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Prospective application of an index of neonatal necrotizing enterocolitis.

Fifty-five patients were scored 1 to 3 according to the criteria: the character of stools, abdominal findings on palpation, x-ray evidence of pneumatosis intestinalis, the development of pulmonary insufficiency, and the duration of symptoms to positive x-rays. Fifteen patients with scores of less than five were considered to have subclinical NEC with one late death. Twenty-nine of 30 patients with scores of 5-10 responded to medical management with 2 deaths related to recurrent bouts of sepsis without recurrent NEC. Eleven patients required surgery with index scores of 10-14 with 6 deaths occurring uniformly in those patients with scores of 12 or more. Two patients were scored inappropriately low due to the lack of the passage of a stool for analysis. One patient with a score of 4 did not pass a stool but had the other diagnostic criteria for the single false negative of the series. This index correctly determined the severity of NEC of 53 of 55 patients, identified the patients who required surgical intervention and predicted survival.

Enterocolitis, Pseudomembranous

Selective Omission of Oncotype Dx Genomic Testing in Ultra-Low-Risk Luminal A Breast Cancer.

INTRODUCTION: Older women with early-stage luminal A breast cancer have an excellent prognosis with a 5-year relative survival >99%. Research on curtailing overtreatment has challenged historical standards of care by reducing radiotherapy dose and volume, and selectively omitting sentinel lymph node biopsy. This study assessed the utility of Oncotype Dx genomic testing in ultra-low-risk luminal A breast cancer. PATIENTS AND METHODS: A community hospital cancer registry was queried to identify consecutive breast cancer patients from 2014 to 2022. An ultra-low-risk population was defined as age ≥60 years, hormone-receptor positive, HER2-negative, pathologic stage T1b-T2N0 without lymphovascular invasion, and Ki-67 ≤13.25%. Analyses examined the distribution of Oncotype Dx scores categorized as low risk (0-18), intermediate risk (19-25), or high risk (26-100), as well as recurrence and overall survival. RESULTS: Of 1711 patients, 91 met ultra-low-risk eligibility criteria with available Oncotype Dx results. The median age was 70 years with a median follow-up of 5.1 years, and no patients received chemotherapy. Only 1 patient (1.1%) had a high-risk Oncotype Dx score of ≥26, while 12 (13.2%) had intermediate scores and 78 (85.7%) were low risk. Five-year local control and overall survival were 100% and 93%, respectively. Ten non-breast cancer deaths occurred, and no patients developed distant metastases. CONCLUSION: We describe a pragmatic method using common clinical and pathological features to define an ultra-low-risk cohort. Older luminal A patients with favorable pathology have a very low probability of receiving a high-risk Oncotype Dx score and demonstrate an excellent prognosis with standard adjuvant therapy.

Chemotherapy

Dynamics of HER2 status in recurrent cervical cancer: Highlighting the clinical value of reassessment.

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugates have emerged as a promising therapy, making accurate HER2 assessment important. We assessed HER2 expression in recurrent cervical cancer, examined clinicopathological factors associated with HER2 positivity at recurrence, and analyzed HER2 discordance between matched primary and recurrent tumors. METHODS: We retrospectively identified patients with recurrent cervical cancer treated at a single center between 2013 and 2024. HER2 immunohistochemistry was performed on recurrent and matched primary tumors and scored according to the 2017 ASCO/CAP guideline for gastroesophageal adenocarcinoma. Tumors scoring 2+ or 3+ were classified as HER2-positive. Factors associated with HER2 positivity were analyzed by logistic regression. RESULTS: Among 118 patients, the HER2-positive rate in recurrent tumors was 15.3% (18/118). HER2 positivity was higher in endocervical adenocarcinoma than in squamous cell carcinoma (30.6% vs 8.6%, P = 0.009). Adenocarcinoma (adjusted odds ratio [OR] 4.80; 95% confidence interval [CI], 1.60-15.66) and recurrence outside the prior radiotherapy field (adjusted OR 7.92; 95% CI, 1.68-77.86) were independently associated with HER2 positivity. Among the 72 matched pairs, HER2 discordance was observed in 7 (9.7%), including HER2 gain in 4 of 61 (6.6%) and HER2 loss in 3 of 11 (27.3%). Adenocarcinoma was the only factor associated with discordance (OR 10.33; 95% CI, 1.99-104.04). CONCLUSIONS: In recurrent cervical cancer, HER2 positivity was associated with endocervical adenocarcinoma and recurrence outside the prior radiotherapy field. Reassessing HER2 by re-biopsy at relapse may inform treatment selection in a subset of patients.

Humans

[Prognostic evaluation of severe viral hepatitis].

The Cox's regression model is used for analysis of registered survival data of severe viral hepatitis. The final regression model showed six covariates, i.e. grade of coma, prothrombin time, the interval between jaundice to bleeding, the interval between jaundice to coma, LDH, and pathological scores as well as the recurrence frequency were associated with survival significantly. The final model can be presented as a "pocket chart" by which a prognostic index (PI) for a new subject can easily be obtained. By a simple graph, the PI can be translated to estimates of the probability of surviving within a given time and the median survival time. A small sample of prospective study showed the predicted survival length did not differ from the observed survival length significantly.

Analysis of Variance

Comparative Analysis of Somatic and Germline Polymerase Proofreading Deficiencies in Cancer: Molecular and Clinical Implications.

Polymerases ε and δ maintain genome integrity through exonuclease proofreading. Germline and somatic pathogenic variants (PVs) in the exonuclease domain (ED) of POLE and POLD1 impair proofreading, causing hypermutated tumors. Despite shared mutational features that make these tumors highly immunogenic, molecular and clinical distinctions between POLE and POLD1 mutations and between somatic and germline variants remain incompletely understood. We compared the molecular and clinical characteristics of POLE and POLD1 ED PVs (n = 31), assessing their location, pathogenicity, clinical phenotypes, mismatch repair (MMR) status, tumor mutational burden, and signatures. We analyzed 360 proofreading-deficient tumors (source: The Cancer Genome Atlas [TCGA] and Catalogue Of Somatic Mutations In Cancer [COSMIC]) and 70 families (249 individuals) with polymerase proofreading-associated polyposis. All germline and somatic PVs had high AlphaMissense scores (0.87-1) and clustered within or near Exo motifs. Recurrent, nonfounder germline PVs, POLE L424V and POLD1 S478N, showed low/modest REVEL scores. Somatic variants occurred mainly in endometrial cancers (75% of proofreading-deficient TCGA cancers), whereas colorectal cancer predominated in polymerase proofreading-associated polyposis (56% of carriers). Cancer risks and tumor spectra differed between POLE and POLD1 PV carriers. Aggressive hereditary phenotypes were linked to either specific POLE PVs (eg, S297F, V411L, P436R, M444K, A456P, and S461T) or the co-occurrence of germline ED PVs with germline MMR gene PVs. Distinct hypermutator profiles were confirmed for polymerase ε and polymerase δ proofreading deficiencies via unique mutational signatures (Polymerase ε: SBS10a/b, SBS28; Polymerase δ: SBS10c/d). Tumors with combined proofreading and MMR deficiencies had significantly higher tumor mutational burden and a shift in the associated mutational spectra. Unlike POLE, POLD1 ED PVs exhibited haplosufficiency, typically requiring a somatic second hit (eg, loss of heterozygosity) or MMR deficiency to drive hypermutation. In conclusion, differences between POLE and POLD1 and between somatic and germline mutations influence clinical presentation, mutagenic potential, and reliance on cooperating defects in tumorigenesis. These insights advance the understanding of proofreading-deficient cancers, with implications for diagnostics, genetic counseling, and precision oncology.

Humans

Primary Tumor Epigenetic and Transcriptomic Alterations Associated with Nodal Burden and Metastatic Risk in ER+/HER2- Breast Cancer.

De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2- disease. We examined whether primary tumors differed molecularly according to the extent of this regional dissemination. Genome-wide DNA methylation profiling of primary ER+/HER2- tumors from 47 patients with pN1 (n = 29) vs. >pN1 (n = 18) disease showed differences concentrated at promoters of developmental and cell-adhesion genes. By integrating methylomes with transcriptomes from the TCGA-BRCA cohort (n = 148) and clinical outcomes from KM Plotter (RFS, n = 1154; OS, n = 442; DMFS, n = 423), we identified four genes (ARL10, RIC3, CXCL14, KCNH2) showing concordant molecular and clinical associations, from which we derived the Lymph-node Involvement Outcome Numerator (LION) score. Lower LION scores were observed in metastatic lesions from the AURORA US cohort (n = 45). In SCAN-B (n = 3969), lower scores were associated with shorter distant recurrence-free intervals (HR = 0.38; 95% CI 0.23-0.62); this association persisted after adjustment for age, nodal and tumor category but was lost after adjustment for histological grade (HR = 0.83; 95% CI 0.48-1.44), indicating that the score and grade capture overlapping biology. These findings suggest that primary tumors already display coordinated epigenetic and transcriptional alterations associated with the extent of metastatic dissemination.

Humans

Birth asphyxia alters neonatal intestinal motility in term neonates.

