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Synaptic processes and immune-related pathways implicated in Tourette syndrome

Tsetsos, Fotis; Yu, Dongmei; Sul, Jae Hoon; Huang, Alden Y; Illmann, Cornelia; Osiecki, Lisa; Darrow, Sabrina M; Hirschtritt, Matthew E; Greenberg, Erica; Muller-Vahl, Kirsten R; Stuhrmann, Manfred; Dion, Yves; Rouleau, Guy A; Aschauer, Harald; Stamenkovic, Mara; Schlögelhofer, Monika; Sandor, Paul; Barr, Cathy L; Grados, Marco A; Singer, Harvey S; Nöthen, Markus M; Hebebrand, Johannes; Hinney, Anke; King, Robert A; Fernandez, Thomas V; Barta, Csaba; Tarnok, Zsanett; Nagy, Peter; Depienne, Christel; Worbe, Yulia; Hartmann, Andreas; Budman, Cathy L; Rizzo, Renata; Lyon, Gholson J; McMahon, William M; Batterson, James R; Cath, Danielle C; Malaty, Irene A; Okun, Michael S; Berlin, Cheston; Woods, Douglas W; Lee, Paul C; Jankovic, Joseph; Robertson, Mary M; Gilbert, Donald L; Brown, Lawrence W; Coffey, Barbara J; Dietrich, Andrea; Hoekstra, Pieter J; Kuperman, Samuel; Zinner, Samuel H; Wagner, Michael; Knowles, James A; Jeremy Willsey, A; Tischfield, Jay A; Heiman, Gary A; Cox, Nancy J; Freimer, Nelson B; Neale, Benjamin M; Davis, Lea K; Coppola, Giovanni; Mathews, Carol A; Scharf, Jeremiah M; Paschou, Peristera; Barr, Cathy L; Batterson, James R; Berlin, Cheston; Budman, Cathy L; Cath, Danielle C; Coppola, Giovanni; Cox, Nancy J; Darrow, Sabrina; Davis, Lea K; Dion, Yves; Freimer, Nelson B; Grados, Marco A; Greenberg, Erica; Hirschtritt, Matthew E; Huang, Alden Y; Illmann, Cornelia; King, Robert A; Kurlan, Roger; Leckman, James F; Lyon, Gholson J; Malaty, Irene A; Mathews, Carol A; McMahon, William M; Neale, Benjamin M; Okun, Michael S; Osiecki, Lisa; Robertson, Mary M; Rouleau, Guy A; Sandor, Paul; Scharf, Jeremiah M; Singer, Harvey S; Smit, Jan H; Sul, Jae Hoon; Yu, Dongmei; Aschauer, Harald Aschauer Harald; Barta, Csaba; Budman, Cathy L; Cath, Danielle C; Depienne, Christel; Hartmann, Andreas; Hebebrand, Johannes; Konstantinidis, Anastasios; Mathews, Carol A; Müller-Vahl, Kirsten; Nagy, Peter; Nöthen, Markus M; Paschou, Peristera; Rizzo, Renata; Rouleau, Guy A; Sandor, Paul; Scharf, Jeremiah M; Schlögelhofer, Monika; Stamenkovic, Mara; Stuhrmann, Manfred; Tsetsos, Fotis; Tarnok, Zsanett; Wolanczyk, Tomasz; Worbe, Yulia; Brown, Lawrence; Cheon, Keun-Ah; Coffey, Barbara J; Dietrich, Andrea; Fernandez, Thomas V; Garcia-Delgar, Blanca; Gilbert, Donald; Grice, Dorothy E; Hagstrøm, Julie; Hedderly, Tammy; Heiman, Gary A; Heyman, Isobel; Hoekstra, Pieter J; Huyser, Chaim; Kim, Young Key; Kim, Young-Shin; King, Robert A; Koh, Yun-Joo; Kook, Sodahm; Kuperman, Samuel; Leventhal, Bennett L; Madruga-Garrido, Marcos; Mir, Pablo; Morer, Astrid; Münchau, Alexander; Plessen, Kerstin J; Roessner, Veit; Shin, Eun-Young; Song, Dong-Ho; Song, Jungeun; Tischfield, Jay A; Willsey, A Jeremy; Zinner, Samuel; Aschauer, Harald; Barr, Cathy L; Barta, Csaba; Batterson, James R; Berlin, Cheston; Brown, Lawrence; Budman, Cathy L; Cath, Danielle C; Coffey, Barbara J; Coppola, Giovanni; Cox, Nancy J; Darrow, Sabrina; Davis, Lea K; Depienne, Christel; Dietrich, Andrea; Dion, Yves; Fernandez, Thomas; Freimer, Nelson B; Gilbert, Donald; Grados, Marco A; Greenberg, Erica; Hartmann, Andreas; Hebebrand, Johannes; Heiman, Gary; Hirschtritt, Matthew E; Hoekstra, Pieter; Huang, Alden Y; Illmann, Cornelia; Jankovic, Joseph; King, Robert A; Kuperman, Samuel; Lee, Paul C; Lyon, Gholson J; Malaty, Irene A; Mathews, Carol A; McMahon, William M; Müller-Vahl, Kirsten; Nagy, Peter; Neale, Benjamin M; Nöthen, Markus M; Okun, Michael S; Osiecki, Lisa; Paschou, Peristera; Rizzo, Renata; Robertson, Mary M; Rouleau, Guy A; Sandor, Paul; Scharf, Jeremiah M; Schlögelhofer, Monika; Singer, Harvey S; Stamenkovic, Mara; Stuhrmann, Manfred; Sul, Jae Hoon; Tarnok, Zsanett; Tischfield, Jay; Tsetsos, Fotis; Willsey, A Jeremy; Woods, Douglas; Worbe, Yulia; Yu, Dongmei; Zinner, Samuel
Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.
PMID: 33462189
ISSN: 2158-3188
CID: 4760342

