Publications by authors named "Mahmoud Ismail"

117 Publications

Survival and Prognostic Nomogram for Primary Gastrointestinal Melanoma (PGIM): A Population-based Study.

Anticancer Res 2021 Feb;41(2):967-974

Department of Radiation Oncology, Charité-Universitätsmedizin Humboldt University Berlin, Berlin, Germany.

Background/aim: Primary gastrointestinal mucosal melanoma (PGIM) is an aggressive and rare disease, commonly with poor prognosis. We aimed to determine the clinical risk and prognosis of this rare entity.

Patients And Methods: Patients (n=962) with PGIM documented in the Surveillance, Epidemiology, and End Results database between 1975-2016 were included. Prognostic factors on overall survival (OS) and cancer-specific survival (CSS) were identified. A nomogram was constructed to predict the OS of PGIM patients.

Results: Primary site, summary stage, and therapeutic method were all independent predictors of OS and CSS, and age was the only factor significantly associated with OS. Independent prognostic factors of OS were selected to develop a predictive nomogram. The Harrell's C-index of the nomogram was 0.712, the area under the curve (AUC) was 0.746, 0.758, 0.810 for the 1-, 3-, and 5-year OS, respectively, and calibration plots were in good agreement.

Conclusion: Several prognostic factors of PGIM were demonstrated and a practical nomogram model was created in this study.
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http://dx.doi.org/10.21873/anticanres.14850DOI Listing
February 2021

No impact of soluble epoxide hydrolase rs4149243, rs2234914 and rs751142 genetic variants on the development of type II diabetes and its hypertensive complication among Jordanian patients.

Int J Clin Pract 2021 Jan 29:e14036. Epub 2021 Jan 29.

Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, Busan, Korea.

Background: Human soluble epoxide hydrolase plays a major role in cardiovascular homoeostasis. Genetic variants in the EPHX2 gene among different ethnic groups are associated with cardiovascular complications, such as hypertension. However, no reports regarding the association of EPHX2 genotype with hypertension among type II diabetic (T2D) patients of Middle Eastern Jordanian origin exist.

Objective: The current study aimed to elucidate the association of the EPHX2 allele, genotype and haplotype with T2D, hypertension and parameters of lipid profile parameters among Jordanian T2D patients.

Methods: Ninety-three genomic DNA samples of non-diabetic controls and 97 samples from T2D patients were genotyped for EPHX2 rs4149243, rs2234914 and rs751142 genetic variants. The DNA samples were amplified using polymerase chain reaction (PCR) and then sequenced using Applied Biosystems Model (ABI3730x1). The functionality of intronic EPHX2 variants was predicted using the in silico Berkely Drosophila Genome Project software.

Results: We found no significant (P >.05) association between the EPHX2 rs4149243, rs2234914 and rs751142 allele, genotype and haplotype and the incidence of T2D and hypertension. Additionally, no association (P >.05) between these EPHX2 genetic variants with the baseline total cholesterol, low- and high-density lipoproteins and triglycerides among both non-diabetic and diabetic volunteers was found. However, we found an inter-ethnic variation (χ -test, P value ˂ .05) in the allele frequency of the EPHX2 rs4149243 and rs2234914 variants between Jordanians and other ethnic populations. Also, the in silico Berkely Drosophila Genome Project software predicted that the intronic EPHX2 rs4149243 could alter the splicing of intron 7.

Conclusions: It can be concluded from this study that EPHX2 rs4149243, rs2234914 and rs751142 genetic variants do not play a role in the development of T2D and hypertension among Jordanian T2D patients. Further genetic studies with larger sample sizes are needed to find out the association of other functional EPHX2 variants with cardiovascular diseases among T2D patients in Jordan.
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http://dx.doi.org/10.1111/ijcp.14036DOI Listing
January 2021

Outcomes of juvenile myasthenia gravis: a comparison of robotic thymectomy with medication treatment.

Ann Thorac Surg 2021 Jan 19. Epub 2021 Jan 19.

Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address:

Background: The study aims to compare the clinical outcomes of patients with juvenile myasthenia gravis (JMG) who underwent robotic thymectomy with that of those who only received medication therapy.

Methods: We retrospectively reviewed patients who visited our institution for the diagnosis or treatment of MG with an age at onset younger than 18 years. Patients who underwent thymectomy comprised the surgical group and those who received only medication therapy comprised the nonsurgical group. The clinical outcomes were assessed according to the Myasthenia Gravis Foundation of America Post Intervention Status.

Results: Forty-seven patients (35 female: 12 male) were included as the surgical group and 20 patients (15 female: 5 male) comprised the nonsurgical group. Significant differences were observed between the surgical and nonsurgical groups in antibody against acetylcholinesterase receptor (91.5% versus 65%, p=0.012), disease duration (16 [7-25] months versus 96 [42-480] months, p<0.001) and corticosteroids requirement (53.2% versus 15%, p=0.004) at baseline. Kaplan-Meier analysis showed a higher cumulative probability of complete stable remission (CSR) in the surgical group (p=0.002), compared with that in the nonsurgical group. Moreover, thymectomy (HR 3.842, 95%CI: 1.116-13.230, p=0.033) and age at onset (HR 0.89, 95%CI: 0.80-0.99, p=0.037) were still associated with the achievement of CSR in the multivariable analysis. Furthermore, a significant steroid-sparing effect was only observed in the surgical group, but not in the nonsurgical group.

