our group has shown a high rate of familial breast cancer (BC) among rural BC patients (pts), with 33% reporting > 1 first-degree family members with BC and 55% meeting NCCN germline genetic testing (GGT) criteria (Shelton CH et al. NC Med. J; 2022). In 2018, we increased GGT to include all BC pts and observed: 1) many pts were out-of-criteria per NCCN guidelines but had actionable pathogenic germline variants (PGVs) and 2) knowledge of GGT factored significantly into shared decision making by providers and patients, including for positive and negative results. Beginning in 2019, concurrent with the recommendation from the American Society of Breast Surgeons, we expanded this model of universal GGT to an IRB-approved study to measure the impact of prospective testing on shared decision-making. Herein we report the real-world implementation of universal GGT for patients with BC and genetics-informed treatment decision-making in a rural community practice. Methods: From 2019-2022 all BC pts at a small, rural community hospital were offered GGT. Demographics, clinical features, and GGT results were collected along with clinician-reported clinical recommendations for treatment based on GGT results. Descriptive statistics and two-tailed Fisher’s exact test were employed and significance was set at p< 0.05. Results: 210 BC pts were offered GGT and 192 (91%) underwent testing [97% female, 95% non-Hispanic White, mean age at diagnosis of 62, 75% Stage I], with all but 7 pts completing GGT before primary treatment decisions. 104 (54%) of patients were in-criteria (IC) and 88 (46%) out-of-criteria (OOC) with NCCN GGT guidelines. PGVs were identified in 25 pts (13%) and 15 genes, most commonly BRCA1/2 (5 pts), PALB2 (3), monoallelic MUTYH (3) and ATM, BARD1, CHEK2 (2 pts each). PGV frequencies were 15% in IC and 11% in OOC patients (p=0.495). 46 (24%) pts had only a variant of uncertain significance (VUS) results. 70% of patients had > 1 clinical management change based on their GGT results. Changes in breast surgery, uptake of risk-reducing bilateral salpingo-oophorectomy, surveillance and clinical follow-up were significantly higher in patients with PGV compared to those with VUS/negative results (p < 0.0001). Compared to those with negative results, patients with PGVs in BRCA1 and BRCA2 were significantly more likely to undergo bilateral mastectomy (BLM) while those with PGVs in other genes or with VUS were not significantly more likely to elect for BLM than those with negative results. Clinicians reported that return of GGT reinforced their recommendation for 73/138 (53%) of patients who underwent breast-conserving therapy. GGT results aided in radiation therapy strategy for 54% of pts, most often resulting in dose de-escalation (accelerated fractionation) for negative/VUS pts (Table). Conclusions: Universal GGT for patients with BC was successfully implemented in a rural community practice with >90% uptake. Treatment was enhanced in those with clinically actionable PGVs and de-escalated in those without PGVs. Universal GGT for patients with BC is feasible to implement as the standard of practice within rural populations, enabling optimization of clinical care to patients’ genetic profile and may reduce unnecessary healthcare resource utilization. Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making Changes in Radiation Therapy Strategy based on GGT Citation Format: Charles Shelton, Sarah Nielsen, Antonio Ruiz, Lauren Shelton, Karen Freas, Sarah Poll, Brandie Heald, Daniel Pineda-Alvarez, Edward Esplin, Rachel Ellsworth, Hannah Montgomery. Universal Germline Genetic Testing for Breast Cancer: Implementation in a Rural Practice and Impact on Shared Decision Making [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-08-04.

The Impact of Videofluoroscopic Pulse Rate on Duration and Kinematic Measures in Infants and Adults with Feeding and Swallowing Disorders.

This investigation assessed the impact of temporal resolution during a videofluoroscopic evaluation of swallowing (VFSS) on measures of duration and kinematics. Thirty adult and ten infant swallow studies, all acquired at 30 frames and 30 pulses per second, were obtained from a New Mexico hospital. All swallow studies were altered to simulate 15 and 5 pulses per second. Duration measures included pharyngeal response time, duration of upper esophageal sphincter (UES) opening, velopharyngeal closure duration and total swallow duration. Kinematic measures were assessed in adults only and included peak hyoid position and extent of UES opening during the swallow. Analysis of outcome measures was performed and compared across the three temporal resolutions (30, 15, and 5 pulses per second). For data points where normative values are available, we evaluated the impact of temporal resolution on clinical determination (i.e., did a change in pulse rate alter the clinical classification). Kinematic and duration measures were altered with changes in pulse rate and these changes increased as temporal resolution decreased. For outcome measures where normative values are available, accuracy of clinical determination decreased with decreased pulse rate. Temporal resolution impacts duration and kinematic measures. However, the direction of these changes is unpredictable, indicating sensitivity and specificity are both affected. Without a predictable impact, the use of lower pulse rates may alter clinical impressions and treatment recommendations yielding inappropriate treatment goals and treatment duration.

