An OxPLORE Initiative Evaluating Children’s Surgery Resources Worldwide: A Cross-sectional Implementation of the OReCS Document

World Journal of Surgery - The Global Initiative for Children's Surgery (GICS) group produced the Optimal Resources for Children’s Surgery (OReCS) document in 2019, listing standards of...     

Anesthesia and surgery in pediatric patients with low hemoglobin values

A low preoperative hemoglobin (Hb) concentration creates a dilemma for the anesthetist to proceed or not. The authors prospectively studied the perioperative morbidity of 200 healthy infants and children (age range 3mon-5 years) with preoperative Hb values >-7 g/dl, undergoing cleft lip and palate surgery under general anesthesia. The patients were later categorized according to preoperative Hb level group A : Hb 7–10 g/dl and group B : Hb > 10 g/dl and the results were compared. One or more episodes of hypoxemia (SpO₂ < 91%) were recorded in 8 patients in group A and 6 in group B during airway management. All patients had stable cardiovascular parameters except for transient bradycardia during desaturations. Recovery was similar and rapid. There were no differences in perioperative morbidity between the two groups. However, the safety of general anesthesia in infants and children with difficult airways is questionable when the oxygen reserve is reduced in anemia.     

Selective inhibition of ICAM-1 and E-selectin expression in human endothelial cells. 2. Aryl modifications of 4-(aryloxy)thieno[2,3-c]pyridines with fine-tuning at C-2 carbamides

The elevated expression of cell adhesion molecules (CAMs) on the lumenal surface of vascular endothelial cells is a critical early event in the complex inflammatory process. The adhesive interactions of these CAMs that include E-selectin, ICAM-1, and VCAM-1 with their counter-receptors on leukocytes, such as integrins of the alpha(L)beta(2) family, result in migration of the leukocytes to the site of inflammation and cause tissue injury. Pharmaceutical agents that could suppress the induced expression of one or more of these cell adhesion molecules would provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A-205804 (1), a potent and selective inhibitor of the induced expression of E-selectin and ICAM-1 over VCAM-1, was further modified with emphasis at the C-4 and C-2 positions to identify a more potent drug candidate with a good pharmacokinetic profile and physical properties. Replacement of the C-4 sulfur linkage in 1 with an oxygen atom eliminated one of the two major metabolites for this lead molecule. The para-position of the 4-phenoxy group of the thieno[2,3-c]pyridine lead is found to be very critical for a higher in vitro potency and selectivity of E-selectin and ICAM-1 over VCAM-1 expression. This position is presumably close to the solvent-accessible region of the target protein-inhibitor complex. An attempt to install a water-solubilizing group at the para-position of the phenoxy group to increase the aqueous solubility of this lead series through various linkages failed to provide an ideal inhibitor. Only small substituents such as fluorine are tolerated at the meta- and ortho-positions of the 4-phenoxy to retain a good in vitro potency. Bromo, trifluoromethyl, pyrazol-1-yl, and imidazol-1-yl are among the better substituents at the para-position. With fine-tuning at the C-2 position we discovered a series of very potent (IC(50) < 5 nM for ICAM-1) and selective (>200-fold vs VCAM-1) inhibitors with a good pharmacokinetic profile. Demonstrated efficacy in a rat rheumatoid arthritis model and in a mice asthma model with selected compounds is also reported.     

Antimicrobial susceptibility and serotypes of Neisseria meningitidis and Streptococcus pneumoniae in Sri Lanka: Experience from the National Reference Laboratory

Objective: To determine the antimicrobial susceptibility and serotypes of Neisseria (N.) meningitidis and Streptococcus (S.) pneumoniae in Sri Lankan patients. ...     

Optimizing the approach to patients with potentially resectable liver metastases from colorectal cancer

Liver metastases are a common event in colorectal carcinoma. Significant advances have been made in managing these patients in the last decade, including improvements in staging and surgical techniques, an increasing armamentarium of chemotherapeutics and multiple local ablative techniques. While combination chemotherapy significantly improves median patient survival, surgical resection provides the only prospect of cure and is the focus of this review. Interpretation of published work in this field is challenging, particularly as there is no consensus to what is resectable disease. Of particular interest recently has been the use of neoadjuvant treatment for downstaging and downsizing disease in patients with initially unresectable liver metastases, in the hope of response leading to potentially curative surgery. This review summarizes the recent developments and consensus guidelines in the areas of staging, chemotherapy, local ablative techniques, radiation therapy and surgery, emphasizing the multidisciplinary approach to this disease and ongoing controversies in this field and examines the changing paradigms in the management of colorectal hepatic metastases.     

Reversal of type 1 diabetes in mice by brown adipose tissue transplant

Current therapies for type 1 diabetes (T1D) involve insulin replacement or transplantation of insulin-secreting tissue, both of which suffer from numerous limitations and complications. Here, we show that subcutaneous transplants of embryonic brown adipose tissue (BAT) can correct T1D in streptozotocin-treated mice (both immune competent and immune deficient) with severely impaired glucose tolerance and significant loss of adipose tissue. BAT transplants result in euglycemia, normalized glucose tolerance, reduced tissue inflammation, and reversal of clinical diabetes markers such as polyuria, polydipsia, and polyphagia. These effects are independent of insulin but correlate with recovery of the animals' white adipose tissue. BAT transplants lead to significant increases in adiponectin and leptin, but with levels that are static and not responsive to glucose. Pharmacological blockade of the insulin receptor in BAT transplant mice leads to impaired glucose tolerance, similar to what is seen in nondiabetic animals, indicating that insulin receptor activity plays a role in the reversal of diabetes. One possible candidate for activating the insulin receptor is IGF-1, whose levels are also significantly elevated in BAT transplant mice. Thus, we propose that the combined action of multiple adipokines establishes a new equilibrium in the animal that allows for chronic glycemic control without insulin.     

A retrospective analysis of cannabis use in a cohort of mentally ill patients in Sri Lanka and its implications on policy development

Background  

Several epidemiological studies have shown that cannabis; the most widely used illegal drug in the world, is associated with schizophrenia spectrum disorders (SSD).