A Successful Treatment of Broncho-Esophageal Fistula with Esophageal Stenting Using Direct Endoscopic Visualization.

Broncho-esophageal fistula (BEF) is a severe yet relatively rare connection between the bronchus and esophagus usually caused by esophageal and pulmonary malignancies. We present a case report of a 49-year-old man diagnosed with terminal lung carcinoma who developed a BEF. The thoracic computed tomography scan detected a mass in the left bronchi that partially covers and disrupts the bronchial contour in certain regions and extends to the esophageal wall. After thoroughly evaluating alternative treatment approaches, we opt for the stenting procedure due to the advanced stage of the tumor and the significantly diminished quality of life. The treatment involves the use of a partially covered metal stent that is known to exhibit lower potential to migrate. The treatment is highly successful, resulting in a significant enhancement of the patient's quality of life, a lengthening in his survival, and the ability to pursue additional palliative treatment options. In contrast to the typical prosthesis implantation, our procedure uses a direct endoscopic visualization for the proximal deployment of a partially covered stent, offering a cost-effective and radiation-free alternative that can be particularly beneficial for BEF patients in facilities without radiology services.

Antidiabetic Treatment before Hospitalization and Admission Parameters in Patients with Type 2 Diabetes, Obesity, and SARS-CoV-2 Viral Infection.

BACKGROUND: SARS-CoV-2 viral infection is a current and important topic for patients with comorbidities of type 2 diabetes and obesity, associated with increased risk of mortality and morbidity. This study aims to analyze, compare and describe admission parameters in patients with type 2 diabetes, obesity, and SARS-CoV-2 infection based on whether they received insulin therapy before hospital admission. METHODS: Our study enrolled patients diagnosed with type 2 diabetes, obesity, and SARS-CoV-2 viral infection, 81 patients without insulin treatment before hospital admission, and 81 patients with insulin at "Gavril Curteanu" Municipal Clinical Hospital of Oradea, Romania, between August 2020 and March 2022. RT-PCR/rapid antigen tests were used for detecting SARS-CoV-2 viral infection. RESULTS: The severe form of COVID-19 was found in 66% of all patients (65% in the group without insulin and 67% in the group with insulin). Oxygen saturation at the time of hospital admission was greater or equal to 90% in 62% of all patients. The most associated comorbidities we founded in this study were: hypertension in 75% of all patients (grade two hypertension 63% in the group without insulin and 64% in the group with insulin), ischemic heart disease in 35% of patients (25% in the group without insulin and 44% in the group with insulin, n = 0.008), heart failure in 9.3% of all patients (8.6% in the group without insulin and 10% in the group with insulin). CRP and procalcitonin are increased in both groups at hospital admission, with a slightly higher trend in the group with insulin therapy before hospital admission. We found that 56% of patients in the group with insulin treatment were with uncontrolled diabetes on admission. Only 10% of patients required a change in antidiabetic treatment with insulin therapy at discharge. In our study, 89% of all patients did not require short-term home oxygen therapy at discharge. CONCLUSIONS: Antidiabetic therapy taken before hospital admission did not protect patients against cytokine storm in COVID-19, but is very important in the pathophysiological stage of comorbidities. Paraclinical parameters at hospitalization showed differences in correlation with oral antidiabetic treatment like metformin or insulin therapy. Changing the antidiabetic treatment for a small percentage of patients in the group who had not been receiving insulin therapy before discharge was necessary. It is necessary for future studies to see all changes involved in antidiabetic treatment in patients with diabetes type 2 and obesity after SARS-CoV2 viral infection and its long-term evolution.

Assessment of Pulpal Status in Primary Teeth Following Direct Pulp Capping in an Experimental Canine Model.

