Stringent Diagnostic Criteria Research Articles

Targeting Community-Based Palliative and Serious Illness Care Resources: Challenges of More Stringent Diagnostic Criteria for Prospective Enrollment.

Background: For patients with serious illnesses, one aim of palliative care services is to reduce the frequency and severity of hospital-based episodes of care. Since hospital-alternative palliative care may consume costly resources, providers need to efficiently target high-intensity services toward those most at risk for such adverse episodes of care. Objective: Our objective was to investigate progressively more restrictive diagnosis-based indications of serious illness as used to prospectively identify patients with higher average rates of hospitalization. Design/Setting: We designed an observational cohort quality improvement study using historical Medicare claims records to evaluate diagnostic inclusion criteria for targeting palliative and serious illness care resources. We first isolated a Seriously Ill Population (SIP) and then defined More SIP and Most SIP subgroups. Measurements: Our primary outcome measure was the 2019 acute-care count of hospitalizations for patients in the SIP, More SIP, and Most SIP subgroups, respectively. Results: The More SIP and Most SIP subgroups exhibited higher hospitalization rates. However, they also excluded progressively more seriously ill patients who did experience hospitalizations. In addition, almost half of the Most SIP subgroup were not hospitalized at all, despite having an average hospitalization rate greater than one. Conclusion:Allocating resources (personnel and services) toward reducing hospitalizations when almost half of the targeted population never goes to the hospital could result in unnecessary expenditures and exclude patients that could potentially benefit. Engaging community-based services to detect changes in status could provide supplemental indications of when and for whom to target palliative care resources.

Chromatin assembly factor subunit CHAF1A as a monogenic cause for oculo-auriculo-vertebral spectrum.

Oculo-auriculo-vertebral spectrum (OAVS) is characterized by abnormal development of the 1st and 2nd branchial arches. Despite arguments against a monogenic condition, a few genes have been involved in a minority of cases. We now report heterozygous, presumably loss-of function variants in the CHAF1A gene in 8 individuals, including 3 members of the same family. Four cases fulfill stringent diagnostic criteria for OAVS, including asymmetric ear dysplasia, preauricular tags, mandibular asymmetry +/- vertebral malformations. Two patients also presented with kidney malformations. CHAF1A encodes a subunit of CAF-1 (chromatin assembly factor-1), a heterotrimeric protein complex responsible for the deposition of newly synthesized histones H3-H4 onto the newly synthetized DNA strand during replication. The identification of loss-of-unction variants in CHAF1A is consistent with the hypothesis of early developmental genes dysregulation driving OAVS and other associations recently lumped under the acronym Recurrent Constellations of Embryonic Malformations (RCEM).

Postoperative pneumonia after femoral fracture surgery: an in-depth retrospective analysis

BackgroundFemoral fractures significantly contribute to disability, predominantly in the elderly. Despite this, data on postoperative pneumonia following femoral fracture surgeries remains sparse. Our study sought to explore the incidence and impact of postoperative pneumonia on outcomes following such surgeries.MethodsA retrospective study analyzed femoral fracture patients hospitalized from 2016 to 2022. We scrutinized postoperative outcomes, including pneumonia, hospital stay duration, intensive care unit (ICU) admissions, and in-hospital mortality. We established stringent diagnostic criteria for postoperative pneumonia, incorporating both clinical signs and radiological evidence, excluding patients with prior infections or those discharged within 24 h post-surgery. Statistical analyses involved Chi-square and t-tests, linear regression, and logestic regression using SPSS.ResultsOut of 636 patients, 10.8% were diagnosed with postoperative pneumonia. The average age was 79.55 ± 8.57 years, with a male prevalence of 47.8%. Common comorbidities were hypertension (78.3%), diabetes (60.9%), and cardiovascular diseases (40.6%). Surgical interventions were categorized as intramedullary nailing (40.6%), partial hip replacement (37.7%), and dynamic hip screw (21.7%). Postoperative pneumonia was associated with older age (AOR = 1.053, 95% CI 1.020 to 1.087, p = 0.002), ICU admission (AOR = 2.283, 95% CI 1.256 to 4.148, p = 0.007), and longer length of hospital stay (AOR = 1.079, 95% CI 1.030 to 1.130, p = 0.001). The presence of pneumonia was associated with a 2.621-day increase in hospitalization after adjusting for other variables (p < 0.001, 95% CI: 1.454 to 3.789).ConclusionThis study accentuates the clinical significance of postoperative pneumonia in femoral fracture patients, with a noted incidence of 10.8%. A notable association with older age, prolonged hospital stays, and ICU admissions was observed, underscoring the necessity of addressing this complication to improve patient outcomes and healthcare resource allocation.

