Antimicrobial therapy during cancer treatment: Beyond antibacterial effects.

Cancer treatment options have evolved to include immunotherapy and targeted therapy, in addition to traditional chemoradiation. Chemoradiation places the patient at a higher risk of infection through a myelosuppressive effect. High clinical suspicion and early use of antimicrobials play a major role in decreasing any associated morbidity and mortality. This has led to a widespread use of antimicrobials in cancer patients. Antimicrobial use, however, does not come without its perils. Dysbiosis caused by antimicrobial use affects responses to chemotherapeutic agents and is prognostic in the development and severity of certain cancer treatment-related complications such as graft-versus-host disease and Clostridioides difficile infections. Studies have also demonstrated that an intact gut microbiota is essential in the anticancer immune response. Antimicrobial use can therefore modulate responses and outcomes with immunotherapy targeting immune checkpoints. In this review, we highlight the perils associated with antimicrobial use during cancer therapy and the importance of a more judicious approach. We discuss the nature of the pathologic changes in the gut microbiota resulting from antimicrobial use. We explore the effect these changes have on responses and outcomes to different cancer treatment modalities including chemotherapy and immunotherapy, as well as potential adverse clinical consequences in the setting of stem cell transplant.

Quality of life after mandibulectomy: the impact of the resected subsite.

The purpose of this study was to identify the factors that impact the quality of life (QOL) scores of patients undergoing mandibulectomy. All patients with a diagnosis of an oral cavity neoplasm involving the mandible who underwent a mandibulectomy between January 1, 2000 and December 31, 2015 and completed a University of Washington QOL questionnaire (UW-QOL) were included in the study. Fifty-eight patients fulfilled all inclusion criteria and completed the UW-QOL questionnaire. Forty patients (69%) underwent a segmental mandibulectomy and 18 patients underwent a marginal mandibulectomy. Forty-eight patients (82.7%) had a free flap reconstruction. There was no significant difference in the QOL scores between patients who underwent a marginal or a segmental mandibulectomy. In contrast, patients who underwent symphysial resection reported significantly worse scores in various domains compared to patients with body or ramus segmental mandibulectomy. Patients who underwent a segmental mandibulectomy that included the symphysis had worse outcomes in chewing, recreation, health-related and social QOL domains compared to those whose mandibulectomy did not include the symphysis.

Involvement of the heparanase procoagulant domain in bleeding and wound healing.

Essentials Heparanase forms a complex with tissue factor and enhances the generation of factor Xa. The present study was aimed to identify the procoagulant domain of heparanase. Procoagulant peptides significantly shortened bleeding time and enhanced wound healing. Tissue factor pathway inhibitor (TFPI)-2 derived peptides inhibited the procoagulant peptides. SUMMARY: Background Heparanase, which is known to be involved in angiogenesis and metastasis, was shown to form a complex with tissue factor (TF) and to enhance the generation of activated factor X (FXa). Our study demonstrated that peptides derived from TF pathway inhibitor (TFPI)-2 impeded the procoagulant effect of heparanase, and attenuated inflammation, tumor growth, and vascularization. Aims To identify the procoagulant domain in the heparanase molecule, and to evaluate its effects in a model of wound healing that involves inflammation and angiogenesis. Methods Twenty-four potential peptides derived from heparanase were generated, and their effect was studied in an assay of FXa generation. Peptides 14 and 16, which showed the best procoagulant effect, were studied in a bleeding mouse model and in a wound-healing mouse model. Results Peptides 14 and 16 increased FXa levels by two-fold to three-fold, and, at high levels, caused consumption coagulopathy. The TFPI-2-derived peptides explored in our previous study were found to inhibit the procoagulant effect induced by peptides 14 and 16. In the bleeding model, time to clot formation was shortened by 50% when peptide 14 or peptide 16 was topically applied or injected subcutaneously. In the wound-healing model, the wound became more vascular, and its size was reduced to one-fifth as compared with controls, upon 1 week of exposure to peptide 14 or peptide 16 applied topically or injected subcutaneously. Conclusions The putative heparanase procoagulant domain was identified. Peptides derived from this domain significantly shortened bleeding time and enhanced wound healing.

Characterization of influenza outbreaks in Lebanon during the 2013/14 and 2014/15 seasons.

Despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the Middle East, including Lebanon. In this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in Lebanon. Influenza A(H3N2) was dominant in the 2013/14 season while the A(H1N1)pdm09 and B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates were susceptible to 4 neuraminidase inhibitors (oseltamivir, zanamivir, peramivir and laninamivir). Genetic analysis of the haemagglutinin gene revealed multiple introductions of influenza viruses into Lebanon from different geographic sources during each season. Additionally, large data gaps were identified in the Middle East region, as indicated by the lack of current influenza sequences in the database from many countries in the region.

Characterization of influenza outbreaks in Lebanon during the 2013/14 and 2014/15 seasons

Despite the significant burden of influenza outbreaks, active disease monitoring has been largely absent in the Middle East, including Lebanon. In this study we characterized influenza virus in 440 nasopharyngeal swabs collected from patients with acute respiratory infections during two influenza seasons in Lebanon. Influenza A[H3N2] was dominant in the 2013/14 season while the A[H1N1]pdm09 and B/Yamagata strains were most prevalent in the 2014/15 season. All tested isolates were susceptible to 4 neuraminidase inhibitors [oseltamivir, zanamivir, peramivir and laninamivir]. Genetic analysis of the haemagglutinin gene revealed multiple introductions of influenza viruses into Lebanon from different geographic sources during each season. Additionally, large data gaps were identified in the Middle East region, as indicated by the lack of current influenza sequences in the database from many countries in the region

Malgré la lourde charge que représentent les flambées de grippe, la surveillance active de la maladie était jusqu'à présent inexistante au Moyen-Orient, et notamment au Liban. Dans la présente étude, le virus de la grippe a été caractérisé dans 440 sécrétions rhinopharyngées prélevées par écouvillonnage chez des patients ayant souffert d'infections respiratoires aiguës pendant deux saisons grippales au Liban. Le virus de la grippe A[H3N2] était prédominant pendant la saison 2013/2014, tandis que celui de la grippe A[H1N1]pdm09 et les souches de grippe B/Yamagata étaient les plus courants pendant la saison 2014/2015. Tous les isolats testés étaient sensibles à quatre inhibiteurs de la neuraminidase [l'oseltamivir, le zanamivir, le peramivir, et le laninamivir]. L'analyse génétique du gène de l'hémagglutinine a révélé de multiples introductions des virus de la grippe au Liban, depuis différentes sources géographiques au cours de chaque saison. De plus, d'importantes lacunes dans les données ont été constatées dans la région du Moyen-Orient, comme le montre l'absence des séquences génétiques actuelles de la grippe dans les bases de données de nombreux pays de la region

[One stage combined endoscopic and per-oral buccal fat pad approach for large oro-antral-fistula closure with secondary chronic maxillary sinusitis].

There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per-oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean ± SD age of 53.5 ± 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9%), foreign body in sinus (n = 10, 22.2%) nasal congestion (n = 7, 15.5%), halitosis (n = 6, 13.3%) and pain (n = 5, 12.2%). Surgical complications included local pain (n = 2, 4.4%), persistent rhinitis (n = 2, 4.4%) and synechia (n = 1, 2.2%). One patient required revision surgery due, to an unresolved OAF. The OAF of all the other 44 patients (97.8%) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 ± 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis.

Regulation of expression of sodA and msrA genes of Corynebacterium glutamicum in response to oxidative and radiative stress.

Promoters of genes encoding superoxide dismutase (sodA) and peptide methionine sulfoxide reductase (msrA) from Cory-nebacterium glutamicum were cloned and sequenced. Promoter region analysis of sodA-msrA was unable to identify putative sites of fixed eventual regulators except for possible sites of fixed OxyR and integra-tion host factor. A study of the regulation of these genes was performed using the lacZ gene of Escherichia coli as a reporter placed under the control of sequences downstream of sodA and msrA. In silico analysis was used to identify regulators in the genome of C. glutamicum, which revealed the absence of homologs of soxRS and arcA and the presence of inactive oxyR and putative candidates of the homologs of ahpC, ohrR, integration host factor, furA, IdeR, diphtheria toxin repressor, and mntR.

Effect of temperature on the setting time of Mineral Trioxide Aggregate (MTA).

Introduction: Mineral trioxide aggregate (MTA) has numerous applications in dentistry due to various advantages. However, its long setting time has still remained a problem. The current study was conducted to investigate the effect of temperature (ambient and distilled water temperature) on the setting time of mineral trioxide aggregate (MTA). Materials and methods: This experimental study comprised of two parts. In the first part, MTA and distilled water samples were kept at ambient temperature for 24 hours (before mixing: effect of distilled water temperature on the setting time of MTA and after mixing: effect of distilled water and ambient temperature on the setting time of MTA), and analyzed and divided into three groups: group 1 (4°C), group 2 (37°C) and group 3 (90°C). The mixed samples were placed in the glass cylinders with an internal diameter of 8 mm and a height of 10 mm, and kept at 37°C temperature and 100% humidity. In the second part, the samples were prepared the same as those of the first part and divided into three groups according to the terms of maintenance: group 1 (4°C), group 2 (37°C) and group 3 (75°C). The mixed samples were then put in glass cylinders with an internal diameter of 8 mm and a height of 10 mm and the samples of groups 1, 2 and 3 were kept at 4, 37 and 75 °C, respectively. At the end of each part, the primary and final setting times were measured by Gilmore needle. Data were analyzed by SPSS using Kruskal-Wallis test (p<0.05). Results: The findings of this study showed a significant reduction of the primary and final setting time of MTA for the samples of both parts of the study with an increase in ambient temperature (p<0.05). Conclusion: This study indicated that increased ambient temperature caused a reduction in the setting time of MTA.

Adjuvant aromatase inhibitor therapy in patients with stage I breast cancer at a regional oncology center in Israel: implementation of a 'switching' policy in postmenopausal patients after initial tamoxifen.

OBJECTIVE: To analyze the implementation of a switching policy of adjuvant aromatase inhibitor (AI) therapy sequentially after tamoxifen in consecutively treated stage I (T1N0M0) hormone receptor (HR)-positive breast cancer (BC) patients. METHODS: The records of 279 consecutive HR-positive BC patients diagnosed between 2002 and 2006 and followed at the Soroka Medical Center were reviewed. RESULTS: Two-hundred-seventeen patients who initially received tamoxifen were suitable for switching and 28 received an AI as initial adjuvant treatment. The switch was accomplished in 82.5% of the 217 patients. Those who switched to an AI had a higher proportion of T1c stage than patients eligible who were not switched, but did not differ in age, histologic grade, or having received chemotherapy. Of the 179 patients who switched, 155 (86.6%) completed at least 4.5-5 years of adjuvant tamoxifen/AI therapy. Eighteen patients discontinued AI therapy prematurely because of toxicity. CONCLUSIONS: In this stage I BC population, despite the toxicities of AI therapy, >84% of eligible patients received an AI as adjuvant therapy. Measures to improve the management of AI toxicity, such as changing to a different AI, may reduce early stopping.

Modulation of Beta2 and Beta3 integrins in experimental colitis induced by iodoacetamide and enteropathogenic E. coli.

Integrins can modulate the infiltration of inflammatory cells and the secretion of various inflammatory mediators, essential players in the pathogenesis of colitis. This study explores the role of beta2 and beta3 integrin signaling and their possible role in experimental colitis. A total of 160 adult male Sprague-Dawly rats were divided into 4 equal groups: methylcellulose, bacteria, iodoacetamide and iodoacetamide plus bacteria. Clinical symptoms and signs of colitis were checked daily and colonic tissues were biopsied on days 3, 14, 28, and 56 post induction. Histological studies along with histochemical analysis and polymerase chain reaction of beta2, beta3 and alphavbeta3 were performed according to standard procedures. The symptoms and signs were consistent with previously reported data on active colitis. The highest expression of beta3 integrin was in the combined treatment mostly on platelets, endothelial and inflammatory cells. In the same group, the expression of alphavbeta3 integrin complex reached the highest score after 56 days in all colonic layers. Beta2 integrin expression showed a 3-4-fold increase in the combined treatment group at all time points and kept increasing till day 56. It was mostly expressed in the mucosa and submucosa. In addition, the expression of both αvβ3 and αiiβ3 integrins was also elevated 2- to 10-fold, respectively, in the same colitis groups throughout the duration of the experiment. In conclusion, the combined treatment of IA and Enteropathogenic E. coli led to a significant upregulation of all the tested integrins throughout the experimental duration. Such upregulation of integrins could have contributed to the increase and chronicity of inflammation.

An experience of laparoscopic sleeve gastrectomy in obese, morbidly obese, and super morbid obese patients.

OBJECTIVE: To report experience with laparoscopic sleeve gastrectomy (LSG) in obese, morbidly obese, and super morbid obese patients, and to evaluate comparative efficacy of LSG among these patient groups. METHODS: A total of 147 patients underwent LSG between March 2008 and December 2011 at the Department of Surgery, King Saud Medical City, Riyadh, Kingdom of Saudi Arabia. Patients were grouped according to the preoperative body mass index (BMI) into obese (35-39.9 kg/m2), morbidly obese (40-49.9 kg/m2), and super morbid obese (>50 kg/m2). Patients who did not have a regular follow-up (n=38) were excluded, and 108 patients were included in this prospective study. RESULTS: The mean total weight loss (TWL) among the super morbid obese group (41.31 +/- 21.23 kg) was statistically significantly greater compared to the obese group (24.31 +/- 13.00 kg, p=0.009) and morbidly obese group (26.81 +/- 15.56 kg, p=0.001). The mean percentage excess weight loss (EWL) was clinically significant among obese (57.8%), morbidly obese (42.5%), and super morbid obese patients (45.7%), however, it was not statistically significant between the groups (F[2,105]=2.132, p=0.124). There was no mortality; however, 6 major complications occurred including intra-abdominal collection with suspected leak, staple line bleeding, bowel ischemia, and inferior vena cava injury. CONCLUSION: Laparoscopic sleeve gastrectomy resulted in satisfactory and effective EWL in all 3 groups of obesity patients at 30-months follow-up.

Postoperative pain is undertreated: results from a local survey at Jordan University Hospital.

Postoperative pain management is nowadays considered an integral part of modern surgical practice. An audit was made in 2010 to assess the status of acute postoperative pain management at Jordan University Hospital. Data were collected from patients' files and through face-to-face interviews of all patients aged over 16 years who underwent general, gynaecological, ear-nose-throat and orthopaedic surgery. Of 275 patients, 72.0% experienced moderate to severe pain postoperatively at rest and 89.3% on movement. No analgesics were prescribed to 4.7% of the patients and of the remainder, a single analgesic was prescribed to 51.5%. Pethidine and paracetamol were the drugs most commonly prescribed (to 66.9% and 42.5% of patients respectively), most often on a regular schedule rather than on-demand. Despite improvements in pain management worldwide, patients at this hospital were still suffering from postoperative pain. Awareness among professionals and the public is needed and a structured acute pain management programme is essential.

Postoperative pain is undertreated: results from a local survey at Jordan university hospital

Postoperative pain management is nowadays considered an integral part of modern surgical practice. An audit was made in 2010 to assess the status of acute postoperative pain management at Jordan University Hospital. Data were collected from patients' files and through face-to-face interviews of all patients aged over 16 years who underwent general, gynaecological, ear-nose-throat and orthopaedic surgery. Of 275 patients, 72.0% experienced moderate to severe pain postoperatively at rest and 89.3% on movement. No analgesics were prescribed to 4.7% of the patients and of the remainder, a single analgesic was prescribed to 51.5%. Pethidine and paracetamol were the drugs most commonly prescribed [to 66.9% and 42.5% of patients respectively], most often on a regular schedule rather than on-demand. Despite improvements in pain management worldwide, patients at this hospital were still suffering from postoperative pain. Awareness among professionals and the public is needed and a structured acute pain management programme is essential

Study on some factors affecting survivability of airborne fungi.

The aim of the present study was to investigate the effect of some air pollutants and meteorological parameters on the survivability of airborne fungi. Fungi were collected by using a slit impactor sampler calibrated to draw 20 L/min, for 3 min. Nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), particulate matter (PM), relative humidity (RH %), temperature (T °C) and wind speed (WS) were also measured. Air samples were taken during the period from March 2006 to February 2007. Fungal concentrations ranged between 45 and 451 CFU/m(3) with an annual mean concentration of 216 CFU/m(3). The lowest fungal concentration was found in the summer, however the highest one was found in the autumn. NO(2,) SO(2) and PM averaged 83.66 µg/m(3), 67.01 µg/m(3), and 237.69 µg/m(3), respectively. T °C was positively and negatively correlated with Aspergillus (P = 0.000) and Penicillium (P = 0.007), respectively. RH% was positively correlated with total fungi (P = 0.001), Aspergillus (P = 0.002) and Cladosporium (P = 0.047). Multiple regression analysis showed that T °C and RH% were the most predicted variants. Non-significant correlations were found between fungal concentrations and air pollutants. Meteorological parameters were the critical factors affecting fungal survivability.

Cloning of the nptII gene of Escherichia coli and construction of a recombinant strain harboring functional recA and nptII antibiotic resistance.

In an attempt to clone the ORF of the nptII gene of Escherichia coli K12 (ATCC 10798), two degenerate primers were designed based on the nptII sequence of its Tn5 transposon. The nptII ORF was placed under the control of the E. coli hybrid trc promoter, in the pKK388-1 vector, transformed into E. coli DH5α ΔrecA (recombinant, deficient strain). Transferred cells were tested for ampicillin, tetracycline, kanamycin, neomycin, geneticin, paromomycin, penicillin, and UV resistance. The neomycin phosphotransferase gene of E. coli was cloned successfully and conferred kanamycin, neomycin, geneticin, and paromomycin resistance to recombinant DH5α; this did not inhibit insertion of additional antibiotic resistance against ampicillin and tetracycline, meaning the trc promoter can express two different genes carried by two different plasmids harbored in the same cell. This resistance conferral process could be considered as an emulation of horizontal gene transfer occurring in nature and would be a useful tool for understanding mechanisms of evolution of multidrug-resistant strains.

The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy.

BACKGROUND: The 21-gene recurrence score (RS) assay has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). There is limited published data on the impact of the assay on clinical practice, particularly in the context of a single practice with a unified treatment policy. PATIENTS AND METHODS: Between 2006 and 2009, RS was obtained on 135 patients in a single practice with a uniform treatment policy. Treatment recommendations before and after RS result were analyzed retrospectively. Pre-RS treatment recommendations were based on clinicopathological features and Adjuvant! Online (AO) calculated survival advantage. RS and AO survival advantage for adding chemotherapy were compared for each patient. RESULTS: The distribution by risk group of RS was low- 49.6%, intermediate-37.8%, and high-12.6%. In 34 patients (25.2%, 95% confidence interval 17.9% to 32.5%), recommendation for chemotherapy was changed after obtaining assay result. Most changes (70.6%) were from chemotherapy to no chemotherapy. The RS correlated poorly with AO predictions. CONCLUSION: The 21-gene assay, when applied in a consistent manner in early-stage BC, changes treatment recommendations in one-quarter of patients tested.

Diurnal distribution of airborne bacteria and fungi in the atmosphere of Helwan area, Egypt.

Airborne bacterial and fungal composition in an industrial town of Helwan, Egypt, was studied using a slit impactor sampler during the period from March 2006 to February 2007. Airborne bacterial concentrations were usually higher than fungi. Bacteria and fungi had similar diurnal variation patterns. Airborne microorganisms reached their concentration peaks in the evening and gradually decreased during the night time. The hourly concentration peaks of the bacteria and fungi appeared at 20:00h. A significant difference (P < or =0.05) was found between the hourly mean concentrations of airborne fungi in winter compared to other seasons. Fungi concentrations were significantly higher (P< or =0.05) on working weekdays than weekends. Aspergillus, Penicillium, Alternaria and Cladosporium were the most predominant airborne fungal genera. Aspergillus showed double peak patterns whereas Penicillium, Alternaria and Cladosporium showed one peak pattern. The diurnal variations of the bacteria and fungi could be divided into four periods: 1) the morning maximum concentration (6:00h-10:00h), 2) midday to afternoon pattern (10:00h-16:00h), 3) the evening concentration peak (18:00h-20:00h) and 4) the gradual decrease of night time concentration (22:00h-24:00h). Geographical location, human activity, growth cycle of organisms and meteorological factors were the main criteria controlling the temporal variations of the air microorganisms in the Wadi Hof area.

Corynebacterium glutamicum superoxide dismutase is a manganese-strict non-cambialistic enzyme in vitro.

Superoxide dismutase (SOD) of Corynebacterium glutamicum was purified and characterized. The enzyme had a native molecular weight of about 80kDa, whereas a monomer with molecular weight of 24kDa was found on SDS-PAGE suggesting it to be homotetramer. The native SOD activity stained gel revealed a unique cytosolic enzyme. Supplementing growth media with manganese increased the specific activity significantly, while adding iron did not result in significant difference. No growth perturbation was observed with the supplemented media. In vitro metal removal and replacement studies revealed conservation of about 85% of the specific activity by substitution with manganese, while substitution with copper, iron, nickel or zinc did not restore any significant specific activity. Manganese was identified by atomic absorption spectrometer, while no signals corresponding to fixing other metallic elements were detected. Thus, C. glutamicum SOD could be considered a strict (non-cambialistic) manganese superoxide dismutase (MnSOD).

Electrocorticography in the management of surgically treated epileptic patients.

OBJECTIVE: To report our experience on 8 patients with mean age of onset of seizures of 8 years, who had intra-operative electrocorticography monitoring during the surgical treatment of their medically intractable partial epilepsy. METHODS: Post-resection electrocorticography grades were according to Jay et al and seizure outcome was a according to Kobayashi et al grades. RESULTS: Five patients had temporal lobe surgery and 3 patients had extra temporal surgery. Four patients had post-resection electrocorticography grade A (no residual epileptic activity), two of them had seizure outcome grade 1 (free of seizures) and the other 2 had grade 11 (free of seizures on medication). The other 4 patients had post-resection electrocorticography grade B (minimal residual epileptic activity) and all had seizure outcome grade 11 except one patient who had grade 111 (more than 50% reduction in seizure frequency). CONCLUSION: Despite the small size of our study, our results suggest that intra-operative electrocorticography may be an important tool in the surgical management of medically intractable epilepsy.