Conclusions: Robotic thymectomy seems to be more effective than medication therapy on JMG in terms of inducing remission and reducing the use of corticosteroids.
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http://dx.doi.org/10.1016/j.athoracsur.2020.12.045DOI Listing
January 2021

A role for Rab30 in retrograde trafficking and maintenance of endosome-TGN organization.

Exp Cell Res 2021 Feb 5;399(2):112442. Epub 2021 Jan 5.

The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, 3010, Australia. Electronic address:

Rab30 is a poorly characterized small GTPase. Here we show that Rab30 is localised primarily to the TGN and recycling endosomes in a range of cell types, including primary neurons; minor levels of Rab30 were also detected throughout the Golgi stack and early endosomes. Silencing of Rab30 resulted in the dispersal of both early and recycling endosomes and TGN compartments in HeLa cells. By analyzing cargo trafficking in Rab30-silenced and Rab30-overexpressing HeLa cells, we demonstrate that Rab30 plays a role in retrograde trafficking of TGN38 from endosomes to the Golgi, but has no apparent role in the endocytic recycling of the transferrin receptor to the plasma membrane. Five interactive partners with Rab30 were identified by pull-down and MS analysis using GFP-tagged Rab30 mutant, Rab30(Q68L). Two of the interactive partners identified were Arf1 and Arf4, known regulators of endosome to TGN retrograde transport. Knockdown of Arf1 and Arf4 results in GFP-Rab30 decorated tubules arising from the recycling endosomes, suggesting association of Rab30 with tubular carriers. Overall our data demonstrates a role for Rab30 in regulating retrograde transport to the TGN and maintenance of endosomal-TGN organization.
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http://dx.doi.org/10.1016/j.yexcr.2020.112442DOI Listing
February 2021

Effect of Lymph Node Dissection on the Prognosis of Thymic Carcinomas and Thymic Neuroendocrine Tumors.

Semin Thorac Cardiovasc Surg 2020 Nov 9. Epub 2020 Nov 9.

Department of Thoracic Surgery, Klinikum Ernst von Bergmann Potsdam, Academic Hospital of the Charité-Universitätsmedizin Humboldt University Berlin, Potsdam, Germany. Electronic address:

We aimed to analyze the effect of lymph node dissection (LND) and accurate lymph node (LN) status on the survival and prognosis of patients with thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) undergoing surgical treatment. The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgical resection for TCs and TNETs during 1998-2016. LN status were defined as no LND (LND-), pathologically negative with LND (N0), and LN metastasis positive (N+). We investigated outcomes of LN status together with other clinicopathological features for overall survival (OS). Subgroup analyses were performed between LND-, N0, and N+ cohorts using propensity score matching, to analyze the significance of LND in prognosis. A total of 812 patients were enrolled, including 623 with TCs and 189 with TNETs. The proportion of LN metastasis positive in TNETs was 58.8% which was significantly higher than that in TCs (30%) (P < 0.001). In multivariable Cox analysis of OS, patients with LND- had a significantly worse prognosis than those with N0 (P = 0.018); there was no difference between N+ and LND- (P = 0.560). After propensity score matching, patients with N0 still had better survival than those with LND- and N+ in subgroup univariable and multivariable analyses of OS; however, the survival of patients with LND- and N+ was not significantly different in multivariable analysis. It was demonstrated that LND in TCs and TNETs can clarify the status of LN metastasis, to more accurately evaluate patients' long-term prognosis.
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http://dx.doi.org/10.1053/j.semtcvs.2020.11.004DOI Listing
November 2020

Intragastric single-port surgery (IGS) for gastric endophytic gastrointestinal stromal tumor (GIST): A novel surgical treatment.

Surg Oncol 2020 Dec 23;35:12-13. Epub 2020 Jul 23.

Center for Bariatric and Metabolic Surgery, Klinikum Ernst von Bergmann, Potsdam, Germany. Electronic address:

Background: Intragastric surgery with a single incision has been performed for several diseases, such as gastric tumors[1] and pancreatic pseudocyst[2], safety, feasibility and potential benefits of which have been reported in previous relevant studies[3].

Methods: The video shows a 65-year-old man with upper gastrointestinal hemorrhage, preoperative abdominal CT scan and endoscopy suggested an endophytic tumor located in gastric corpus, suggesting gastrointestinal stromal tumor (GIST). Intragastric single-port surgery (IGS) was indicated.

Results: Under general anesthesia, patient was placed in supine position. Surgeons stood on the right side of the patient. After a 2.5cm transverse incision was made on left upper abdominal wall, gastric anterior wall was exteriorized and fixed to the skin incision. Single-port device was inserted inside the stomach after anterior gastric wall was opened. Next, laparoscope was introduced into gastric cavity and identified the location of tumor. Full thickness resection of the tumor was performed by using linear stapler, then stapler line was embedded with continuous sutures. Finally, after specimen and single-port device removal, the stomach incision was closed extracorporeally. The operation time was 112 minutes. Final pathology confirmed GIST (4.5cm) with negative margins and patient discharged after 4 days, without postoperative complications. In 1-year follow-up time, without recurrence or death.

