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.

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.

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.

[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.

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.

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.

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.

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.

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.

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).

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.

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.

Nosocomial infections in the intensive care units at a university hospital in a developing country: comparison with National Nosocomial Infections Surveillance intensive care unit rates.

OBJECTIVE: As a measure of the quality of care provided to patients in the intensive care unit, comparison of nosocomial infection rates with those of the National Nosocomial Infection surveillance was completed during a 3-year observation period. DESIGN: The study design was a prospective study during 3 years between 1993 and 1995. During that period, patients at the medical/surgical and neurosurgical intensive care units and the high-risk nursery were surveyed for nosocomial infections. Device use, bloodstream infection, urinary tract infection, and ventilator-associated pneumonia nosocomial infection rates were calculated and compared with the National Nosocomial Infection Surveillance published rates for the same period. SETTING: The study setting was the medical/surgical intensive care unit, the neurosurgical intensive care unit, and the high-risk nursery at the Jordan University Hospital. RESULTS: Overall infection rates were 17.2 per 100 patients in the medical/surgical intensive care unit, 14.2 to 18.5 per 100 patients in the neurosurgical intensive care unit, and 13.4 to 73.5 per 100 patients in the high-risk nursery. When compared with the weight of the infants, these rates were 61.9 to 94 per 100 in infants weighing <1500 g, 26 to 30.8 per 100 patients in infants weighing >1500 g to 2500 g, and 11.7 to 14.4 per 100 in infants weighing >2500 g. Whereas device use was moderate, bloodstream infection and ventilator-associated pneumonia rates were >90th percentile for National Nosocomial Infection Surveillance in the high-risk nursery, and urinary tract infection was >90th percentile in the medical/surgical and neurosurgical intensive care units. Nosocomial infections at the intensive care units in developing countries need further investigation and control.

[Cavernous dural fistulas: Importance of trans-ocular Doppler ultrasound in evaluating venous patency and therapeutic choices]. / Fistules durales caverneuses: intéret de l'écho-Doppler transoculaire dans l'évaluation de la perméabilité veineuse et le choix thérapeutique.

Transcranial Duplex scan is a relatively recent diagnostic tool with many unexplored clinical potentials. The authors insist on the role of transocular exploration, as a non-invasive substitute to angiography and discuss two patients with cavernous meningeal arteriovenous fistula, a benign but relatively uncommon disease. In the first patient, in whom symptoms recurred, Duplex scan was able to rule out thrombophlebitis and to show increased flow in the fistula, thus leading to proper treatment. In the second patient, the identification of a periorbital thrombophlebitis innocented the fistula and prompted anti-coagulation. We conclude that besides its diagnostic capabilities, Duplex scan may be helpful in selecting proper treatment and follow-up in specific neurovascular conditions.

[Ultrasonographic evaluation of the kidney, liver and spleen size in children]. / Evaluation échographique de la taille des reins, du foie et de la rate chez l'enfant.

BACKGROUND: The aim of our study was to establish a standard growth curve of renal, hepatic and splenic dimensions with respect to age, and to find if any relationship existed between these different curves. PATIENTS AND METHODS: One hundred and fifty abdominal ultrasound studies were obtained on 62 male and 88 female normal children free of any chronic disease, whose ages ranged from 0 to 15 years. Hepatic, splenic and renal dimensions were obtained in a similar and reproducible fashion for all patients. A statistical study of the measurements obtained compared to the age was performed by dividing the subjects into five groups according to age, and after calculating the mean size and variance. RESULTS: Standard growth curves for the liver, kidney and spleen were constructed. Compared to age, splenic size follows the same growth as that of the kidneys, with a constant ratio. The growth pattern of the liver parallel the renal curve with a mean difference of 2.72 cm. CONCLUSION: A moderate enlargement of spleen and liver is difficult to evaluate only by clinical examination. Ultrasound may detect it by using the kidney size as a reference.

[Value of sonography in prolonged neonatal jaundice. Findings in 13 cases]. / Place de l'échographie dans l'ictère néonatal prolongé. A propos de 13 cas.

BACKGROUND: Different conditions are associated with a prolonged cholestatic jaundice in the neonatal period: viral hepatitis, biliary atresia and choledocal cyst are the most frequent causes. Laboratory findings are necessary, although they do not permit an etiologic diagnosis in all cases. Serial ultrasonographic study could be proposed for the evaluation of biliary excretion before and after feeding, in order to differentiate between these three conditions. PATIENTS AND METHODS: Between February 1993 and January 1997, 13 newborns (seven girls and six boys) aged from 30 to 186 days, presented with jaundice and conjugated hyperbilirubinemia. They were evaluated by laboratory tests; serial ultrasonographic examinations were performed after 4 hours fasting then 1 and 2 hours after meal. RESULTS: The gallbladder (GB) was visualized in nine patients. In five of these patients, it contracted after feeding suggesting the diagnosis of neonatal hepatitis, that was confirmed by the clinical evolution. In three patients, the GB did not change in size and the diagnosis of biliary atresia was surgically proven. In one patient, a choledocal cyst was visualized and confirmed by surgery. The GB was not identified after 4 hours of fasting in four patients; biliary atresia was suspected and confirmed by surgery. CONCLUSION: Serial ultrasound of the GB is an easy and non-invasive method. It was useful in identifying those conditions requiring surgery in eight patients. We recommend its use as the initial method in the evaluation of neonatal jaundice before the other invasive methods.

[Aneurysm of the hepatic artery treated by embolization]. / Anévrisme de l'artère hépatique traité par embolisation.

The hepatic artery aneurysm represent 16 to 20% of visceral artery aneurysms. The man of 40 years of age is often affected. This aneurysm is often asymptomatic. The rupture menace its evolution and justify the treatment. Echo-doppler-color constitute a non invasive exam of choice for diagnosis. Embolisation has a more extent indications. A case is reported of an aneurysm of the hepatic artery treated with embolisation with review of the literature.

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.

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.