As an extension of an earlier study showing that manometry can identify preterm newborns at risk for feeding intolerance, the authors investigated whether abnormalities of intestinal motor activity underlie the feeding intolerance seen in asphyxiated newborns. Low-compliance perfusion manometry was recorded within the first postnatal week in 25 term neonates admitted consecutively for respiratory diseases. Eleven of these neonates were identified to have experienced birth asphyxia because three concurrent features were present: 1-minute Apgar score of less than 2; 5-minute Apgar score of less than 4; and recurrent seizures within the first 48 postnatal hours. The remaining 14 neonates, who did not have any of these three characteristics, were considered to be nonasphyxiated control neonates. Motor activity differed in nonasphyxiated and asphyxiated neonates during fasting and feeding. During fasting, asphyxiated neonates had less migrating activity than nonasphyxiated neonates. In addition, episodes of motor quiescence and clustered phasic activity were less well organized in asphyxiated neonates. Both groups of neonates displayed a change in motor activity in response to a feeding infusion; however, the response was initiated significantly sooner in asphyxiated than in control neonates. All of the 11 asphyxiated neonates were intolerant of enteral feedings during the first poststudy week, but no control neonate was feeding intolerant. Six of the asphyxiated neonates were reevaluated 1 to 2 weeks later. During this latter study, motor activity in these asphyxiated neonates was similar to that of nonasphyxiated neonates; 5 of 6 of these neonates subsequently tolerated enteral feedings. It is speculated that changes in motor activity underlie the feeding intolerance that asphyxiated neonates typically exhibit.(ABSTRACT TRUNCATED AT 250 WORDS)

Asphyxia Neonatorum

Topologically distinct intratumoral heterogeneity scores for predicting high-risk pathological grades in invasive lung adenocarcinoma: A multicenter study across four institutions.

High-risk subtypes of invasive lung adenocarcinoma (IAC), particularly micropapillary- or solid-predominant patterns, are closely associated with poor prognosis. This multicenter retrospective study developed and validated a predictive model for the preoperative identification of these high-risk subtypes using topologically distinct intratumoral heterogeneity (ITH) scores derived from CT images. The study included 1,051 patients with IAC. Two complementary ITH scores were developed: a two-dimensional ITH score, which integrated local radiomics features with global pixel distribution patterns on the largest cross-sectional CT slice, and a three-dimensional ITH score, which extended this quantification across the entire tumor volume. Clinicoradiological features and ITH scores were incorporated as model inputs to construct six base machine learning classifiers and a final stacking ensemble classifier. Model interpretability and robustness were evaluated using SHapley Additive exPlanations (SHAP)-based ablation analyses. An independent dataset from The Cancer Imaging Archive (TCIA) was used for external validation to investigate associations between ITH scores and pathological characteristics, genomic features, recurrence-free survival, and overall survival. The stacking ensemble classifier achieved the best predictive performance, with an area under the receiver operating characteristic curve of 0.875, outperforming models based solely on radiomics features (0.834) or clinicoradiological features (0.792). SHAP analysis identified the 3D ITH score as the most influential contributor to model output, and TCIA validation showed that higher 3D ITH scores were associated with more aggressive tumor biology and poorer survival outcomes. The topologically distinct 3D ITH score may provide a clinically meaningful imaging biomarker for preoperative risk stratification in IAC.

Journal Article

Mucoepidermoid carcinoma of intraoral salivary glands. Evaluation and application of grading criteria in 143 cases.

The histopathologic criteria most useful for grading of mucoepidermoid carcinomas are controversial. To identify those histologic features most important in the grading of intraoral mucoepidermoid carcinomas, 143 cases of this disease with clinicopathologic correlations were studied. Twelve histopathologic features of each tumor and their clinical presentation were correlated with patient outcome. Seven patients died of disease, 5 had regional metastases only, 10 had recurrences only, and 121 had no additional problems. Clinical features suggesting aggressive behavior were short duration, presence of clinical symptoms, and location of tumor in the tongue and floor of the mouth. The histopathologic features that indicated high-grade behavior were an intracystic component of less than 20%, four or more mitotic figures per ten high-power fields, neural invasion, necrosis, and cellular anaplasia. The simultaneous assessment of these features showed improved prognostic correlation over individual parameters. A quantitative grading system was devised using these features. Tumors with a point score of 0 to 4 were considered low grade, and none of 122 patients with scores in this range died of their tumor, although 9 had recurrences only and 3 had regional metastases. Point scores of 7 or above indicated highly aggressive behavior. Six of ten patients with these high scores died of tumor. Most of these six patients had recurrences and regional metastases, and all had distant metastases. Two other patients had regional metastases only. Scores of 5 to 6 were considered intermediate between low-grade and high-grade scores because only 1 of 13 patients with these scores died of disease. Three of the five patients with regional metastasis had low-grade tumors, indicating the inability of the grading system to identify them. Nonetheless, with an average follow-up on these patients of 10 years after treatment of the metastasis, no patient had additional problems. The relative objectivity of our proposed grading system for intraoral mucoepidermoid carcinomas may help achieve more accurate and consistent grading of these rare tumors.

