Carnosic acid ameliorates depressive‐like symptoms along with the modulation of FGF9 in the hippocampus of middle carotid artery occlusion‐induced Sprague Dawley rats

The increased survival rate of stroke patients has led to the higher incidences of post‐stroke depression. Carnosic acid has the ability to cross blood brain barrier with good neuro‐modulatory actions. Recently, inclined level of fibroblast growth factor 9 (FGF9) in the postmortem brain of the depressed patients was noted. Therefore, in the present study, the effect of carnosic acid on post‐stroke depression‐like behavior, and the expression of FGF9 were evaluated. After 3 weeks of middle carotid artery occlusion in Sprague Dawley rats, carnosic acid (20 and 40 mg/kg) was administered for 2 weeks. Sucrose preference test, forced swimming test, and open field test were performed and hippocampi were analyzed for FGF9 and FGFR‐3. In comparison to post‐stroke depressed rats, carnosic acid increased the sucrose preference, and reduced the immobility time of the rats by ~2×. The speed and distance‐covered were also increased. At 40 mg/kg, FGF9 was reduced by ~3× while FGFR‐3/Actin was increased by ~1.5×. Altogether results suggest anti‐depressant‐like activity of carnosic acid in post‐stroke depressed rats with decreased expression of hippocampal FGF9.     

Robot-assisted Laparoscopic Adrenalectomy: Step-by-Step Technique and Comparative Outcomes

Background

Recent evidence supports the use of robotic surgery for the minimally invasive surgical management of adrenal masses.

Objective

To describe a contemporary step-by-step technique of robotic adrenalectomy (RA), to provide tips and tricks to help ensure a safe and effective implementation of the procedure, and to compare its outcomes with those of laparoscopic adrenalectomy (LA).

Design, setting, and participants

We retrospectively reviewed the medical charts of consecutive patients who underwent RA performed by a single surgeon between April 2010 and October 2013. LA cases performed by the same surgeon between January 2004 and May 2010 were considered the control group.

Surgical procedure

The main steps of our current surgical technique for RA are described in this video tutorial: patient positioning, port placement, and robot docking; exposure of the adrenal gland; identification and control of the adrenal vein; circumferential dissection of the adrenal gland; and specimen retrieval and closure.

Outcome measurements and statistical analysis

Demographic parameters and main surgical outcomes were assessed.

Results and limitations

A total of 76 cases (RA: 30; LA: 46) were included in the analysis. Median tumor size on computed tomography (CT) was significantly larger in the LA group (3 cm [interquartile range (IQR): 3] vs 4 cm [IQR: 3]; p = 0.002). A significantly lower median estimated blood loss was recorded for the robotic group (50 ml [IQR: 50] vs 100 ml [IQR: 288]; p = 0.02). The RA group presented five minor complications (16.7%) and one major (Clavien 3b) complication (3.3%), whereas four minor complications (8.7%) and one major (Clavien 3b) complication (2.3%) were observed in the LA group. No significant difference was noted between groups in terms of malignant histology (p = 0.66) and positive margin rate (p = 0.60). Distribution of pheochromocytomas in the LA group was significantly higher than in the RA group (43.5% vs 16.7%; p = 0.02).

Conclusions

The standardization of each surgical step optimizes the RA procedure. The robotic approach can be applied for a wide range of adrenal indications, recapitulating the safety and effectiveness of open surgery and potentially improving the outcomes of standard laparoscopy.

Patient summary

In this report we detail our surgical technique for robotic removal of adrenal masses. This procedure has been standardized and can be offered to patients, with excellent outcomes.     

Perioperative blood transfusion and resection of colorectal cancer liver metastases: outcomes in routine clinical practice

BackgroundPrior work has shown associations between blood transfusion (BT) and inferior outcomes during resection for colorectal cancer liver metastases (CRLM). Herein, we describe short and long-term outcomes relating to perioperative BT in routine clinical practice.MethodsAll CRLM resections in Ontario, Canada from 2002 to 2009 were identified using the Ontario Cancer Registry. Log-binomial regression and Cox regression were used to explore factors associated with receipt of BT and the association of BT with 5-year cancer specific (CSS) and overall survival (OS), respectively.ResultsThe study included 1310 patients; 31% (403/1310) had perioperative BT. Transfused patients had longer median length of stay (9 vs. 7 days, p < 0.001), higher 90-day mortality (9% vs. 1%, p < 0.001), greater 90-day readmission (28% vs. 16%, p < 0.001), and inferior 5-year CSS (41% vs. 48%, p = <0.001) and OS (38% vs. 47%, p < 0.001). Transfusion was independently associated with inferior CSS (HR = 1.35, 95% CI: 1.11–1.63) and OS (HR = 1.30, 95% CI: 1.10–1.53), however, excluding 90-day postoperative deaths showed these associations were no longer significant.ConclusionPerioperative BT is common in patients undergoing resection of CRLM. While transfusion is associated with greater morbidity, mortality, and inferior survival, after excluding early postoperative deaths, BT does not appear to be independently associated with CSS or OS.     