Upper Extremity Arterial Thromboembolism in a Coronavirus Patient. A Case Report

Scott, Beverley-Ann; Garg, Karan; Johnson, William; Al-Ajam, Mohammad; Patalano, Peter; Rotella, Vittorio; Edwards, Jodi-Ann; Aboushi, Haytham; Lee, Paul; Daniel, Melissa; Rancy, Schneider; Heimann, David
The coronavirus disease 2019 pandemic has impacted millions of people worldwide. This novel virus has a variety of presentations and complications. Notably, patients with this infection have an associated coagulopathy, presenting with symptoms such as gastrointestinal bleeds, deep vein thrombosis, ischemic cerebrovascular events, and pulmonary embolism. Although there are documented cases of venous thromboembolism in patients with coronavirus disease 2019, the authors present an interesting case of upper extremity arterial thromboembolism in a 75-year-old patient surgically treated for arterial thrombus removal. We also discuss diagnosis, medical management, and surgical approach to an upper extremity arterial thromboembolism in a patient with coronavirus disease 2019, to highlight the challenges of hypercoagulability in such patients.
PMCID:7788384
PMID: 33432306
ISSN: 2523-8973
CID: 5005692

Subnational mapping of HIV incidence and mortality among individuals aged 15-49 years in sub-Saharan Africa, 2000-18: a modelling study

