BACKGROUND: Severe acute malnutrition (SAM) can be diagnosed using weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC). Although some favor using MUAC alone, valuing its presumed ability to identify children at greatest need for nutritional care, the functional severity and physiological responses to treatment in children with varying deficits in WHZ and MUAC remain inadequately characterized.
OBJECTIVE: We aimed to compare clinical and biochemical responses to treatment in children with 1) both low MUAC and low WHZ, 2) low MUAC-only, and 3) low WHZ-only.
METHODS: A multicenter, observational cohort study was conducted in children aged 6-59 mo with nonedematous, uncomplicated SAM in Bangladesh, Burkina Faso, and Liberia. Anthropometric measurements and critical indicators were collected 3 times during treatment; metrics included clinical status, nutritional status, viability, and serum leptin, a biomarker of mortality risk in SAM.
RESULTS: Children with combined MUAC and WHZ deficits had greater increases in leptin levels during treatment than those with low MUAC alone, showing a 34.4% greater increase on the second visit (95% confidence interval [CI]: 7.6%, 43.6%; P = 0.02) and a 34.3% greater increase on the third visit (95% CI: 13.2%, 50.3%; P = 0.01). Similarly, weight gain velocity was higher by 1.56 g/kg/d in the combined deficit group (95% CI: 0.38, 2.75; P = 0.03) compared with children with low MUAC-only. Children with combined deficits had higher rates of iron deficiency and wasting while those with low WHZ alone and combined deficits had higher rates of tachypnea and pneumonia during treatment.
CONCLUSIONS: Given the comparable treatment responses of children with low WHZ alone and those with low MUAC alone, and the greater vulnerability at admission and during treatment in those with combined deficits, our findings support retaining WHZ as an independent diagnostic and admission criterion of SAM, alongside MUAC. This trial was registered at www.
RESULTS: gov/study/NCT03400930 as NCT03400930.

Background: Response to antipsychotics is subject to a wide interindividual variability, due to genetic and non-genetic factors. Several single nucleotide polymorphisms (SNPs) have been associated with response to antipsychotics in genome-wide association studies (GWAS). Polygenic risk scores (PRS) are a powerful tool to aggregate into a single measure the small effects of multiple risk alleles. Materials and methods: We studied the association between a PRS composed of SNPs associated with response to antipsychotics in GWAS studies (PRSresponse) in a real-world sample of patients (N = 460) with different diagnoses (schizophrenia spectrum, bipolar, depressive, neurocognitive, substance use disorders and miscellaneous). Two other PRSs composed of SNPs previously associated with risk of schizophrenia (PRSschizophrenia1 and PRSschizophrenia2) were also tested for their association with response to treatment. Results: PRSresponse was significantly associated with response to antipsychotics considering the whole cohort (OR = 1.14, CI = 1.03-1.26, p = 0.010), the subgroup of patients with schizophrenia, schizoaffective disorder or bipolar disorder (OR = 1.18, CI = 1.02-1.37, p = 0.022, N = 235), with schizophrenia or schizoaffective disorder (OR = 1.24, CI = 1.04-1.47, p = 0.01, N = 176) and with schizophrenia (OR = 1.27, CI = 1.04-1.55, p = 0.01, N = 149). Sensitivity and specificity were sub-optimal (schizophrenia 62%, 61%; schizophrenia spectrum 56%, 55%; schizophrenia spectrum plus bipolar disorder 60%, 56%; all patients 63%, 58%, respectively). PRSschizophrenia1 and PRSschizophrenia2 were not significantly associated with response to treatment. Conclusion: PRSresponse defined from GWAS studies is significantly associated with response to antipsychotics in a real-world cohort; however, the results of the sensitivity-specificity analysis preclude its use as a predictive tool in clinical practice.

Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12-86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0-25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA.

UNASSIGNED: Periodontitis is a chronic infectious disease affecting periodontium having multifactorial etiology, can cause significant systemic challengein addition to localized inflammation, tissue damage, and bone resorption. A serological marker of systemic inflammation known as C-reactive protein has been linked to an increased risk for a number of pathological conditions, including cardiovascular diseases.
UNASSIGNED: To estimate levels of serum C-reactive protein in healthy individuals and subjects with periodontal diseases and to compare serum C-reactive protein levels in subjects having periodontal disease pre-operatively & post-operatively.
UNASSIGNED: The study was conducted on 60 subjects age ranging from 35 to 60 years. 30 individuals with healthy periodontium were in group 1 (control group) and the remaining 30 were diagnosed as adult periodontitis were in group 2 (experimental group). Periodontal examination done using gingival index, plaque index, periodontal pocket depth, and Russel\'s index. CRP levels were examined between group 1 and group 2 and in group 2 between baseline visit before treatment and 2 months after treatment.
UNASSIGNED: The findings of this study show a significant connection between periodontal disease and the inflammatory marker CRP in the body, as well as a tendency for a significant decrease in serumCRP levels following periodontitis therapy. At baseline, there was a positive correlation among C-reactive protein, probing pocket depth, and Russell\'s index.
UNASSIGNED: As CRP is a key mediator for cardiovascular disease, an increase in C- reactive protein levels in periodontal diseases suggests a significant connection between periodontitis and cardiovascular diseases. Early periodontal treatment might decrease the severity of cardiovascular disease that already exists. This suggests that periodontal examination should be part of routine practicealong with cardiovascular examination.

