Browsing by Author "Mithani, Suhail K"

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    A Cluster of Nontuberculous Mycobacterial Tenosynovitis Following Hurricane Relief Efforts.
    (Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2021-06) Turner, Nicholas A; Sweeney, Mollie I; Xet-Mull, Ana M; Storm, Jeremy; Mithani, Suhail K; Jones, David B; Miles, Jeremy J; Tobin, David M; Stout, Jason E

    Background

    Nontuberculous mycobacteria (NTM) are a rare cause of infectious tenosynovitis of the upper extremity. Using molecular methods, clinical microbiology laboratories are increasingly reporting identification down to the species level. Improved methods for speciation are revealing new insights into the clinical and epidemiologic features of rare NTM infections.

    Methods

    We encountered 3 cases of epidemiologically linked upper extremity NTM tenosynovitis associated with exposure to hurricane-damaged wood. We conducted whole-genome sequencing to assess isolate relatedness followed by a literature review of NTM infections that involved the upper extremity.

    Results

    Despite shared epidemiologic risk, the cases were caused by 3 distinct organisms. Two cases were rare infections caused by closely related but distinct species within the Mycobacterium terrae complex that could not be differentiated by traditional methods. The third case was caused by Mycobacterium intracellulare. An updated literature review that focused on research that used modern molecular speciation methods found that several species within the M. terrae complex are increasingly reported as a cause of upper extremity tenosynovitis, often in association with environmental exposures.

    Conclusions

    These cases illustrate the importance of molecular methods for speciating phenotypically similar NTM, as well as the limitations of laboratory-based surveillance in detecting point-source outbreaks when the source is environmental and may involve multiple organisms.
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    Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.
    (PLoS One, 2009) Smith, Ian M; Glazer, Chad A; Mithani, Suhail K; Ochs, Michael F; Sun, Wenyue; Bhan, Sheetal; Vostrov, Alexander; Abdullaev, Ziedulla; Lobanenkov, Victor; Gray, Andrew; Liu, Chunyan; Chang, Steven S; Ostrow, Kimberly L; Westra, William H; Begum, Shahnaz; Dhara, Mousumi; Califano, Joseph
    BACKGROUND: Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. METHODOLOGY/PRINCIPAL FINDINGS: We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. CONCLUSIONS/SIGNIFICANCE: Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs in aerodigestive cancers, and BORIS is implicated in the coordinated promoter demethylation and reactivation of epigenetically silenced genes in human cancers.
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    Mitochondrial mutations in adenoid cystic carcinoma of the salivary glands.
    (PLoS One, 2009-12-30) Mithani, Suhail K; Shao, Chunbo; Tan, Marietta; Smith, Ian M; Califano, Joseph A; El-Naggar, Adel K; Ha, Patrick K
    BACKGROUND: The MitoChip v2.0 resequencing array is an array-based technique allowing for accurate and complete sequencing of the mitochondrial genome. No studies have investigated mitochondrial mutation in salivary gland adenoid cystic carcinomas. METHODOLOGY: The entire mitochondrial genome of 22 salivary gland adenoid cystic carcinomas (ACC) of salivary glands and matched leukocyte DNA was sequenced to determine the frequency and distribution of mitochondrial mutations in ACC tumors. PRINCIPAL FINDINGS: Seventeen of 22 ACCs (77%) carried mitochondrial mutations, ranging in number from 1 to 37 mutations. A disproportionate number of mutations occurred in the D-loop. Twelve of 17 tumors (70.6%) carried mutations resulting in amino acid changes of translated proteins. Nine of 17 tumors (52.9%) with a mutation carried an amino acid changing mutation in the nicotinamide adenine dinucleotide dehydrogenase (NADH) complex. CONCLUSIONS/SIGNIFICANCE: Mitochondrial mutation is frequent in salivary ACCs. The high incidence of amino acid changing mutations implicates alterations in aerobic respiration in ACC carcinogenesis. D-loop mutations are of unclear significance, but may be associated with alterations in transcription or replication.
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    Surgical Techniques for Revascularization in Abdominal Wall Transplantation.
    (Journal of reconstructive microsurgery, 2020-04-25) Atia, Andrew; Hollins, Andrew; Shammas, Ronnie; Phillips, Brett T; Ravindra, Kadiyala V; Sudan, Debra L; Giele, Henk; Mithani, Suhail K; Erdmann, Detlev
    BACKGROUND: Abdominal wall vascularized composite allotransplantation (AW-VCA) can be considered as a technically feasible option for abdominal wall reconstruction in patients whose abdomen cannot be closed using traditional methods. However, successful initial abdominal wall revascularization in the setting of visceral organ transplantation can pose a major challenge as graft ischemia time, operating in a limited surgical field, and variable recipient and donor anatomy must be considered. Several techniques have been reported to accomplish abdominal wall revascularization. METHODS: A literature review was performed using PubMed for articles related to "abdominal wall transplantation (AWT)." The authors of this study sorted through this search for relevant publications that describe abdominal wall transplant anatomy, technical descriptions, and outcomes of various techniques. RESULTS: A total of four distinct revascularization techniques were found in the literature. Each of these techniques was described by the respective authors and reported varying patient outcomes. Levi et al published a landmark article in 2003 that described technical feasibility of AWT with anastomosis between donor external iliac and inferior epigastric vessels with recipient common iliac vessels in end-to-side fashion. Cipriani et al described a microsurgical technique with anastomosis between donor and recipient inferior epigastric vessels in an end-to-end fashion. Giele et al subsequently proposed banking the abdominal wall allograft in the forearm to reduce graft ischemia time. Recently, Erdmann et al described the utilization of an arteriovenous loop for synchronous revascularization of abdominal wall and visceral transplants for reduction of ischemia time, operative time, while eliminating the need for further operations. CONCLUSION: Vascularized composite allotransplantation continues to advance with improving immunotherapy and outcomes in solid organ transplantation. Optimizing surgical techniques remains paramount as the field continues to grow. Refinement of the presented methods will continue as additional evidence and outcomes become available in AW-VCA.
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    Synchronous Abdominal Wall and Small-bowel Transplantation: A 1-year Follow-up.
    (Plastic and reconstructive surgery. Global open, 2020-07-24) Atia, Andrew; Hollins, Andrew; Erdmann, Ralph F; Shammas, Ronnie; Sudan, Debra L; Mithani, Suhail K; Ravindra, Kadiyala V; Erdmann, Detlev
    Abdominal wall-vascularized composite allotransplantation (AW-VCA) has evolved as a technically feasible but challenging option in the rare event of abdominal wall reconstruction in patients whose abdomen cannot be closed by applying conventional methods. The authors conducted the first synchronous child-to-adult recipient AW-VCA using an arteriovenous loop technique. This article presents a 1-year follow-up of the patient's postoperative course. Frequent skin biopsies were performed in accordance with Duke Institutional Review Board protocol, with 3 episodes of rejection treated with high-dose steroids and Thymoglobulin (Genzyme Corp, Cambridge, Mass.). The patient developed an opportunistic fungal brain abscess secondary to immunosuppression, which led to temporary upper extremity weakness. Future considerations for AW-VCA include a modified surgical technique involving utilization of donor vein graft for arteriovenous loop formation. In addition, reduction in postoperative biopsy schedule and changes in immunosuppression regimen may lead to improved outcomes and prevent unnecessary high-dose immunosuppression.