Early Detection of Allergy Symptoms in Children and Adolescents, Characteristics of Possible Pathogens, Pre-Treatment Prevention Measures (in Poland)

Background: The purpose of this study was to investigate the main allergens and signs of the onset of allergic diseases and explore methods of prevention that do not include medicines. Methods: Non-parametric statistical methods were used. A retrospective study was conducted, which included 270 case histories. The average age of the patients was 19 (12.5; 40.1) years, 127 (47%) were men and 143 (53%) were women. Clinical diagnoses, early symptoms, allergen spectrum, and treatment recommendations provided by doctors were analyzed. It was established that the early signs of allergic rhinitis and rhinoconjunctivitis are nasal congestion, runny nose, and lacrimation, and the onset of atopic dermatitis is -characterized by dry and itchy skin. Results: Allergy to triggers from one group was present in 136 (50.4%) patients, irritants from two groups – in 95 (35.2%) patients, and irritants from three groups – in 39 (14.4%) patients. Polish doctors advised patients to limit their exposure to allergens but did not give recommendations for concrete actions. Conclusion: The results of the study can be used to help in the identification of the most common symptoms of allergic diseases and allergens, which is vital for the early diagnosis of this pathology by clinicians.

Review of recommendations for bisphosphonate treatment interruption-discontinuation

Bisphosphonates are the main medications in the treatment of osteoporosis, which are effective in reducing the risk of fractures in patients with osteoporosis. It is known that after treatment with bisphosphonates, bone mineral density remains quite stable for a certain time, as well as markers of bone metabolism remain reduced, which, along with the side effects of long-term bisphosphonate therapy, determines the possibility of “Drug holidays”. At the same time, during a break in bisphosphonate treatment, the risk of fractures begins to increase, which is a reason to resume therapy.Currently, there is no uniform worldwide data of starting a “drug holidays” on bisphosphonates. The duration of the “drug holidays” also differs in clinical recommendations from different countries. When to conduct a risk assessment of fractures during a “drug holidays”? To answer these questions, we assessed existing clinical recommendations for treatment interruption/discontinuation of bisphosphonates. A literature search was conducted using the following resources: PubMed®, the Cochrane Library, websites of major international osteoporosis associations, and other targeted Internet searches. The main search terms were “Clinical Guideline of Osteoporosis”, “Bisphosphonates”, “Drug holidays in osteoporosis”, “Discontinuation of bisphosphonates”. Тhe search was carried out using articles in Russian and English published between January 1, 2016 and September 15, 2023. 17 clinical guidelines from different countries (Russian, American, European, Asian and Australian) were found and analyzed in which was information about the break in the treatment and withdrawal of bisphosphonates.The majority of clinical recommendations have the same opinion on the issue of starting “drug holidays”: with a moderate risk of fractures, you can take a break from treatment with tableted bisphosphonates after 5 years, after zoledronic acid — after 3 years of therapy. At high and very high risk of fractures, the duration of treatment is 10 and 6 years, respectively. The duration of “drug holidays” vary in the recommendations, but in most cases the decision-making is based not on the duration, but on the assessment of the risk of fractures with their regular reassessment, which includes previous and new low-energy fractures, the emergence of new risk factors, a decrease in BMD, the dynamics of bone markers, re-evalua­tion of FRAX®.

Publication Bias in Upper Gastrointestinal Oncology Clinical Trials.

Evidence-based medicine requires evaluation of the medical literature to guide clinical reasoning and treatment recommendations. The presence of publication bias towards exclusion of non-statistically significant clinical trials may be leading to an incomplete evaluation of the literature and cause potentially incomplete guidance for patients. We aimed to compare publication rates and impact of publications of positive and negative outcome clinical trials. We queried the US National Library of Medicine Clinical Trials database identifying clinical trials with reported results on the topics of pancreatic, liver, and gastric cancer. A "positive" trial was defined as having a statistically significant difference between the treatment arms, while a "negative" did not. Data collected included termination cause, intervention, funding type, publication rates, and journal characteristics. In total, 535 clinical trials were examined, across all pathologies clinical trials with significant findings for the primary outcome were published at a higher rate (99%) compared to those with non-significant findings (77%) (p < 0.01). Significantly, more studies with significant findings reached at least 80% of their estimated enrollment goal versus non-significant studies, 72% and 53% respectively (p < 0.01). Three of four metrics for impact of publication showed no difference between significant and non-significant studies once they reached publication. These findings suggest that clinical trials of three of the most common upper gastrointestinal malignancies have a publication bias towards studies with significant primary outcome findings. This study has implications to the way evidence-based medicine is practiced as the medical literature appears to be failing to capture important data for consideration of clinical decision making.