In patients with low-risk differentiated thyroid cancer (DTC), remnant ablation with radioiodine (RA) after total thyroidectomy (TT) is controversial. No benefits have been demonstrated in terms of mortality or disease-free survival. Recent evidence found that RA did not improve mid-term outcomes.
To evaluate initial response to treatment and long-term follow-up status in low-risk DTC patients after TT vs. TT + RA with 131I 1.11 GBq (30 mCi).
Prospective multicenter non-randomized study; 174 low-risk DTC that underwent TT were recruited an divided in two groups according to RA (87 ablated and 87 non-ablated). Response to treatment was evaluated at 6-18 months after thyroidectomy and at the end of follow-up with measurements of thyroglobulin, and anti-thyroglobulin antibodies levels, and neck ultrasonography.
Baseline characteristics of both groups were similar. Ablated patients: median age 45.5 years, 84% females, 95.4% papillary thyroid carcinoma (PTC), mean tumor size 16 mm; non-ablated: median age 45 years, 88.5% females, 96.6% PTC, mean tumor size 14 mm. Response to initial treatment was similar between both groups, with < 2% of structural incomplete response. Final status was evaluated in 139 cases (median follow-up of 60 months). Among ablated patients, 82.8% had no evidence of disease (NED), 12% had an indeterminate response (IR) and 5% a biochemical incomplete response (BIR). Non-ablated patients had NED in 90%, IR in 8.7% and BIR in 1.2%. No statistical difference was found between groups (p = 0.29). No patient had evidence of structural disease at the end of follow-up.
Our findings support the recommendation against routine RA in low-risk DTC patients.

BACKGROUND: Despite ongoing treatment advancements in chronic heart failure (HF), mortality and readmission rates remain high for patients hospitalized for decompensated acute HF. These patients represent a distinct HF group, which requires emergent echocardiographic evaluation in an attempt to provide optimal and individualized acute care. The role of serial advanced echocardiographic assessment in acute HF for risk stratification and treatment guidance has not been thoroughly explored.
METHODS: The \"Beyond Myo-HF Study\" is a prospective, non-interventional cohort trial designed to enroll acutely admitted patients with symptoms and/or signs of HF. The aim of this study is to investigate whether intrahospital changes of conventional and novel echocardiographic indices of myocardial function and congestion-related markers can predict early mortality, late mortality, and HF rehospitalization. As per the protocol, all patients undergo a pair of state-of-the-art echocardiographic assessments, with a rigorous protocol including speckle tracking analysis of all cardiac chambers and myocardial work analysis for the left and right ventricle, upon admission and pre-discharge. Their laboratory profile is captured at those two time-points, and their therapeutic management is recorded. Patients will be followed-up for a median period of 12 months after enrollment.
CONCLUSIONS: The \"Beyond Myo-HF\" study is an ongoing, prospective trial aspiring to provide deep insight into the pathophysiology of acute HF, to enlighten the reverse cardiac functional and anatomical remodeling during hospitalization, and to recognize echocardiographic patterns capable of predicting adverse outcomes during and post decompensation of acute HF.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.

