Primary colorectal small cell carcinoma: A clinicopathological and immunohistochemical study of 10 cases

Colorectal small cell carcinoma (SmCC) is a rare tumor with an aggressive course. The aim of this study is to summarize our experience with this tumor and to highlight its immunohistochemical profile. Ten cases of colorectal SmCC were identified in our files and a panel of immunostains was performed. Follow up was available for the average of 3 years, during which 7 patients died and 3 were alive with disease. All cases were positive for LMWK, CK 19 and pancytokeratin but were negative for TTF-1 and CA 125. EGFR was positive in 7 cases. TTF-1 negative staining may be valuable in differentiating it from its pulmonary counterpart. CDX2, mCEA, CD56, synaptophysin, NSE and chromogranin can help differentiate it from non-endocrine poorly differentiated adenocarcinoma. The expression of EGFR in a subset of patients has not been reported earlier and has to be evaluated in larger series to assess its role in the planning of targeted biologic therapy

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

PLGA Nanoparticles as Subconjunctival Injection for Management of Glaucoma

Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), could be a promising system for targeting ocular drug delivery. The objective of this work was to investigate the possibility of encapsulating brinzolamide in PLGA nanoparticles in order to be applied as a subconjunctival injection that could represent a starting point for developing new therapeutic strategies against increase in ocular pressure. The brinzolamide-loaded PLGA nanoparticles were fabricated using emulsion-diffusion-evaporation method with varying concentrations of Tween 80 or poloxamer 188 (Plx) in aqueous and organic phases. The nanoparticles were characterized in terms of particle size and size distribution, entrapment efficiency and in-vitro drug release pattern as well as DSC and X-ray analysis. Nanoparticles prepared using Tween 80 in the aqueous phase showed higher encapsulation efficiency and smaller particle size-values compared to those prepared using Plx. Furthermore, the addition of Plx 188 or Brij 97 to the organic phase in the formulation containing Tween 80 in the aqueous phase led to an increase in the particle diameter-values of the obtained nanoparticles. The nanoparticles had the capacity to release the brinzolamide in a biphasic release profile. The nanoparticles were spherical in shape and the drug was entraped in the nanoparticles in an amorphous form. Selected nanoparticles, injected subconjunctivally in normotensive Albino rabbits, were able to reduce the IOP for up to 10 days. Nanoparticles loaded with brinzolamide with lower particle size were able to reduce the IOP for longer period compared to those with higher particle size. Histopathological studies for the anterior cross sections of the rabbits’ eyes revealed that the tested nanoparticles were compatible with the ocular tissue. The overall results support that PLGA nanoparticles, applied as subconjunctival injection, can be considered as a promising carrier for ocular brinzolamide delivery with targeting delivery of the drug to the eye tissues

Formulation of risperidone in floating microparticles to alleviate its extrapyramidal side effects

Risperidone is effective in the treatment of positive as well as negative symptoms of schizophrenia. But, there is a strong correlation between plasma levels of risperidone and its adverse effects. Objective: This study aimed to develop risperidone in floating microparticles to overcome its extrapyramidal side effects. Methods: Floating microparticles were prepared using Eudragit S100, hydroxypropylmethyl cellulose (HPMC), Gelucires (Gelucire 43/01 pellets, Gelucire 44/14 and Gelucire 50/13), Geleol mono and diglyceride NF, glyceryl monostearate, Compritol 888 ATO, methyl-betacyclodextrin (MβCD) and hydroxypropyl-betacyclodextrin (HPβCD), by emulsion solvent diffusion technique. In-vitro experiments were conducted to optimize formulation parameters regarding floating ability, yield value, drug loading and in-vitro release properties. The best formula was investigated for its in-vivo floating ability and for its pharmacokinetics as well as its extrapyramidal side effects in human volunteers. Results: The optimized floating microparticles showed promising in-vitro experiment performance with floating ability up to 95.93% for 12 h. Also, this floating ability was confirmed using in-vivo x-ray studies. Pharmacokinetics studies revealed significant (p < 0.05) lower Cmax, longer Tmax and higher AUC values for the optimized formula compared to the marketed oral product (Risperidal® 4 mg tablets) indicating gradually release properties which lead to high treatment efficacy of the drug with obvious reduced extrapyramidal side effects. Conclusion: These results proved that formulating risperidone as floating microparticles is a suitable dosage form for overcoming risperidone side effects

