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Adham M. Khalafallah, Sakibul Huq, Adrian E. Jimenez, Henry Brem, and Debraj Mukherjee

OBJECTIVE

Health measures such as the Charlson Comorbidity Index (CCI) and the 11-factor modified frailty index (mFI-11) have been employed to predict general medical and surgical mortality, but their clinical utility is limited by the requirement for a large number of data points, some of which overlap or require data that may be unavailable in large datasets. A more streamlined 5-factor modified frailty index (mFI-5) was recently developed to overcome these barriers, but it has not been widely tested in neuro-oncology patient populations. The authors compared the utility of the mFI-5 to that of the CCI and the mFI-11 in predicting postoperative mortality in brain tumor patients.

METHODS

The authors retrospectively reviewed a cohort of adult patients from a single institution who underwent brain tumor surgery during the period from January 2017 to December 2018. Logistic regression models were used to quantify the associations between health measure scores and postoperative mortality after adjusting for patient age, race, ethnicity, sex, marital status, and diagnosis. Results were considered statistically significant at p values ≤ 0.05. Receiver operating characteristic (ROC) curves were used to examine the relationships between CCI, mFI-11, and mFI-5 and mortality, and DeLong’s test was used to test for significant differences between c-statistics. Spearman’s rho was used to quantify correlations between indices.

RESULTS

The study cohort included 1692 patients (mean age 55.5 years; mean CCI, mFI-11, and mFI-5 scores 2.49, 1.05, and 0.80, respectively). Each 1-point increase in mFI-11 (OR 4.19, p = 0.0043) and mFI-5 (OR 2.56, p = 0.018) scores independently predicted greater odds of 90-day postoperative mortality. Adjusted CCI, mFI-11, and mFI-5 ROC curves demonstrated c-statistics of 0.86 (CI 0.82–0.90), 0.87 (CI 0.83–0.91), and 0.87 (CI 0.83–0.91), respectively, and there was no significant difference between the c-statistics of the adjusted CCI and the adjusted mFI-5 models (p = 0.089) or between the adjusted mFI-11 and the adjusted mFI-5 models (p = 0.82). The 3 indices were well correlated (p < 0.01).

CONCLUSIONS

The adjusted mFI-5 model predicts 90-day postoperative mortality among brain tumor patients as well as our adjusted CCI and adjusted mFI-11 models. The simplified mFI-5 may be easily integrated into clinical workflows to predict brain tumor surgery outcomes in real time.

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Sakibul Huq, Jeffrey Ehresman, Ethan Cottrill, A. Karim Ahmed, Zach Pennington, Erick M. Westbroek, and Daniel M. Sciubba

OBJECTIVE

Scheuermann kyphosis (SK) is an idiopathic kyphosis characterized by anterior wedging of ≥ 5° at 3 contiguous vertebrae managed with either nonoperative or operative treatment. Nonoperative treatment typically employs bracing, while operative treatment is performed with either a combined anterior-posterior fusion or posterior-only approach. Current evidence for these approaches has largely been derived from retrospective case series or focused reviews. Consequently, no consensus exists regarding optimal management strategies for patients afflicted with this condition. In this study, the authors systematically review the literature on SK with respect to indications for treatment, complications of treatment, differences in correction and loss of correction, and changes in treatment over time.

METHODS

Using PubMed, Embase, CINAHL, Web of Science, and the Cochrane Library, all full-text publications on the operative and nonoperative treatment for SK in the peer-reviewed English-language literature between 1950 and 2017 were screened. Inclusion criteria involved fully published, peer-reviewed, retrospective or prospective studies of the primary medical literature. Studies were excluded if they did not provide clinical outcomes and statistics specific to SK, described fewer than 2 patients, or discussed results in nonhuman models. Variables extracted included treatment indications and methodology, maximum pretreatment kyphosis, immediate posttreatment kyphosis, kyphosis at last follow-up, year of treatment, and complications of treatment.

RESULTS

Of 659 unique studies, 45 met our inclusion criteria, covering 1829 unique patients. Indications for intervention were pain, deformity, failure of nonoperative treatment, and neural impairment. Among operatively treated patients, the most common complications were hardware failure and proximal or distal junctional kyphosis. Combined anterior-posterior procedures were additionally associated with neural, pulmonary, and cardiovascular complications. Posterior-only approaches offered superior correction compared to combined anterior-posterior fusion; both groups provided greater correction than bracing. Loss of correction was similar across operative approaches, and all were superior to bracing. Cross-sectional analysis suggested that surgeons have shifted from anterior-posterior to posterior-only approaches over the past two decades.

CONCLUSIONS

The data indicate that for patients with SK, surgery affords superior correction and maintenance of correction relative to bracing. Posterior-only fusion may provide greater correction and similar loss of correction compared to anterior-posterior approaches along with a smaller complication profile. This posterior-only approach has concomitantly gained popularity over the combined anterior-posterior approach in recent years.