Methodology for Creating a Risk Management System for Drug-Drug Interactions

Drug-drug interactions (DDIs) are a major cause of hospital admissions, accounting for 16.6% of ADRs and about 1% of all hospital admissions. Polypharmacy is on the rise, with a Swedish population-based study of people aged ;;;75 years showing that the prevalence of polypharmacy increased from 27% in 1988 to 54% in 2001 and to 65% in 2006. The aim of the study was to analyze the databases on DDI and to assess the possibility of their use in managing the risks of pharmacotherapy in the Russian Federation and the EAEU. Results. The main DDI databases are characterized. The degree of inconsistency in data on the number of DDI, severity and clinical recommendations was determined. The basic requirements for the completeness of information in databases are formulated. The necessity to harmonize approaches to providing information about DDI, as well as the need to create local databases for medical organizations were revealed. A computer program has been created to minimize the risks of DDI in clinical practice, for expert and scientific purposes. Conclusions. Databases and programs for DDI have different goals, a different set of data on DDI with varying degrees of evidence, differences in assessment of severity, likelihood of occurrence, clinical recommendations for treatment and correction of DDI. The variability of information is due to the lack of a unified system for assessing the severity and likelihood of potential negative consequences of DDI; different purposes for creation; difference in budgets at creation. This situation leads to warning redundancy and physician fatigue from insignificant or unproven DDIs. Based on the identified requirements for local databases, a computer program for modeling rational pharmacotherapy for lower respiratory tract infections was created and received a certificate of state registration.

A Practical Guide to Understanding and Treating Peripheral Artery Disease.

Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic morbidity after coronary heart disease and stroke yet is widely underdiagnosed and undertreated. Treatment of risk factors such as diabetes and cigarette smoking can benefit patients with PAD. Patients should have adequate blood pressure and lipid control to decrease clinical manifestations and symptoms of PAD. Use of antithrombotic medications should be individualized to the patient depending on the presence of symptoms, revascularization, and comorbidities. All patient care providers, including physicians, pharmacists, nurse practitioners, and physician assistants, should incorporate PAD screening in their at-risk patients to improve access for appropriate earlier diagnosis, initiation of guideline directed therapy, and risk factor modification to reduce both major adverse CV and limb outcomes. The purpose of this narrative review is to provide an overview of PAD and summarize clinical trial evidence and guideline recommendations for screening and treatment to increase awareness among health care providers to ultimately have a positive impact on patient care.

Identification and validation of the clinical prediction model and biomarkers based on chromatin regulators in colon cancer by integrated analysis of bulk- and single-cell RNA sequencing data.

Chromatin regulators (CRs) are implicated in the development of cancer, but a comprehensive investigation of their role in colon adenocarcinoma (COAD) is inadequate. The purpose of this study is to find CRs that can provide recommendations for clinical diagnosis and treatment, and to explore the reasons why they serve as critical CRs. We obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted Gene Co-Expression Network Analysis (WGCNA) screened tumor-associated CRs. LASSO-Cox regression was used to construct the model and to screen key CRs together with support vector machine (SVM), the univariate Cox regression. We used single-cell data to explore the expression of CRs in cells and their communication. Immune infiltration, immune checkpoints, mutation, methylation, and drug sensitivity analyses were performed. Gene expression was verified by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Pan-cancer analysis was used to explore the importance of hub CRs. We finally obtained 32 tumor-associated CRs. The prognostic model was constructed based on RCOR2, PPARGC1A, PKM, RAC3, PHF19, MYBBP1A, ORC1, and EYA2 by the LASSO-Cox regression. Single-cell data revealed that the model was immune-related. Combined with immune infiltration analysis, immune checkpoint analysis, and tumor immune dysfunction and exclusion (TIDE) analysis, the low-score risk group had more immune cell infiltration and better immune response. Mutation and methylation analysis showed that multiple CRs may be mutated and methylated in colon cancer. Drug sensitivity analysis revealed that the low-risk group may be more sensitive to several drugs and PKM was associated with multiple drugs. Combined with machine learning, PKM is perhaps the most critical gene in CRs. Pan-cancer analysis showed that PKM plays a role in the prognosis of cancers. We developed a prognostic model for COAD based on CRs. Increased expression of the core gene PKM is linked with a poor prognosis in several malignancies.