(1) Background: This study aimed to assess the pulpal response of primary teeth by pulse-oximetry (PO) in a canine model, following direct pulp capping (DPC). (2) Methods: Forty-eight primary teeth from eight canine subjects were divided into three treatment groups, based on the DPC material­calcium hydroxide (CH), MTA, BiodentineTM)­and three corresponding control groups. Data from PO pulp testing were correlated with laser Doppler flowmetry (LDF) testing, computer tomographic (CT) densitometry and histological analysis; the experiment lasted 14 days. (3) Results: SpO2 recordings revealed statistically significant differences (p = 0.002, <0.05) between the treatment and control groups, and no significant differences (p = 0.257, >0.05) were observed between treatment groups. LDF recordings showed significant differences (p = 0.002, <0.05) between the treatment and control groups and identified significant differences between materials (p = 0.001, <0.05). CT densitometry indicated vital pulps in all teeth, with pulpal inflammation detected in 6/8 CH-capped teeth and 2/8 MTA-capped teeth. Histologic evaluation confirmed vital pulp in all specimens, with different degrees of inflammation. (4) Conclusions: Within its limitations, the present study confirms the diagnostic value of PO evaluation of pulpal status in primary teeth with histologic means after pulp-capping procedures in a canine model. However, various degrees of pulpal inflammation elicited by different pulp-capping materials seem not to correlate with the obtained PO values.

Clinical and microbiological effects of a single application of sodium hypochlorite gel during subgingival re-instrumentation: a triple-blind randomized placebo-controlled clinical trial.

OBJECTIVES: The aim of this study is to assess the clinical and microbiological effects of a single subgingival administration of sodium hypochlorite gel (NaOCl) and compare it with 1% chlorhexidine (CHX) gel and a placebo gel following mechanical re-instrumentation during supportive periodontal therapy (SPT). MATERIALS AND METHODS: Sixty-two patients who had been treated for stage III-IV periodontitis and enrolled in SPT were included in the study based on following criteria: (1) active periodontal therapy completed at least 6 months before enrollment in the study, (2) presence of at least 4 non-adjacent sites with probing pocket depths (PPDs) ≥ 4 mm with bleeding on probing (BOP), or presence of 5-8 mm PPDs with or without BOP. All sites presenting PPD ≥ 4 mm and BOP at baseline and 3-, 6-, and 9-month follow-up timepoints were subgingivally re-instrumented with ultrasounds. Selected patients were randomly assigned into three groups and treated additionally with a single subgingival administration of NaOCl gel (group A); 1% CHX gel (group B); and placebo gel (group C). Main outcome variable was pocket closure at 12 months. Secondary outcome variables were changes in mean PPD, BOP, and clinical attachment level (CAL) along with changes in the numbers of the following five keystone bacterial pathogens: Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Tannerella forsythia (T.f.), and Treponema denticola (T.d.). RESULTS: At 12 months, pocket closure was obtained in 77.5% in the NaOCl treated sites. The reduction in PPD was higher with CHX than with NaOCl, although a statistically significant adjunctive effect for NaOCl (P = 0.028) was only observed in comparison with placebo only. Mean CAL improved in all groups and at all timepoints, compared to the baseline (P < 0.05). However, after 6 months, CAL gain was statistically significantly higher in the NaOCl treated group than following application of CHX (P = 0.0026). CONCLUSION: In SPT patients, a single adjunctive use of a NaOCl gel may provide benefits in controlling inflammation and residual pockets. TRIAL REGISTRATION: ISRCTN Registry of Clinical Trials (ISRCTN11387188). CLINICAL RELEVANCE: A baseline single application of NaOCl gel in conjunction with mechanical debridement may achieve substantial pocket closure in patients enrolled in SPT; treatment time, cost, and applicability considerations should be taken into account when selecting this therapy.

Hollongdione arylidene derivatives induce antiproliferative activity against melanoma and breast cancer through pro-apoptotic and antiangiogenic mechanisms.

The use of natural compounds as starting point for semisynthetic derivatives has already been proven as a valuable source of active anticancer agents. Hollongdione (4,4,8,14-tetramethyl-18-norpregnan-3,20-dion), obtained by few steps from dammarane type triterpenoid dipterocarpol, was chemically modified at C2 and C21 carbon atoms by the Claisen-Schmidt aldol condensation to give a series of arylidene derivatives. The anticancer activity of the obtained compounds was assessed on NCI-60 cancer cell panel, revealing strong antiproliferative effects against a large variety of cancer cells. 2,21-Bis-[3-pyridinyl]-methylidenohollongdione 9 emerged as the most active derivative as indicated by its GI50 values in the micromolar range which, combined with its high selectivity index values, indicated its suitability for deeper biological investigation. The mechanisms involved in compound 9 antiproliferative activity, were investigated through in vitro (DAPI staining) and ex vivo (CAM assay) tests, which exhibited its apoptotic and antiangiogenic activities. In addition, compound 9 showed an overall inhibition of mitochondrial respiration. rtPCR analysis identified the more intimate activity at pro-survival/pro-apoptotic gene level. Collectively, the hollongdione derivative stand as a promising therapeutic option against melanoma and breast cancer provided that future in vivo analysis will certify its clinical efficacy.