Nitric oxide functionalized molybdenum(0) pyrazolone Schiff base complexes: thermal and biochemical study

This work describes the synthesis and characterization of three molybdenum dinitrosyl Schiff base complexes of the general formula [Mo(NO)₂(L)(OH)], where L is N-(dehydroacetic acid)-4-aminoantipyrene (dha-aapH), N-(4-acetylidene-3-methyl-1-phenyl-2-pyrazolin-5-one)-4-aminoantipyrine (amphp-aapH) or N-(3-methyl-1-phenyl-4-propionylidene-2-pyrazolin-5-one)-4-aminoantipyrine (mphpp-aapH). The complexes were formulated on the basis of spectroscopic analyses, elemental composition, magnetic susceptibility measurements, molar conductance behaviour and determination of the respective decomposition temperatures. A comparative experimental-theoretical approach was followed to elucidate the structure of the complexes. Fourier transform infra-red (FT-IR) spectroscopy, thermo-gravimetry (TG) and electronic spectral insights were mainly focused on the confirmation of the formation of the complexes. The computational density functional theory (DFT) calculations evaluated in the study involve the molecular specification for the use of LANL2DZ/RB3LYP formalism for metal atoms and 6-311G/RB3LYP for the remaining non-metal atoms. The study reveals a suitable cis-octahedral geometry for the complexes. The TG curve of one of the representative complexes was evaluated to find the respective thermodynamic and kinetic parameters using various physical methods. The Freeman & Carroll (FC) differential method, the Horowitz and Metzger (HM) approximation method, the Coats–Redfern method and the Broido method were employed to present a comparative thermal analysis of the complex. The Broido method proved the best fit to the results for the compound under question. In addition to structural and thermal analyses, the study also deals with the in vitro antimicrobial and anticancer sensitivity of the complexes. The results revealed potent biological properties of the representative complex containing dha-aapH. Cell toxicity tests against COLO-205 human cancer cell line using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay showed an IC₅₀ value of 53.13 μgm mL⁻¹ for the Schiff base and 10.51 μgm L⁻¹ for the respective complex. Similarly the same complex proved to be an effective antimicrobial agent against Aspergillus, Pseudomonas, E. coli and Streptococcus. The results indicated a more pronounced activity against Pseudomonas and Streptococcus than the other two microbial species.

This work describes the thermal and biological implications of three pyrazolone-dinitrosylmolybdenum(0) complexes.     

Prevalence and impact of comorbidities on disease prognosis among patients with COVID-19 in Bangladesh: A nationwide study amid the second wave

BackgroundSocio-demographics and comorbidities are involved in determining the severity and fatality in patients with COVID-19 suggested by studies in various countries, but study in Bangladesh is insufficient.AimsWe designed the study to evaluate the association of sociodemographic and comorbidities with the prognosis of adverse health outcomes in patients with COVID-19 in Bangladesh.MethodsA multivariate retrospective cohort study was conducted on data from 966 RT-PCR positive patients from eight divisions during December 13, 2020, to February 13, 2021. Variables included sociodemographic, comorbidities, symptoms, Charlson comorbidity index (CCI) and access to health facilities. Major outcome was fatality. Secondary outcomes included hospitalization, duration of hospital stay, requirement of mechanical ventilation and severity.ResultsMale (65.8%, 636 of 966) was predominant and mean age was 39.8 ± 12.6 years. Fever (79%), dry cough (55%), and loss of test/smell (51%) were frequent and 74% patients had >3 symptoms. Fatality was recorded in 10.5% patients. Comorbidities were found in 44% patients. Hypertension (21.5%) diabetes (14.6%), and cardiovascular diseases (11.3%) were most prevalent. Age >60 years (OR: 4.83, 95% CI: 2.45–6.49), and CCI >3 (OR: 5.48, 95% CI: 3.95–7.24) were predictors of hospitalizations. CCI >4 (aOR: 3.41, 95% CI: 2.57–6.09) was predictor of severity. Age >60 years (aOR: 3.77, 95% CI: 1.07–6.34), >3 symptoms (aOR: 2.14, 95% CI: 0.97–4.91) and CCI >3 vs. CCI <3 (aOR: 5.23, 95% CI: 3.77–8.09) were independently associated with fatality.ConclusionsIncreased age, >3 symptoms, increasing comorbidities, higher CCI were associated with increased hospitalization, severity and fatality in patients with COVID-19.     

Re-visiting pH-adjusted potassium to avoid hypokalemic crisis during management of diabetic ketoacidosis: A conceptual framework

Background and aimsDiabetic ketoacidosis (DKA) treatment guidelines recommend to initiate potassium-replacement when serum potassium (S_K) drops within normal range, and to withhold insulin if S_K is below normal. Despite strict recommendations, hypokalemia is frequently observed in DKA.MethodsScientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia.ResultsAcidosis affects S_K and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing S_K level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated.ConclusionIn light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge.