Mexican consensus on cow's milk protein allergy.

BACKGROUND: The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. MATERIAL AND METHODS: The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). RESULTS: Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. CONCLUSIONS: The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.

Postoperative Radiologic Imaging in Secondary Alveolar Bone Grafting for Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

INTRODUCTION: Radiographs (XRs), computed tomography (CT) scans, and cone-beam CT (CBCT) scans are utilized for assessment of secondary alveolar bone graft (SABG) in patients with cleft lip and palate (CLP). However, the optimal choice for imaging modality remains unclear. This study compares the image fidelity and safety profile for XR, CT, and CBCT in the assessment of patients with CLP who have undergone SABG. METHODS: Articles from MEDLINE and Elsevier Embase were screened. The primary outcome was graft success rate. Secondary outcomes were percent-by-volume of graft maintained and patient safety, defined by radiation exposure. A random effects model was used to calculate the pooled outcomes for each imaging modality. Chi-squared analysis was used to compare pooled outcomes between different imaging modalities. RESULTS: Of the 149 articles identified initially, 14 were included. Computed tomography exhibited a significantly higher image fidelity demonstrated by a lower graft success rate (62.0%) compared with both XR (72.6%, P<0.01) and CBCT (69.8%, P<0.01). Cone-beam CT had the lowest reported percent-by-volume of graft maintained (32.1%). Computed tomography had a higher mean radiation dosage (39.7 milligray) than what has been reported for both XR and CBCT. CONCLUSION: Computed tomography demonstrated lower graft success rates than both XR and CBCT, possibly indicating a higher image fidelity. However, compared with CBCT, CT may have a higher radiation exposure. Randomized trials and longitudinal studies are necessary to perform a direct comparison between CT and CBCT and to correlate the image fidelity of these modalities with clinical outcomes.

Effectiveness of Risk Analysis Index Frailty Scores as a Predictor of Adverse Outcomes in Lower Extremity Reconstruction.

BACKGROUND: The rising clinical importance of assessing frailty is driven by its predictive capability for postoperative outcomes. This study assesses the effectiveness of RAI-rev (Revised Risk Analysis Index) in predicting adverse outcomes in lower extremity (LE) flap reconstruction. METHODS: Analyzing NSQIP (National Surgical Quality Improvement Program) data from 2015 to 2020, we compared demographics, perioperative factors, and 30-day outcomes in all locoregional and free-flap cases. Frailty scores, calculated using RAI-rev, were categorized with <15 as nonfrail and >35 as the most frail. Adjusted odds ratios (aORs) for specific complications were calculated using nonfrail as the reference group. Frailty scores in locoregional flaps were compared with those in free flaps. RESULTS: We identified 270 locoregional and 107 free-flap cases. Higher RAI-rev scores in locoregional flaps correlated with increased complications, such as deep surgical site infection (1% nonfrail vs. 20% RAI 31-35), stroke (0% nonfrail vs. 17% most frail), and mortality (0% nonfrail vs. 17% most frail). Locoregional flap cases with RAI-rev scores in the most frail group had a significantly elevated aOR for stroke (51.0, 95% confidence interval [CI]: 1.8-1402.5, p = 0.02), mortality (43.1, 95% CI: 1.6-1167.6, p = 0.03), and any complication (6.8, 95% CI: 1.2-37.4, p = 0.03). In free-flap cases, higher RAI-rev scores were associated with increased complications, with only sepsis showing a statistically significant difference (6% nonfrail vs. 100% most frail; aOR: 42.3, CI: 1.45-1245.3, p = 0.03). Free-flap cases had a significantly lower RAI-rev score compared with locoregional flap cases (14.91 vs. 17.64, p = 0.01). CONCLUSION: Elevated RAI-rev scores (>35) correlated with more complications in locoregional flaps, while free-flap reconstruction patients had generally low RAI-rev scores. This suggests that free flaps are less commonly recommended for presumed higher risk patients. The study demonstrates that RAI-rev may be able to serve as a risk calculator in LE reconstruction, aiding in the assessment of candidates for limb salvage versus amputation.

Elevating Lower Extremity Reconstruction: An Algorithmic Approach to Free Flap Re-elevation.

BACKGROUND: Free flap (FF) reconstruction is frequently required for soft-tissue coverage after significant orthopaedic trauma of the lower extremity (LE). While usually the final step in limb salvage, re-elevation of the previously inset FF may be necessary to restore a functional limb. In this study, we present our algorithm for LE FF re-elevation and review our experience to identify factors associated with successful limb salvage and return to ambulation. METHODS: A retrospective, single-institution review was conducted of adult patients with LE wounds who required FF reconstruction from 2016 to 2021. From this cohort, patients who required re-elevation of their LE FF were identified. Successful FF re-elevation was defined by limb salvage and return to ambulation. RESULTS: During the study period, 412 patients with LE wounds required flap reconstruction. Of these patients, 205 (49.8%) underwent free tissue transfer, and 39 (9.5%) met our inclusion criteria. From this cohort, 34 had successful FF re-elevation, while 1 was non-weight bearing and 4 were elected for amputation due to chronic complications unrelated to their FF. Univariate analysis revealed the total number of FF re-elevations (p < 0.001), the frequency of re-elevation indicated for orthopaedic access (p < 0.001), and infections necessitating return to the operating room (p = 0.001) were each negatively associated with limb salvage and return to ambulation. CONCLUSION: The described algorithm highlights the preoperative planning and meticulous flap preservation necessary for the successful coverage of critical structures following FF re-elevation. Our data demonstrate that LE FFs can be safely re-elevated for hardware access or flap revision. In these complex cases of LE trauma, management by a multidisciplinary team is essential for successful limb salvage.

Who's your data? Primary immune deficiency differential diagnosis prediction via machine learning and data mining of the USIDNET registry.

PURPOSE: There are currently more than 480 primary immune deficiency (PID) diseases and about 7000 rare diseases that together afflict around 1 in every 17 humans. Computational aids based on data mining and machine learning might facilitate the diagnostic task by extracting rules from large datasets and making predictions when faced with new problem cases. In a proof-of-concept data mining study, we aimed to predict PID diagnoses using a supervised machine learning algorithm based on classification tree boosting. METHODS: Through a data query at the USIDNET registry we obtained a database of 2396 patients with common diagnoses of PID, including their clinical and laboratory features. We kept 286 features and all 12 diagnoses to include in the model. We used the XGBoost package with parallel tree boosting for the supervised classification model, and SHAP for variable importance interpretation, on Python v3.7. The patient database was split into training and testing subsets, and after boosting through gradient descent, the predictive model provides measures of diagnostic prediction accuracy and individual feature importance. After a baseline performance test, we used the Class Weighting Hyperparameter, or scale_pos_weight to correct for imbalanced classification. RESULTS: The twelve PID diagnoses were CVID (1098 patients), DiGeorge syndrome, Chronic granulomatous disease, Congenital agammaglobulinemia, PID not otherwise classified, Specific antibody deficiency, Complement deficiency, Hyper-IgM, Leukocyte adhesion deficiency, ectodermal dysplasia with immune deficiency, Severe combined immune deficiency, and Wiskott-Aldrich syndrome. For CVID, the model found an accuracy on the train sample of 0.80, with an area under the ROC curve (AUC) of 0.80, and a Gini coefficient of 0.60. In the test subset, accuracy was 0.76, AUC 0.75, and Gini 0.51. The positive feature value to predict CVID was highest for upper respiratory infections, asthma, autoimmunity and hypogammaglobulinemia. Features with the highest negative predictive value were high IgE, growth delay, abscess, lymphopenia, and congenital heart disease. For the rest of the diagnoses, accuracy stayed between 0.75 and 0.99, AUC 0.46-0.87, Gini 0.07-0.75, and LogLoss 0.09-8.55. DISCUSSION: Clinicians should remember to consider the negative predictive features together with the positives. We are calling this a proof-of-concept study to continue with our explorations. A good performance is encouraging, and feature importance might aid feature selection for future endeavors. In the meantime, we can learn from the rules derived by the model and build a user-friendly decision tree to generate differential diagnoses.

Virtual Surgical Planning for Patients with Skeletal-Dental and Obstructive Sleep Apnea Syndrome.

The integration of virtual surgical planning (VSP) for the treatment of skeletal, dental, and facial abnormalities and obstructive sleep apnea (OSA) with maxillofacial surgery has catapulted surgical planning. Although reported for treating skeletal-dental abnormalities and dental implant surgery, a paucity of knowledge existed reporting the feasibility and resultant outcome measures when VSP was employed for planning maxillary and mandibular surgery for OSA patients. The surgery-first approach is at the forefront of advancing maxillofacial surgery. Case series reporting success with the surgery-first approach for patients with skeletal-dental and sleep apnea patients have been reported. In sleep apnea patients, clinically significant reductions in apnea-hypopnea index and improvement of low oxyhemoglobin saturation have been achieved. More so, significant improvement in the posterior airway space at the occlusal and mandibular planes were achieved, while preserving aesthetic norms as measured by tooth to lip measurements. VSP is a feasible tool used for predicting surgical outcome measures in maxillomandibular advancement surgery for patients with skeletal, dental, facial, and OSA derangements.