Age-Related Variation of Pulpal Oxygen Saturation in Healthy Primary and Permanent Teeth in Children: A Clinical Study.

(1) Background: Pulse oximetry (PO) is an effective method of dental pulp status monitorization but still lacks practical implementation in dentistry, as well as clear reference values for different tooth types. The study's aim was to investigate the age-related variation of blood oxygen saturation (SpO2) from the dental pulp during different stages of tooth development in all types of primary and permanent teeth of children. (2) Methods: The pulps of 600 healthy primary and permanent teeth (incisors, canines, premolars, and molars) of patients aged 2−15 years were tested with an adapted PO device, and the results were statistically analyzed; (3) Results: Statistically significant differences (p < 0.05) were found between open-apex and closed-apex teeth and between the canines and other tooth types in both primary and permanent dentitions. (4) Conclusions: Values of SpO2 tended to decrease with age progression in both primary and permanent dentitions. Enamel and dentine thickness and their optical properties and the shape and volume of coronal pulp, which differed among tooth types, seemed to have some influence on the reading as well. The study indicates that factors such as the root development and the tooth type must be taken into account when establishing reference SpO2 values for the dental pulp.

Autopsy Findings and Inflammatory Markers in SARS-CoV-2: A Single-Center Experience.

Purpose: The systemic inflammatory response related to COVID-19 can be easily investigated in living patients. Unfortunately, not every biomarker is suitable for postmortem analysis since several factors may interfere. The aim of this study was to summarize key histopathological findings within each organ system due to COVID-19 and to assess if serological inexpensive and widely available biomarkers such as CRP, IL-6, fibrinogen and d-Dimers, associated with adverse outcomes in COVID-19, can be implemented in a post-mortem assessment. Patients and Methods: A total of 60 subjects divided in 2 groups were included. All subjects died outside a hospital setting and therefore did not receive specific or symptomatic therapies that could have modulated the inflammatory response. The first group included 45 subjects in which mandatory autopsy was performed in order to establish the cause of death and macroscopic examination of the lungs was highly suggestive of SARS-CoV-2 infection. As controls (Group 2), 20 subjects who died from polytrauma in high velocity car accidents and suicide were selected. Bronchial fluids collected during the autopsy procedure were used for the RT-PCR diagnosis of SARS-CoV-2 and serum samples were sent for analysis of IL-6, CRP, d-Dimers and fibrinogen. Results: Compared with the control group, the subjects of the COVID-19 group were older (59±19.5 vs.38±19.15 years, p=0.0002) and had more underlying comorbidities such as hypertension (60% vs 35%, p=0.06) or were overweight (53.3% vs 30%, p=0.08). The levels of CRP, IL-6, fibrinogen and d-Dimers in postmortem plasma samples were significantly higher in COVID-19 subjects than in control group (p< 0.0001). Moreover, the level of IL-6 was significantly higher in overweight patients (r=0.52, P<0.001). In all COVID-19 subjects, the histological examination revealed features corresponding to the exudative and/or proliferative phases of diffuse alveolar damage. Large pulmonary emboli were observed in 7 cases. Gross cardiac enlargement with left ventricular hypertrophy was observed in 19 cases. The most frequent pathological finding of the central nervous system was acute/early-subacute infarction. Conclusion: Due to the complexity of the inflammatory response, we postulate that a combination of biomarkers, rather than a single laboratory parameter, might be more effective in obtaining a reliable postmortem COVID-19 diagnosis.

New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design.

Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.

3-Pyridinylidene Derivatives of Chemically Modified Lupane and Ursane Triterpenes as Promising Anticancer Agents by Targeting Apoptosis.