Association between idiopathic hypersomnia and a genetic variant in the PER3 gene.

We aim to identify genetic markers associated with idiopathic hypersomnia, a disabling orphan central nervous system disorder of hypersomnolence that is still poorly understood. In our study, DNA was extracted from 79 unrelated patients diagnosed with idiopathic hypersomnia with long sleep time at the National Reference Center for Narcolepsy-France according to very stringent diagnostic criteria. Whole exome sequencing on the first 30 patients withidiopathic hypersomnia (25 females and 5 males) allowed the single nucleotide variants to be compared with a control population of 574 healthy subjects from the French Exome project database. We focused on the identification of genetic variants among 182 genes related to the regulation of sleep and circadian rhythm. Candidate variants obtained by exome sequencing analysis were then validated in a second sample of 49 patients with idiopathic hypersomnia (37 females and 12 males). Our study characterised seven variants from six genes significantly associated with idiopathic hypersomnia compared with controls. A targeted sequencing analysis of these seven variants on 49 other patients with idiopathic hypersomnia confirmed the relative over-representation of the A➔C variant of rs2859390, located in a potential splicing-site of PER3 gene. Our findings support a genetic predisposition and identify pathways involved in the pathogeny of idiopathic hypersomnia. A variant of the PER3 gene may predispose to idiopathic hypersomnia with long sleep time.

Inflammatory breast cancer: Epidemiologic data and therapeutic results.

Since the early description more than a century ago, inflammatory breast cancer (IBC) remains an aggressive disease, with a different geographic repartition, with the highest ones incidence reported in the North of Africa (Tunisia, Algeria, Morocco, and Egypt), and the lowest incidence in Western countries (USA, Europe…). In this study, we reviewed the literature using the Surveillance, Epidemiology, and End Results (SEER) database compared to other published series. We observed that in the high incidence areas (North of Africa) when compared to "classical" breast cancer, IBC was associated to younger age (less than 50 years) with rapid evolution of signs and symptoms (in less than 3 up to 6 months), and more aggressive clinical and histopathological-molecular parameters, due to the predominance of triple-negative and HER2+ subtypes in around 60% of cases. An epidemiologic trend was observed in both high and low incidence areas since the eighties are towards reduction of IBC prevalence. Concerning Tunisia, in comparison with the historical series of the 1980s, the incidence decreased in part by applying more stringent diagnostic criteria but also probably due to a slight improvement of the socio-economic level (SEL). This trend was also observed in the US, due to the efforts of collaborative IBC groups from MD Anderson Cancer Center (MDACC), Duke and IBC patient advocacy groups. Therapeutic results are slightly better due to the standardization of a multidisciplinary approach and the use of combined primary chemotherapy and/or targeted therapies (especially in HER2 positive patients), followed by mastectomy plus radiotherapy. The 5-year overall and disease-free survival is at more than 60%, related to an IBC mortality decrease observed in the cohorts of patients treated in the last decade.

Perinatal Hypoxic-Ischemic Encephalopathy: Incidence Over Time Within a Modern US Birth Cohort

BackgroundRecent studies suggest that the incidence of perinatal hypoxic-ischemic encephalopathy (HIE) may be increasing in developed countries. However, this observed increase may be due to increased ascertainment and increased treatment with therapeutic hypothermia rather than an increase in disease burden. In a US population-based cross-sectional study, we determined the incidence of perinatal HIE over time. MethodsThe study population included all 289,793 live-born infants ≥35 weeks gestational age born at 15 Kaiser Permanente Northern California hospitals between 2012 and 2019. Perinatal HIE was defined as the presence of both neonatal acidosis (i.e., cord blood pH < 7 or base deficit ≥10, or base deficit ≥10 on first infant gas) and neonatal encephalopathy confirmed by medical record review. Hospital discharge diagnoses of HIE were determined by extracting International Classification of Disease diagnostic codes for HIE assigned upon hospital discharge. ResultsThe population incidence of perinatal HIE was 1.7 per 1000. Although the incidence of perinatal HIE did not change significantly, both hospital discharge diagnoses of HIE and treatment with therapeutic hypothermia increased significantly during the study period. The sensitivity and positive predictive value of a hospital discharge diagnosis of HIE for identifying perinatal HIE confirmed by chart review were 72% and 79%, respectively. ConclusionsDuring the study years, the incidence of perinatal HIE remained stable despite increases in hospital discharge diagnoses of HIE and in the use of therapeutic hypothermia. Our findings underscore the importance of applying stringent diagnostic criteria when diagnosing this complex condition.

A Case of Seropositive Autoimmune Glial Fibrillary Acidic Protein Encephalitis with Renal Cell Carcinoma (P4-5.010)

<h3>Objective:</h3> NA <h3>Background:</h3> Autoimmune glial fibrillary acidic protein (GFAP) encephalitis is a novel disorder characterized for subacute neuropsychiatric symptom development and rapid remission with corticosteroid therapy. Here we describe a case of GFAP encephalitis presenting with renal cell carcinoma (RCC). <h3>Design/Methods:</h3> A 71-year-old man with a history of diabetic retinopathy and monoclonal gammopathy of undetermined significance (MGUS) presented for four months history of memory problems, intermittent word-finding difficulties and later development of auditory hallucinations requiring assistance with activities of daily living. On admission, he was oriented to person, his language was affected with decreased fluency and difficulty following commands. On work up, metabolic causes, toxins, and nutritional deficiencies were ruled out. Brain MRI was degraded by motion artifacts, but no obvious abnormality was appreciated. Lumbar puncture was remarkable for leukocytosis (37 WBC), but infectious workup was negative. Creutzfeldt Jakob Disease was ruled out with a negative RT-QUiC following a 14-3-3 protein level elevation. Mayo autoimmune panel detected GFAP IgG (1:16, reference &lt;1:2), with follow up imaging showing RCC confirmed on nephrectomy. Patient was treated with daily intravenous methylprednisolone 1000mg for 5 days and showed improvement. However, the day after treatment was stopped, he had a rapid decline in cognition. Long term steroid treatment with 1mg/kg/day prednisone and steroid sparing agent, mycophenolate 500mg BID were started. Patient returned to baseline after four days and was discharged. <h3>Results:</h3> NA <h3>Conclusions:</h3> Although there is no specific diagnostic criteria, the identification of GFAP-IgG in serum or CSF is a marker of disease and the patient’s response to corticosteroid treatment further supports an autoimmune etiology. Further work is needed to create stringent diagnostic criteria and treatment protocols for GFAP encephalopathy and its associations with neoplasms. <b>Disclosure:</b> Ms. Arrabothu has nothing to disclose. Mr. Govindan has nothing to disclose. Dr. Rodriguez has nothing to disclose. Ms. Xie has nothing to disclose. Dr. Tapia has nothing to disclose.

Clinical Characteristics of Patients With Ineffective Esophageal Motility by Chicago Classification Version 4.0 Compared to Chicago Classification Version 3.0

Chicago classification version 4.0 (CCv4.0) of esophageal motility disorders developed a more stringent diagnostic criteria for ineffective esophageal motility (IEM) than version 3.0. We studied the implications of the new diagnostic criteria on the prevalence of IEM, and clinically characterized and compared the population of patients who no longer meet diagnostic criteria for IEM to those who retain the diagnosis. We included all consecutively performed high-resolution esophageal impedance manometries from 2014 to 2021. Three cohorts of patients with IEM were created: Patients with IEM by Chicago classification version 3.0 (CCv3.0; CC3 group), by CCv4.0 only (CC4 group), and by CCv3.0 who are now considered normal (Normal group). Demographics, manometric and reflux parameters, and clinical outcomes were compared. A total of 594 manometries were analyzed. Of those, 66 (11.1%) met criteria for IEM by CCv3.0 (CC3), 41 (62.0%) retained an IEM diagnosis using CCv4.0 criteria (CC4), while 25 (38.0%) patients no longer met criteria for IEM (Normal). The CC4 group had higher esophageal acid exposure, especially supine (% time - 18.9% vs 2.2%; P = 0.005), less adequate peristaltic reserve (22.0% vs 88.0%; P = 0.003), and higher Demeester score (49.0 vs 21.2; P = 0.017) compared to the Normal group. There was no difference in bolus clearance between the groups. IEM under CCv4.0 has a stronger association with pathologic reflux, especially supine reflux, and inadequate peristaltic reserve, but impairment in bolus clearance is unchanged when compared with IEM diagnosed based on CCv3.0. Further studies are required to determine the implications of these findings on management strategies.

Interobserver reproducibility of cribriform cancer in prostate needle biopsies and validation of International Society of Urological Pathology criteria.

There is strong evidence that cribriform morphology indicates a worse prognosis of prostatic adenocarcinoma. Our aim was to investigate its interobserver reproducibility in prostate needle biopsies. A panel of nine prostate pathology experts from five continents independently reviewed 304 digitised biopsies for cribriform cancer according to recent International Society of Urological Pathology criteria. The biopsies were collected from a series of 702 biopsies that were reviewed by one of the panellists for enrichment of high-grade cancer and potentially cribriform structures. A 2/3 consensus diagnosis of cribriform and noncribriform cancer was reached in 90% (272/304) of the biopsies with a mean kappa value of 0.56 (95% confidence interval 0.52-0.61). The prevalence of consensus cribriform cancers was estimated to 4%, 12%, 21%, and 20% of Gleason scores 7 (3 + 4), 7 (4 + 3), 8, and 9-10, respectively. More than two cribriform structures per level or a largest cribriform mass with ≥9 lumina ora diameter of ≥0.5 mm predicted a consensus diagnosis of cribriform cancer in 88% (70/80), 84% (87/103), and 90% (56/62), respectively, and noncribriform cancer in 3% (2/80), 5% (5/103), and 2% (1/62), respectively (all P < 0.01). Cribriform prostate cancer was seen in a minority of needle biopsies with high-grade cancer. Stringent diagnostic criteria enabled the identification of cribriform patterns and the generation of a large set of consensus cases for standardisation.

Exploring the Sensitivity of Prodromal Dementia with Lewy Bodies Research Criteria.

Dementia with Lewy bodies (DLB) is an insidious neurodegenerative disease characterised by a precipitous decline in cognition, sleep disturbances, motor impairment and psychiatric features. Recently, criteria for prodromal DLB (pDLB) including clinical features and biomarkers have been put forward to aid the classification and research of this ambiguous cohort of patients. Researchers can use these criteria to classify patients with mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) as either possible (either one core clinical feature or one biomarker are present) or probable pDLB (at least two core clinical features, or one core clinical feature and at least one biomarker present). However, as isolated REM sleep behaviour disorder (iRBD) confirmed with polysomnography (PSG) can be included as both a clinical and a biomarker feature, potentially reducing the specificity of these diagnostic criteria. To address this issue, the current study classified a cohort of 47 PSG-confirmed iRBD patients as probable prodromal DLB only in the presence of an additional core feature or if there was an additional non-PSG biomarker. Thirteen iRBD patients demonstrated MCI (iRBD-MCI). In the iRBD-MCI group, one presented with parkinsonism and was thus classified as probable pDLB, whilst the remaining 12 were classified as only possible pDLB. All patients performed three tasks designed to measure attentional deficits, visual hallucinations and visuospatial impairment. Patients also attended clinical follow-ups to monitor for transition to DLB or another synucleinopathy. Findings indicated that the only patient categorised by virtue of having two core clinical features as probable pDLB transitioned over 28 months to a diagnosis of DLB. The performance of this probable pDLB patient was also ranked second-highest for their hallucinatory behaviours and had comparatively lower visuospatial accuracy. These findings highlight the need for more stringent diagnostic research criteria for pDLB, given that only one of the 13 patients who would have satisfied the current guidelines for probable pDLB transitioned to DLB after two years and was indeed the patient with two orthogonal core clinical features.

Chicago classification v4.0 protocol improves specificity and accuracy of diagnosis of oesophagogastric junction outflow obstruction.