Sartorius, Benn; Van der Heide, John; Yang, Mingyou; Goosmann, Erik; Hon, Julia; Haeuser, Emily; Cork, Michael; Perkins, Samantha; Jahagirdar, Deepa; Schaeffer, Lauren; Serfes, Audrey; LeGrand, Kate; Abbastabar, Hedayat; Abebo, Zeleke; Abosetugn, Akine; Abu-Gharbieh, Eman; Accrombessi, Manfred; Adebayo, Oladimeji; Adegbosin, Adeyinka; Adekanmbi, Victor; Adetokunboh, Olatunji; Adeyinka, Daniel; Ahinkorah, Bright; Ahmadi, Keivan; Ahmed, Muktar; Akalu, Yonas; Akinyemi, Oluwaseun; Akinyemi, Rufus; Aklilu, Addis; Akunna, Chisom; Alahdab, Fares; Al-Aly, Ziyad; Alam, Noore; Alamneh, Alehegn; Alanzi, Turki; Alemu, Biresaw; Alhassan, Robert; Ali, Tilahun; Alipour, Vahid; Amini, Saeed; Ancuceanu, Robert; Ansari, Fereshteh; Anteneh, Zelalem; Anvari, Davood; Anwer, Razique; Appiah, Seth; Arabloo, Jalal; Asemahagn, Mulusew; Jafarabadi, Mohammad; Asmare, Wondwossen; Atnafu, Desta; Atout, Maha; Atreya, Alok; Ausloos, Marcel; Awedew, Atalel; Quintanilla, Beatriz; Ayanore, Martin; Aynalem, Yared; Ayza, Muluken; Azari, Samad; Azene, Zelalem; Babar, Zaheer-Ud-Din; Baig, Atif; Balakrishnan, Senthilkumar; Banach, Maciej; Barnighausen, Till; Basu, Sanjay; Bayati, Mohsen; Bedi, Neeraj; Bekuma, Tariku; Bezabhe, Woldesellassie; Bhagavathula, Akshaya; Bhardwaj, Pankaj; Bhattacharyya, Krittika; Bhutta, Zulfiqar; Bibi, Sadia; Bikbov, Boris; Birhan, Tsegaye; Bitew, Zebenay; Bockarie, Moses; Boloor, Archith; Brady, Oliver; Bragazzi, Nicola; Briko, Andrey; Briko, Nikolay; Nagaraja, Sharath; Butt, Zahid; Cardenas, Rosario; Carvalho, Felix; Charan, Jaykaran; Chatterjee, Souranshu; Chattu, Soosanna; Chattu, Vijay; Chowdhury, Mohiuddin; Chu, Dinh-Toi; Cook, Aubrey; Cormier, Natalie; Cowden, Richard; Culquichicon, Carlos; Dagnew, Baye; Dahlawi, Saad; Damiani, Giovanni; Daneshpajouhnejad, Parnaz; Daoud, Farah; Daryani, Ahmad; das Neves, Jose; Weaver, Nicole; Molla, Meseret; Deribe, Kebede; Desta, Abebaw; Deuba, Keshab; Dharmaratne, Samath; Dhungana, Govinda; Diaz, Daniel; Djalalinia, Shirin; Doku, Paul; Dubljanin, Eleonora; Duko, Bereket; Eagan, Arielle; Earl, Lucas; Eaton, Jeffrey; Effiong, Andem; Zaki, Maysaa; El Tantawi, Maha; Elayedath, Rajesh; El-Jaafary, Shaimaa; Elsharkawy, Aisha; Eskandarieh, Sharareh; Eyawo, Oghenowede; Ezzikouri, Sayeh; Fasanmi, Abidemi; Fasil, Alebachew; Fauk, Nelsensius; Feigin, Valery; Ferede, Tomas; Fernandes, Eduarda; Fischer, Florian; Foigt, Nataliya; Folayan, Morenike; Foroutan, Masoud; Francis, Joel; Fukumoto, Takeshi; Gad, Mohamed; Geberemariyam, Biniyam; Gebregiorgis, Birhan; Gebremichael, Berhe; Gesesew, Hailay; Getacher, Lemma; Ghadiri, Keyghobad; Ghashghaee, Ahmad; Gilani, Syed; Ginindza, Themba; Glagn, Mustefa; Golechha, Mahaveer; Gona, Philimon; Gubari, Mohammed; Gugnani, Harish; Guido, Davide; Guled, Rashid; Hall, Brian; Hamidi, Samer; Handiso, Demelash; Hargono, Arief; Hashi, Abdiwahab; Hassanipour, Soheil; Hassankhani, Hadi; Hayat, Khezar; Herteliu, Claudiu; de Hidru, Hagos; Holla, Ramesh; Hosgood, H.; Hossain, Naznin; Hosseini, Mostafa; Hosseinzadeh, Mehdi; Househ, Mowafa; Hwang, Bing-Fang; Ibitoye, Segun; Ilesanmi, Olayinka; Ilic, Irena; Ilic, Milena; Irvani, Seyed; Iwu, Chidozie; Iwu, Chinwe; Iyamu, Ihoghosa; Jain, Vardhmaan; Jakovljevic, Mihajlo; Jalilian, Farzad; Jha, Ravi; Johnson, Kimberly; Joshua, Vasna; Joukar, Farahnaz; Jozwiak, Jacek; Kabir, Ali; Kalankesh, Leila; Kalhor, Rohollah; Kamath, Ashwin; Kamyari, Naser; Kanchan, Tanuj; Matin, Behzad; Karch, Andre; Karimi, Salah; Kasa, Ayele; Kassahun, Getinet; Kayode, Gbenga; Karyani, Ali; Keiyoro, Peter; Kelkay, Bayew; Khalid, Nauman; Khan, Gulfaraz; Khan, Junaid; Khan, Md; Khatab, Khaled; Khazaei, Salman; Kim, Yun; Kisa, Adnan; Kisa, Sezer; Kochhar, Sonali; Kopec, Jacek; Kosen, Soewarta; Laxminarayana, Sindhura; Koyanagi, Ai; Krishan, Kewal; Defo, Barthelemy; Kugbey, Nuworza; Kulkarni, Vaman; Kumar, Manasi; Kumar, Nithin; Kurmi, Om; Kusuma, Dian; Kuupiel, Desmond; Kyu, Hmwe; La Vecchia, Carlo; Lal, Dharmesh; Lam, Jennifer; Landires, Ivan; Lasrado, Savita; Lazarus, Jeffrey; Lazzar-Atwood, Alice; Lee, Paul; Leshargie, Cheru; Li, Bingyu; Liu, Xuefeng; Lopukhov, Platon; Amin, Hawraz; Madi, Deepak; Mahasha, Phetole; Majeed, Azeem; Maleki, Afshin; Maleki, Shokofeh; Mamun, Abdullah; Manafi, Navid; Mansournia, Mohammad; Martins-Melo, Francisco; Masoumi, Seyedeh; Mayala, Benjamin; Meharie, Birhanu; Meheretu, Hailemariam; Meles, Hagazi; Melku, Mulugeta; Mendoza, Walter; Mengesha, Endalkachew; Meretoja, Tuomo; Mersha, Abera; Mestrovic, Tomislav; Miller, Ted; Mirica, Andreea; Alavijeh, Mehdi; Mohamad, Osama; Mohammad, Yousef; Mohammadian-Hafshejani, Abdollah; Mohammed, Jemal; Mohammed, Salahuddin; Mohammed, Shafiu; Mokdad, Ali; Mokonnon, Taklu; Molokhia, Mariam; Moradi, Masoud; Moradi, Yousef; Moradzadeh, Rahmatollah; Moraga, Paula; Mosser, Jonathan; Munro, Sandra; Mustafa, Ghulam; Muthupandian, Saravanan; Naderi, Mehdi; Nagarajan, Ahamarshan; Naghavi, Mohsen; Naveed, Muhammad; Nayak, Vinod; Nazari, Javad; Ndejjo, Rawlance; Nepal, Samata; Netsere, Henok; Ngalesoni, Frida; Nguefack-Tsague, Georges; Ngunjiri, Josephine; Nigatu, Yeshambel; Nigussie, Samuel; Nnaji, Chukwudi; Noubiap, Jean; Nunez-Samudio, Virginia; Oancea, Bogdan; Odukoya, Oluwakemi; Ogbo, Felix; Oladimeji, Olanrewaju; Olagunju, Andrew; Olusanya, Bolajoko; Olusanya, Jacob; Omer, Muktar; Omonisi, Abidemi; Onwujekwe, Obinna; Orisakwe, Orish; Otstavnov, Nikita; Owolabi, Mayowa; Mahesh, P.; Padubidri, Jagadish; Pakhale, Smita; Pana, Adrian; Pandi-Perumal, Seithikurippu; Patel, Urvish; Pathak, Mona; Patton, George; Pawar, Shrikant; Peprah, Emmanuel; Pokhrel, Khem; Postma, Maarten; Pottoo, Faheem; Pourjafar, Hadi; Pribadi, Dimas; Syed, Zahiruddin; Rafiei, Alireza; Rahim, Fakher; Rahman, Mohammad; Rahmani, Amir; Ram, Pradhum; Rana, Juwel; Ranabhat, Chhabi; Rao, Satish; Rao, Sowmya; Rathi, Priya; Rawaf, David; Rawaf, Salman; Rawassizadeh, Reza; Renjith, Vishnu; Reta, Melese; Rezaei, Nima; Rezapour, Aziz; Ribeiro, Ana; Ross, Jennifer; Rumisha, Susan; Sagar, Rajesh; Sahu, Maitreyi; Sajadi, S.; Salem, Marwa; Samy, Abdallah; Sathian, Brijesh; Schutte, Aletta; Seidu, Abdul-Aziz; Sha, Feng; Shafaat, Omid; Shahbaz, Mohammad; Shaikh, Masood; Shaka, Mohammed; Sheikh, Aziz; Shibuya, Kenji; Shin, Jae; Shivakumar, K.; Sidemo, Negussie; Singh, Jasvinder; Skryabin, Valentin; Skryabina, Anna; Soheili, Amin; Soltani, Shahin; Somefun, Oluwaseyi; Sorrie, Muluken; Spurlock, Emma; Sufiyan, Mu\awiyyah; Taddele, Biruk; Tadesse, Eyayou; Tamir, Zemenu; Tamiru, Animut; Tanser, Frank; Taveira, Nuno; Tehrani-Banihashemi, Arash; Tekalegn, Yohannes; Tesfay, Fisaha; Tessema, Belay; Tessema, Zemenu; Thakur, Bhaskar; Tolani, Musliu; Topor-Madry, Roman; Torrado, Marco; Tovani-Palone, Marcos; Traini, Eugenio; Tsai, Alexander; Tsegaye, Gebiyaw; Ullah, Irfan; Ullah, Saif; Umeokonkwo, Chukwuma; Unnikrishnan, Bhaskaran; Vardavas, Constantine; Violante, Francesco; Vo, Bay; Wado, Yohannes; Waheed, Yasir; Wamai, Richard; Wang, Yanzhong; Ward, Paul; Werdecker, Andrea; Wickramasinghe, Nuwan; Wijeratne, Tissa; Wiysonge, Charles; Wondmeneh, Temesgen; Yamada, Tomohide; Yaya, Sanni; Yeshaw, Yigizie; Yeshitila, Yordanos; Yilma, Mekdes; Yip, Paul; Yonemoto, Naohiro; Yosef, Tewodros; Yusefzadeh, Hasan; Zaidi, Syed; Zaki, Leila; Zamanian, Maryam; Zastrozhin, Mikhail; Zastrozhina, Anasthasia; Zewdie, Dejene; Zhang, Yunquan; Zhang, Zhi-Jiang; Ziapour, Arash; Hay, Simon; Dwyer-Lindgren, Laura
ISI:000657477600012
ISSN: 2352-3018
CID: 5017102