Tympanic membrane perforations cannot be reliably detected using computed tomography based on 15 cadaver dogs.

The integrity of the tympanic membrane is an important factor when deciding treatment and therapeutic recommendations for dogs with ear disease; however, otoscopic examination may be difficult to perform due to features of external ear canal disease or patient compliance. CT is useful for the evaluation of middle ear disease, including cases in which middle ear disease is detected incidentally. The tympanic membrane is detectable using CT, but anecdotally, apparent focal defects or discontinuities of the tympanic membrane are often seen in patients with and without ear disease. The purpose of this prospective, observer agreement study was to determine if perforations of the tympanic membrane are reliably detectable on CT. Fifteen cadaver dogs underwent CT and video otoscopy to verify the integrity of each tympanic membrane. Cadavers were randomly assigned to have the tympanic membranes left intact or to undergo a myringotomy on either the left, the right, or both sides. CT was performed immediately following the myringotomies. Four blinded evaluators evaluated the pre- and post-myringotomy scans for a total of 30 scans (60 tympanic membranes). Average accuracy was low (44%), and interobserver agreement for all four evaluators was fair. Although the tympanic membrane is visible on CT, perforations of the tympanic membrane are unlikely to be accurately detected or excluded. The appearance of an intact tympanic membrane or defect in the membrane on CT should not be used as criteria to guide clinical treatment recommendations based on this cadaver model.

First report of a p.Cys484Tyr Notch3 mutation in a CADASIL patient with acute bilateral multiple subcortical infarcts—case report and brief review

BackgroundCADASIL(Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy)is an inherited small vessel disease caused by mutations in NOTCH3 gene. Although NOTCH3 has numerous hotspots of gene mutations, mutations in exons 9 are rare. The p.C484T gene mutation type associated with it has not been reported in any relevant cases yet. Furthermore, CADASIL patients rarely present with acute bilateral multiple subcortical infarcts.Case presentationWe report the case of a Chinese female patient with CADASIL who experienced “an acute bilateral subcortical infarction” because of“hemodynamic changes and hypercoagulability”. In genetic testing, we discovered a new Cys484Tyr mutation in exon 9, which has also been found in the patient’s two daughters.ConclusionsIt is important to note that this discovery not only expands the mutation spectrum of Notch3 mutations in CADASIL patients, but also examines the mechanism behind acute bilateral subcortical infarction in CADASIL patients via case reviews and literature reviews, in order to provide some clinical recommendations for early intervention, diagnosis, and treatment in similar cases in the future.

A novel prognostic signature and therapy guidance for hepatocellular carcinoma based on STEAP family

BackgroundThe six-transmembrane epithelial antigen of prostate (STEAP) family members are known to be involved in various tumor-related biological processes and showed its huge potential role in tumor immunotherapy.MethodsBiological differences were investigated through Gene set enrichment analysis (GSEA) and tumor microenvironment analysis by CIBERSORT. Tumor mutation burden (TMB), immunotherapy response and chemotherapeutic drugs sensitivity were estimated in R.ResultsWe established a prognostic signature with the formula: risk score = STEAP1 × 0.3994 + STEAP4 × (− 0.7596), which had a favorable concordance with the prediction. The high-risk group were enriched in cell cycle and RNA and protein synthesis related pathways, while the low-risk group were enriched in complement and metabolic related pathways. And the risk score was significantly correlated with immune cell infiltration. Most notably, the patients in the low-risk group were characterized with increased TMB and decreased tumor immune dysfunction and exclusion (TIDE) score, indicating that these patients showed better immune checkpoint blockade response. Meanwhile, we found the patients with high-risk were more sensitive to some drugs related to cell cycle and apoptosis.ConclusionsThe novel signature based on STEAPs may be effective indicators for predicting prognosis, and provides corresponding clinical treatment recommendations for HCC patients based on this classification.

Chapter 9: Management of Medullary Thyroid Cancer

ABSTRACT Medullary thyroid cancer (MTC) is a thyroid cancer. Compared to differentiated thyroid cancer, MTC differs in its management and prognosis. Appropriate management of this cancer is essential to achieve better disease outcomes. In this article, the Indian Society of Thyroid Surgeons guidelines panel members conferred and developed a consensus on various clinical questions and recommendations for optimal workup, treatment, and follow-up. Surgery is the mainstay treatment option in curative and even palliative settings. Newer systemic treatments and prophylactic surgeries hold promise for the future.

