PLACENTAL CALCIUM PUMP: CLINICAL-BASED EVIDENCE

Placenta can be considered as a pump of calcium necessary for the normal development of the fetus. We believe that the location of this pump is in the placental basement membrane. The calcification of this membrane has been described only in cases of in utero fetal death. In this study we describe for the first time a case of placental calcification in a living fetus. The fetus of a normal 21-year-old pregnant woman showed heart abnormalities but the genetic analysis showed a normal male karyotype. The histology of the placenta demonstrated multiple intravillous linear and granular calcific incrustations The hemtoxylin/eosin stain of the sections revealed basement membrane calcific incrustations and intravillous calcium deposits. We postulate that the fetal circulation in the villi was impaired and the calcium that reached the villi from the mother was deposited at this level.     

Signet-ring cell or mucinous histology after preoperative chemoradiation and survival in patients with esophageal or esophagogastric junction adenocarcinoma.

PURPOSE: The survival of patients with local-regional adenocarcinoma of the esophagus or esophagogastric junction (EGJ) treated with preoperative chemoradiation is much better in patients with pathologic complete response than those with residual tumor. Some adenocarcinomas have mixed patterns, including signet-ring cell and mucinous histology, but the clinical significance of these subtypes is unknown. EXPERIMENTAL DESIGN: We studied 412 consecutive patients with esophageal or EGJ adenocarcinoma treated with chemoradiation followed by esophagectomy (193 patients) or surgery alone (219 patients). We evaluated signet-ring cell and mucinous histology in the resection and pretherapy biopsy specimens and compared clinicopathologic features with overall survival. RESULTS: The fraction of signet-ring cell and mucinous histology was similar in evaluated specimens of patients treated with preoperative chemoradiation or surgery alone (17% and 18%, respectively). The overall survival rate at 5 years of patients treated with preoperative chemoradiation was significantly better if residual signet-ring cell or mucinous histology was present in the esophagectomy specimen (63% versus 28%; P = 0.02). All 13 patients with acellular mucin pools and no residual carcinoma are still alive after an average follow-up time of 36 months. By contrast, in patients treated with surgery alone, overall survival rate was significantly worse if signet-ring cell or mucinous histology was present (14% versus 30%; P = 0.05). In multivariate analysis, overall survival was independently predicted by presence of signet-ring cell or mucinous histology (P = 0.04). CONCLUSIONS: Our study showed that patients with esophageal or EGJ adenocarcinoma who have signet-ring cell or mucinous histology benefited substantially from preoperative chemoradiation and esophagectomy.     

Collagen-Carboxymethylcellulose Biocomposite Wound-Dressings with Antimicrobial Activity

Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects.     

Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

Lower functioning patients demonstrate atypical hip joint loading before and following total hip arthroplasty for osteoarthritis

Previous studies have established that up to 1 year post total hip arthroplasty (THA), patients do not recover normal function and the magnitude of hip joint loading remains reduced compared to healthy individuals. However, the temporal nature of the loading profile has not been considered to identify individuals who are at a greater risk of poor functional outcomes following THA. This study aimed to determine changes to the profile and magnitude of the resultant hip joint reaction force before and up to 6 months post-primary THA, and factors associated with atypical loading profiles. Hip joint loading was computed using a personalized lower-limb musculoskeletal model in 43 participants awaiting primary THA for osteoarthritis (mean age: SD = 65, 14 years; body mass index: SD = 30, 5 kg/m²) before and up to 6 months after THA. Atypical, single-peak loading profiles were observed for 11 patients before surgery, where four showed a single peak at 6 months. Patients displaying a single-peak profile walked slower (mean difference: −0.4 m/s) compared to individuals displaying double-peak profile (P = <.001) and had significantly reduced sagittal plane hip range of motion during gait (mean difference −9.6°, P = <.001). Self-reported pain, function, and stiffness did not differentiate between patients with a single or double-peak loading profile. Individuals with a single-peak force profile did not meet the minimal clinically important hip range of motion during gait and would be classified as low-functioning THA patients. Clinical Relevance: The temporal nature of the force profile may help to identify individuals who are at the greatest risk of poor functional outcomes after THA.     

FindZebra: A search engine for rare diseases

BackgroundThe web has become a primary information resource about illnesses and treatments for both medical and non-medical users. Standard web search is by far the most common interface to this information. It is therefore of interest to find out how well web search engines work for diagnostic queries and what factors contribute to successes and failures. Among diseases, rare (or orphan) diseases represent an especially challenging and thus interesting class to diagnose as each is rare, diverse in symptoms and usually has scattered resources associated with it.MethodsWe design an evaluation approach for web search engines for rare disease diagnosis which includes 56 real life diagnostic cases, performance measures, information resources and guidelines for customising Google Search to this task. In addition, we introduce FindZebra, a specialized (vertical) rare disease search engine. FindZebra is powered by open source search technology and uses curated freely available online medical information.ResultsFindZebra outperforms Google Search in both default set-up and customised to the resources used by FindZebra. We extend FindZebra with specialized functionalities exploiting medical ontological information and UMLS medical concepts to demonstrate different ways of displaying the retrieved results to medical experts.ConclusionsOur results indicate that a specialized search engine can improve the diagnostic quality without compromising the ease of use of the currently widely popular standard web search. The proposed evaluation approach can be valuable for future development and benchmarking. The FindZebra search engine is available at http://www.findzebra.com/.