SummaryBackgroundChicago classification version 4.0 (CCv4.0) introduced stringent diagnostic criteria for oesophagogastric junction outflow obstruction (EGJOO), in order to increase the clinical relevance of the diagnosis, although this has not yet been demonstrated.AimsTo determine the prevalence of EGJOO using CCv4.0 criteria in patients with CCv3.0‐based EGJOO, and to assess if provocative manoeuvres can predict a conclusive CCv4.0 diagnosis of EGJOO.MethodsClinical presentation, high resolution manometry (HRM) with rapid drink challenge (RDC), and timed barium oesophagogram (TBE) data were extracted for patients diagnosed with EGJOO as per CCv3.0 between 2018 and 2020. Patients were then re‐classified according to CCv4.0 criteria, using clinically relevant symptoms (dysphagia and/or chest pain), and abnormal barium emptying at 5 min on TBE. Receiver operating characteristic (ROC) analyses identified HRM predictors of EGJOO.ResultsOf 2010 HRM studies, 144 (7.2%) fulfilled CCv3.0 criteria for EGJOO (median age 61 years, 56.9% female). Upon applying CCv4.0 criteria, EGJOO prevalence decreased to 1.2%. On ROC analysis, integrated relaxation pressure during RDC (RDC‐IRP) was a significant predictor of a conclusive EGJOO diagnosis by CCv4.0 criteria (area under the curve: 96.1%). The optimal RDC‐IRP threshold of 16.7 mm Hg had 87% sensitivity, 97.1% specificity, 95.7% negative predictive value and 91.3% positive predictive value for a conclusive EGJOO diagnosis; lower thresholds (10 mmHg, 12 mmHg) had better sensitivity but lower specificity.ConclusionCCv4.0 criteria reduced the prevalence of EGJOO by 80%, thereby refining the diagnosis and identifying clinically relevant outflow obstruction. Elevated RDC‐IRP can predict conclusive EGJOO per CCv4.0.

Prevalence of eating disorders in adolescent girls in Siberia

IntroductionEating disorders (ED) are an urgent public health problem, however, many adolescents with clinical symptoms fail to meet stringent diagnostic criteria.ObjectivesTo estimate the prevalence of eating disorders (ED) and subthreshold eating disorders (SED) in adolescent girls.MethodsA cross-sectional study of girls attending secondary schools (n = 917) was carried out. The sample comprised of 18.3% early adolescents (aged 12-13), 51% middle adolescents (aged 14-15), and 30.6% late adolescents (aged 16-17). We used the Body Image and Eating Distress scale (Koskelainen et al., 2001) coded on a 1-3 scale. The answers were scored on a scale of 1-3. Adolescents scoring 12 or above on four items measuring body dissatisfaction were considered as dissatisfied with their bodies and were further divided into two subgroups: girls scoring 10 or above on three items measuring eating distress were considered as having ED, whereas girls scoring less than 10 were considered as having SED.ResultsThe prevalence of ED was 2.1% (CI 1.4-3.3), the prevalence of SED was 9.6% (CI 7.8-11.7). In early adolescence, the prevalence of SED was 1.6% (CI 0.9-2.7). In middle adolescence, the prevalence of SED was 5.1% (CI 3.9-6.7), the prevalence of ED was 0.9% (CI 0.5-1.8). In late adolescence, the prevalence of SED was 2.8% (CI 1.9-4.1), the prevalence of ED was 1.2% (CI 0.7-2.1).ConclusionsIn adolescent girls, the SED are 4.6 times commoner than overt above-threshold ED. During adolescence, the prevalence of SED decreases, while the prevalence of ED increases with age.DisclosureThe reported study was funded by grant RNF according to the research project № 21-15-00033

Lymph node metastasis of papillary thyroid carcinoma in the context of Hashimoto\u2019s thyroiditis

BackgroundWhether Hashimoto’s thyroiditis (HT) affects the lymph node metastasis of papillary thyroid carcinoma (PTC) remains uncertain. The diagnostic criteria for HT differed in previous studies. Our study focused on analysing the influence of HT on PTC lymph node metastasis (LNM) with stringent diagnostic criteria for HT.MethodsA total of 444 patients diagnosed with PTC from 2019 to 2020 were enrolled and divided into two groups: HT group and non-HT group. Diagnostic criteria of HT were as follows: thyroid peroxidase antibody (+) and postoperative histopathology of Hashimoto’s disease.ResultsThere was no significant difference in the LNM rate between HT group and non-HT group. Patients in the HT group had fewer numbers of metastatic LNs and lower metastatic LNs ratio in central region. In the HT group, age < 55 and tumor size ≥10 mm were independent risk factors for central LNM.ConclusionThe autoimmune response of HT seems to reduce the central lymph node metastasis of HT PTCs. Age < 55 and tumor size ≥10 mm were independent risk factors of central lymph node metastasis in HT PTCs.