A comparison of an absorbable nasal implant versus functional rhinoplasty for nasal obstruction.

PURPOSE: An absorbable nasal implant for the treatment lateral nasal wall collapse was approved for use in patients with nasal obstruction. It remains to be seen whether this treatment is equivalent to open techniques for the treatment of nasal valve incompetence from collapsibility. MATERIALS AND METHODS: Two groups were analyzed for the study. One group had surgery which included the implant, septoplasty, and inferior turbinate submucous reduction and the other group had a variety of functional rhinoplasty techniques for lateral wall insufficiency in addition to septoplasty and inferior turbinate submucous reduction. NOSE and SNOT-22 were used to demonstrate pre and post-operative changes. RESULTS: Ninety total patients were identified. Fifty patients underwent insertion of an absorbable nasal implant and 40 underwent a traditional open technique to stabilize the LNW. For the implant group the mean NOSE score was 63.4 (SD 24) and post-operative was 22.9 (SD 19.9), in addition, the SNOT-22 score was 38.8 (SD 19.8) and post-operative was 18.5 (SD 15.2). For the open rhinoplasty group, the mean NOSE score was 57.9 (SD 23.2) and post-operative was 17.6 (SD 16.4). The SNOT-22 score was 33.6 (SD 14.9) and post-operative score was 11.5 (SD 15.2) The delta between pre and post-operative NOSE and SNOT-22 test were not different at an average of 3.95 months post-operatively between the groups (NOSE, P = 0.94 and SNOT-22, p = 0.53). CONCLUSION: In patients with multiple structural causes of nasal obstruction, including lateral wall insufficiency, insertion of an absorbable nasal implant, to support the LNW, seems to be equally effective as functional rhinoplasty techniques over a 4 month timeframe.

Mechanisms of Soft Tissue Injury and Repair from Ballistics.

Projectile injuries to the face deserve particular attention to evaluate for involvement of critical structures and functional elements and treat the devastating effects on facial aesthetics. Ballistic trauma to the maxillofacial region often has significant soft tissue and bony defects, creating a greater challenge to the reconstructive surgeon. The main goals of treatment of projectile injuries to the face are decreasing the amount of contaminants and nonviable tissue at the site, ensuring functionality, and restoring aesthetic appearance. There exists a lack of robust research on the subject. Soft tissue injuries from high-velocity projectiles have changed the perspective on treating acute injuries to the face and neck. Injuries encountered during both Operation Iraqi Freedom and Operation Enduring Freedom give the author pause to reflect upon a different wounding pattern than that encountered in stateside trauma centers. Given the dissemination of high-velocity weaponry by enemy combatants such as the improvised explosive device, mortar round, and high-velocity rifles, a higher incidence of facial wounds has been reported. The mechanism of injury and a stepwise approach for surgical repair are discussed incorporating advanced trauma life support principles and a reconstructive ladder of repair.

Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development.

The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using a Gaussia luciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria.IMPORTANCE The mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production.

Extravasation accidents with liposomal/liposomal pegylated anthracyclines treated with dexrazoxane: an overview and outcomes.

The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in clinical practice guidelines, including general measures and specific antidotes, such as dexrazoxane. However, there is little scientific evidence on the management of liposomal and pegylated liposomal anthracyclines. The aim of this paper was to review the scientific literature on the extravasation of liposomal and pegylated liposomal anthracyclines and determine the clinical impact of this type of extravasation, focusing on dexrazoxane. The literature was searched using two databases: PubMed and Embase. Three searches were conducted, using liposomal anthracycline extravasation, pegylated liposomal anthracycline extravasation, and liposomal doxorubicin extravasation as keywords, respectively. Seven articles fulfilled the study eligibility criteria and included seventeen cases in humans. Extravasation occurred with three drugs: liposomal doxorubicin in nine (53%) patients, liposomal daunorubicin in four (23.5%) patients, and pegylated liposomal doxorubicin in four (23.5%) patients. General measures for extravasations were applied in all patients, but only three patients received dexrazoxane. All cases were completely resolved at 2-3 months, except for one patient, in whom dexrazoxane was not used. In animals, dexrazoxane decreased both the frequency of wounds produced by pegylated liposomal doxorubicin and their extent. The pharmacokinetic profiles of liposomal and pegylated liposomal anthracyclines differ from those of conventional anthracyclines, modifying their effectiveness and safety. General measures may be inadequate to heal areas affected by extravasation, which may require the administration of dexrazoxane. However, each case should be evaluated individually for the administration of dexrazoxane in off-label use until scientific evidence is available on its effectiveness and safety as an antidote for these formulations of anthracyclines.

Efficacy of an adenovirus-vectored foot-and-mouth disease virus serotype A subunit vaccine in cattle using a direct contact transmission model.

BACKGROUND: A direct contact transmission challenge model was used to simulate natural foot-and-mouth disease virus (FMDV) spread from FMDV A24/Cruzeiro/BRA/55 infected 'seeder' steers to naïve or vaccinated steers previously immunized with a replication-deficient human adenovirus-vectored FMDV A24/Cruzeiro/BRA/55 capsid-based subunit vaccine (AdtA24). In two independent vaccine efficacy trials, AdtA24 was administered once intramuscularly in the neck 7 days prior to contact with FMDV A24/Cruzeiro/BRA/55-infected seeder steers. RESULTS: In Efficacy Study 1, we evaluated three doses of AdtA24 to estimate the 50%/90% bovine protective dose (BPD50/90) for prevention of clinical FMD. In vaccinated, contact-challenged steers, the BPD50/90 was 3.1 × 1010 / 5.5 × 1010 AdtA24 particles formulated without adjuvant. In Efficacy Study 2, steers vaccinated with 5 × 1010 AdtA24 particles, exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers, did not develop clinical FMD or transmit FMDV to other vaccinated or naïve, non-vaccinated steers. In contrast, naïve, non-vaccinated steers that were subsequently exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers developed clinical FMD and transmitted FMDV by contact to additional naïve, non-vaccinated steers. The AdtA24 vaccine differentiated infected from vaccinated animals (DIVA) because no antibodies to FMDV nonstructural proteins were detected prior to FMDV exposure. CONCLUSIONS: A single dose of the AdtA24 non-adjuvanted vaccine conferred protection against clinical FMD at 7 days post-vaccination following direct contact transmission from FMDV-infected, naïve, non-vaccinated steers. The AdtA24 vaccine was effective in preventing FMDV transmission from homologous challenged, contact-exposed, AdtA24-vaccinated, protected steers to co-mingled, susceptible steers, suggesting that the vaccine may be beneficial in reducing both the magnitude and duration of a FMDV outbreak in a commercial cattle production setting.

Effects of a primary care intervention to improve the quality of zolpidem prescriptions in elderly patients.

PURPOSE: The objective of this study was to measure the impact of an intervention on the prescription habits of general practitioners (GPs) in order to improve the quality of zolpidem prescriptions in patients aged 75 or older. METHODS: A prospective multicentric non-randomized trial was performed in the Metropolitan Granada Primary Healthcare Area (Andalusian Public Healthcare Service, Spain), which serves a total population of approximately 675,000 inhabitants. All health centers volunteering to participate in the trial were included. The intervention consisted of training sessions, individualized feedback, clinical information, and financial incentives. A daily dose over 5 mg was considered non-safe. Reduction in non-safe prescriptions of zolpidem in the elderly population became a quality prescribing indicator in a pay-for-performance scheme. RESULTS: Statistically significant differences versus baseline were found between the intervention and control groups in mean zolpidem prescription prevalence (28.5 vs. 37.5‰, respectively; p = 0.008) and mean non-safe zolpidem prescription prevalence (16.5 vs. 34.2‰, respectively; p < 0.001). At the end of the study period, the total number of non-safe prescriptions was 1309, 35% lower versus baseline, with a significant difference of p < 0.001; the number in the intervention (510 vs. 1118; p < 0.001) and control (799 vs. 893; p = 0.0064) groups was also significantly lower, with a significantly greater percentage reduction in the intervention group (54.4 vs. 10.5%, p < 0.001). CONCLUSION: The quality prescribing indicator in our area was improved by the intervention developed. Further studies that include an intervention group of GPs who receive no financial incentive are required to evaluate the relative importance of an economic reward in achieving this improvement.

The Maritime Declaration of Health (MDH) as a tool to detect maritime traffic-related health risks: analysis of MDH forms submitted to Spanish ports, October 2014 to March 2015.