Monitoring treatment response is an important precaution in spinal tuberculosis (TB), particularly when the condition was clinically diagnosed rather than bacteriologically confirmed and when drug susceptibility testing was not performed. Conventional monitoring measures have limitations and there is a need for favourable alternatives. Therefore, this study aimed to investigate changes in immune biomarkers over the course of treatment for spinal TB and to compare these responses to the conventional monitoring measure, erythrocyte sedimentation rate (ESR).
Patients with spinal TB were recruited from a tertiary hospital in the Western Cape, South Africa, and provided blood samples at 0, 3, 6, 9 and 12 months of TB treatment. Blood samples were analysed for ESR, using standard techniques, and for 19 cytokines, using a multiplex platform. Changes in ESR and cytokine levels were investigated using a mixed model ANOVA and Least Significant Difference post-hoc testing.
Twenty-six patients with spinal TB were included in the study although only fifteen remained in follow-up at 12 months. Seven biomarkers changed significantly over the course of treatment (CRP, Fibrinogen, IFN-γ, Ferritin, VEGF-A, ApoA1 and NCAM, p < 0.01) with a further three showing a strong trend towards change (CCL1, CXCL9 and GDF-15, 0.05 ≥ p ≤ 0.06). Responsive biomarkers could be approximately grouped according to patterns of progressive, initial or delayed change. ESR performed similarly to CRP, Fibrinogen and IFN-γ with all showing significant decreases between 0, 6 and 12- months of treatment. Individual ESR responses were variable.
Individual ESR responses may be unreliable and support the investigation of multi-marker approaches to evaluating treatment response in spinal TB. Biomarkers of treatment response identified in the current study require validation in a larger study, which may also incorporate aspects such as evaluating biomarkers within the first week of treatment and the inclusion of a healthy control group.

OBJECTIVE: Although a few recent articles describe adults with treatment-resistant anorexia nervosa (TR-AN), no study addresses the specific features of subjects not responding to treatment in the developmental age. This study reports on the clinical and psychopathological variables that distinguish children and adolescents who did not respond to treatment (here \"TR-AN\") from good-outcome controls, in a multidisciplinary hospital treatment setting.
METHODS: Naturalistic, case-control study conducted on individuals showing lack of response to treatment and good-outcome controls. TR-AN was defined as two or more incomplete admissions and no complete admissions, consistently with studies in adults. Good-outcome was defined as complete first admission, availability for follow-up visit after 6 months, and maintaining at follow-up a %BMI > 70% in the absence of binging or purging in the preceding 3 months. Psychopathological (Eating Disorders Inventory-3 EDI-3; Beck Depression Inventory-II), clinical, and treatment variables at admission were compared. Significant differences in the univariate analyses were included in an exploratory binary logistic regression.
RESULTS: Seventy-six patients (30 TR-AN, 46 good-outcome AN controls) were enrolled (mean age 14.9 ± 1.9 years, F = 94.7%). TR-AN individuals had a higher age at admission and higher EDI-3 Eating Disorder Risk (EDRC) scores, were treated less frequently with a nasogastric tube (NGT), and achieved a lower BMI improvement at discharge than good-outcome controls. A predictive model for TR-AN status was found (X2 = 19.116; Nagelkerke-R2 = 0.478, p < 0.001), and age at admission (OR = 0.460, p = 0.019), EDI-3 EDRC (OR = 0.938, p = 0.043), and NGT (OR = 8.003, p = 0.019) were associated with a TR-AN status.
CONCLUSIONS: This is the first report on the psychopathological and clinical characteristics of children and adolescents not responding to treatment. These patients showed higher age and eating disorder scores, and were less frequently fed with NGT than controls. Despite the multiple incomplete admissions of our subjects, the short included follow-up limits the possibility for direct comparisons with adult samples of treatment-resistant patients. Thus, the specific features of children and adolescents with TR-AN should be assessed in longitudinal studies.
METHODS: III, Observational, case-control study.

Heat shock proteins (Hsp) are chaperones playing essential roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cells. We aimed to assess Hsp90 in patients with idiopathic inflammatory myopathies (IIM) and its association with IIM-related features.
Hsp90 plasma levels were analyzed in a cross-sectional cohort (277 IIM patients and 157 healthy controls [HC]) and two longitudinal cohorts to assess the effect of standard-of-care pharmacotherapy (n=39 in early disease and n=23 in established disease). Hsp90 and selected cytokines/chemokines were measured by commercially available ELISA and human Cytokine 27-plex Assay.
Hsp90 plasma levels were increased in IIM patients compared to HC (median [IQR]: 20.2 [14.3-40.1] vs 9.8 [7.5-13.8] ng/mL, p<0.0001). Elevated Hsp90 was found in IIM patients with pulmonary, cardiac, esophageal, and skeletal muscle involvement, with higher disease activity or damage, and with elevated muscle enzymes and crucial cytokines/chemokines involved in the pathogenesis of myositis (p<0.05 for all). Plasma Hsp90 decreased upon pharmacological treatment in both patients with early and established disease. Notably, Hsp90 plasma levels were slightly superior to traditional biomarkers, such as C-reactive protein and creatine kinase, in differentiating IIM from HC, and IIM patients with cardiac involvement and interstitial lung disease from those without these manifestations.
Hsp90 is increased systemically in patients with IIM. Plasma Hsp90 could become an attractive soluble biomarker of disease activity and damage and a potential predictor of treatment response in IIM.