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Sakibul Huq, Adham M. Khalafallah, David Botros, Adrian E. Jimenez, Shravika Lam, Judy Huang, and Debraj Mukherjee

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Phillip A. Bonney, Frank J. Attenello, and William J. Mack

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Jeff Ehresman, Zach Pennington, Aditya V. Karhade, Sakibul Huq, Ravi Medikonda, Andrew Schilling, James Feghali, Andrew Hersh, A. Karim Ahmed, Ethan Cottrill, Daniel Lubelski, Erick M. Westbroek, Joseph H. Schwab, and Daniel M. Sciubba

OBJECTIVE

Incidental durotomy is a common complication of elective lumbar spine surgery seen in up to 11% of cases. Prior studies have suggested patient age and body habitus along with a history of prior surgery as being associated with an increased risk of dural tear. To date, no calculator has been developed for quantifying risk. Here, the authors’ aim was to identify independent predictors of incidental durotomy, present a novel predictive calculator, and externally validate a novel method to identify incidental durotomies using natural language processing (NLP).

METHODS

The authors retrospectively reviewed all patients who underwent elective lumbar spine procedures at a tertiary academic hospital for degenerative pathologies between July 2016 and November 2018. Data were collected regarding surgical details, patient demographic information, and patient medical comorbidities. The primary outcome was incidental durotomy, which was identified both through manual extraction and the NLP algorithm. Multivariable logistic regression was used to identify independent predictors of incidental durotomy. Bootstrapping was then employed to estimate optimism in the model, which was corrected for; this model was converted to a calculator and deployed online.

RESULTS

Of the 1279 elective lumbar surgery patients included in this study, incidental durotomy occurred in 108 (8.4%). Risk factors for incidental durotomy on multivariable logistic regression were increased surgical duration, older age, revision versus index surgery, and case starts after 4 pm. This model had an area under curve (AUC) of 0.73 in predicting incidental durotomies. The previously established NLP method was used to identify cases of incidental durotomy, of which it demonstrated excellent discrimination (AUC 0.97).

CONCLUSIONS

Using multivariable analysis, the authors found that increased surgical duration, older patient age, cases started after 4 pm, and a history of prior spine surgery are all independent positive predictors of incidental durotomy in patients undergoing elective lumbar surgery. Additionally, the authors put forth the first version of a clinical calculator for durotomy risk that could be used prospectively by spine surgeons when counseling patients about their surgical risk. Lastly, the authors presented an external validation of an NLP algorithm used to identify incidental durotomies through the review of free-text operative notes. The authors believe that these tools can aid clinicians and researchers in their efforts to prevent this costly complication in spine surgery.

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Sakibul Huq, Nivedha V. Kannapadi, Joshua Casaos, Tarik Lott, Raphael Felder, Riccardo Serra, Noah L. Gorelick, Miguel A. Ruiz-Cardozo, Andy S. Ding, Arba Cecia, Ravi Medikonda, Jeff Ehresman, Henry Brem, Nicolas Skuli, and Betty M. Tyler

OBJECTIVE

Medulloblastoma, the most common pediatric brain malignancy, has Sonic Hedgehog (SHH) and group 3 (Myc driven) subtypes that are associated with the activity of eukaryotic initiation factor 4E (eIF4E), a critical mediator of translation, and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and master regulator of transcription. Recent drug repurposing efforts in multiple solid and hematologic malignancies have demonstrated that eIF4E and EZH2 are both pharmacologically inhibited by the FDA-approved antiviral drug ribavirin. Given the molecular overlap between medulloblastoma biology and known ribavirin activity, the authors investigated the preclinical efficacy of repurposing ribavirin as a targeted therapeutic in cell and animal models of medulloblastoma.

METHODS

Multiple in vitro assays were performed using human ONS-76 (a primitive SHH model) and D425 (an aggressive group 3 model) cells. The impacts of ribavirin on cellular growth, death, migration, and invasion were quantified using proliferation and Cell Counting Kit-8 (CCK-8) assays, flow cytometry with annexin V (AnnV) staining, scratch wound assays, and Matrigel invasion chambers, respectively. Survival following daily ribavirin treatment (100 mg/kg) was assessed in vivo in immunodeficient mice intracranially implanted with D425 cells.

RESULTS

Compared to controls, ribavirin treatment led to a significant reduction in medulloblastoma cell growth (ONS-76 proliferation assay, p = 0.0001; D425 CCK-8 assay, p < 0.0001) and a significant increase in cell death (flow cytometry for AnnV, ONS-76, p = 0.0010; D425, p = 0.0284). In ONS-76 cells, compared to controls, ribavirin significantly decreased cell migration and invasion (Matrigel invasion chamber assay, p = 0.0012). In vivo, ribavirin significantly extended survival in an aggressive group 3 medulloblastoma mouse model compared to vehicle-treated controls (p = 0.0004).

CONCLUSIONS

The authors demonstrate that ribavirin, a clinically used drug known to inhibit eIF4E and EZH2, has significant antitumor effects in multiple preclinical models of medulloblastoma, including an aggressive group 3 animal model. Ribavirin may represent a promising targeted therapeutic in medulloblastoma.