The international maritime traffic of people and goods has often contributed to the spread of pathogens affecting public health. The Maritime Declaration of Health (MDH), according to the International Health Regulations (IHR) (2005), is a document containing data related to the state of health on board a ship during passage and on arrival at port. It is a useful tool for early detection of public health risks. The main objective of our study was to evaluate compliance with the model provided in the IHR, focusing on the format and degree of completion of MDH forms received at Spanish ports. We reviewed the content of 802 MDH forms submitted to nine Spanish ports between October 2014 and March 2015. Study results show that 22% of MDH forms presented did not comply with the recommended model and 39% were incomplete. The proportion of cargo ships with correct and complete MDH forms was lower than passenger ships; thus, the nine health questions were answered less frequently by cargo ships than passenger ships (63% vs 90%, p value < 0.001). The appropriate demand and usage of MDH forms by competent authorities should improve the quality of the document as a tool and improve risk assessment.

Influence of the HER2 Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients: a meta-analysis.

BACKGROUND: The HER2 655 A>G genetic variant has recently been associated with trastuzumab-induced cardiotoxicity in HER2 breast cancer patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients. METHODS: Our study population was composed of 78 HER2 breast cancer patients receiving trastuzumab. The HER2 655 A>G (rs1136201) genetic variant was genotyped using TaqMan allelic discrimination technology. Patients were classified on the basis of the occurrence of cardiotoxic events or the absence of cardiotoxic events during 1 year after the first infusion. RESULTS: The HER2 655 A>G polymorphism was significantly associated with cardiotoxicity: AG versus AA [P=0.012, odds ratio (OR)=5.12, 95% confidence interval (CI) 1.43-18.36], AG+GG versus AA (P=0.01, OR=5.72, 95% CI 1.50-21.76), AG versus AA+GG (P=0.005, OR=7.17, 95% CI 1.82-28.29). A meta-analysis combining these data with the results from previous studies confirmed this association. CONCLUSION: Our results support the role of the HER2 655 A>G polymorphism as a genetic marker of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.

Prevalence of fractures in women with rheumatoid arthritis and/or systemic lupus erythematosus on chronic glucocorticoid therapy.

BACKGROUND: Glucocorticoid (GC) therapy is associated with an increased risk of fractures. The main objective of this study was to determine the prevalence of undiagnosed vertebral fractures in women chronically using GC therapy for autoimmune disorders. We also determined the prevalence of non-vertebral fractures, and investigated whether factors such as quality-of-life and future fracture risk are associated with vertebral/non-vertebral fractures. METHODS: This was a multicenter cross-sectional study conducted in Spain. All women had rheumatoid arthritis (RA) and/or systemic lupus erythematosus (SLE). Radiological morphometric vertebral fractures were evaluated centrally (Genant semiquantitative method), whereas non-vertebral fractures were not assessed by radiography. Before radiography, patients were asked whether they had vertebral/non-vertebral fractures, hereafter referred to as 'self-reported' fractures. Assessment tools included the Disease Activity Score (DAS28), the SF-36 questionnaire, and FRAX®. RESULTS: Complete data were obtained for 576 outpatients with RA and/or SLE (83.3 % had RA); mean [SD] age 59.6 [15] years. Of all patients, 6.4 % had self-reported vertebral fractures, whereas 18.9 % had morphometric vertebral fractures (RA: 7.1 % self-reported vs. 20.0 % morphometric; SLE: 3.2 % self-reported vs. 13.7 % morphometric). Non-vertebral fractures were self-reported by 9.8 % of RA and 5.3 % of SLE patients. Low physical functioning was associated with morphometric vertebral fractures (mean [SD] SF-36 score 18.8 [6.0] when present vs. 20.1 [5.9] when absent; p = 0.028) and self-reported non-vertebral fractures (16.7 [5.2] when present vs. 20.1 [5.9] when absent; p < 0.001). Mean [SD] DAS28 was higher (p = 0.013) when any self-reported fractures were present (4.0 [1.3]) than absent (3.6 [1.3]). Based on FRAX® analysis, patients with vs. without morphometric vertebral fractures had higher 10-year probabilities of major osteoporotic fractures (mean [SD] 17.9 [12.9]% vs. 9.9 [9.6]%; p < 0.001) and hip fractures (11.0 [11.7]% vs. 4.6 [8.1]%; p < 0.001). CONCLUSIONS: Morphometric vertebral fractures were detected in 18.9 % of patients, i.e. 3-times more frequently than verbally reported by patients. Patients with vs. without fractures had worse quality-of-life and increased fracture risk. Accordingly, it is of utmost importance that women chronically using GCs are assessed for fractures, including morphometric vertebral fractures.