Clinical Predictors of Nodal Metastases in Peripherally Clinical T1a N0 Non-Small Cell Lung Cancer

Ghaly, Galal; Rahouma, Mohamed; Kamel, Mohamed K; Nasar, Abu; Harrison, Sebron; Nguyen, Andrew B; Port, Jeffrey; Stiles, Brendon M; Altorki, Nasser K; Lee, Paul C
BACKGROUND:Despite the relatively high sensitivity of fluorodeoxyglucose-positron emission tomography (PET) and computed tomography (CT) scans used for staging of non-small cell lung cancer (NSCLC), a subset of patients with peripherally located clinical T1a N0 will be upstaged due to pathologic nodal disease. It is important to study this risk of upstaging, especially if local treatments, such as wedge resection or stereotactic body radiation therapy, are potential treatment modalities. Our aim was to determine the rate of pathologic N1/N2 disease in peripherally located clinical T1a N0 NSCLC and predictive factors for nodal metastasis. METHODS:A retrospective review of a prospective database (2000 to 2015) identified 1,342 patients with clinical T1a N0 NSCLC, and 914 (68%) underwent lobectomy. Among this group, 449 patients had peripherally located tumors and were deemed node negative by fluorodeoxyglucose-PET/CT scan. The relationship between clinicopathologic features and the PET maximal-standardized uptake value (SUVmax) of the primary tumor was investigated. Predictors for nodal metastasis were determined by multivariable logistic regression analysis. The receiver operating characteristic curve was used to assess the cutoff value of PET-SUVmax on the incidence of nodal metastasis. RESULTS:Nodal metastasis was detected in 9.6% (43 of 449) of the patients: 4.5% (n = 20) had pN1 and 5.1% (n = 23) had pN2 metastasis. The relationship between SUVmax and development of pathologic nodal metastasis was calculated using the receiver operating characteristic curve with cutoff point at SUVmax of 3.3. In multivariable analysis, PET-SUVmax exceeding 3.3 was the only independent predictor for N1/N2 metastasis (p = 0.016). Disease-free survival showed a trend of poor survival for patients with nodal metastasis (p = 0.068). CONCLUSIONS:High PET-SUVmax of the primary tumor is associated with elevated risk of nodal disease for peripheral T1a N0 NSCLC patients. Further diagnostic procedures, such as endobronchial ultrasound, may be required, especially if wedge resection or stereotactic body radiation therapy are being considered.
PMID: 28551047
ISSN: 1552-6259
CID: 3917802

The importance of lymph node dissection accompanying wedge resection for clinical stage IA lung cancer

Stiles, Brendon M; Kamel, Mohamed K; Nasar, Abu; Harrison, Sebron; Nguyen, Andrew B; Lee, Paul; Port, Jeffrey L; Altorki, Nasser K
Objectives:For patients undergoing lobectomy for non-small cell lung cancer (NSCLC), a survival benefit exists with increased number of lymph nodes (LNs) resected. We sought to evaluate the associations of LN removal with outcomes in clinical stage I lung cancer patients undergoing wedge resection. Methods:We evaluated all patients undergoing wedge resection for peripheral, clinical stage IA NSCLC and grouped patients into those with and without LN assessment. Data were compared and survival analysed using Kaplan-Meier, with differences compared using log-rank. Propensity score matching controlling for age, gender, Charlson comorbidity index, patient tolerability of lobectomy, surgery year, tumour size and surgical approach was done (51 patients in each group, caliper 0.2). Results:We identified196 patients undergoing wedge resection, of whom 138 patients (70%) had LNs resected (median = 4 nodes), while the remaining 58 patients (30%) had none. There were no significant differences in the clinical or pathologic characteristics between the two groups. There was no difference in terms of OR time, estimated blood loss, chest tube duration or length of stay. Median pT size was 1.5 cm in each group ( P  = 0.73). Among patients with LNs removed, 6 (4.3%) had positive nodes Patients in the LN assessed group had higher probability of freedom from loco-regional recurrence compared to the no lymph node (NLN) group (5-year: 92 vs 74%, P  = 0.025).In propensity matched groups, patients who underwent LN dissection also had higher probability of freedom from local recurrence ( P  = 0.024). Conclusions:Accompanying wedge resection for lung cancer, LN sampling adds no morbidity and does not increase length of stay. Positive nodes are identified in 4.3% of patients thought eligible for wedge resection. LN removal appears to decrease locoregional recurrence and may be associated with a survival benefit.
PMID: 28007869
ISSN: 1873-734x
CID: 3917502

Clinical Predictors of Persistent Mediastinal Nodal Disease After Induction Therapy for Stage IIIA N2 Non-Small Cell Lung Cancer

Kamel, Mohamed K; Rahouma, Mohamed; Ghaly, Galal; Nasar, Abu; Port, Jeffrey L; Stiles, Brendon M; Nguyen, Andrew B; Altorki, Nasser K; Lee, Paul C
BACKGROUND:Patients with persistent N2 disease after induction have poor survival. Many of these patients may have had mediastinoscopy before induction therapy, making reassessment of the mediastinum by repeat mediastinoscopy hazardous and inaccurate. The sensitivity and specificity of endobronchial ultrasonography and nodal fine-needle aspiration in this setting is unclear. In this study, we sought to identify the clinical predictors of persistent N2 disease after induction therapy, which may help in selecting the patients most likely to benefit from surgical resection. METHODS:A retrospective review of a prospective database (1990 to 2014) was performed to identify patients who had surgical resection after induction therapy for clinical stage IIIA-N2 non-small cell lung cancer. Multivariable logistic regression analysis was performed to determine independent predictors of persistent N2 disease. RESULTS:203 patients (56% female; median age 64 years) underwent potentially curative lung resection after induction therapy. Ninety-seven patients (48%) had pathologic nodal downstaging (pN0/N1), which was associated with significantly better overall survival compared with patients with persistent N2 disease (5 years, 56% versus 35%, p = 0.047). Univariate and multivariate analysis showed that upper or middle lobe location and less than 60% reduction of N2 SUVmax were independent predictors of persistent N2 disease. CONCLUSIONS:Patients with upper lobe tumors and less than 60% reduction in N2 SUVmax are more likely to have persistent N2 disease, which is often associated with poor survival rates. These clinical prognostic criteria may help surgeons in stratifying patients and properly selecting optimal surgical candidates.
PMID: 27623273
ISSN: 1552-6259
CID: 3917482

Anatomical Segmentectomy and Wedge Resections Are Associated with Comparable Outcomes for Patients with Small cT1N0 Non-Small Cell Lung Cancer

Altorki, Nasser K; Kamel, Mohamed K; Narula, Navneet; Ghaly, Galal; Nasar, Abu; Rahouma, Mohamed; Lee, Paul C; Port, Jeffery L; Stiles, Brendon M
OBJECTIVES: Sublobar resection is advocated for patients with NSCLC and compromised cardiopulmonary reserve, and for selected patients with early stage disease. Anatomic segmentectomy (AS) has traditionally been considered superior to wedge resection (WR), but well-balanced comparative studies are lacking. We hypothesize that WR and AS are associated with comparable oncologic outcomes for patients with cT1N0 NSCLC. METHODS: A retrospective review of a prospective database was performed (2000-2014) for cT1N0 patients, excluding patients with multiple primary tumors, carcinoid tumors, adenocarcinoma in situ, and minimally invasive adenocarcinoma. Demographic, clinical, and pathological data were reviewed. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method and differences compared using log-rank test. Multivariable analysis (MVA) of factors affecting DFS was performed by Cox regression analysis. For further comparison of the effect of resection type on survival, propensity score matching (i.e., by age, sex, Charlson comorbidity index, percent forced expiratory volume in 1 second (FEV1%), clinical tumor size, and tumor maximum standardized uptake value) was performed to obtain balanced cohorts of patients undergoing WR and AS (n = 76 per group). RESULTS: Two hundred eighty-nine patients met our selection criteria, including WR in 160 and AS in 129. Poor performance status and limited cardiopulmonary reserve were the primary indications for sublobar resection in 76% of WR patients and in 62% of AS patients (p = 0.011). Thirteen patients (4.5%) had pN1/2 disease. Patients undergoing AS were more likely to have nodal sampling/dissection [123 (95%) versus 112 (70%); p < 0.001], more stations sampled (3 versus 2; p < 0.001), and more total nodes resected (7 versus 4; p = 0.001). However, there was no difference between patients undergoing WR versus AS in local recurrence [15 versus 14; p = 0.68] or 5-year DFS (51% versus 53%; p = 0.7; median follow-up 34 months). Univariate analysis showed no effect of extent of resection on DFS [hazard ratio 1.07 (95% confidence interval 0.74-1.56); p = 0.696]. MVA showed that only tumor maximum standardized uptake value was associated with worse DFS [hazard ratio 1.07 (95% confidence interval 1.01-1.13); p = 0.016]. In the propensity-matched analysis of balanced subgroups, there was also no difference (p = 0.950) in 3- or 5-year DFS in cT1N0 patients undergoing WR (65% and 49%) or AS (68% and 49%). CONCLUSIONS: Our data show that WR and AS are comparable oncologic procedures for carefully staged cT1N0 NSCLC patients. Although AS is associated with a more thorough lymph node dissection, this did not translate to a survival benefit in this patient population with a low rate of nodal metastases.
PMID: 27496651
ISSN: 1556-1380
CID: 2768622

Predictors of Pleural Implants in Patients With Thymic Tumors

Kamel, Mohamed K; Stiles, Brendon M; Ghaly, Galal; Rahouma, Mohamed; Nasar, Abu; Port, Jeffrey L; Lee, Paul C; Altorki, Nasser K
BACKGROUND:In patients with thymic neoplasms, the pleural space is a frequent site of either synchronous or metachronous tumor dissemination after surgical resection. The objective of this study was to identify factors that predict pleural dissemination, which would allow for better surgical planning and consideration of novel adjuvant or surveillance strategies. METHODS:A retrospective review of a prospective database (2000 to 2014) was performed to identify patients with thymic tumors (excluding neuroendocrine). Demographic, clinical, and pathologic data were reviewed. Multivariable Cox regression analysis was performed to determine independent predictors of pleural implants (either occult synchronous or metachronous). Univariate predictors (p < 0.20) were selected for inclusion in a multivariable model. Receiver operating characteristic (ROC) curve was used to assess the effect and cutoff value of tumor size on the incidence of pleural metastasis. RESULTS:One hundred sixty-two patients with thymic tumors were identified. Pleural deposits were incidentally identified intraoperatively in 4 patients (2.5%) and developed during follow-up in 15 patients (10%), with a median follow-up of 34 months (interquartile range, 12 to 71). Univariate predictors of pleural metastasis were macroscopic capsular/organ invasion, preoperative core/surgical biopsy, induction therapy, pathologic tumor size, and World Health Organization type B3/C. In the multivariable model, core/surgical biopsy (hazard ratio [HR] 9.45, p = 0.002), macroscopic capsular invasion (HR 10.18, p = 0.008), and larger tumor size (HR 1.34, p = 0.044) were found to be independent predictors of pleural metastasis. The relation between the pathologic tumor size and development of pleural metastasis was further investigated with the ROC curve (area under the curve 0.78, p < 0.001), and the cutoff tumor size that gave the best combined sensitivity and specificity was 6.5 cm. Overall survival of patients with pleural implants was 88% and 50% at 5 and 10 years, respectively. Five- and 10- year disease-free survival for the whole cohort was 80% and 30%, respectively. CONCLUSIONS:Development of pleural metastasis is predictable. Pathologic tumor size, an independent predictor of pleural implants, can be assessed intraoperatively. Because preoperative core needle biopsy is also an independent predictor of pleural dissemination, its use and execution should be carefully considered. Pleural exploration at the index operation should be considered in high-risk patients. Further studies are needed to confirm these findings and to assess the role of novel therapeutic strategies in reducing pleural disease.
PMID: 27324527
ISSN: 1552-6259
CID: 3917462

Training model for laparoscopic Heller and Dor fundoplication: a tool for laparoscopic skills training and assessment-construct validity using the GOALS score

Bellorin, Omar; Kundel, Anna; Sharma, Saurabh; Ramirez-Valderrama, Alexander; Lee, Paul
BACKGROUND: Laparoscopic training demands practice. The transfer of laparoscopic skills from training models to real surgical procedures has been proven. The global operative assessment of laparoscopic skills (GOALS) score is a 5-item global rating scale developed to evaluate laparoscopic skills by direct observation. This scale has been used to demonstrate construct validity of several laparoscopic training models. Here, we present a low-cost model of laparoscopic Heller-Dor for advanced laparoscopic training. The aim of this study was to determine the capability of a training model for laparoscopic Heller-Dor to discriminate between different levels of laparoscopic expertise. METHODS: The performance of two groups with different levels of expertise, novices (<30 laparoscopic procedures PGY1-2) and experts (>300 laparoscopic procedures PGY4-5) was assessed. All participants were instructed to perform two tasks (esophageal myotomy and fundoplication). All the performances were recorded in a digital format. A laparoscopic expert who was blinded to subject's identity evaluated the recordings using the GOALS score. Autonomy, one of the five items of GOALS, was removed since the evaluator and the trainee did not have interaction. The time required to finish each task was also recorded. Performance was compared using the Mann-Whitney U test (p < 0.05 was significant). RESULTS: Twenty subjects were evaluated: ten in each group, using the GOALS score. The mean total GOALS score for novices was 7.5 points (SD: 1.64) and 13.9 points (SD: 1.66) for experts (p < 0.05).The expert group was superior in each domain of the GOALS score compared to novices: depth perception (mean: 3.3 vs 2 p < 0.05), bimanual dexterity (mean 3.4 vs 2.1 p < 0.05), efficiency (mean 3.4 vs 1.7 p < 0.05) and tissue handling (mean 3.6 vs 1.7 p < 0.05). With regard to time, experts were superior in task 1 (mean 9.7 vs 14.9 min p < 0.05) and task 2 (mean 24 vs 47.1 min p < 0.05) compared to novices. CONCLUSIONS: The laparoscopic Heller-Dor training model has construct validity. The model may be used as a tool for training of the surgical resident.
PMID: 26514134
ISSN: 1432-2218
CID: 1817612

Predictors of Disease-free Survival and Recurrence in Patients with Resected Bronchial Carcinoid Tumors

Lee, Paul C; Osakwe, Nonso C; Narula, Navnett; Port, Jeffrey L; Paul, Subroto; Stiles, Brendon M; Andrews, Weston G; Nasar, Abu; Altorki, Nasser K
BACKGROUND:Bronchial carcinoids are characterized by neuroendocrine differentiation and have distinct biological behavior, recurrence patterns, and prognosis compared with adenocarcinomas or squamous cell carcinomas. Because of their often indolent nature, it has been suggested that routine postoperative imaging surveillance may not be warranted in the majority of patients. This study aims to define the factors that predict disease-free survival (DFS) and recurrence after resection of these tumors, with the goal of identifying high-risk patients for whom image surveillance may be warranted. METHODS:We conducted a retrospective review of a prospective database to identify patients with completely resected bronchial carcinoid tumors. Surgical procedure, histology, pathological stage, follow-up, tumor recurrence, and survival were assessed. RESULTS:One hundred and forty-two patients were identified. Median age was 62 years and the majority was women (106). Surgical procedures included 20 wedge resections, 10 segmentectomies, 99 lobectomies, 3 bilobectomies, 2 pneumonectomies, 6 sleeve resections, and 2 bronchectomies. Pathologic stages included I (81%), II (10%), III (8%), and IV (1%). With a median follow-up of 31 months, there were seven recurrences. The 5- and 10-year overall survival rates were 92% and 75% and DFS rates were 88% and 72%, respectively. There were 34 patients with atypical carcinoids, and 6 (18%) developed recurrence, compared with 1 recurrence (1%) in the group of 108 patients with typical carcinoids (p = 0.0008). For atypical carcinoid tumors, the 5- and 10-year DFS rates were 72% and 32% versus 92% and 85% in typical carcinoid tumors (p = 0.001). Patients with more advanced tumor stage pT2-4 and pathologic N1/N2 nodal metastases had a significantly decreased 5- and 10-year DFS compared with those with early pT1 stage (p = 0.029) or those without nodal disease (p = 0.043). Multivariate Cox regression analyses showed advancing age (p = 0.001), atypical histology (p = 0.021), and advanced tumor stage (p = 0.047) were significant negative predictors for DFS. CONCLUSION/CONCLUSIONS:Long-term survival after resection of bronchial carcinoids is common, especially for patients with typical carcinoid tumors. DFS can be negatively influenced by atypical histology, advanced tumor, and nodal statuses. Efforts at postoperative image surveillance should target those patients with such high-risk factors.
PMID: 25756243
ISSN: 1439-1902
CID: 3146972