Clinicopathological and Genomic Profiles of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma Identify Overlapping Signatures with a High Mutational Burden.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare tumors developing in chronically sun-exposed skin. Clinicopathological features are similar, but they differ in prognosis, while PDS has a more aggressive course with a higher risk for local recurrence and metastases. In current clinical practice, they are diagnosed by exclusion using immunohistochemistry. Thus, stringent diagnostic criteria and correct differentiation are critical in management and treatment for optimal outcomes. This retrospective single-center study collected clinicopathological data and tumor samples of 10 AFX and 18 PDS. Extracted genomic DNA from tumor specimens was analyzed by a next-generation sequencing (NGS) platform (FoundationOne-CDx™). Among 65 identified mutations, TP53 inactivating mutations were observed in all tumor specimens. In both AFX and PDS, the known pathogenic gene alterations in CDKN2A, TERT promoter, and NOTCH1 were frequently present, along with high mutational burden and stable Micro-Satellite Instability status. The mutational profiles differed only in ASXL1, which was only present in AFX. Further differences were identified in likely pathogenic and unknown gene alterations. Similarities in their genomic signatures could help to distinguish them from other malignancies, but they are not distinguishable between each other using the FoundationOne-CDx™ NGS panel. Therefore, histological criteria to determine diagnosis remain valid. For further insight, performing deep tumor profiling may be necessary.

1043-P: Diabetic Cardiomyopathy: A Systematic Analysis of Epidemiological Studies

Diabetic cardiomyopathy (DbCM) is a sequela of diabetes. DbCM is characterized by abnormal cardiac structure and/or performance in the absence of coronary artery disease or hypertensive, valvular or congenital heart disease. We aimed to determine the prevalence of DbCM in the United States and EU5. PubMed was queried for epidemiological studies on DbCM from 2010 onwards using the terms (“diabetes” AND “cardiomyopathy”) OR (“diabetic cardiomyopathy”) AND (“incidence” OR “prevalence”). 563 articles were identified, 40 of which were screened for full text review based on the abstract indicating the reporting of original data captured in a general diabetic population. Ten of these were used either directly or to inform our analysis. Four of these studies reported data on DbCM having made appropriate exclusions for atherosclerosis mediated heart failure. However, only 2 of these were ultimately included based on the representativeness of the study population and thus generalisability of results. Many studies were excluded due to heterogeneity in definition of DbCM. Some studies clearly stated DbCM as the indication of interest, taking appropriate measures to exclude cases with a history of atherosclerosis mediated precursors such as coronary artery disease, hypertension, or valvular heart disease. Other studies were not clear in the exclusion criteria and for this reason were excluded. Based on our review, estimates in the literature for DbCM in type 2 diabetes without stringent clinical diagnostic criteria range from 12% to 48%. Of the two studies included in our analysis which clinically define DbCM according to diagnostic guidelines, estimates ranged from 17% to 24%. Our final estimate based on an average of these two was 21%, with some imputations for variation by age. There are ~30 million diabetics in the United States alone and we estimate 21% of diagnosed diabetics also have DbCM, which represents a huge burden of disease for which there is very limited robust epidemiological data. Disclosure R. Perfetti: Stock/Shareholder; Self; Applied Therapeutics. S. Shendelman: Stock/Shareholder; Self; Applied Therapeutics.

Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0©.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.