Bazedoxifene and conjugated estrogen prevent diet-induced obesity, hepatic steatosis, and type 2 diabetes in mice without impacting the reproductive tract.

Despite the capacity of estrogens to favorably regulate body composition and glucose homeostasis, their use to combat obesity and type 2 diabetes is not feasible, because they promote sex steroid-responsive cancers. The novel selective estrogen receptor modulator (SERM) bazedoxifene acetate (BZA) uniquely antagonizes both breast cancer development and estrogen-related changes in the female reproductive tract. How BZA administered with conjugated estrogen (CE) or alone impacts metabolism is unknown. The effects of BZA or CE + BZA on body composition and glucose homeostasis were determined in ovariectomized female mice fed a Western diet for 10-12 wk. In contrast to vehicle, estradiol (E2), CE, BZA, and CE + BZA equally prevented body weight gain by 50%. In parallel, all treatments caused equal attenuation of the increase in body fat mass invoked by the diet as well as the increases in subcutaneous and visceral white adipose tissue. Diet-induced hepatic steatosis was attenuated by E2 or CE, and BZA alone or with CE provided even greater steatosis prevention; all interventions improved pyruvate tolerance tests. Glucose tolerance tests and HOMA-IR were improved by E2, CE, and CE + BZA. Whereas E2 or CE alone invoked a uterotrophic response, BZA alone or CE + BZA had negligible impact on the uterus. Thus, CE + BZA affords protection from diet-induced adiposity, hepatic steatosis, and insulin resistance with minimal impact on the female reproductive tract in mice. These combined agents may provide a valuable new means to favorably regulate body composition and glucose homeostasis and combat fatty liver.

Confirmation of -174G/C interleukin-6 gene promoter polymorphism as a genetic marker predicting antitumor necrosis factor treatment outcome.

BACKGROUND: The IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA. MATERIALS AND METHODS: Our study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion. RESULTS: The -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months). CONCLUSION: Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.

[Guía latinoamericana para el diagnóstico y tratamiento de alergia a las proteínas de la leche de vaca (GL-APLV)].

Cow's milk allergy (CMA) is an immune-based disease that has become an increasing problem. The diagnosis and management of CMA varies from one clinical setting to another and represents a challenge in pediatric practice. In addition, because nonallergic food reactions can be confused with CMA symptoms, there is an overdiagnosis of the disease. In response to these situations, pediatric specialties from recognized institutions throughout Latin America decided to develop a clinical guideline for diagnosis and management of cow's milk allergy. These guidelines include definitions, epidemiology, pathophysiology overview, clinical and evidencebased recommendations for the diagnosis and treatment of CMA. They also include prevention and prognosis sections and identify gaps in the current knowledge to be addressed through future research.

Comparison of Dorsal Preservation Rhinoplasty Techniques: Functional and Aesthetic Review of Subdorsal Septal Strip Methods.

Objective: To compare subdorsal strip excisions in patients undergoing dorsal preservation (DP) rhinoplasty using patient-related outcome measures (PROMS). Methods: Patients were treated from 2020 to 2022 using the modified subdorsal strip method (MSSM) or Z flap approach. A two-sample t-test determined whether there was a difference in functional and aesthetic scores using the NOSE, Sinonasal Outcome Test (SNOT-22), SCHNOS, and ESS scales. Results: Seventy-one primary rhinoplasty patients met inclusion criteria at 12 months with an average age of 23 years (62 female, 9 male), with 35 (49%) undergoing the MSSM technique, while 36 (51%) receiving the Z flap. PROMS at 1, 3, 6, and 12 months postoperatively were compared. The average preoperative and postoperative NOSE score was 9.36 and -4.4 (standard deviation [SD] 3.1, p < 0.001). The average preoperative SNOT-22 score was 23.9 and -16.4 (SD 10.2, p < 0.001). ESS scores was average was 6.2 and -1.6 (SD 3.2, p = 0.01). The average SCHNOS total, functional, and cosmetic scores were 27.6 (6-47), 8.2 (0-20) and 18.7 (0-37), respectively, and -5.7 (SD 8.2, p < 0.001), -5.73 (SD 6.24, p < 0.001), -18.1 (SD 9.7, p < 0.001). No significant complications were found and no difference in PROMs among groups. Conclusion: There was no difference in septal strip techniques as evaluated by PROMS.