CDX2 as a marker for intestinal differentiation: Its utility and limitations

CDX2 is a nuclear homeobox transcription factor that belongs to the caudal-related family of CDX homeobox genes. The gene encoding CDX2 is a nonclustered hexapeptide located on chromosome 13q12-13. Homeobox genes play an essential role in the control of normal embryonic development. CDX2 is crucial for axial patterning of the alimentary tract during embryonic development and is involved in the processes of intestinal cell proliferation, differentiation, adhesion, and apoptosis. It is considered specific for enterocytes and has been used for the diagnosis of primary and metastatic colorectal adenocarcinoma. CDX2 expression has been reported to be organ specific and is normally expressed throughout embryonic and postnatal life within the nuclei of epithelial cells of the alimentary tract from the proximal duodenum to the distal rectum. In this review, the authors elaborate on the diagnostic utility of CDX2 in gastrointestinal tumors and other neoplasms with intestinal differentiation. Limitations with its use as the sole predictor of a gastrointestinal origin of metastatic carcinomas are also discussed

Improving tadalafil dissolution via surfactant-enriched tablets approach: Statistical optimization, characterization, and pharmacokinetic assessment

Tadalafil suffers from poor aqueous solubility that could lead to fluctuating blood levels and unreproducible effect. Thus, this work aimed at improving tadalafil dissolution utilizing the approach of surfactant-enriched tablets. The feasibility of minimizing various surfactants quantities was investigated by establishing the ratio of the surfactant to drug that is required for drug solubilization in micellar solutions. Based on the computed ratios, Tween was precluded from formulation studies due to its poor solubilizing capacity towards the drug. 23 factorial design was employed to assess the impact of formulation attributes on tablets' characteristics. Based on the statistical analysis and the desirability function approach, tablet formulation F6 prepared using CTAB, Avicel PH 102, and 5% Ac-Di-Sol was selected as the optimum formulation. The selected formulation showed adequate stability after storage at 40 C and 75% R.H. for twelve weeks. Pharmacokinetic study revealed that the selected surfactantenriched tablet formulation F6 showed enhanced bioavailability compared to the market product Cialis®

Reservoir characterization utilizing the well logging analysis of Abu Madi Formation, Nile Delta, Egypt

The petrophysical evaluation of the Late Miocene Abu Madi Formation were accomplished based on the open hole logs of eighteen wells in Abu Madi–El Qar’a gas fields, onshore Nile Delta, Egypt. The lithological contents of this rock unit were analyzed using the cross plots of petrophysical parameters including shale volume, porosity and hydrocarbon saturation. The neutron /density cross-plots, M-N and RHOMAA–DTMAA and litho-saturation cross plots of the studied wells show that the main lithology of the lower part of Abu Madi Formation is calcareous sandstones with shale intercalations in most of the studied wells while its lithology is mainly shale with sand intercalations in wells AM-13, AM-21 and AM-7. The lithology of the upper part of Abu Madi Formation in most wells is composed mainly of shale while its lithology in AM-13, AM-21 and AM-7 wells is composed of sandstone with shale intercalations. The thorium-potassium cross plots indicate that, Abu Madi Formation was deposited mostly in fluvial to shallow marine environments according to the presence of mica and illite in the southern area and montmorillonite at the northern area as dominant clay minerals. Contour maps of several petrophysical parameters such as effective thickness, average shale volume, average porosity and hydrocarbon saturation showed that both lower and upper parts of Abu Madi Formation in the study area have promising reservoirs characteristics; in which the prospective area for gas accumulation located toward the central part