Carbapenem resistance in Bacteroides fragilis: A review of molecular mechanisms.

Carbapenems are an applicable subclass of ß-lactam drugs in the antibiotic therapy of anaerobic infections, especially for poly-microbial cases, due to their broad antimicrobial spectrum on aerobic and anaerobic bacteria. Bacteroides fragilis is the most commonly recovered anaerobic bacteria in the clinical laboratories from mono- and poly-microbial infections. B. fragilis is relatively non-susceptible to different antibiotics, including ß-lactams, tetracyclines, fluoroquinolones, and macrolides. Carbapenems are among the most effective drugs against B. fragilis strains with high-level resistance to different antibiotics. Increased antibiotic resistance of B. fragilis strains has been reported following the overuse of an antimicrobial agent. Earlier contact with carbapenems is linked with increased resistance to them that limits the options for treatment of B. fragilis caused infections, especially in cases caused by multidrug-resistant strains. Several molecular mechanisms of resistance to carbapenems have been described for different carbapenem-resistant bacteria. Understanding the mechanisms of resistance to antimicrobial agents is necessary for selecting alternative antimicrobial agents and the application of control strategies. In the present study, we reviewed the mechanisms contributing to resistance to carbapenems in B. fragilis strains.

Comparison of end-to-side hand-sewn and side-to-side stapled cervical esophagogastric anastomosis in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy: an Iranian retrospective cohort study.

BACKGROUND: Controversies in terms of efficacy and postoperative advantages surround stapled esophagogastric anastomosis compared with the hand-sewn technique as a treatment for patients with esophageal cancer. The purpose of this study was to compare the clinical outcomes of hand-sewn end-to-side esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis after esophagectomy for the aforementioned patients. METHODS: This retrospective cohort study involved examining the medical records of 433 patients who underwent transhiatal esophagectomy for esophageal cancer from March 2010 to March 2016. All the patients were operated using end-to-side hand-sewn esophago-gastrostomy and side-to-side stapled cervical esophagogastric anastomosis. 409 of the patients received a year's worth of follow-up evaluations. All the cases were revisited in 2 weeks as well as in four, eight, and 12 months after surgery. The patients were assessed in terms of postoperative outcomes, including reflux symptoms, anastomotic leakage and stricture, and the need for anastomotic dilatation. RESULTS: Hand-sewn anastomosis was carried out in 271 (62.5%) patients, whereas stapled anastomosis was performed in 162 (37.4%) patients. The mean operative times were 214.46 ± 84.33 min and 250.55 ± 43.31 min for the stapled and hand-sewn anastomosis groups, respectively (P = 0.028). The two groups showed no significant differences with respect to stays in intensive care units and hospitals. Postoperatively, 38 (14.67%) cases of anastomotic leakage were detected in the hand-sewn anastomosis group, with incidence being significantly higher than that in the stapled anastomosis group (8 cases or 5.33%; P = 0.002). Anastomotic stricture occurred less frequently in the patients who underwent stapled anastomosis (P = 0.004). Within the one-year follow-up period, the patients treated via hand-sewn anastomosis more frequently required anastomotic dilatation (P = 0.02). CONCLUSION: Side-to-side stapled cervical esophagogastric anastomosis may reduce operation times and decrease the rates of anastomotic leakage, anastomotic stricture, and anastomotic dilatation in patients with lower thoracic esophageal cancer undergoing transhiatal esophagectomy.

Effects of adding Braun jejunojejunostomy to standard Whipple procedure on reduction of afferent loop syndrome - a randomized clinical trial.

BACKGROUND: Whipple surgery (pancreaticodeudenectomy) has a high complication rate. We aimed to evaluate whether adding Braun jejunojejunostomy (side-to-side anastomosis of afferent and efferent loops distal to the gastrojejunostomy site) to a standard Whipple procedure would reduce postoperative complications. METHODS: We conducted a randomized clinical trial comparing patients who underwent standard Whipple surgery (standard group) and patients who underwent standard Whipple surgery with Braun jejunojejunostomy (Braun group). Patients were followed for 1 month after the procedure and postoperative complications were recorded. RESULTS: Our study included 30 patients: 15 in the Braun and 15 in the standard group. In the Braun group, 4 (26.7%) patients experienced 6 complications, whereas in the standard group, 7 (46.7%) patients experienced 11 complications (p = 0.14). Complications in the Braun group were gastrointestinal bleeding and wound infection (n = 1 each) and delayed gastric emptying and pulmonary infection (n = 2 each). Complications in the standard group were death, pancreatic anastomosis leak and biliary anastomosis leak (n = 1 each); gastrointestinal bleeding (n = 2); and afferent loop syndrome and delayed gastric emptying (n = 3 each). There was no significant difference between groups in the subtypes of complications. CONCLUSION: Our results showed that adding Braun jejunojejunostomy to standard Whipple procedure was associated with lower rates of afferent loop syndrome and delayed gastric emptying. However, more studies are needed to define the role of Braun jejunojejunostomy in this regard. TRIAL REGISTRATION: IRCT2014020316473N1 (www.irct.ir).

CONTEXTE: La chirurgie de Whipple (pancréatoduodénectomie) s'accompagne de taux de complications élevés. Nous avons voulu vérifier si l'ajout d'une jéjunojéjunostomie de Braun (anastomose latérolatérale des anses afférente et efférente à la partie distale de la gastrojéjunostomie) à une chirurgie de Whipple standard permet de réduire les complications postopératoires. MÉTHODES: Nous avons procédé à un essai clinique randomisé pour comparer des patients soumis à une chirurgie de Whipple standard (groupe standard) à des patients soumis à une chirugie de Whipple standard avec jéjunojéjunostomie de Braun (groupe Braun). Les patients ont été suivis pendant 1 mois après l'intervention et les complications postopératoires ont été notées. RÉSULTATS: Notre étude a regroupé 30 patients : 15 dans le groupe Braun et 15 dans le groupe standard. Dans le groupe Braun, 4 patients (26,7 %) ont présenté 6 complications, tandis que dans le groupe standard, 7 patients (46,7 %) ont présenté 11 complications (p = 0,14). Les complications dans le groupe Braun ont été saignements gastro- intestinaux et infection de plaie (n = 1 chacun) et retard de la vidange gastrique et infection pulmonaire (n = 2 chacun). Les complications dans le groupe standard ont été décès, fuite de l'anastomose pancréatique et fuite de l'anastomose biliaire (n = 1 chacun); saignement gastro- intestinal (n = 2); et syndrome de l'anse afférente et retard de la vidange gastrique (n = 3 chacun). On n'a noté aucune différence significative entre les groupes pour ce qui est des sous-types de complications. CONCLUSION: Nos résultats ont montré que l'ajout de la jéjunojéjunostomie de Braun à une chirurgie de Whipple standard a été associé à des taux moindres de syndrome de l'anse afférente et de retard de la vidange gastrique. Il faudra toutefois procéder à d'autres études pour définir le rôle de la jéjunojéjunostomie de Braun à cet égard. ENREGISTREMENT DE L'ESSAI: IRCT2014020316473N1 (www.irct.ir).

Pulmonary Mucormycosis and hydatid cyst: A case report.

Mucormycosis is a group of life-threatening diseases caused by a fungus of the Mucoraceae family and has a higher mortality rate compared with other known fungal infections. Hydatid cyst, caused by Echinococcus, is a crucial health concern in endemic areas and the disease is characterized by slow-growing cysts in the liver, lungs, or other organs. In this report, a woman with coexistence of hydatid cyst and Mucormycosis is introduced. The patient was a 52-year-old woman with approximately 6 years' history of uncontrolled diabetes mellitus and hypothyroidism, who presented with cough, sputum, and dyspnea 2 months ago. On the initial auscultation of the lungs, there was a decreased sound at the base of the left lung, and she had a fever. In blood tests, she had a high titer of erythrocyte sedimentation rate and 3+ C-Reactive Protein. The symptoms in favor of hydatid cyst were observed in lung computed tomography and in pleural needle biopsy, hydatid cyst was confirmed. With this indication, she underwent wedge resection, and resection of the left lower lung cyst. Two samples are taken from the cyst side and the pathology report was consistent with Mucormycosis (wide filaments with a 90-degree angle). The patient was immediately treated with liposomal amphotericin for 4 weeks. The Lung CT scan was performed before and after treatment. Albendazole was treated to treat hydatid cyst. After discharge, the treatment of the patient continued with oral Posaconazole, and after the treatment finalization, the general condition of the patient was good, and she did not have any complaints. In pulmonary diseases that do not respond significantly to surgical treatment (such as hydatid cyst), fungal disease (mucor) must be considered simultaneously. Mucormycosis is more prevalent in patients with uncontrolled diabetes, and it is necessary to be considered if these patients were infected with pneumonia and their symptoms did not improve with usual treatments.

Recent Advances in Therapeutic Peptides for Breast Cancer Treatment.

Breast cancer is a heterogeneous malignancy and is the second leading cause of mortality among women around the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapeutic approaches for the treatment of this malignancy. Among the novel methods, therapeutic peptides that target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acid monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides, such as specific binding on tumor cells surface, low molecular weight, and low toxicity on normal cells, make the peptides appealing therapeutic agents against solid tumors, particularly breast cancer. Also, the National Institutes of Health (NIH) describes therapeutic peptides as a suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells that can be used in the treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines that have been developed for the treatment of breast cancer.

Evaluation of Mutations in 23S rRNA, rdxA and frxA Genes of Helicobacter pylori in Paraffin-Embedded Gastric Biopsy Specimens from Iranian Gastric Cancer and Gastritis Patients.

PURPOSE: Helicobacter pylori (H. pylori) infection is considered as one of the main cause of gastric cancer. Treatment failure of the infection often occurs due to antibiotic resistance. Herein, we aimed to evaluate the mutations in 23S rRNA gene of H. pylori which are associated with clarithromycin resistance and in rdxA and frxA genes of the bacterium which may be associated with metronidazole resistance, in paraffin-embedded gastric biopsies from patients with gastric adenocarcinoma and gastritis in Tabriz, the northwest of Iran. METHODS: In the study, 80 paraffin-embedded tissue sections from 40 gastric cancer and 40 gastritis patients in the Imam Reza hospital, Tabriz, Iran were collected. The existence of ureC gene was verified by PCR method. Genotypical clarithromycin resistance was investigated by real-time PCR method and determination of the melting temperature. PCR reaction and sequencing were used for the evaluation of mutations in rdxA and frxA genes. RESULTS: The results of ureC amplification showed that DNA of H. pylori was present in the 82.66% of the obtained DNA samples. About 45.16% of samples were resistant to the clarithromycin and 53.22% of them were resistant to the metronidazole. Based on the results from real-time PCR, the frequency of mutations was as follow A2143G 64.28%, A2142G 44.44% and A2142C 1.11%. The mutations of rdxA gene were 66.66% missense, 30.30% frameshift and 3.03% non-sense. The mutations of frxA gene were 36.36% missense, 54.54% frameshift and non-sense 9.09%. CONCLUSION: A2143G mutation is the most frequent mutation among clarithromycin resistant genes in Iran. Also, missense and frameshift mutations are frequent in rdxA and frxA genes. Screening for these mutations could help researchers to investigate the most effective anti-H. pylori antibiotics and to prevent antibiotic resistance.

Effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in obstructive jaundice: A randomized controlled trial.

BACKGROUND: It has been shown that N-acetylcysteine may be useful in correcting postoperative hepatic and renal function in many pathological conditions. The present study aimed to examine the effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in patients with obstructive jaundice. METHODS: & Materials: A total of 30 patients with obstructive jaundice who were candidates for bypass surgery were enrolled in this randomized clinical trial. In the case group, intravenous N-acetylcysteine (200 mg/kg per hour in the first 8 h, followed by 100 mg/kg per hour for another 16 h, the same dose for another 24 h) was administered postoperatively. Liver and renal function tests (serum AST, ALT, ALP, GGT, bilirubin, and creatinine) were compared between two groups, as well as duration of hospitalization and ICU stay. RESULTS: Postoperatively, decrease in mean serum AST (p = 0.01), ALT (p = 0.02), ALP (p = 0.01), GGT (p = 0.04) and bilirubin (total, p = 0.02, direct, p = 0.01) levels compared to the preoperative values was significantly more among cases compared to those in controls. Changes in serum creatinine, however, did not differ significantly between two groups (p = 0.18). Hospital and ICU stays were also not different between two study groups (p = 0.27 and p = 0.94 respectively). CONCLUSION: On the basis of our findings, intravenous N-acetylcysteine in patients with obstructive jaundice could significantly preserve liver function after bypass surgery. Effect of this medication on renal function; however, was not statistically significant. TRIAL REGISTRATION: Iranian Registry of Clinical Trial: IRCT2016041016473N7.

The Role of Immunohistochemistry Studies in Distinguishing Malignant Mesothelioma from Metastatic Lung Carcinoma in Malignant Pleural Effusion.

BACKGROUND AND OBJECTIVE: Early diagnosis of malignant pleural mesothelioma (MPM) is the key point of its treatment. The main problem is the precise diagnosis of mesothelioma and its differentiation from metastatic lung adenocarcinoma. Mesothelioma exhibits complex immunohistochemical characteristics. The aim of this study was to study hybrid immunohistochemistry in the differential diagnosis of primary malignant pleural effusion from metastatic pulmonary cancers. MATERIAL AND METHODS: Twenty tissue samples in paraffin blocks from the pathology department of Imam Reza Hospital in Tabriz whose pathology reports cited mesothelioma or metastatic lung adenocarcinomas, were included in the studies. These tissues were deemed appropriate for IHC in terms of tissue quality and quantity. They were studied and evaluated for pathological markers. RESULTS: In patients with adenocarcinoma CK7 in 100% of patients (13 patients), TTF1 in 61.5% of patients (8 patients) and CEA in 53.8% of patients (7 patients) were positive, but HBME1 and Calretinin were negative for all patients. In patients with mesothelioma, HBME1 and Calretinin were positive in 100% of patients (7 patients) and TTF1, CEA and CK7 were negative. CONCLUSION: The results of this study showed that CEA, CK7, TTF1, Calretinin and HBME1 are suitable criteria for differentiating between metastatic lung adenocarcinoma and mesothelioma, and can differentiate the mesothelioma and adenocarcinoma with high accuracy.

nim gene-independent metronidazole-resistant Bacteroides fragilis in surgical site infections.

Background:Bacteroides fragilis is the most common anaerobic pathogen isolated from surgical site infections (SSIs). Metronidazole resistance is increasing and the mechanisms of resistance are not clear in some isolates. The aim of the present study was to investigate the metronidazole susceptibility prevalence, and detect nim genes in B. fragilis isolates from SSIs. Methods: This study included 100 surgery patients with signs and symptoms indicative of SSIs. Syringe aspiration of the infected site was used to collect specimens. All specimens were cultured on BBA (Brucella blood agar), KVLB (kanamycin-vancomycin laked blood), and BBE (Bacteroides bile esculin) agar. The MIC (minimum inhibitory concentration) of metronidazole was determined by the agar dilution method according to the Clinical and Laboratory Standard Institute (CLSI). Then the PCR method was used to determine the presence of the nim gene. Results: In the present study, 26 B. fragilis were isolated from 100 SSIs specimens. Eight isolates were metronidazole resistant; the metronidazole MIC was 32 µg/mL for 7 isolates and 64 µg/mL for one isolate. All isolates were nim gene negative. Conclusion: The emergence of metronidazole-resistant B. fragilis limits the application of this drug for treatment and prophylaxis of SSIs. Thus, rapid identification of metronidazole-resistant B. fragilis is essential to restrict inappropriate, superfluous administration. In spite of various metronidazole resistance mechanisms other than that depending on the nim gene, detection of nim by PCR is unsuitable for identifying resistant isolates. Therefore, phenotypic methods are better to screen for and identify metronidazole-resistant B. fragilis.

Surgical treatment of gallbladder carcinoma: a critical review.

Gallbladder carcinoma is a relatively uncommon cancer of gastrointestinal (GI) tract. Medical literature is full of nihilistic reports about the treatment of gallbladder carcinoma, especially due to its resistance to current radiotherapeutic or chemotherapeutic treatment modalities and difficult surgical approach for complete resection of these tumors. Herein, we review current diagnostic and therapeutic approaches to this rare GI cancer.

A rare case of aphallia with right kidney hypoplasia and left kidney dysplasia.

Aphallia or penile agenesis is an extremely rare congenital anomaly with an estimated incidence rate of 1 in 10 to 30 million births. We report a rare case of aphallia with right kidney hypoplasia and left kidney dysplasia in a 10-day old Iranian-Azeri male. The patient had creatinine rise and renal failure due to dysplastic left kidney and hypoplastic right kidney and expired on fifth day of admission. There were only six cases of renal malformation associated with aphallia in the literature review. Three of the cases were complicated by Potter sequence and one of them was accompanied by chronic renal failure. Our case had a unique presentation because of bilateral renal malformation and subsequent renal failure without the Potter sequence.

Antibiotic Susceptibility Pattern of Aerobic and Anaerobic Bacteria Isolated From Surgical Site Infection of Hospitalized Patients.

BACKGROUND: Surgical Site Infections (SSIs) are infections of incision or deep tissue at operation sites. These infections prolong hospitalization, delay wound healing, and increase the overall cost and morbidity. OBJECTIVES: This study aimed to investigate anaerobic and aerobic bacteria prevalence in surgical site infections and determinate antibiotic susceptibility pattern in these isolates. MATERIALS AND METHODS: One hundred SSIs specimens were obtained by needle aspiration from purulent material in depth of infected site. These specimens were cultured and incubated in both aerobic and anaerobic condition. For detection of antibiotic susceptibility pattern in aerobic and anaerobic bacteria, we used disk diffusion, agar dilution, and E-test methods. RESULTS: A total of 194 bacterial strains were isolated from 100 samples of surgical sites. Predominant aerobic and facultative anaerobic bacteria isolated from these specimens were the members of Enterobacteriaceae family (66, 34.03%) followed by Pseudomonas aeruginosa (26, 13.4%), Staphylococcus aureus (24, 12.37%), Acinetobacter spp. (18, 9.28%), Enterococcus spp. (16, 8.24%), coagulase negative Staphylococcus spp. (14, 7.22%) and nonhemolytic streptococci (2, 1.03%). Bacteroides fragilis (26, 13.4%), and Clostridium perfringens (2, 1.03%) were isolated as anaerobic bacteria. The most resistant bacteria among anaerobic isolates were B. fragilis. All Gram-positive isolates were susceptible to vancomycin and linezolid while most of Enterobacteriaceae showed sensitivity to imipenem. CONCLUSIONS: Most SSIs specimens were polymicrobial and predominant anaerobic isolate was B. fragilis. Isolated aerobic and anaerobic strains showed high level of resistance to antibiotics.

Video assisted rigid thoracoscopy in the diagnosis of unexplained exudative pleural effusion.

INTRODUCTION: An undiagnosed exudative pleural effusion is often a difficult diagnostic dilemma that needs further histological study for a definitive etiological diagnosis. Video assisted rigid thoracoscopy is a minimally invasive procedure with a minor morbidity and mortality risk that could resolve this problem. METHODS: Between January 2010 and December 2011, we performed thoracoscopy in 26 patients for diagnosis of undiagnosed exudative pleural effusion. Clinical and paraclinical data of patients were collected prospectively and analyzed. RESULTS: Sole pleural effusion was the most common CT scan finding seen in 17 (65.4%) patients. Thoracoscopy was diagnostic in 24 patients (92.3%). The pathologic findings were carcinoma (46.2%), tuberculosis (30.8%) and chronic inflammation without a definitive microbiologic culture (15.4%). Surprisingly mean ADA level in the tuberculosis group was in normal range. No mortality or complication related to our operation was observed. CONCLUSION: Video assisted thoracoscopy is a minimally invasive procedure with a high definitive diagnostic accuracy in the evaluation of tuberculosis and malignant pleural effusions. Pulmonologist should refer these patients sooner to decrease the waiting period of diagnosis and treatment of such conditions.

Hydatid cyst in children: A 10-year experience from Iran.

BACKGROUND: Hydatid disease is one of the major world-wide health problems especially in endemic countries. Due to lack of statistics about this disease, various aspects of hydatidosis in children in North-West of Iran have been studied in this study. MATERIALS AND METHODS: We studied 59 children with hydatidosis referring Tabriz Children Hospital, Tabriz, Iran from 2001 up to 2011. We surveyed chief complaint of patients, number, size and location of cysts in children and also we studied cysts as if they are infected or ruptured or not. RESULTS: Average age of 59 patients (32 [54.2%] males and 27 [45.8%] females) was 7.93 ± 3.0. The most common chief complaints were cough and pain. Number of cysts was higher in females (2.00 ± 2.8 vs. 1.52 ± 1.0). The most common locations of cysts are lung and liver (52 patients); however, other organs had been also affected. CONCLUSIONS: Lung hydatidosis is more common than hepatic hydatidosis in children than adults and it is more frequent in males. Hydatid disease should be considered in differential diagnoses of liver and lung cystic lesions in children.