Conclusion: IGS is safe and effective for gastric endophytic GIST resection, which not only preserves all advantages of conventional laparoscopic operation, but also includes other benefits like obviating the need of abdominal cavity exploration, potential reduction of risk of neoplasm seeding, and offering good postoperative cosmetic result.
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http://dx.doi.org/10.1016/j.suronc.2020.06.001DOI Listing
December 2020

Biological Properties, Bioactive Constituents, and Pharmacokinetics of Some spp. and Capsaicinoids.

Int J Mol Sci 2020 Jul 22;21(15). Epub 2020 Jul 22.

Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.

Pepper originated from the genus, which is recognized as one of the most predominant and globally distributed genera of the Solanaceae family. It is a diverse genus, consisting of more than 31 different species including five domesticated species, , , , , and Pepper is the most widely used spice in the world and is highly valued due to its pungency and unique flavor. Pepper is a good source of provitamin A; vitamins E and C; carotenoids; and phenolic compounds such as capsaicinoids, luteolin, and quercetin. All of these compounds are associated with their antioxidant as well as other biological activities. Interestingly, fruits have been used as food additives in the treatment of toothache, parasitic infections, coughs, wound healing, sore throat, and rheumatism. Moreover, it possesses antimicrobial, antiseptic, anticancer, counterirritant, appetite stimulator, antioxidant, and immunomodulator activities. Capsaicin and creams are accessible in numerous ways and have been utilized in HIV-linked neuropathy and intractable pain.
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http://dx.doi.org/10.3390/ijms21155179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432674PMC
July 2020

Fibrin sealant for esophageal anastomosis: A phase II study.

World J Gastrointest Oncol 2020 Jun;12(6):651-662

Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.

Background: Esophagectomy is a pivotal curative modality for localized esophageal or esophagogastric junction cancer (EC or EJC). Postoperative anastomotic leakage (AL) remains problematic. The use of fibrin sealant (FS) may improve the strength of esophageal anastomosis and reduce the incidence of AL.

Aim: To assess the efficacy and safety of applying FS to prevent AL in patients with EC or EJC.

Methods: In this single-arm, phase II trial (Clinicaltrial.gov identifier: NCT03529266), we recruited patients aged 18-80 years with resectable EC or EJC clinically staged as T1-4aN0-3M0. An open or minimally invasive McKeown esophagectomy was performed with a circular stapled anastomosis. After performing the anastomosis, 2.5 mL of porcine FS was applied circumferentially. The primary endpoint was the proportion of patients with AL within 3 mo.

Results: From June 4, 2018, to December 29, 2018, 57 patients were enrolled. At the data cutoff date (June 30, 2019), three (5.3%) of the 57 patients had developed AL, including two (3.5%) with esophagogastric AL and one (1.8%) with gastric fistula. The incidence of anastomotic stricture and other major postoperative complications was 1.8% and 17.5%, respectively. The median time needed to resume oral feeding after operation was 8 d (Interquartile range: 7.0-9.0 d). No adverse events related to FS were recorded. No deaths occurred within 90 d after surgery.

Conclusion: Perioperative sealing with porcine FS appears safe and may prevent AL after esophagectomy in patients with resectable EC or EJC. Further phase III studies are warranted.
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http://dx.doi.org/10.4251/wjgo.v12.i6.651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340992PMC
June 2020

SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention.

Biochimie 2020 Aug 29;175:93-98. Epub 2020 May 29.

Faculty of Medicine, The University of Jordan, Amman, 11942, Jordan; Qatar Genome Project, Qatar Foundation, Doha, Qatar.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the much updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 infections.
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http://dx.doi.org/10.1016/j.biochi.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258854PMC
August 2020

Scaphoid excision with lunatocapitate fusion for the treatment of scaphoid nonunion with advanced collapsed wrist.

Int Orthop 2020 06 17;44(6):1153-1157. Epub 2020 Apr 17.

Alzhraa University Hospital, Faculty of Medicine for Girls, Al-Azhar University, Cairo, 11517, Egypt.

Purpose: To investigate the union rate after lunatocapitate arthrodesis for the treatment of scaphoid nonunion advanced collapse (SNAC) wrists and to evaluate the clinical results of this technique.

Methods: We conducted a prospective study between January 2014 and July 2017. Fifteen males with painful stage III SNAC wrists (average age, 32 years, range, 20-37 years; average follow-up time, 25.2 months, range, 20-36 months) underwent scaphoid excision and lunatocapitate fusion. Lunatocapitate fusions were fixed with headless Herbert screws with K-wire fixation (retrograde direction). Radiographs, wrist range of motion, and Mayo wrist score were examined.

Results: All patients achieved radiographic and clinical union after lunatocapitate fusion during follow-up (average 10 months post-operatively). The flexion-extension arc was 70°, and the average Mayo wrist score was 74.3 points (eight with excellent, four with good, three with satisfactory, and one with poor result). Thirteen patients returned to work, whereas two with nonunion required surgical graft revision. Complete union was achieved at an average of 12 weeks after graft revision, with improved range of motion, and the patients returned to work with a change in their occupation.

Conclusions: Lunatocapitate arthrodesis is a satisfactory therapeutic alternative to four-corner fusion for SNAC wrists.
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http://dx.doi.org/10.1007/s00264-020-04570-5DOI Listing
June 2020

Uniportal video assisted thoracoscopy versus open surgery for pulmonary hydatid disease-a single center experience.

J Thorac Dis 2020 Mar;12(3):794-802

Department of Cardiothoracic Surgery, Makassed Charitable Society Hospital, East Jerusalem, Palestine.

Background: Although rare in the Western world, the incidence of hydatid disease is still prevalent and strikingly endemic among the Palestinians. Until 2017, surgical treatment of lung pathologies was performed through the traditional incision (open thoracotomy). Uniportal video-assisted thoracoscopic surgery (VATS) approach has recently been applied in the cases of the pulmonary hydatid cysts with very satisfactory results.

Methods: Between January 2010 and January 2019, 39 patients with pulmonary HC disease have been surgically treated. The cases divided into two cohorts: operations performed by thoracotomy classified as group A, (n=16). Operations performed by uniportal VATS classified as group B, (n=23). Prospectively collected data was analysed retrospectively, and the results compared between both groups.

Results: No significant statistical differences were noticed in terms of demographics and comorbidity. Laboratory tests were similar except haemoglobin level, which was higher in group A (P=0.001). Despite that, blood transfusion was higher in group A (P=0.016). Moreover, operation time was longer in group A (P=0.000). Chest drainage remained longer in group A (P=0.077). The level of postoperative pain was significantly higher in group A certainly in POD 1 (P=0.000). Patients in group B discharged earlier from the hospital (P=0.011) and experienced lower complications (P=0.060). No significant difference in length of ICU stay. Neither recurrence nor 30-day mortality recorded in either group.

Conclusions: Uniportal VATS can be safely applied for pulmonary hydatidosis. It also seems to have a preference in several aspects compared to open Thoracotomy approach.
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http://dx.doi.org/10.21037/jtd.2019.12.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139009PMC
March 2020

Outcomes of inflammatory bowel disease in patients with eosinophil-predominant colonic inflammation.

BMJ Open Gastroenterol 2020 16;7(1):e000373. Epub 2020 Feb 16.

Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

Background: Inflammatory bowel disease (IBD) is characterised by acute intestinal mucosal inflammation with chronic inflammatory features. Various degrees of mucosal eosinophilia are present along with the typical acute (neutrophil-predominant) inflammation. The effect of intestinal eosinophils on IBD outcomes remains unclear.

Methods: This is a retrospective study. Archived intestinal mucosal biopsy specimens of treatment-naïve IBD patients were examined by two pathologists. The number of eosinophils per high-power field was counted, and the mucosal inflammation was classified according to the eosinophilic inflammatory patterns. Clinical outcomes during the follow-up period were recorded.

Results: 142 treatment-naïve IBD patients were included. Mean age was 39 years. 83% of patients had ulcerative colitis, and median follow-up was 3 years. 41% of patients had disease flare(s) and 24% required hospitalisation. Eosinophil count was not associated with risk of disease flare or hospitalisation. Patients with neutrophil-predominant inflammation (>70% neutrophils) had greater risk of disease flare(s): 27(55%) versus 24(36%) and 7(28%) in patients with mixed and eosinophil-predominant inflammation, respectively (p=0.04). Overall, patients with neutrophil-predominant inflammation were more likely to have a disease flare; HR: 2.49, 95% CI (1.0 to 5.6). Hospitalisation rate was higher in patients with neutrophil-predominant inflammation: 17(35%) compared to 17(19%) in patients with eosinophil-rich inflammation (p=0.04). Kaplan-Meier analysis showed higher flare-free survival in patients with eosinophil-predominant inflammation compared to mixed and neutrophil-predominant inflammation.

Conclusion: IBD patients with eosinophil-predominant inflammation phenotype might have reduced risk of disease flares and hospitalisation. Larger prospective studies to assess IBD outcomes in this subpopulation are warranted.
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http://dx.doi.org/10.1136/bmjgast-2020-000373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039632PMC
February 2020

Smoking cessation services in the Eastern Mediterranean Region: highlights and findings from the WHO Report on the Global Tobacco Epidemic 2019.

East Mediterr Health J 2020 Jan 30;26(1):110-115. Epub 2020 Jan 30.

Tobacco Free Initiative, Department Noncommunicable Diseases and Mental Health, World Health Organization, Regional Office for the Eastern Mediterranean, Cairo, Egypt.

The report aimed to review and assess the status of tobacco cessation services in the Eastern Mediterranean Region (EMR). Nearly 70% of people in the Region have legal access to nicotine-replacement therapy but for 77% of these people the costs of the treatment are not covered. Bupropion and Varenicline are legally available in 10 and 11 EMR countries respectively. Just under 50% of people in the Region have access to at least some cessation support in primary health care facilities. Around 32% of people have access to a national toll-free quit line. Costs for cessation services are fully covered in few EMR countries; however, cessation services in the Region must be improved. Member States should aim to increase the availability of, and financial support for, cessation treatments and support, which should be prioritized in primary health care facilities.
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http://dx.doi.org/10.26719/2020.26.1.110DOI Listing
January 2020

Co-encapsulation of thymoquinone with docetaxel enhances the encapsulation efficiency into PEGylated liposomes and the chemosensitivity of MCF7 breast cancer cells to docetaxel.

Heliyon 2019 Nov 27;5(11):e02919. Epub 2019 Nov 27.

Faculty of Medicine, The University of Jordan, Amman, Jordan.

Combinatorial therapeutic strategies to eradicate tumors can be superior to a single therapeutic modality. Docetaxel (DT) has been approved for the treatment of local or metastasized breast cancer alone or in combination with other chemotherapeutic agents. Thymoquinone (TQ) originated from the seeds of plant has been reported to possess and antitumor activity against variety of tumors. In the current study, we have investigated the synergistic anticancer efficacy of a novel combination of DT and TQ on MCF7 breast cancer cell line using MTT cell viability assay. Moreover, this study describes for the first time the co-encapsulation of DT and TQ into PEGylated liposomes. The results showed that the combination of DT and TQ resulted in significant synergistic cytotoxicity compared to DT and TQ alone. Moreover, DT and TQ have been successfully co-encapsulated into PEGylated liposomes with higher encapsulation efficiency compared to DT and TQ alone. In conclusion, DT and TQ combination poses a synergistic effect and may aid in decreasing the required doses of DT. Also, the co-encapsulation of DT and TQ into PEGylated liposomes can provide a promising DT and TQ delivery system into cancer cells.
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http://dx.doi.org/10.1016/j.heliyon.2019.e02919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895652PMC
November 2019

Teres major transfer to restore external rotation of shoulder in Erb palsy patients.

J Shoulder Elbow Surg 2020 May 20;29(5):941-945. Epub 2019 Nov 20.

Alzhraa University Hospital, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt.

Background: The lack of external rotation and shoulder abduction as sequelae of obstetric brachial plexus palsy requires a release of the subscapularis muscle associated with tendon transfer of the internal rotator of the shoulder. The aim of this study was to present the results of a teres major transfer to the infraspinatus tendon.

Methods: This study included 20 patients (9 boys and 11 girls) with a mean age of 3 years 8 months (range, 1.5-14 years). The average follow-up time was 42 months (range, 12-48 months) to determine whether external rotation weakness and internal rotation contracture sequelae were managed by anterior release of the subscapularis and teres major tendon transfer to the infraspinatus tendon.

Results: We found marked improvement in shoulder abduction from 67° before surgery to 158° after surgery. We also found marked improvements in active external rotation from 8° before surgery to 85° after surgery and in passive external rotation from 0° preoperatively to 72° postoperatively. Two cases showed a loss of the last degrees of internal rotation, but this improved after physiotherapy.

Conclusions: Anterior release of the subscapularis tendon with a teres major transfer to the infraspinatus tendon significantly improves shoulder function in Erb palsy patients with internal rotation contracture.
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http://dx.doi.org/10.1016/j.jse.2019.09.017DOI Listing
May 2020

Robotic-Extended Rethymectomy for Refractory Myasthenia Gravis: A Case Series.

Semin Thorac Cardiovasc Surg 2020 Autumn;32(3):593-602. Epub 2019 Nov 2.

Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Berlin, Germany. Electronic address:

To assess the safety and efficacy of robotic-extended rethymectomy in selected refractory myasthenia gravis (MG) patients with suspected residual thymic tissue. Robotic-extended rethymectomy was performed in 6 MG patients with seropositive acetylcholine receptors (AChR) antibody who had undergone a previous thymectomy (1 cervicotomy, 2 video-assisted thoracoscopic surgeries, and 3 sternotomies). The median observation time before robotic rethymectomy was 108 (24-171) months. The main outcomes were perioperative morbidity, mortality, conversion to open surgery, and clinical outcomes according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS). Before rethymectomy, all patients required immunosuppressants and 5 patients (83.3%) required intravenous immune globulin and/or plasma exchange to control the symptoms. The median specimen weight was 24.5 (14-144) g after rethymectomy, and residual thymic tissue was found in 5 patients (83.3%). No conversion to open surgery or perioperative morbidity and mortality was observed. With a median follow-up time of 46.5 (13-155) months, 3 patients (50%) achieved "improved" and 3 (50%) were "unchanged" according to the MGFA-PIS. Compared with preoperative use, the median daily dose of corticosteroids statistically decreased (25 [7.5-60] vs 0 [0-5] mg, P = 0.002) without significant change in azathioprine use (100 [0-200] vs 50 [0-150] mg, P = 0.360). AChR antibody positive MG patients with a treatment refractory long-term course after thymectomy might have remaining thymic tissue with the 2 commonly associated thymus pathologies, thymoma, and follicular hyperplasia. Robotic-extended rethymectomy might be considered as a safe and beneficial treatment option in these patients.
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http://dx.doi.org/10.1053/j.semtcvs.2019.10.016DOI Listing
October 2020

Unraveling the role of ectopic thymic tissue in patients undergoing thymectomy for myasthenia gravis.

J Thorac Dis 2019 Sep;11(9):4039-4048

Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Berlin, Germany.

Extended thymectomy has been considered the goal of surgery for myasthenia gravis (MG) mainly due to the existence of ectopic thymic tissue. Recently, ectopic thymic tissue has attracted increasing attention in patients with MG following thymectomy. However, the specific role of ectopic thymic tissue in patients with MG is still under debate. A systematic search of the literature was performed on PubMed and Medline according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISM) statement. Studies evaluating the rate of ectopic thymic tissue in patients with MG with or without thymoma were included. Extraction was performed for all eligible studies and the rate of ectopic thymic tissue at common locations was calculated. Eighteen out of fifty-nine studies were eligible for inclusion, of which ten studies reported the common locations of ectopic thymic tissue in mediastinal fat. Of these ten studies, the presence of ectopic thymic tissue was investigated in different anatomical locations in 882 patients, of whom, 509 patients (58%) have at least one positive location with the most common ones being anterior mediastinal fat, pericardiophrenic angles, aortopulmonary window, cervical region (pretracheal fat) and lateral to phrenic nerves. On the other hand, nine studies analyzed the influence of the presence of ectopic thymic tissue on the clinical outcomes of MG patients. Of these, six found that the presence of ectopic thymic tissue in MG patients is a significant predictor of poor outcome after thymectomy, however, the other three did not find a significance. Altogether, ectopic thymic tissue is likely to present in more than a half of patients undergoing thymectomy for MG. Besides, MG patients who have ectopic thymic tissue after thymectomy do not seem to have as good outcome as those who have not.
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http://dx.doi.org/10.21037/jtd.2019.08.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790439PMC
September 2019

Synthesis, Antiproliferative, and Antioxidant Evaluation of 2-Pentylquinazolin-4(3)-one(thione) Derivatives with DFT Study.

Molecules 2019 Oct 21;24(20). Epub 2019 Oct 21.

Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

The current study was chiefly designed to examine the antiproliferative and antioxidant activities of some novel quinazolinone(thione) derivatives -. The present work focused on two main points; firstly, comparing between quinazolinone and quinazolinthione derivatives. Whereas, antiproliferative (against two cell lines namely, HepG2 and MCF-7) and antioxidant (by two methods; ABTS and DPPH) activities of the investigated compounds, the best quinazolinthione derivatives were and which exhibited excellent potencies comparable to quinazolinone derivatives and , respectively. Secondly, we compared the activity of four series of Schiff bases which included the quinazolinone moiety (-). In addition, the antiproliferative and antioxidant activities of the compounds with various aryl aldehyde hydrazone derivatives (-) analogs were studied. The compounds exhibited potency that increased with increasing electron donating group in -position (OH > OMe > Cl) due to extended conjugated systems. Noteworthy, most of antiproliferative and antioxidant activities results for the tested compounds are consistent with the DFT calculations.
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http://dx.doi.org/10.3390/molecules24203787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832655PMC
October 2019

Devising the guidelines: the concept of uniportal video-assisted thoracic surgery-instrumentation and operatory room staff.

J Thorac Dis 2019 Sep;11(Suppl 16):S2079-S2085

Department of Thoracic Surgery, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.

In the last years, uniportal video-assisted thoracic surgery (VATS) has been gaining more and more popularity, becoming a common procedure in several thoracic centers all over the world not only for minor procedures but also for major and complex cases. This technique combines the advantages of the less invasiveness with the oncological principles of open surgery. A standardization of the different peri- and intraoperative steps can help in the establishment and development of this technique. The aim of this paper is to set the basic steps for operating room set-up and instrumentation for starting or improving a uniportal VATS program in thoracic surgery centers.
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http://dx.doi.org/10.21037/jtd.2019.08.69DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783704PMC
September 2019

Thymectomy in ocular myasthenia gravis before generalization results in a higher remission rate.

Eur J Cardiothorac Surg 2020 03;57(3):478-487

Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Berlin, Germany.

Objectives: This study aimed to compare the outcomes of patients with ocular myasthenia gravis (OMG) who underwent thymectomy before generalization with the outcomes of those who underwent thymectomy after generalization.

Methods: We retrospectively reviewed patients who underwent robotic thymectomy for myasthenia gravis between January 2003 and February 2018. Patients who presented with purely ocular symptoms at myasthenia gravis onset were eligible for inclusion. Exclusion criteria were patients who were lost to follow-up and patients who underwent re-thymectomy. Patients with OMG who developed generalization before thymectomy were categorized into gOMG group and those who did not were categorized into OMG group. The primary outcome was complete stable remission according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS).

Results: One hundred and sixty-five (66 males and 99 females) out of 596 patients with myasthenia gravis were eligible for inclusion. Of these, there were 73 and 92 patients undergoing thymectomy before and after the generalization of OMG, respectively. After propensity score matching, a data set of 130 patients (65 per group) was formed and evaluating results showed no statistical differences between the 2 groups. The estimated cumulative probabilities of complete stable remission at 5 years were 49.5% [95% confidence interval (CI) 0.345-0.611] in the OMG group and 33.4% (95% CI 0.176-0.462) in the gOMG group (P = 0.0053). Similar results were also found in patients with non-thymomatous subgroup [55 patients per group, OMG vs gOMG, 53.5% (95% CI 0.370-0.656) vs 28.9% (95% CI 0.131-0.419), P = 0.0041].

Conclusions: Thymectomy in OMG before generalization might result in a higher rate of complete stable remission than thymectomy after generalization.
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http://dx.doi.org/10.1093/ejcts/ezz275DOI Listing
March 2020

FcRn mediates fast recycling of endocytosed albumin and IgG from early macropinosomes in primary macrophages.

J Cell Sci 2019 10 1;133(5). Epub 2019 Oct 1.

The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia

The neonatal Fc receptor (FcRn) rescues albumin and IgG from degradation following endocytosis and thereby extends the half-life of these plasma proteins. However, the pathways for the uptake of these soluble FcRn ligands, and the recycling itinerary of the FcRn-ligand complexes, have not been identified in primary cells. Here, we have defined the recycling of human albumin and IgG in primary mouse macrophages selectively expressing the human FcRn. Albumin is internalised by macropinocytosis; in the absence of FcRn, internalised albumin is rapidly degraded, while in the presence of FcRn albumin colocalises to SNX5-positive membrane domains and is partitioned into tubules emanating from early macropinosomes for delivery in transport carriers to the plasma membrane. Soluble monomeric IgG was also internalised by macropinocytosis and rapidly recycled by the same pathway. In contrast, the fate of IgG bound to surface Fcγ receptors differed from monomeric IgG endocytosed by macropinocytosis. Overall, our findings identify a rapid recycling pathway for FcRn ligands from early macropinosomes to the cell surface of primary cells.
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http://dx.doi.org/10.1242/jcs.235416DOI Listing
October 2019

Level of evidence on long-term results after VATS lobectomy: state of the art.

J Thorac Dis 2019 Jun;11(6):2192-2194

Department of Thoracic Surgery, Klinikum Ernst von Bergmann Potsdam, Academic Hospital of the Charité - Universitätsmedizin Humboldt University Berlin, Germany.

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http://dx.doi.org/10.21037/jtd.2019.06.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626795PMC
June 2019

Salvage treatment with sole high-dose-rate endobronchial interventional radiotherapy (brachytherapy) for isolated endobronchial tumor recurrence in non-small-cell lung cancer patients: a 20-year experience.

Brachytherapy 2019 Sep - Oct;18(5):727-732. Epub 2019 Jun 18.

Department of Clinical Radiation Oncology, Ernst von Bergmann Medical Center, Academic Teaching Hospital of Humboldt University Berlin (Charité), Potsdam, Germany.

Purpose: The purpose of this study was to report on the use of high-dose-rate (HDR) endobronchial interventional radiotherapy (brachytherapy) for isolated endobronchial tumor recurrence in patients with non-small-cell lung cancer, in whom a surgery or external radiation treatment is not possible.

Methods And Materials: A retrospective review of the patients with endobronchial tumors treated with HDR-endobronchial interventional radiotherapy at our institution (1995-2015) was performed. Treatment results and treatment-related toxicity were recorded. Clinical response was evaluated by bronchoscopy 3 months after treatment. Disease-free survival and overall survival were analyzed.

Results: One hundred twenty-six patients were identified. The median age was 63 years, and median followup time was 67.2 months. Three-month complete local response was 86.5%. At 5 years, disease-free survival was 41.4% and overall survival was 23.6%. 12.7% of the patients died from massive hemoptysis.

Conclusion: HDR-endo brochial brachytherapy is an effective treatment option with acceptable toxicity for patients with endobronchial tumor recurrence in whom surgery and external beam radiotherapy are contraindicated.
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http://dx.doi.org/10.1016/j.brachy.2019.04.271DOI Listing
March 2020

Uniportal VATS Coil-Assisted Resections for GGOs.

J Oncol 2019 12;2019:5383086. Epub 2019 May 12.

UOC di Chirurgia Toracica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

Backgrounds: Although uniportal video-assisted thoracic surgery (VATS) theoretically allows the direct palpation of any zone of the lung through a small incision, sometimes it can be difficult to localize pure ground-glass opacities anyway. The aim of this study is to evaluate the usefulness and safety of preoperative computed tomography (CT)-guided microcoil localization of GGO nodules in patients undergoing uniportal VATS lung resection.

Methods: The clinical data and CT images of 30 consecutive patients (30 pulmonary nodules) who underwent preoperative CT-guided coil localization and subsequent uniportal VATS resection, from January 2017 to October 2018, were reviewed.

Results: All the CT-localization procedures have been performed with success (30/30) and the mean procedure time was 35±15 minutes. The mean size of the nodules was 15,53±6,72 mm, and the mean distance of the nodules from the pleural surface was 19,08±12,08 mm. Eleven nodules (36,7%) were pure ground-glass opacities and 19 (63,3%) were mixed ground-glass with a solid component of 50% or more. In 5 cases, the localization procedure was complicated by asymptomatic pneumothoraxes and in 1 case the pneumothorax required chest tube insertion. In any case a conversion to thoracotomy was avoided because all nodules were identified and resected through uniportal VATS.

Conclusions: Preoperative CT-guided coil localization seems to be a feasible, safe, and accurate procedure. It makes uniportal VATS an easy approach even for resecting small, deep, and impalpable nodules.
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http://dx.doi.org/10.1155/2019/5383086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535831PMC
May 2019

A comparison of mutation status in tissue and plasma cell-free DNA detected by ADx-ARMS in advanced lung adenocarcinoma patients.

Transl Lung Cancer Res 2019 Apr;8(2):135-143

The Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.

Background: Previous studies have shown that there are different methods used to detect the epidermal growth factor receptor () mutation status in plasma cell-free DNA (cfDNA) for advanced lung adenocarcinoma patients including the ADx-Amplification Refractory Mutation System (ADx-ARMS). We explored the performance of the ADx-ARMS in detecting the mutations in cfDNA.

Methods: This prospective cohort study enrolled patients who presented with advanced (stage IIIb/IV) lung adenocarcinoma. mutations in plasma cfDNA and tumor tissues by ADx-ARMS were detected. Next-generation sequencing (NGS) in plasma was performed in patients with inconsistent gene region mutations in the plasma and matched tissue samples. We calculated the clinical parameters of the ADx-ARMS for mutation status in the plasma of cfDNA, using the tumor tissues as the standard for measurement. The objective response rate (ORR) and progression-free survival (PFS) were also calculated for patients receiving first-generation EGFR-tyrosine kinase inhibitors (TKIs) therapy.

Results: In total, 203 patients were included in the final analysis. Mutations were discovered in 58.6% (119/203) of the tumor tissues and 31.0% (63/203) were detected mutations in both tumor tissues and matched plasma. The sensitivity and the specificity setting for detecting the mutations in the plasma using the ADx-ARMS were configured to 52.9% and 98.8%. An ORR of 64.8% was observed among the 71 patients who were identified as being -positive in their tumor tissues, who had received treatments using Gefitinib or Icotinib. Next, the ORR was observed to be 69.0% among the 42 patients with an mutation in their plasma. The median PFS of the patients with an mutation in tumor tissues and plasma were 10.0 11.0 months (P=0.175). The median PFS of the patients with an wild-type in the plasma was 8.7 months, which was significantly shorter than the mutant-type in plasma (P=0.001).

Conclusions: Using ADx-ARMS as an approach with high specificity but moderate sensitivity to detect the mutations in plasma cfDNA and mutation status in plasma cfDNA using the ADx-ARMS can predict the tumor response for EGFR-TKIs.
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http://dx.doi.org/10.21037/tlcr.2019.03.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504650PMC
April 2019

Uniportal video-assisted thoracic surgery lobectomy: a consensus report from the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS).

Eur J Cardiothorac Surg 2019 Aug;56(2):224-229

Department of Surgery, Thoracic Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Objectives: Our goal was to report the results of the first consensus paper among international experts in uniportal video-assisted thoracoscopic surgery (UniVATS) lobectomy obtained through a Delphi process, the objective of which was to define and standardize the main procedural steps, optimize its indications and perioperative management and identify elements to assist in future training.

Methods: The 40 members of the working group were convened and organized on a voluntary basis by the Uniportal VATS Interest Group (UVIG) of the European Society of Thoracic Surgeons (ESTS). An e-consensus finding exercise using the Delphi method was applied to require 75% agreement for reaching consensus on each question. Repeated iterations of anonymous voting continued for 3 rounds.

Results: Overall, 31 international experts from 18 countries completed all 3 rounds of questionnaires. Although a technical quorum was not achieved, most of the responders agreed that the maximum size of a UniVATS incision should be ≤4 cm. Agreement was reached on many points outlining the currently accepted definition of a UniVATS lobectomy, its indications and contraindications, perioperative clinical management and recommendations for training and future research directions.

Conclusions: The UVIG Consensus Report stated that UniVATS offers a valid alternative to standard VATS techniques. Only longer follow-up and randomized controlled studies will predict whether UniVATS represents a valid alternative approach to multiport VATS for major lung resections or whether it should be performed only in selected cases and by selected centres. The next step for the ESTS UVIG is the establishment of a UniVATS section inside the ESTS databases.
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http://dx.doi.org/10.1093/ejcts/ezz133DOI Listing
August 2019

Surgical Techniques for Myasthenia Gravis: Robotic-Assisted Thoracoscopic Surgery.

Thorac Surg Clin 2019 May;29(2):177-186

Department of Surgery, Competence Center of Thoracic Surgery, Charité University Hospital Berlin, Charitéplatz 1, Berlin 10117, Germany. Electronic address:

Robotic-assisted thoracoscopic surgery (RATS) creates an extended approach for thymectomy in terms of locating contralateral phrenic nerve and upper poles of the thymus. RATS thymectomy is indicated in all non-thymomatous myasthenia gravis (MG) patients and thymomatous MG patients with resectable thymoma, typically Masaoka-Koga I and II. Left-sided RATS thymectomy is superior for anatomic reasons and in the special care patients with MG. Up to now, left-sided three-trocar RATS thymectomy is the perfect combination of radical resection and minimal invasiveness among various approaches for thymectomy.
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http://dx.doi.org/10.1016/j.thorsurg.2018.12.006DOI Listing
May 2019