Prospective comparison of single encounter versus distributed laparoscopic training in novice learners: A controlled trial.

BACKGROUND: The traditional model of teaching surgical skills on "real" patients using graded responsibility is being seriously questioned, and there is a paradigm shift toward exploiting simulators. There is a lack of clarity on the impact of using simulation as a teaching strategy in novice learners. The purpose of our study was to determine if the number and duration of training sessions influence the acquisition and retention of laparoscopic skills in naïve learners. There are some data to suggest that distributed training programs might have better outcomes, but the results are inconclusive. We designed a controlled trial at Aga Khan University, Karachi, with the hypothesis that students trained using the distributed method may have enhanced learning outcomes. MATERIALS AND METHODS: 100 medical students were assigned in a 1:1 ratio to one of two groups. Group A underwent a single orientation and supervised practice session of 3 h duration. Group B underwent distributed teaching with three learning sessions of 1 h each spread over 3 consecutive weeks. Participant scores were analyzed before and after the intervention and at 3- and 6-month intervals using repeat measures of ANOVA. RESULTS: Pretest and immediate posttest scores were comparable between the two groups. The 3-month interval test showed significantly higher scores in Group B (difference = -2.90, P < 0.001). The 6-month interval test showed no differences in scores between the two groups (P = 0.178). CONCLUSIONS: Distributed teaching resulted in significantly enhanced scores at 3-month assessment. However, similar scores at 6 months suggest the need for repeated intervention.

Photochemical Internalization of Gemcitabine Is Safe and Effective in Locally Advanced Inoperable Cholangiocarcinoma.

BACKGROUND: Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA). METHODS: The in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy. RESULTS: Preclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose. CONCLUSION: Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA.

Gastro-intestinal stromal tumor (GIST): Experience from a tertiary care center in a low resource country.

Objectives: The aim of this retrospective study was to review the overall survival (OS) and disease-free survival (DFS) of GISTs treated surgically at our center over the past decade. Material and Methods: We undertook a 12-year retrospective review of our experience in treating this condition with a focus on long-term outcomes of treated patients in a resource-constrained environment. Incomplete follow-up information continues to be a major problem with studies conducted in low resource settings, and in order to overcome this, we undertook telephonic contact with patients or their relatives to get the necessary information about their clinical status. Results: Fifty-seven patients with GIST underwent surgical resection during this period of time. The stomach was the most common organ involved in the disease, with 74% of the patients. Surgical resection was the main treatment approach, with R0 resection possible in 88%. Nine percent of the patients were given Imatinib as neoadjuvant treatment and 61% were offered the same, as adjuvant therapy. The duration of adjuvant treatment changed from one year to three years over the study period. Pathological risk assessment categorized the patients as Stage I, 33%; Stage II, 19%; Stage III, 39%; and Stage IV, 9%. Of the 40 patients who were at least three years from surgery, 35 were traceable giving an 87.5%, overall three-year survival. Thirty-one patients (77.5%) were confirmed to be disease-free at three years. Conclusion: This is the first report of mid-long-term outcomes of the multimodality treatment of GIST from Pakistan. Upfront surgery continues to be the main modality. OS & DFS in resource-poor environments can be similar to those seen in a better-structured healthcare setting.

A clinical decision rule predicting outcomes of emergency department patients with altered mental status.

STUDY OBJECTIVE: Approximately 5% of emergency department patients present with altered mental status (AMS). AMS is diagnostically challenging because of the wide range of causes and is associated with high mortality. We sought to develop a clinical decision rule predicting admission risk among emergency department (ED) patients with AMS. METHODS: Using retrospective chart review of ED encounters for AMS over a 2-month period, we recorded causes of AMS and numerous clinical variables. Encounters were split into those admitted to the hospital ("cases") and those discharged from the ED ("controls"). Using the first month's data, variables correlated with hospital admission were identified and narrowed using univariate and multivariate statistics, including recursive partitioning. These variables were then organized into a clinical decision rule and validated on the second month's data. The decision rule results were also compared to 1-year mortality. RESULTS: We identified 351 encounters for AMS over a 2-month period. Significant contributors to AMS included intoxication and chronic disorder decompensation. ED data predicting hospital admission included vital sign abnormalities, select lab studies, and psychiatric/intoxicant history. The decision rule sorted patients into low, moderate, or high risk of admission (11.1%, 44.3%, and 89.1% admitted, respectively) and was predictive of 1-year mortality (low-risk group 1.8%, high-risk group 34.3%). CONCLUSIONS: We catalogued common causes for AMS among patients presenting to the ED, and our data-driven decision tool triaged these patients for risk of admission with good predictive accuracy. These methods for creating clinical decision rules might be further studied and improved to optimize ED patient care.

Efficacy and Selectivity of FGF2-Saporin Cytosolically Delivered by PCI in Cells Overexpressing FGFR1.

Fibroblast growth factor receptors (FGFRs) have become an attractive target in cancer research and therapy due to their implication in several cancers. Limitations of current treatment options require a need for additional, more specific and potent strategies to overcome cancers driven by FGFRs. Photochemical internalization (PCI) is a light-controlled method for cytosolic delivery of drugs that are entrapped in endosomes and lysosomes. We here evaluated the efficacy and selectivity of PCI of FGF2-saporin (FGF-SAP) in cells overexpressing FGFR1. FGF-SAP is a conjugate of FGF2 and the highly cytotoxic ribosome-inactivating protein (RIP) saporin, which is used as payload to eliminate cancer cells. Evaluation of the targeting effect of PCI of FGF-SAP was done by comparing the cytotoxic response in osteosarcoma cells with very low levels of FGFR1 (U2OS) to cells overexpressing FGFR1 (U2OS-R1). We demonstrate that PCI greatly enhances cytotoxicity of the drug showing efficient cell killing at pM concentrations of the drug in U2OS-R1 cells. However, U2OS cells were also sensitive to the toxin after PCI. Binding experiments using confocal microscopy and Western blotting techniques indicate that FGF-SAP is taken up by cells through heparan sulfate proteoglycans (HSPGs) in U2OS cells. We further show that the cytotoxicity of FGF-SAP in U2OS cells was reduced when cells were co-treated with heparin to compete out binding to HSPG, demonstrating that the cytotoxic effect was due to internalization by HSPGs. We conclude that to prevent off-target effects of FGF-based toxins, it will be necessary to circumvent binding to HSPGs, for example by mutating the binding site of FGF2 to HSPGs.

Association Between Perioperative Hypothermia and Surgical Site Infection After Elective Abdominal Surgery: A Prospective Cohort Study.

Introduction Surgical site infections (SSIs) account for 14-16% of nosocomial infections and are one of the major causes of increased morbidity, hospital stay, cost of care, and even mortality. Hypothermia as a risk factor for SSI is debated but there is lack of conclusive evidence. The present study explores the association of hypothermia with SSI. Methodology This is a prospective cohort study conducted on adult patients who underwent elective laparotomy. Patients were divided into two cohorts, the Hypothermia Cohort and the Normothermia Cohort, based upon episodes of hypothermia of <360C in the perioperative period. SSI was diagnosed based upon criteria defined by the Center for Disease Control and Prevention (CDC). Postoperative follow-up to detect SSI was done until 30 days after the operation. Results A total of 183 patients met the selection criteria and were included in the study. Ninety patients (49%) had perioperative hypothermia and were followed in the Hypothermia Cohort, while 93 patients (51%) who remained normothermic in the perioperative period were followed in the Normothermia Cohort. Mean age of the patients was 49.77 +/- 14.82 years. Almost two-thirds of the participants were females (63.9%). Patients who developed hypothermia were significantly older and had lower BMI. Also the proportion of female patients was significantly higher in the Normothermic Cohort. Rate of SSI was similar in both groups (10% versus 10.8%) with p-value of 0.867. Multivariable regression analysis also failed to show any significant association between hypothermia and SSI. Conclusion Our study failed to show any statistically significant association between hypothermia and surgical site infection.

Rare Hereditary Burden associated with a Hypercalcemic Small-Cell Carcinoma of Cervix in a Young Female Patient.

BACKGROUND: Oncological diseases have, in most cases, a multifactorial etiology, composed of a combination of external and internal environmental factors. Hereditary tumorous syndromes are mostly autosomal dominant diseases with incomplete but very high penetrance. OBSERVATION: The patient, an 18-year-old virgin female, consulted a gynecologist in June 2018 because of metrorrhagia. Magnetic resonance imaging revealed a cervical tumor with the dimensions 80 × 90 × 80 mm. Histological analysis confirmed the presence of a very rare hypercalcemic type of small-cell carcinoma of the cervix. Further investigation of the germinal exom of the patient showed pathological variations in genes PALB2 and BRCA2, presented with recommendation of detailed examination by medical genetics. CONCLUSION: Clinical experience with this type of tumor is very limited, but it still comes with some useful outcome. Small cell carcinomas of the gynecologic tract are very rare, aggressive diseases, with very poor prognosis, affecting mainly young women. Their origin is most often the ovaries, based on most clinical data, but these tumor also localize to the endometrium, cervix, vagina and vulva. It is an extremely rare type of cancer, for which clinical data is scant due to the extremely low number of reported cases. In this patient, the carcinoma had an unusual genetical mutation burden, which she inherited from her parents. In the light of these findings, we recommend that patients suspected of having a small-cell of the gynecologic tract provide a detailed family history, and that genetic testing be considered in similar cases. This work was supported by MH CR grant 16-33209A and research program of Charles University Progress Q40/06. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 10. 6. 2019 Accepted: 9. 9. 2019.

The impact of completion thyroidectomy.

INTRODUCTION: The oncological benefit of completion thyroidectomy (CT) following thyroid lobectomy (TL) is presumed to be similar to that of upfront total thyroidectomy(TT), from a patient's perspective the risk and inconvenience of further surgery adds significantly to the impact of the overall treatment. The aim of this study is to assess the impact of CT in terms of the duration of admission and associated complications. METHODS: A study of consecutive patients with DTC identified from prospective MDT records of South-East Scotland from 2009 to 2015. Surgical data was extracted from electronic medical record. RESULTS: Of 361 patients diagnosed with DTC, 161 (45%) had CT. The median postoperative stay was 1 day (range 1-5days). In total 22 patients (14%)suffered complications. Four patients (3%) developed postoperative haematoma. Two (1%) had an identified permanent nerve palsy on the completion side. 13 patients (8%) remained on calcium supplementation for more than 6 months postoperatively and three patients (2%) developed wound complications. CONCLUSIONS: Our study confirms that CT is regularly performed (45%). Recent changes in international guidelines recognize increasing number of patients as eligible for a conservative approach but recommend CT based on whether upfront TT would have been recommended if the TL pathology were known from the outset. Such an approach fails to consider the additional risk and inconvenience of CT on the overall patient experience. Due to a relatively high rate of complications, only those patients who are most likely to benefit from further surgery to facilitate adjuvant radioactive iodine should be offered additional surgery.

Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination.

Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs) is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI) provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs) in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.

Role of Percutaneous Cholecystostomy Tube Placement in the Management of Acute Calculus Cholecystitis in High Risk Patients.

OBJECTIVE: To evaluate the utility of percutaneous cholecystostomy tube in patients with acute calculus cholecystitis, who are considered unfit for immediate surgery. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, Pakistan, from January 2010 to December 2014. METHODOLOGY: All adult patients who underwent percutaneous cholecystostomy tube placement for acute calculous cholecystitis were included. These patients were divided into two groups for further analysis. Group-I consisted those who had interval cholecystectomy after tube placement and Group-II were those who had no further treatment. Recurrence of symptoms, infections and operation related complications were noted. RESULTS: Sixty-five patients met the inclusion criteria. Mean age was 58.5 years. Forty-four patients (67.7%) were males. Forty-three patients underwent interval cholecystectomy (Group-I) and 22 did not (Group-II). Mean operative time was 134.9 +57.8 minutes. Five (11.6%) patients were converted to open cholecystectomy, two (4.6%) developed CBD injury, and seven (16.2%) developed surgical site infection. In Group-II, three patients (13.6%) developed recurrence of symptoms and 19 (86.4%) remained symptom-free. Catheter related problems occurred in four (18%) patients. Mean follow-up was 19 +8 months. CONCLUSION: Percutaneous cholecystostomy is a good alternative for patients unfit to undergo immediate surgery. Recurrence of symptoms after tube removal are in a low range; therefore, it can be considered a definitive management for high risk patients. Laparoscopic cholecystectomy after tube placement becomes technically challenging.

Prevention of chemotherapy toxicity by agents that neutralize or degrade cell-free chromatin.

BACKGROUND: Toxicity associated with chemotherapy is a major therapeutic challenge and is caused by chemotherapy-induced DNA damage and inflammation. We have recently reported that cell-free chromatin (cfCh) fragments released from dying cells can readily enter into healthy cells of the body to integrate into their genomes and induce DNA double-strand breaks, apoptosis and inflammation in them. We hypothesized that much of the toxicity of chemotherapy might be due to release of large quantities of cfCh from dying cells that could trigger an exaggerated DNA damage, apoptotic and inflammatory response in healthy cells over and above that caused by the drugs themselves. METHODS: We tested this hypothesis by administering cfCh neutralizing/degrading agents namely, anti-histone antibody complexed nanoparticles, DNase I and a novel DNA degrading agent-Resveratrol-Cu concurrently with five different chemotherapeutic agents to examine if chemotherapy-induced toxicity could be minimized. RESULTS: We observed (i) significant reduction in chemotherapy-induced surge of cfCh in blood; (ii) significant reduction in chemotherapy-induced surge of inflammatory cytokines CRP, IL-6, IFNγ and TNFα in blood; (iii) abolition of chemotherapy-induced tissue DNA damage (γH2AX), apoptosis (active caspase-3) and inflammation (NFκB and IL-6) in multiple organs and peripheral blood mononuclear cells; (iv) prevention of prolonged neutropenia following a single injection of adriamycin and (v) significant reduction in death following a lethal dose of adriamycin. CONCLUSION: Our results suggest that toxicity of chemotherapy is caused to a large extent by cfCh released from dying cells and can be prevented by concurrent treatment with cfCh neutralizing/degrading agents.

Role of early contrast enhanced CT scan in severity prediction of acute pancreatitis.

Severe pancreatitis occurs in approximately 15-25% of patients with acute pancreatitis. The objective of our study was to compare the CT Severity Index (CTSI) with a clinical score (BISAP score) to predict severity of acute pancreatitis. Forty-eight consecutive patients with acute pancreatitis who underwent contrast enhanced CT scan within 72 hours of presentation were included. Results of our study showed that both CTSI and BISAP score were reliable predictors of mortality (p value = 0.019 and <0.001 respectively) and need for mechanical ventilation (p value = .002 and .006 respectively). Positive predictive value of CTSI to predict recovery without intervention was 91.4% as compared to 78% for that of BISAP score. Receiver Operating Characteristics (ROC) Curves showed CT scan was superior to BISAP Score in predicting need of percutaneous or surgical intervention. Early CT scan may be utilized for prediction of clinical course of patients with acute pancreatitis.

Hookworm infestation as a cause of melena and severe anaemia in farmer.

Hookworm infections remain a major cause of morbidity in the developing world. Prevalence is highest in agricultural areas, where use of waste water for irrigation and poor hygiene increases infection rates among farmers. Infections present with gastrointestinal symptoms and chronic anaemia, and there are usually no signs of overt blood loss. The following report describes a case of melena in a middle-aged farmer, where the diagnosis of hookworm infestation was delayed due to the unusual presentation. The patient underwent multiple blood transfusions before referral to the Aga Khan University Hospital (AKUH), Karachi and was managed conservatively with mebendazole at our hospital after exclusion of other possible causes of gastrointestinal bleeding. This case highlights the importance of considering hookworm infestations as a cause of melena in the older age group, where other critical differentials such as peptic ulcer disease and occult malignancy may result in delay in initiation of treatment and a significant financial burden on the patient.

T-tube placement as a method for treating penetrating oesophageal injuries.

INTRODUCTION: Penetrating oesophageal injuries are extremely rare. Their timely recognition can be difficult and optimal treatment remains controversial. Early recognition of injury is possible with the help of a high index of suspicion and early radiological and endoscopic examinations. Prompt surgical intervention with primary repair of injury, should be the goal. PRESENTATION OF CASES: We describe two cases of penetrating oesophageal trauma where T-Tube placement through the oesophageal defect, was successfully employed. Both cases proved to be challenging due to time lapse after injury and anatomical location. DISCUSSION: Penetrating injuries to the Oesophagus are rare with a reported incidence of 11-17%, most are due to gunshot injuries or stabbings, cervical followed by the thoracic Oesophagus are most at risk. In delayed presentations and sepsis related multi-organ instability, diversion and drainage are considered appropriate. T-tube placement through defects in difficult situations of delayed presentation is well described in setting of iatrogenic perforations. Their use has been described in penetrating injuries but much less frequently. CONCLUSION: T-tube placement though oesophageal defects can prove to be an effective treatment option to repair both iatrogenic and penetrating injuries of the Oesophagus, whether early or delayed.

Natural gum modified emulsion gel as single carrier for the oral delivery of probiotic-drug combination.

Single formulation based delivery of probiotic-drug combination is envisioned as a superior therapeutic delivery modality for the diseases like Crohn's diseases, ulceritive colitis and Recurrent Clostridium difficile-Associated Diarrhoea (RCDAD). Keeping this perspective in mind, here we have developed natural gum [using a combination of aqueous solution of xantham gum (X) and guar gum (G)] modified sunflower oil based emulsion gels for the delivery of probiotics-drugs combination. FT-IR analysis and fluorescence microscopy together confirmed the formation of oil-in-water type emulsion gel by physical gelation in presence of the physical gelator sorbitan monopalmitate (SM). Other studies (XRD, DSC, mechanical properties and disintegration study) revealed that the variation in relative proportion of the two gums has a sporadic but significant effect on the physico-chemical properties of the gel. Post storage viability of commercially used probiotic Lactobacillus plantarum 299v (Lp 299v) at different storage conditions (4°C, -20°C, -196°C) was found higher in the emulsion gels with respect to the control. Moreover, the gels were found suitable for sustained delivery of metronidazole (the lipophilic drug often used with Lp 299v). In conclusion, the natural gum modified emulsion gel may be used as a delivery system for the probiotic-drug combination.

Molecular Docking and Interactions of Pueraria Tuberosa with Vascular Endothelial Growth Factor Receptors.

Pueraria tuberosa is known for its therapeutic potentials in cardiovascular disorders, but its effect in angiogenesis has not been studied so far. In this study, a computational approach has been applied to elucidate the role of the phytochemicals in inhibition of angiogenesis through modulation of vascular endothelial growth factor receptors: Vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, major factors responsible for angiogenesis. Metabolite structures retrieved from PubChem and KNApSAcK - 3D databases, were docked using AutoDock4.2 tool. Hydrogen bond and molecular docking, absorption, distribution, metabolism and excretion and toxicity predictions were carried out using UCSF Chimera, LigPlot(+) and PreADMET server, respectively. From the docking analysis, it was observed that puerarone and tuberostan had significant binding affinity for the intracellular kinase domain of vascular endothelial growth factor receptors-1 and vascular endothelial growth factor receptor-2 respectively. It is important to mention that both the phytochemicals shared similar interaction profile as that of standard inhibitors of vascular endothelial growth factor receptors. Also, both puerarone and tuberostan interacted with Lys861/Lys868 (adenosine 5'-triphosphate binding site of vascular endothelial growth factor receptors-1/vascular endothelial growth factor receptors-2), thus providing a clue that they may enforce their inhibitory effect by blocking the adenosine 5'-triphosphate binding domain of vascular endothelial growth factor receptors. Moreover, these molecules exhibited good drug-likeness, absorption, distribution, metabolism and excretion properties without any carcinogenic and toxic effects. The interaction pattern of the puerarone and tuberostan may provide a hint for a novel drug design for vascular endothelial growth factor tyrosine kinase receptors with better specificity to treat angiogenic disorders.

Intra abdominal hypertension; incidence, prevalence and outcomes in a mixed intensive care unit: Prospective cohort study.

BACKGROUND: This study was conducted primarily to determine the prevalence and incidence of intra-abdominal hypertension (IAH) in a mixed ICU (medical & surgical) population and, secondarily, to compare outcomes between patients with and without IAH. METHODS: The prospective cohort study was conducted from April to July 2011 on adult patients admitted in ICU, on mechanical ventilation and with an indwelling urinary catheter. Intra-vesicular pressure was measured. Primary endpoint was IAH and it was defined as Intra-abdominal pressure>12 mm Hg on two consecutive readings 6 h apart. RESULTS: Total 83 patients were enrolled in the study; 61% from medical services and 39% from surgical services. Mean age in years±SD was 47 ± 17.5 with male preponderance (66%). IAH was detected in 23/83 (28%) at the time of admission, while six out of remaining 60 patients (10%) developed the condition during their ICU stay; the incidence and prevalence was 10% and 35%, respectively. Secondary end points of the study comparing outcomes between patients with and without IAH, though different in the two groups, did not achieve statistical significance. In-hospital mortality 65.5% vs. 44.4% p-value 0.054. New onset renal failure 34.5% vs. 16.7% p-value 0.054%. Difficulty in weaning from mechanical ventilation 37.9% vs. 25.9% p-value 0.008. CONCLUSION: IAH is a poorly recognized clinical entity with potentially devastating impact on patient outcomes. Since majority of patients had IAH at the time of admission, all ICU patients especially on ventilator should have baseline intra-abdominal pressures measured at the time of admission and subjected to appropriate management to prevent them from developing abdominal compartment syndrome.

Photochemical activation of drugs for the treatment of therapy-resistant cancers.

Resistance to chemotherapy, molecular targeted therapy as well as radiation therapy is a major obstacle for cancer treatment. Cancer resistance may be exerted through multiple different mechanisms which may be orchestrated as observed in multidrug resistance (MDR). Cancer resistance may be intrinsic or acquired and often leaves patients without any treatment options. Strategies for alternative treatment modalities for resistant cancer are therefore highly warranted. Photochemical internalization (PCI) is a technology for cytosolic delivery of macromolecular therapeutics based on the principles of photodynamic therapy (PDT). The present report reviews the current knowledge of PCI of therapy-resistant cancers. In summary, PCI may be able to circumvent several of the major mechanisms associated with resistance towards chemotherapeutics including increased expression of drug efflux pumps, altered intracellular drug distribution and increased ROS scavenging. Current data also suggest PCI of targeted toxins as highly effective in cancers resistant to clinically available targeted therapy such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). PCI may therefore, in general, represent a future treatment option for cancers resistant to other therapies.

Modulating the properties of sunflower oil based novel emulgels using castor oil fatty acid ester: prospects for topical antimicrobial drug delivery.

The current study describes the effect of polyglycerol polyricinoleate (PGPR) on the properties of sunflower oil and span-40 based emulgels. The prepared emulgels contained PGPR in varied concentrations. The microstructure of the emulgels was characterized by bright-field microscopy. The molecular interactions amongst the components of the emulgels were studied using FTIR spectroscopy. The flow and mechanical behaviors of the emulgels were studied using cone-and-plate viscometer and static mechanical tester, respectively. The efficiency of the metronidazole-loaded emulgels as antimicrobial formulations was tested in vitro. E. coli was used as the model microorganism for the antimicrobial study. The emulgels were also explored for iontophoretic delivery applications. The biocompatibility of the emulgels was tested using human keratinocytes (HaCaT). The microscopic evaluation of the emulgels indicated formation of biphasic formulations. FTIR studies suggested a decrease in the hydrogen bonding amongst the components of the emulgels as the concentration of the PGPR was increased. Viscosity studies indicated shear-thinning property of the emulgels. An increase in the PGPR concentration resulted in the reduction in the mechanical properties of the emulgels. Incorporation of PGPR resulted in the decrease in the drug released (both passive and iontophoresis) from the emulgels. The emulgels were found to be cytocompatible in the presence of keratinocytes. The drug loaded emulgels showed good antimicrobial activity against E. coli. In gist, the developed emulgels can be tried for controlled delivery of antimicrobial drugs. The physical and the release properties of the emulgels can be modulated by incorporating PGPR in varied proportions.

Stearic acid based oleogels: a study on the molecular, thermal and mechanical properties.

Stearic acid and its derivatives have been used as gelators in food and pharmaceutical gel formulations. However, the mechanism pertaining to the stearic acid based gelation has not been deciphered yet. Keeping that in mind, we investigated the role of stearic acid on physic-chemical properties of oleogel. For this purpose, two different oil (sesame oil and soy bean oil) formulations/oleogels were prepared. In depth analysis of gel kinetics, gel microstructure, molecular interactions, thermal and mechanical behaviors of the oleogels were done. The properties of the oleogels were dependent on the type of the vegetable oil used and the concentration of the stearic acid. Avrami analysis of DSC thermograms indicated that heterogeneous nucleation was coupled with the one-dimensional growth of gelator fibers as the key phenomenon in the formation of oleogels. Viscoelastic and pseudoplastic nature of the oleogels was analyzed in-depth by fitting the stress relaxation data in modified Peleg's model and rheological studies, respectively. Textural studies have revealed that the coexistence of hydrogen bond dissipation and formation of new bonds is possible under stress conditions in the physical oleogels.