The conundrum of differentiating Cushing's syndrome from non-neoplastic hypercortisolism: a systematic review and meta-analysis.

CONTEXT: Once hypercortisolemia is confirmed, differential diagnosis between Cushing's syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing's syndrome) is crucial. Due to worldwide corticotropin-releasing hormone (CRH) unavailability, accuracy of alternative tests to dexamethasone (Dex)-CRH, is clearly needed. OBJECTIVE: Assess the diagnostic accuracy of Dex-CRH test, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. METHODS: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. DATA SYNTHESIS: A total of 24 articles (1900 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 86% (81-90%; I2 28%) and 90% (84-94%; I2 15%), MSC 91% (85-94%; I2 66%) and 81% (70-89%; I2 71%), and LNSC 80% (67-89%; I2 57%) and 90% (84-93%; I2 21%), respectively. Summary receiver operating characteristics areas under the curve were Dex-CRH 0.949, desmopressin test 0.936, MSC 0.942, and LNSC 0.950 without visual or statistical significance. The overall risk of studies bias was moderate. CONCLUSION: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. When facing this challenging differential diagnosis, the results presented here should increase clinicians' confidence when deciding which test to perform.

Interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms: A systematic review.

BACKGROUND: Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism; however, 10-15% of patients have persistent hypothyroid symptoms despite normalizing thyroid hormone levels with LT4. This study aims to summarize the best available evidence on interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms. METHODS: A systematic search was conducted in March 2022 for randomized controlled trials and observational studies on interventions for adult patients with persistent hypothyroid symptoms despite biochemical euthyroidism on thyroid hormone replacement. RESULTS: A total of 277 articles were reviewed and seven fulfilled the inclusion criteria. 455 participants were included. Most intervention participants were female (78.6%) with a mean age of 47.5 (±2.8) years. Five clinical trials evaluating ginger (vs. starch), L-carnitine (vs. placebo), combination LT4 and liothyronine (LT3) (vs. LT4 or placebo), and surgery for patients with serum antithyroid peroxidase (TPO Ab) titers greater than 1000 IU/ml (vs. LT4) found inconsistent improvement in hypothyroidism related symptoms and general health. The two clinical trials with the largest improvement in fatigue scores were the use of ginger and surgery. One observational study comparing thyroidectomy vs observation found no significant difference on general health. Lastly, another observational study evaluating combination LT4/LT3 (vs. LT4 monotherapy) found improvement in fatigue and quality of life. There were 31 (12%) adverse events in the intervention group and 18 (10.8%) in the comparator group. CONCLUSIONS: There is no high-quality evidence supporting any intervention for persistent symptoms in hypothyroidism. Available evidence, limited by the risk of bias, inconsistency, and heterogeneity, suggests that some persistent symptoms, particularly fatigue, could improve with ginger and thyroidectomy.

Gallbladder perforation with fistulous communication.

BACKGROUND: The management of gallbladder perforation (GBP) with fistulous communication (Neimeier type I) is controversial. AIM: To recommend management options for GBP with fistulous communication. METHODS: A systematic review of studies describing the management of Neimeier type I GBP was performed according to the PRISMA guidelines. The search strategy was conducted in Scopus, Web of Science, MEDLINE, and EMBASE (May 2022). Data extraction was obtained for patient characteristics, type of intervention, days of hospitalization (DoH), complications, and site of fistulous communication. RESULTS: A total of 54 patients (61% female) from case reports, series, and cohorts were included. The most frequent fistulous communication occurred in the abdominal wall. Patients from case reports/series had a similar proportion of complications between open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) (28.6 vs 12.5; P = 0.569). Mortality was higher in OC (14.3 vs 0.0; P = 0.467) but this proportion was given by only one patient. DoH were higher in OC (mean 26.3 d vs 6.6 d). There was no clear association between higher rates of complications of a given intervention in cohorts, and no mortality was observed. CONCLUSION: Surgeons must evaluate the advantages and disadvantages of the therapeutic options. OC and LC are adequate options for the surgical management of GBP, with no significant differences.

Incidence of Cerebral Palsy, Risk Factors, and Neuroimaging in Northeast Mexico.

BACKGROUND: Cerebral palsy (CP) comprises a group of lifelong motor and postural development disorders that can cause static motor encephalopathy. The etiology of CP is attributed to nonprogressive lesions of the central nervous system during fetal or infant brain development. A diagnosis of CP is based on a combination of clinical and neurological signs, typically identified between 12 and 24 months. A medical history, several available standardized tools, including the Neoneuro assessment, and the Hammersmith infant neurological examination (HINE) can be used to predict risk. Magnetic resonance imaging (MRI) can contribute to the diagnosis of CP. The incidence of CP is 2 to 3 per 1000 live births, and in Western industrialized nations, it is 2.0-2.5 per 1000 live births; to our knowledge, no epidemiological studies have reported the incidence of CP in Mexico. AIM: To assess the incidence of CP in children aged up to 18 months in northeast Mexico and analyze the risk factors and neuroimaging findings. METHODS: This was a multicenter, randomized, prospective, cohort, analytical study of newborn children in three community hospitals and an early intervention and CP center in Nuevo Leon, Mexico, from 2017 to 2021. This study included 3861 newborns randomly selected from a population of 75,951 mothers in the immediate puerperium. According to the Neoneuro tool, high-risk children (n = 432) had abnormal neurological results at birth; they were followed and assessed with the Spanish version of the HINE test by a pediatric neurologist and underwent neuroimaging studies. Neonates with normal results were randomly selected to be in the low-risk group (n= 864). These neonates were followed and assessed with the HINE by a neonatologist. RESULTS: The incidence of CP was 4.4 of 1000 up to 18 months old, which was higher than that reported in developed countries. Perinatal risk factors were predominantly recognized in the etiology of CP, such as brain hemorrhage, and prematurity, in addition to congenital anomalies. The most frequent neuroimaging findings were ventricular dilation/cortical atrophy and intraventricular/subependymal hemorrhage and periventricular leukomalacia on MRI. CONCLUSIONS: This study is the first on the incidence/prevalence of CP in Mexico, and there are no formal studies in this field in other Latin American countries either. The incidence of CP in northeast Mexico is higher than that reported in developed countries. The follow-up of high-risk young children must be reinforced in the Mexican population, as children with disabilities have high and sequential health-care needs and may usually be lost to follow-up. Neuroimaging of PVL was the more frequent finding by MRI in this population.

Correlation Between CD133+ Stem Cells and Clinical Improvement in Patients with Autism Spectrum Disorders Treated with Intrathecal Bone Marrow-derived Mononuclear Cells.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental pathologies characterized by social and communication deficits, for which treatments are limited. Cell therapies, including intrathecal (IT) administration of bone marrow (BM) mononuclear cells (BM-MNC), improves symptoms in patients with ASD. Twenty-four patients diagnosed with ASD, according to the Diagnostic and Statistical Manual of Mental Disorders Text Revision Fourth Edition (DSM-IV-TR) criteria, were autologously treated with IT BM-MNC, and the clinical effect was evaluated using the Childhood Autism Rating Scale (CARS) on Days 30 (n=24) and 180 (n=14) post-treatment. IT BM-MNC improved clinical outcomes by Day 30 (p=0.0039), and those benefits remained and were further accentuated by Day 180 post-treatment (n=14; p=<0.0001). Clinical benefit at Days 30 (p=0.001; r= -0.51) and 180 (p=0.01; r= -0.60) posttreatment positively correlated with the enrichment of a putative BM stem cell population expressing the cluster of differentiation 133+ (CD133+) surface marker.

Interventions supporting cost conversations between patients and clinicians: A systematic review.

BACKGROUND AND AIM: Discussing cost during medical encounters may decrease the financial impact of medical care on patients and align their treatment plans with their financial capacities. We aimed to examine which interventions exist and quantify their effectiveness to support cost conversations. METHODS: Several databases were queried (Embase; Ovid MEDLINE(R); Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; the Cochrane databases; and Scopus) from their inception until January 31, 2020 using terms such as "clinician*", "patient*", "cost*", and "conversation*". Eligibility assessment, data extraction and risk of bias assessment were performed independently and in duplicate. We extracted study setting, design, intervention characteristics and outcomes related to patients, clinicians and quality metrics. RESULTS: We identified four studies (1327 patients) meeting our inclusion criteria. All studies were non-randomised and conducted in the United States. Three were performed in a primary care setting and the fourth in an oncology. Two studies used decision aids that included cost information; one used a training session for health care staff about cost conversations, and the other directly delivered information regarding cost conversations to patients. All interventions increased cost-conversation frequency. There was no effect on out-of-pocket costs, satisfaction, medication adherence or understanding of costs of care. CONCLUSION: The body of evidence is small and comprised of studies at high risk of bias. However, an increase in the frequency of cost conversations is consistent. Studies with higher quality are needed to ascertain the effects of these interventions on the acceptability, frequency and quality of cost conversations.

Does axillary lymph node size predict better metastatic involvement than apparent diffusion coefficient (ADC) value in women with newly diagnosed breast cancer?

BACKGROUND: It has been demonstrated that the number of metastatic axillary lymph nodes (mALNs) influence disease-free and overall survival in patients with breast cancer. PURPOSE: To determine if the ALN size is more accurate than the ALN apparent diffusion coefficient (ADC) value to predict metastatic involvement in newly diagnosed breast cancer. MATERIAL AND METHODS: A total of 44 patients with breast cancer were included. Magnetic resonance imaging (MRI) examinations were performed on a 1.5-T system with sagittal T1-weighted fast spin-echo non-fat saturated, sagittal T2-weighted fast spin-echo non-fat saturated, axial diffusion-weighted imaging echo-planar (b values of 0 and 700 s/mm2), and non-contrast axial VIBRANT sequences. The size and the ADC value were obtained for ALN ipsilateral and contralateral to breast cancer. The reference standard was the histopathologic lymph node status. RESULTS: mALN had a greater cortical thickness compared to contralateral non-mALN (10.3 ± 5.32 mm vs. 4 ± 1.17 mm, P ≤ 0.001). The threshold of ≥6.7 mm for predicting axillary metastatic involvement had a sensitivity and a specificity of 80.0% and 97.7%, respectively. The ADC value of mALN was significantly higher than the contralateral non-mALN (0.90 ± 0.12 × 10-3mm2/s vs. 0.78 ± 0.12 × 10-3mm2/s; P = 0.001). The threshold of ≥0.86 × 10-3mm2/s had a sensitivity and a specificity of 66.7% and 76.7%, respectively. CONCLUSION: Our results indicate that the cortical thickness has a better diagnostic performance in the differentiation of metastatic and non-metastatic lymph nodes than the lymph node ADC.

Impact of decision aids used during clinical encounters on clinician outcomes and consultation length: a systematic review.

BACKGROUND: Clinicians' satisfaction with encounter decision aids is an important component in facilitating implementation of these tools. We aimed to determine the impact of decision aids supporting shared decision making (SDM) during the clinical encounter on clinician outcomes. METHODS: We searched nine databases from inception to June 2017. Randomised clinical trials (RCTs) of decision aids used during clinical encounters with an unaided control group were eligible for inclusion. Due to heterogeneity among included studies, we used a narrative evidence synthesis approach. RESULTS: Twenty-five papers met inclusion criteria including 22 RCTs and 3 qualitative or mixed-methods studies nested in an RCT, together representing 23 unique trials. These trials evaluated healthcare decisions for cardiovascular prevention and treatment (n=8), treatment of diabetes mellitus (n=3), treatment of osteoporosis (n=2), treatment of depression (n=2), antibiotics to treat acute respiratory infections (n=3), cancer prevention and treatment (n=4) and prenatal diagnosis (n=1). Clinician outcomes were measured in only a minority of studies. Clinicians' satisfaction with decision making was assessed in only 8 (and only 2 of them showed statistically significantly greater satisfaction with the decision aid); only three trials asked if clinicians would recommend the decision aid to colleagues and only five asked if clinicians would use decision aids in the future. Outpatient consultations were not prolonged when a decision aid was used in 9 out of 13 trials. The overall strength of the evidence was low, with the major risk of bias related to lack of blinding of participants and/or outcome assessors. CONCLUSION: Decision aids can improve clinicians' satisfaction with medical decision making and provide helpful information without affecting length of consultation time. Most SDM trials, however, omit outcomes related to clinicians' perspective on the decision making process or the likelihood of using a decision aid in the future.