Cancer persists as a global challenge due to the extent to which conventional anticancer therapies pose high risks counterbalanced with their therapeutic benefit. Naturally occurring substances stand as an important safer alternative source for anticancer drug development. In the current study, a series of modified lupane and ursane derivatives was subjected to in vitro screening on the NCI-60 cancer cell line panel. Compounds 6 and 7 have been identified as highly active with GI50 values ranging from 0.03 µM to 5.9 µM (compound 6) and 0.18-1.53 µM (compound 7). Thus, these two compounds were further assessed in detail in order to identify a possible antiproliferative mechanism of action. DAPI (4',6-diamidino-2-phenylindole) staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that both compounds induced upregulation of proapoptotic Bak and Bad genes while downregulating Bcl-XL and Bcl-2 antiapoptotic genes. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, while compound 7 showed higher in silico Bcl-XL inhibition potential as compared to the native inhibitor ATB-737, suggesting that compounds may induce apoptotic cell death through targeted antiapoptotic protein inhibition, as well.

Novel Synthesized N-Ethyl-Piperazinyl-Amides of C2-Substituted Oleanonic and Ursonic Acids Exhibit Cytotoxic Effects through Apoptotic Cell Death Regulation.

A series of novel hybrid chalcone N-ethyl-piperazinyl amide derivatives of oleanonic and ursonic acids were synthesized, and their cytotoxic potential was evaluated in vitro against the NCI-60 cancer cell line panel. Compounds 4 and 6 exhibited the highest overall anticancer activity, with GI50 values in some cases reaching nanomolar values. Thus, the two compounds were further assessed in detail in order to identify a possible apoptosis- and antiangiogenic-based mechanism of action induced by the assessed compounds. DAPI staining revealed that both compounds induced nuclei condensation and overall cell morphological changes consistent with apoptotic cell death. rtPCR analysis showed that up-regulation of pro-apoptotic Bak gene combined with the down-regulation of the pro-survival Bcl-XL and Bcl-2 genes caused altered ratios between the pro-apoptotic and anti-apoptotic proteins' levels, leading to overall induced apoptosis. Molecular docking analysis revealed that both compounds exhibited high scores for Bcl-XL inhibition, suggesting that compounds may induce apoptotic cell death through targeted anti-apoptotic protein inhibition, as well. Ex vivo determinations showed that both compounds did not significantly alter the angiogenesis process on the tested cell lines.

The rcdk and cluster R packages applied to drug candidate selection.

The aim of this article is to show how thevpower of statistics and cheminformatics can be combined, in R, using two packages: rcdk and cluster.We describe the role of clustering methods for identifying similar structures in a group of 23 molecules according to their fingerprints. The most commonly used method is to group the molecules using a "score" obtained by measuring the average distance between them. This score reflects the similarity/non-similarity between compounds and helps us identify active or potentially toxic substances through predictive studies.Clustering is the process by which the common characteristics of a particular class of compounds are identified. For clustering applications, we are generally measure the molecular fingerprint similarity with the Tanimoto coefficient. Based on the molecular fingerprints, we calculated the molecular distances between the methotrexate molecule and the other 23 molecules in the group, and organized them into a matrix. According to the molecular distances and Ward 's method, the molecules were grouped into 3 clusters. We can presume structural similarity between the compounds and their locations in the cluster map. Because only 5 molecules were included in the methotrexate cluster, we considered that they might have similar properties and might be further tested as potential drug candidates.

Adiponectin, leptin and high sensitivity C-reactive protein values in obese children - important markers for metabolic syndrome?

Background Obesity is a chronic inflammatory disorder in which leptin, adiponectin and C-reactive protein (CRP) play an important role. This study aimed to investigate the relationship between markers of adiposity such as leptin, adiponectin and high sensitivity C-reactive protein (hs-CRP) in obese children, and to determine whether these adipokines are significant markers in defining metabolic syndrome (MetS) in pediatric population. Methods A cross-sectional study was conducted over a period of 1 year, between July 2013 and June 2014, on 122 cases of obesity in children diagnosed at the Louis Turcanu Emergency Hospital for Children Timisoara, in the departments of Diabetes and Nutritional Diseases, Endocrinology and Cardiology. The patients were divided into two groups, according to the presence of MetS. Results MetS was present in 27% of obese children. The groups were homogenous with respect to age, sex and body mass index (BMI). Adiponectin, leptin and hs-CRP were significantly modified in the group with MetS (p=0.04, p=0.04, p=0.01, respectively). Conclusions hs-CRP, leptin and adiponectin can be used as predictors of cardiovascular risk in pediatric population.