Myocardial perfusion segmentation and partitioning methods in personalized models of coronary blood flow

Abstract In this work we present methods and algorithms for construction of a personalized model of coronary haemodynamics based on computed tomography images. This model provides estimations of fractional flow reserve, coronary flow reserve, and instantaneous wave-free ratio taking into account transmural perfusion ratio indices obtained from perfusion images. The presented pipeline consists of the following steps: aorta segmentation, left ventricle wall segmentation, coronary arteries segmentation, construction of 1D network of vessels, partitioning of left ventricle wall, and personalization of the model parameters. We focus on a new technique, which generates specific perfusion zones and computes transmural perfusion ratio according to the quality of available medical images with a limited number of visible terminal coronary vessels. Numerical experiments show that accurate evaluation of stenosis before precutaneous coronary intervention should take into account both fractional flow reserve indices and myocardial perfusion, as well as other indices, in order to avoid misdiagnosis. The presented model provides better understanding of the background of clinical recommendations for possible surgical treatment of a stenosed coronary artery.

European multidisciplinary tumor boards support cross-border networking and increase treatment options for patients with rare gynecological tumors

ObjectiveTo evaluate outcomes of European cross-border multidisciplinary tumor boards in terms of participation, adherence to treatment recommendations, and access to novel treatment strategies.MethodsThe European reference network for rare gynecological tumors...

Comorbid OCD and ADHD in youth: Clinical implications and treatment recommendations

Obsessive compulsive disorder (OCD) affects up to 4% of children and adolescents (Nazeer et al., 2020). Childhood OCD impairs overall quality of life, particularly in familial, social and academic settings. For individuals with OCD, obsessions — unwanted, intrusive thoughts, images, or impulses that cause distress are subsequently reduced by compulsions — behaviors that are designed to assuage the distress of the obsessions, according to set rules or senses of completion (American Psychiatric Association, 2013). Common obsessions surround core fears of harm avoidance, disgust and/or a sense of incompleteness, leading to common compulsions of repeating, checking, avoidance, and/or other rituals.

Update points for the 2022 edition of the European Association for the Study of Liver Diseases Clinical Practice Guidelines for the Management of Hepatic Encephalopathy and comparison with China's 2018 edition guidelines

The European Association for the Study of Liver Diseases issued the "Clinical Practice Guidelines for the Management of Hepatic Encephalopathy" in 2022, which included recommendations for clinical diagnosis, assessment, treatment, management, and prevention. The Society's "Hepatic Encephalopathy Clinical Practice Guidelines in Chronic Liver Disease," which was last published in 2014, and the "Guidelines for the Diagnosis and Treatment of Hepatic Encephalopathy in Cirrhosis," which the Chinese Society of Hepatology, Chinese Medical Association, released in 2018, have certain differences and updates in terms of comparison to terminology, grading and classification, diagnosis, clinical evaluation and treatment, management, and prevention. Herein, the updated points of this guideline and the differences between it and our nation's guidelines are summarized in order to refine and understand the guiding role of the new version of the guideline for the clinical treatment of hepatic encephalopathy and provide aid for standardizing clinical diagnosis and treatment.

Федеральные клинические рекомендации по диагностике и лечению саркоидоза: комментарии и акценты

Федеральные клинические рекомендации по диагностике и лечению саркоидоза: комментарии и акценты

Diagnosis and treatment of lymphatic malformations: experience of the surgical department for newborns and infants

Introduction. Lymphatic malformations (LM) are a congenital pathology of lymphatic vessels that arose during embryogenesis. The relevance of the research topic is due to the rarity, variety of clinical manifestations, and the lack of clinical recommendations for treatment. Aim. To evaluate our experience of surgical and conservative treatment of LM in the surgical department for newborns and infants.&#x0D; Materials and methods. We performed a retrospective analysis of infants with various forms of LM treated at our department from 2017 to 2022. The study protocol was approved by the local ethics committee. The patients’ parents gave written voluntary informed consent to participate in the study.&#x0D; Results. Depending on the form of a LM, the infants underwent conservative therapy, sclerotherapy or surgical resection of the LM.&#x0D; Conclusions. Genetic tests for the spectrum of overgrowth syndromes are necessary for all LM patients to clarify the etiology of the process, prevent recurrence and complications.