Apparent Diffusion Coefficient Value to Evaluate Tumor Response After Neoadjuvant Chemotherapy in Patients with Breast Cancer.

RATIONALE AND OBJECTIVES: This study explored tumor behavior in patients with breast cancer during neoadjuvant chemotherapy (NAC) by sequential measurements of tumor apparent diffusion coefficient (ADC) after each chemotherapy cycle. The aim was to determine if the tumor ADC is useful to differentiate complete pathological response (cPR) from partial pathological response (pPR) during NAC. MATERIALS AND METHODS: A total of 16 cases (in 14 patients) with diagnosis of breast cancer eligible to receive NAC were included. There were 70 magnetic resonance imaging examinations performed, 5 for each patient, during NAC cycles. Diffusion-weighted imaging was performed on a 1.5T system (b values of 0 and 700s/mm2). Four ADC ratios between the five MRI examinations were obtained to assess ADC changes during NAC. Absence of invasive breast cancer at surgical specimens (Miller-Payne 5) was considered as cPR and was used as reference for ADC cutoff ratios. RESULTS: In this study, we were able to differentiate between cPR and pPR, after two cycles of NAC until the end of NAC before surgery (ADC ratios 2-4). The thresholds to differentiate between cPR and pPR of ADC ratios 2, 3, and 4, were 1.14 × 10-3mm2/s, 1.08 × 10-3mm2/s, and 1.25 × 10-3mm2/s, respectively, and have a cross-validated sensitivity and specificity of 79.2%, 79.7% (ADC ratio 2); 100%, 66.7% (ADC ratio 3); and 100%, 83.8% (ADC ratio 4), respectively. CONCLUSIONS: The ADC ratios were useful to differentiate cPR from pPR in breast cancer tumors after NAC. Thus, it may be useful in tailoring treatment in these patients.

[Epidemiology of gunshot wounds in the University Hospital "Dr. José Eleuterio González" of the Autonomous University of Nuevo León]. / Epidemiología de las lesiones por proyectil de arma de fuego en el Hospital Universitario "Dr. José Eleuterio González" de la Universidad Autónoma de Nuevo León.

BACKGROUND: The incidence of deaths and injuries associated with gunshot wounds deserves special attention, mainly because of its repercussions on hospital resources and the diagnosis and treatment protocols. OBJECTIVE: To perform an analysis on the epidemiological factors associated with gunshot wounds. MATERIAL AND METHODS: An analysis was made of multiple variables of all patients diagnosed with gunshot wounds during the period between 2005 and 2015. RESULTS: A total of 605 cases were found, and an additional sub-group of 314 cases was obtained for a deeper analysis. The overall mortality rate was 7.9%. The main anatomical region was the abdomen, with 44%. A total of 324 laparotomies were performed, 124 incisions of the thoracic wall, and 72 vascular examinations. In the sub-group of 314 cases, a 16.9% and 42% of laparotomies and vascular examinations, respectably, were reported without evidence of injury to internal organs. DISCUSSION: Morbidity and mortality increases when 2 or more wounds are present with multiple organ injuries, in patients with multiple transfusions, or in those transferred to the intensive care unit. CONCLUSIONS: The incorporation of a physical evaluation format by all the departments involved is suggested for patients that are attended with gunshot wounds, in order to obtain more epidemiological information of these injuries for further studies.

Ovarian and adrenal androgens and their link to high human chorionic gonadotropin levels: a prospective controlled study.

Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (P ≤ 0.001). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 µ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 µ/dL) (P = 0.0001 and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (r = 0.78; P ≤ 0.001, r = 0.74; P ≤ 0.001, and r = 0.71; P ≤ 0.001), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels (P = 0.001) and free T and DHEA-S declined significantly (P = 0.0002 and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction.