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Non‐small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5‐year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in‐depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer morbidity and mortality worldwide and early diagnosis is crucial for the management and treatment of this disease. Non-invasive means of determining tumour information is an appealing diagnostic approach for lung cancers as often accessing and removing tumour tissue can be a limiting factor. In recent years, liquid biopsies have been developed to explore potential circulating tumour biomarkers which are considered reliable surrogates for understanding tumour biology in a non-invasive manner. Most common components assessed in liquid biopsy include circulating tumour cells (CTCs), cell-free DNA (cfDNA), circulating tumour DNA (ctDNA), microRNA and exosomes. This review explores the clinical use of circulating tumour biomarkers found in liquid biopsy for screening, early diagnosis and prognostication of lung cancer patients. [ABSTRACT FROM AUTHOR]

The incidence of cesarean scar pregnancy (CSP), which was extremely rare till recent times, has been rising steadily. We have more of such cases being published in medical literature now. A 38-year-old woman with a past history of previous three cesarean sections presented with five weeks pregnancy and complaints of bleeding per vaginum associated with mild lower abdominal discomfort. The diagnosis of CSP with a live fetus within the gestational sac was made on a transvaginal ultrasound examination and later confirmed with a magnetic resonance imaging (MRI). The management involved injecting potassium chloride into the gestational sac and a combination of local and systemic methotrexate administration. The patient was followed-up by monitoring the beta human chorionic gonadotropin level until it reached non pregnant level and followed-up with scan and MRI until complete resolution of the pregnancy sac. Due to the rarity of this condition, there are no specific guidelines available for its management. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal shock wave lithotripsy (ESWL) is an important tool for the management of urolithiasis. The effects of shockwaves on tissues are established. The aim of this meta-analysis is to evaluate the microscopic semen characteristics of young men before and after ESWL treatment for lower ureteral calculi. Methods: Literature searches were performed following the Cochrane guidelines. We conducted a systematic review and meta-analysis that included six trials that investigated the effects of ESWL on semen parameters, including sperm concentration, motility, and hematospermia. Meta-analyses were performed using fixed and random-effects models with tests for publication bias and heterogeneity. Results: Significant worsening was detected in sperm concentration and motility after ESWL between case and control groups (mean difference -17.23, 95% confidence interval -22.53 to -11.93, p<0.00001, mean difference -10.82, 95% confidence interval -18.56 to -3.07, p = 0.006). Rate of microscopic and macroscopic hematospermia was significantly higher after ESWL between case and control groups [risk ratio (RR) 40.00, 95% confidence interval 10.11-158.30, p<0.00001, RR 14.33, 95% confidence interval 2.82-72.90, p = 0.001]. All parameters recovered after 3 months. Conclusions: This study showed sperm concentration, motility, and rate of hematospermia (microscopic and macroscopic) were affected by ESWL that was used for the treatment of lower ureteral stone. Long-term studies with a focus on male fertility (i.e., pregnancy rates) after ESWL are warranted. [ABSTRACT FROM AUTHOR]

Extended-release naltrexone (XR-NTX) is associated with an increased number of opioid-free days, improved adherence rates in substance use disorder treatment programs, and reduced cravings and drug-seeking behaviors. There is little evidence on the predictive associations between baseline characteristics of opioid-dependent patients and XR-NTX utilization. Some studies have demonstrated better pharmacotherapy adherence and/or retention rates among non-heroin opioid users compared to heroin users. This study examines predictive associations between characteristics of patients and XR-NTX utilization, as well as participants' urge to use opiates. Our findings suggest that XR-NTX may contribute to decreases in urges to use among both heroin and non-heroin opioid users. Non-heroin opioid users and heroin users were retained in XR-NTX treatment for comparable periods of time. However, those who identified as homeless, injected opioids (regardless of opioid-type), or were diagnosed with a mental illness were less likely to be retained in treatment with XR-NTX. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine (MA) which is known as "shisheh" in Iran is a drug that widely is used in many parts of the world and it is near to a decade that is available for the most drug users and has a considerable prevalence of use. Due to high abuse prevalence and very new challenging phenomenon, it is very important that researchers and treatment providers become more familiar with different aspects of MA. Discussion: It has multiple neurobiological impacts on the nervous system, some of which are transitory and some longer lasting. MA activates the reward system of the brain and produces effects that are highly reinforcing, which can lead to abuse and dependence. Routes of administration that produce rapid onset of the drug's effects (i.e., smoking and injection) are likely to lead to more rapid addiction and more medical and psychiatric effects. No effective pharmacotherapies have been developed for the treatment of MA dependence; although, this is an area of very active research. Several behavioral treatments have been shown to reduce MA use, but better treatments are needed. Conclusion: Harm reduction strategies for non-treatment seeking MA users are needed to reduce the risk of human immunodeficiency virus and other medical risks. The research agenda for MA is substantial, with development of effective pharmacotherapies as one of the most important priorities. Appropriate and effective response for prevention, treatment and harm reduction services due to increasing problems regarding MA in Iran and some other countries in the region. [ABSTRACT FROM AUTHOR]

Background: Vancomycin is used abundantly in patients undergoing HSCT, especially during neutropenic fever. Despite its widespread use little is known about vancomycin pharmacokinetics in HSCT patients. We conducted this study to investigate vancomycin pharmacokinetic parameters in our HSCT patients and to evaluate current dosing regimen based on trough vancomycin concentrations measurement. Methods: Vancomycin serum concentration at steady-state was determined prospectively in 46 adult HSCT patients who received vancomycin as empirical treatment of neutropenic fever. Individual steady-steady pharmacokinetic parameters were also determined in 20 patients who had two vancomycin levels from an administered dose, assuming one-compartment model. Acute kidney injury was also evaluated in our patients during vancomycin therapy. Results: Mean (±SD) apparent volume of distribution (L/kg) and clearance (mL/min) were 0.6 (± 0.33) and 109.7 (± 57.5) respectively. With mean (±SD) total daily dose of vancomycin 31.9 (±10.5) mg/kg/day that was administered, more than 90 % of measured vancomycin trough concentrations were outside the range of 15-20 mg/L and 54.3% of patients had trough concentrations below 10 mg/L. Of 46 patients, 21 patients (45.7%) developed acute kidney injury (AKI) during vancomycin therapy; among them 19 patients were receiving nephrotoxic drug(s) concomitantly. Conclusion: Current vancomycin dosage regimen could not lead to recommended therapeutic serum concentrations in our patients. Large variation in vancomycin pharmacokinetic parameters observed among patients of this study along with difference of vancomycin pharmacokinetics in our study and other similar studies further explain the need for therapeutic drug monitoring and individualization of vancomycin dosing. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To demonstrate the role of the laparoscopic approach for management of primary ureteropelvic junction obstruction (UPJO) using two different techniques in the pediatric age group. Material and methods: From April 2005 to October 2008, 63 pediatric patients underwent treatment of primary UPJO via a laparoscopic approach. Dismembered pyeloplasty was elected in 56 renal units while nine patients were managed by upward transposition of accessory renal artery after division of accessory renal vein. No JJ stent was required in these nine patients. Results: Mean age of patients was 61 (2–180) months. Mean operative time was significantly lower in those managed by transposition of aberrant vessels compared with dismembered pyeloplasty. The mean hospital stay was 6.4 (2–14) days for the dismembered technique and 2.1 (1–4) days for the vascular transposition approach. Significant improvement of obstruction was achieved in all of the patients who underwent the modified Hellstrom technique and in 92.81% of the renal units undergoing dismembered pyeloplasty. Conclusion: The technique of laparoscopic transposition of crossing renal artery without violating collecting system may have a role in minimally invasive management of UPJO in selected pediatric patients. Further research with larger samples and a longer follow-up period is required. [Copyright &y& Elsevier]

Significant controversy exists regarding vesicoureteral reflux (VUR) management, due to lack of sufficient prospective studies. The rationale for surgical management is that VUR can cause recurrent episodes of pyelonephritis and long-term renal damage. Several surgical techniques have been introduced during the past decades. Open anti-reflux operations have high success rate, exceeding 95%, and long durability. The goal of this article is to review the Gil-Vernet trigonoplasty technique, which is a simple and highly successful technique but has not gained the attention it deserves. The mainstay of this technique is approximation of medial aspects of ureteral orifices to midline by one mattress suture. A unique advantage of Gil-Vernet trigonoplasty is its bilateral nature, which results in prevention from contralateral new reflux. Regarding not altering the normal course of the ureter in Gil-Vernet procedure, later catheterization of and retrograde access to the ureter can be performed normally. There is no report of ureterovesical junction obstruction following Gil-Vernet procedure. Gil-Vernet trigonoplasty can be performed without inserting a bladder catheter and drain on an outpatient setting. Several exclusive advantages of Gil-Vernet trigonoplasty make it necessary to reconsider the technique role in VUR management. [ABSTRACT FROM AUTHOR]

AbstractObjectives:The objective of this study was to describe our experience with laparoscopic simultaneous bilateral dismembered pyeloplasty in two pediatric cases by using three midline ports.Methods:A 5-year-old boy and a 5-month-old male infant with bilateral ureteropelvic junction obstruction underwent bilateral laparoscopic transperitoneal dismembered pyeloplasty. A 10-mm trocar was placed through the umbilicus, and two 5-mm trocars were also placed in the midline superior and inferior to the umbilicus. On the left side, dismembered pyeloplasty was performed through a transmesocolic approach. Double-J ureteral stent was inserted through one of the trocars on both sides.Results:The postoperative period was uneventful. Patients were discharged on postoperative days 4 and 5. Oral feeding was tolerated on the first postoperative day. In a 6-month follow-up period, excretory urography and renal scan showed resolution of obstruction.Conclusions:Laparoscopic dismembered pyeloplasty can be performed in a single session for pediatric patients with bilateral ureteropelvic junction obstruction. This can obviate the need for two sessions of anesthesia induction and intubation. However, more studies with large number of patients are needed to confirm this result. [ABSTRACT FROM AUTHOR]

Pancreatic panniculitis, characterized by tender, erythematous subcutaneous nodules occurring most commonly on the lower extremities, occurs in 2% of cases of pancreatic disease. We present a rare case of pancreatic panniculitis in a child with complete DiGeorge syndrome. [ABSTRACT FROM AUTHOR]

Purpose: Our goal was to present our experience with ultrasound guided supine or prone percutaneous nephrolithotomy in three pregnant women under spinal anesthesia.Materials and Methods: Three pregnant women in the 16th, 20th and 28th weeks of pregnancy presented with symptomatic large renal stone in the first patient and multiple renal stones in the second and third patients which were unresponsive to conventional medical therapy. They requested a definitive stone treatment. The operations were done in November 2012, June 2014 and February 2015. Data was gathered prospectively. All steps of gaining access to the pyelocalyceal system including needle insertion, tract dilation, and Amplatz sheath placement were performed under ultrasonography guidance. Tract was dilated with a single shot technique. The first two procedures were performed in supine position and the third procedure was performed in lateral flank position.Results: Two patients were stone-free postoperatively and one patient had only an asymptomatic 4 mm residual stone. They were discharged on the 2nd postoperative day and had an uneventful postoperative course. No fever, bleeding or renal colic was noticed during postoperative hospitalization. All patients delivered their fetuses at term without any abnormality reported by the examining pediatric specialist after their birth.Conclusion: Ultrasonography can be used as an imaging modality guiding all steps of obtaining percutaneous access in pregnant women. Supine or flank ultrasound guided percutaneous nephrolithotomy can be offered to pregnant women in whom conservative measures fail to the patients' wellbeing. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy of laparoscopic nephroureterectomy and open bladder cuff excision for management of upper urinary tract urothelial carcinoma. Materials and Methods: Twenty-two patients with upper urinary tract urothelial carcinoma, who had undergone laparoscopic nephroureterectomy and open bladder cuff excision between September 2004 and October 2010, were studied retrospectively. Operation time, blood loss, analgesic dose, and complications were recorded. Local and port site recurrence, distant metastasis, and survival rate were also evaluated. Results: Patients consisted of 18 men and 4 women, with the mean age of 64.1 years (range, 52 to 83 years). Right upper urinary tract was the involved site in 12 patients and left in 10 patients. Mean operation time was 216 minutes (range, 145 to 395 minutes) and mean hospital stay was 4.3 days. Mean follow-up period was 36.57 months (range, 6 to 65 months). No trocar site recurrence occurred. Three-year overall survival and metastasis-free survival were 95% and 90%, respectively. Conclusion: Laparoscopic nephroureterectomy along with open bladder cuff excision harbors an advantage of laparoscopy concomitant with simplicity and safety of open excision of distal ureter and bladder cuff through the same inevitable incision that is needed for specimen retrieval, without adding any more morbidity to the patient, a win-win radical surgery. [ABSTRACT FROM AUTHOR]