Effective Control of Epstein-Barr Virus–Related Hemophagocytic Lymphohistiocytosis With Immunochemotherapy

The familial form of hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder. Although the prognosis for Epstein-Barr virus-associated HLH (EBV-HLH) remains uncertain, numerous reports indicate that it can also be fatal in a substantial proportion of cases. We therefore assessed the potential of immunochemotherapy with a core combination of steroids and etoposide to control EBV-HLH in 17 infants and children who met stringent diagnostic criteria for this reactive disorder of the mononuclear phagocyte system. Treatment of life-threatening emergencies was left to the discretion of participating investigators and typically included either intravenous Ig or cyclosporin A (CSA). Five patients (29%) entered complete remission during the induction phase (1 to 2 months), whereas 10 others (57%) required additional treatment to achieve this status. In 2 cases, immunochemotherapy was ineffective, prompting allogeneic bone marrow transplantation. Severe but reversible myelosuppression was a common finding; adverse late sequelae were limited to epileptic activity in one child and chronic EBV infection in 2 others. Fourteen of the 17 patients treated with immunochemotherapy have maintained their complete responses for 4+ to 39+ months (median, 15+ months), suggesting a low probability of disease recurrence. These results provide a new perspective on EBV-HLH, showing effective control (and perhaps cure) of the majority of EBV-HLH cases without bone marrow transplantation, using steroids and etoposide, with or without immunomodulatory agents.

The utility of screening diagnostic tests in identifying associative immune-mediated haemolytic anaemia in dogs.

The study aimed to (1) define the proportion of dogs with immune-mediated haemolytic anaemia (IMHA) that have associative and non-associative disease and (2) evaluate the utility of screening diagnostic tests in identifying potential triggers of associative IMHA. Medical records of 78 dogs diagnosed with IMHA at a specialist hospital in Sydney from July 2008 to August 2017 were reviewed. The original diagnosis was revised according to published guidelines (Garden et al., 2019) as either diagnostic, supportive or suspicious for IMHA. Associative IMHA was confirmed if immunosuppressive therapy was discontinued within six weeks of effective treatment of a potential trigger. Associative IMHA was considered possible when a potential trigger was identified but its significance could not be confirmed. Associative IMHA was confirmed (3) or suspected (7) in 10 dogs (13%, confidence interval [CI] 7.1%-22%), with 68 cases presumed to be non-associative. Associative IMHA was present in 3/29 (10.3%) of dogs with criteria diagnostic for IMHA, 4/42 (9.5%) of dogs with criteria supportive for IMHA and 3/7 (42.9%) of dogs with criteria suspicious for IMHA. Abdominal ultrasound was performed in 68 dogs and identified possible triggers in five (7.3%, CI 3.2% to 16%). Thoracic radiographs were performed in 70 dogs but did not identify any potential triggers (0%, CI 0% to 5.2%). Urine culture was performed in 22 dogs and was positive in three (14%, CI 4.7% to 33.3%). Routine screening tests, particularly thoracic radiographs, have a low yield in identifying potential triggers of associative IMHA, but are more likely to be useful in dogs fulfilling less stringent diagnostic criteria of IMHA.

Criterios diagnósticos del American College of Cardiology/American Heart Association Hypertension 2017 en México

&lt;p&gt;La guía del American College of Cardiology/American Heart Association Hypertension 2017 (acc/aha 2017) implementó criterios diagnósticos y metas de tratamiento más estrictos para la hipertensión en comparación con otras guías de atención, esto propició diversas dificultades y cuestionamientos para su aplicación a escala global. En México, las guías de práctica clínica y la Norma Oficial Mexicana para el Diagnóstico y Tratamiento de Hipertensión Arterial no contemplan esta nueva clasificación hasta la fecha; en el presente escrito se analizan las contribuciones más importantes de la guía acc/aha 2017, con el propósito de brindar al médico de primera atención elementos que sustenten una correcta valoración de los pacientes para su diagnóstico oportuno y mejor manejo de esta enfermedad.&lt;/p&gt;

Biomarkers of Acromegaly and Growth Hormone Action.

Biological markers (biomarkers) play a key role in drug development, regulatory approval and clinical care of patients and are linked to clinical and surrogate outcomes. Both acromegaly and Growth Hormone Deficiency (GHD) are pathological conditions related to important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers for the definition of treatment, treatment monitoring and follow-up. GH and insulin-like growth factor-I (IGF-I) are the main biomarkers of GH action in children and adults while, in acromegaly, both GH and IGF-I are established biomarkers of disease activity. However, although GH and IGF-I are widely validated biomarkers of GHD and acromegaly, their role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore, new biological markers for acromegaly and GH replacement therapy are strongly needed. The aim of this paper is to review and summarize the current state in the field pointing out new potential biomarkers for acromegaly and GH use/abuse.