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Jeff Ehresman, Zach Pennington, Andrew Schilling, Ravi Medikonda, Sakibul Huq, Kevin R. Merkel, A. Karim Ahmed, Ethan Cottrill, Daniel Lubelski, Erick M. Westbroek, Salia Farrokh, Steven M. Frank, and Daniel M. Sciubba

OBJECTIVE

Blood transfusions are given to approximately one-fifth of patients undergoing elective lumbar spine surgery, and previous studies have shown that transfusions are accompanied by increased complications and additional costs. One method for decreasing transfusions is administration of tranexamic acid (TXA). The authors sought to evaluate whether the cost of TXA is offset by the decrease in blood utilization in lumbar spine surgery patients.

METHODS

The authors retrospectively reviewed patients who underwent elective lumbar or thoracolumbar surgery for degenerative conditions at a tertiary care center between 2016 and 2018. Patients who received intraoperative TXA (TXA patients) were matched with patients who did not receive TXA (non-TXA patients) by age, sex, BMI, ASA (American Society of Anesthesiologists) physical status class, and surgical invasiveness score. Primary endpoints were intraoperative blood loss, number of packed red blood cell (PRBC) units transfused, and total hemostasis costs, defined as the sum of TXA costs and blood transfusion costs throughout the hospital stay. A subanalysis was then performed by substratifying both cohorts into short-length (1–4 levels) and long-length (5–8 levels) spinal constructs.

RESULTS

Of the 1353 patients who met inclusion criteria, 68 TXA patients were matched to 68 non-TXA patients. Patients in the TXA group had significantly decreased mean intraoperative blood loss (1039 vs 1437 mL, p = 0.01). There were no differences between the patient groups in the total costs of blood transfusion and TXA (p = 0.5). When the 2 patient groups were substratified by length of construct, the long-length construct group showed a significant net cost savings of $328.69 per patient in the TXA group (p = 0.027). This result was attributable to the finding that patients undergoing long-length construct surgeries who were given TXA received a lower amount of PRBC units throughout their hospital stay (2.4 vs 4.0, p = 0.007).

CONCLUSIONS

TXA use was associated with decreased intraoperative blood loss and significant reductions in total hemostasis costs for patients undergoing surgery on more than 4 levels. Furthermore, the use of TXA in patients who received short constructs led to no additional net costs. With the increasing emphasis put on value-based care interventions, use of TXA may represent one mechanism for decreasing total care costs, particularly in the cases of larger spine constructs.

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Seyed H. Mousavi, Ajay Niranjan, Berkcan Akpinar, Edward A. Monaco III, Jonathan Cohen, Jagdish Bhatnagar, Yue-Fang Chang, Hideyuki Kano, Sakibul Huq, John C. Flickinger, and L. Dade Lunsford

OBJECTIVE

During the last 25 years, more than 100,000 patients worldwide with trigeminal neuralgia (TN) have undergone stereotactic radiosurgery (SRS) with a standard dose of radiation. However, the radiobiological effect of radiation is determined by the amount of energy delivered to the tissue (integral dose [ID] = mean dose × target volume) and is directly associated with the nerve volume. Although the trigeminal nerve volume varies among patients with TN, the clinical impact of this variation in delivered energy is unknown. The objective of this study was to evaluate the effect of delivered ID on the outcome of TN radiosurgery.

METHODS

The authors evaluated 155 patients with unilateral TN who had undergone SRS as their initial surgical management over a 13-year period. The authors measured the postganglionic ID within the SRS target and retrospectively stratified patients into 3 groups: low (< 1.4 mJ), medium (1.4–2.7 mJ), and high (> 2.7 mJ) ID. Clinical outcomes, which included pain status (scored using the Barrow Neurological Institute Pain Scale) and sensory dysfunction (scored using the Barrow Neurological Institute Numbness Scale), were evaluated at a median follow-up of 71 months.

RESULTS

Patients who were treated with a medium ID had superior pain relief either with or without medications (p = 0.006). In the medium ID group, the rates of complete pain relief without medications at 1, 3, and 6 years after SRS were 67%, 54%, and 33%, respectively, while the rates in the rest of the cohort were 55%, 36%, and 19%, respectively. Patients given a high ID had a higher rate of post-SRS trigeminal sensory deterioration (p < 0.0001). At 1, 3, and 6 years after SRS, the high ID group had an estimated rate for developing sensory dysfunction of 35%, 45%, and 50%, respectively, while the rates in patients receiving low and medium IDs were 3%, 4%, and 9%, respectively. The optimal clinical outcome (maximum pain relief and minimal trigeminal sensory dysfunction) was obtained in patients who had received a medium ID.

CONCLUSIONS

With current dose selection methods, nerve volume affects long-term clinical outcomes in patients with TN who have undergone SRS. This study suggests that the prescribed SRS dose should be customized for each TN patient based on the nerve volume.