Adolescent

Preoperative prediction of mortality following surgery for esophageal cancer.

Ninety-five patients with thoracic esophageal cancer who had undergone radical esophagectomies through right thoracotomies from 1986 to 1989 were statistically analyzed semi-quantitatively to identify the risk factors predicting "operative (within 45 days of operation) or hospital death." Age, pulmonary function (%VC or %FEV1.0), cardiac function (EKG or Master test), renal function (Ccr), hepatic function (R15'ICG), diabetes mellitus (75 OGTT), extent of tumor invasion to the adventitia, and the type of operative procedure were each scored according to severity; 0 (no risk), 1, 2, or 3 (high risk). Patients with no severe postoperative complications had an accumulated score of less than 8 and comprised Group I, while those suffering an an "operative death" had a total score of 8 or more, and comprised Group II. Group III included those suffering a "hospital death." There was a significant difference between Group I and Group II (p < 0.005), but not between Group I and Group III. "Operative deaths" could be preoperatively predicted from the risk factors. However, "hospital deaths" could not be predicted, since they resulted mainly from recurrences of the cancer. In cases with scores of 8 or more the operative procedure should be changed to a simpler one for an improved prognosis.

Adult

Multifactorial analysis of fertility after conservative laparoscopic treatment of ectopic pregnancy in a series of 223 patients.

OBJECTIVES: To lay down the criteria to clearly define whether conservative or radical laparoscopic treatment should be adopted in cases of ectopic pregnancies (EP). DESIGN: Retrospective, noncomparative. SETTING: At the University Hospital of Clermont Ferrand and the La Pergola Clinic at Vichy from July 1974 to December 1987. PATIENTS: This study was carried out in 223 patients who had been treated laparoscopically for EP and who desired future childbearing and who were not lost to follow-up. MAIN OUTCOME MEASURES: The measures chosen to achieve the objective included age, parity, size of hematosalpinx, volume of hemoperitoneum, tubal rupture, location, intrauterine device, ipsilateral and contralateral adhesions, and patient's previous history of salpingitis, EP, solitary tube, and tubal infertility. RESULTS: The general intrauterine pregnancy rate was 67% (149 patients) and the recurrence rate 12% (27 patients). The results according to the studied factors demonstrated that age, parity, and the type of the EP have no influence on the postectopic fertility. The history of the patient, ipsilateral adhesions, or contralateral tubal status significantly reduce the future fertility prognosis and risk of recurrence. CONCLUSIONS: From a multivariable analysis, the authors propose a scoring system to choose the most suitable treatment to preserve fertility and to reduce the risk of recurrence ranging from laparoscopic conservative treatment to laparoscopic salpingectomy with contralateral sterilization.

Abdomen

A numerical scoring system for the classification of multiple sclerosis.

A simple, numerical system for the classification of multiple sclerosis into probable and definite categories is proposed. This system is based upon the analysis of the clinical symptomatology of 111 autopsy-proved cases of the disease from England, Norway and the United States. It is not designed to be used as an aid in the diagnosis and should be applied only to those cases where multiple sclerosis is suspected. It permits the incorporation of data obtained by means of evoked responses studies, psychological evaluations and other methods for confirming anamnestic information or delineating some asymptomatic lesions. The numerical system also provides a means for plotting the temporal evolution of the disease strictly in terms of the appearance of new signs and symptoms since recurrences of previously experienced symptoms cannot be scored; thus it has the advantage of not allowing so-called exacerbation due to physiological or psychological factors to falsely suggest disease progression or activity. The major use of this scoring system is to provide a reasonably reliable means of comparing epidemiologic data from different investigators by more clearly defining the probable and definite categories.

Adolescent

Effect of otitis media on development: a community-based study.

Otitis media history until age 3 years were recorded for 233 children as part of the surveillance in a Community Program for Promotion of Growth and Development (PROD) conducted in a western neighborhood of Jerusalem. Recurrent otitis media (6 or more episodes) occurred more frequently among children who were of North African or Asian origin, of lower social class and maternal education, and whose duration of breast feeding was less than 26 weeks. Children with recurrent otitis media also failed the 7-month hearing test more frequently than other children. The mean Developmental Quotient score at 2 years and the mean Stanford Binet score at 3 years were statistically significantly lower among children with recurrent otitis media, even after controlling for maternal origin and length of breast feeding. These findings underscore the importance of early identification and early intervention for otitis media.

Child Development

The specificity of split renal membranes in hereditary nephritis.

This study was undertaken to assess the specificity of split renal basement membranes in hereditary nephritis (HN). Thirteen specimens from eight patients with HN were mixed in a random fashion with specimens from control patients with either idiopathic nephrotic syndrome or various forms of glomerulonephritis and with specimens from patients with benign recurrent hematuria (BRH). Each biopsy specimen was scored for splitting of glomerular basement membranes (GBMs). Control and BRH specimens contained focal splitting in the GBMs; the biopsy specimens from HN patients had widespread lesions. Evaluation of split GBMs is useful in differentiating patients with HN from those with BRH and other renal diseases that may be confused with HN.

Basement Membrane

Longitudinal comparison of treat-to-target states and clinical outcomes in patients with late-onset versus early-onset systemic lupus erythematosus.

OBJECTIVE: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age &#x2264;50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS: Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.

Journal Article

[Role of tianeptine in the prevention of depression relapse and recurrence. First estimations].

The potential activity of tianeptine in the prevention of depressive relapses or recurrences was evaluated in the course of a long-term multicenter study. Five hundred and ten patients were treated for a one-year period. During the first six months, 22 percent of patients responders to the treatment relapsed into depression or had a methodological equivalent of depressive relapse (a MADRS score equal to or higher than 25). This percentage of depressive relapses is comparable to those obtained with other antidepressants. After six months of treatment, 7 percent of patients with a stabilized recovery recurred into depression or had a methodological equivalent of depressive recurrence (a MADRS score equal to or higher than 25). An analysis compared this percentage with those obtained in the course of other studies. These percentages are classically more important. The role of diagnoses of depression was analysed. Percentages of depressive relapses and recurrences were also evaluated in the sub-sample of patients treated with tianeptine alone.

Adult

Early surgical débridement of symptomatic pancreatic necrosis is beneficial irrespective of infection.

In order to assess the recent trend of nonoperative management of pancreatic necrosis, we reviewed 82 variables in 73 consecutive patients with symptomatic necrotizing pancreatitis. The mortality rate for the series was 25% (18 of 73). The only preintervention variables that correlated with mortality were APACHE II score greater than 15 (p = 0.01), preintervention blood transfusion (p less than 0.001), respiratory failure (p less than 0.001), and shock (p less than 0.01). Patients who developed recurrent sepsis following the initial intervention had a significantly higher mortality rate (17 of 34) than those who did not (1 of 39) (p less than 0.001). The rate of recurrent sepsis varied widely among individual surgeons and correlated with APACHE II score. The presence of infected versus noninfected necrosis did not correlate significantly with outcome. When percutaneous radiologically guided drainage was the initial therapeutic modality (n = 6), recurrent sepsis requiring surgical drainage inevitably occurred. Patients treated with percutaneous drainage (often in combination with surgical drainage) had a longer hospital stay (82 versus 42 days, p less than 0.001), spent more days in the intensive care unit (31 versus 6 days, p less than 0.001), and required more days of total parenteral nutrition (57 versus 27 days, p less than 0.001) than those treated solely by surgical means. We conclude that aggressive initial surgical débridement should be the first step in managing symptomatic pancreatic necrosis and that the presence of infection should not be the sole determinant of intervention.

Bacterial Infections

Risk of new myocardial infarction in middle-aged men with manifest coronary heart disease.

Men incuring coronary heart disease (CHD) during surveillance of an employed population were studied for risk factors associated with additional myocardial infarctions. The coronary-prone Type A behavior pattern measured by a test score, number of cigarettes smoked daily, and serum cholesterol were significantdiscriminators between the 67 men with recurrent CHD and the 220 with but a single clinical CHD event. Diastolic blood pressure and fasting serum triglycerides were not significant discriminators. Statistical analyses directed to possible sources of bias occasioned by the combined retrospective-prospective study design revealed that these problems are negligible and do not alter the findings observed. Type A score appears relatively unaffected by whether the measure was made before or after the initial CHD event. Multivariable discriminant function equations showed Type A score to be the strongest single predictor of recurrent CHD among the variables available. Number of cigarettes smoked and serum cholesterol accounted for additional variance. Future field trials for the secondary prevention of myocardial infarction would be strengthened by consideration of the possible role of Type A behavior.

Adult