Sarcopenia and its effects on outcome of lumbar spine surgeries.

PURPOSE: Sarcopenia, defined as progressive impairment of muscle function secondary to loss of skeletal muscle mass, has prevalence of 24-56% in patients > 60 years. Forty-four per cent of elderly patients undergoing orthopaedic surgery are found to be sarcopenic. It is a known risk factor for fall, fractures, disability, increased post-operative morbidity and mortality. If diagnosed pre-operatively, it can help prepare the patient and surgical team to foresee complications and thereby reduce morbidity and mortality. In the present study, we evaluated and correlated sarcopenia with the surgical outcome of operated patients with lumbar spine pathology. MATERIALS AND METHODS: A prospective, observational study was conducted on 114 patients > 40 years undergoing lumbar spine surgeries, who were studied and followed up for 3 months. They were segregated into 5 groups based on age (40-50 year, 50-60 year, 60-70 year, 70-80 year, and > 80 year) and were assessed separately. Data on demography, grip strength analysis, 30-s chair stand test, Psoas muscle index (calculated on pre-operative MRI), pre- and post-operative ODI (Oswestry Disability Index) scores at 2 weeks and 3 months, Dindo-Clavien Classification of peri-operative complications, 90-day readmission rates and mortality (if any) were included. Patients were segregated into sarcopenic and non-sarcopenic groups based on the definition and set parameters as per the European Working Group on Sarcopenia in Older People (EWGSOP). A comparative analysis between these groups was performed. RESULTS: Of 114 patients, there were 18 patients in 40-49 years, 24 in 50-59 years, 33 in 60-69 years, 30 in 70-79 years and 9 in > 80 years age group. Statistically significant difference in peri-operative ODI scores was seen in sarcopenic vs non-sarcopenic patients in all age groups (p < 0.05) except 40-49 years. The results showed that sarcopenic group had higher rate of peri-operative complications, delayed mobilisation, longer stay and mortality compared to non-sarcopenic group. CONCLUSION: We conclude that sarcopenic patients have poor outcome in lumbar spine surgery compared to those without. So, by diagnosing sarcopenia using tests routinely done as pre-operative requirement, one can reduce radiation exposure and cost of treatment. The management can be revolutionised by predicting those who are at high risk of developing post-operative complications and poor surgical outcomes by mere diagnosis of sarcopenia. This knowledge will benefit both the patients and the surgeons.

A 2-Year Outcomes and Complications of Various Techniques of Lumbar Discectomy: A Multicentric Prospective Study.

STUDY DESIGN: Prospective Study. OBJECTIVES: There are numerous techniques for performing lumbar discectomy, each with its own rationale and stated benefits. The authors set out to evaluate and compare the perioperative variables, results, and complications of each treatment in a group of patients provided by ten hospitals and operated on by experienced surgeons. METHODS: This prospective study comprised of 591 patients operated between February-2017 to February-2019. The procedures included open discectomy, microdiscectomy, tubular microdiscectomy, interlaminar endoscopic lumbar discectomy, transforaminal endoscopic lumbar discectomy and Destandau techniques with a follow-up of minimum 2 years. VAS (Visual Analogue Score) for back and leg pain, ODI (Oswestry Disability Index), duration of surgery, hospital stay, length of scar, operative blood loss and peri-operative complications were recorded in each group. RESULTS: Post-operatively, there was a significant improvement in the VAS score for back pain as well as leg pain, and ODI scores spanning all groups, with no significant distinction amongst them. When compared to open procedures (open discectomy and microdiscectomy), minimally invasive surgeries (tubular discectomy, interlaminar endoscopic lumbar discectomy, transforaminal endoscopic lumbar discectomy, and Destandau techniques) reported shorter operative time, duration of hospital stays, better cosmesis, and lower blood loss. Overall, the complication rate was reported to be 8.62%. Complication rates differed slightly across approaches. CONCLUSION: Minimally invasive surgeries have citable advantages over open approaches in terms of perioperative variables. However, all approaches are successful and provide comparable pain relief with similar functional outcomes at long term follow up.

Prevalence and risk factors of neck pain in spine surgeons - Are we our own patients?

Aim: This survey of spine surgeons aimed to determine the prevalence of neck pain and identify the associated risk factors. The prevalence of neck pain has been reported in various medical sub-specialities including laparoscopy surgeons, dentists, plastic surgeons, ophthalmologist, urologist and orthopaedic surgeons. However, the literature is lacking on prevalence and risk factors for neck pain in spine surgeons. Methods: A survey questionnaire containing demographic, Neck pain and work practice details was administered to 300 spine surgeons (members of an online group) via text message and e-mail. Results: One hundred and eighty surgeons responded to the survey (response rate, 60%). Three spine surgeons had previous cervical spine surgeries. The 1-month prevalence rate of neck pain was 74.4% (134/180 surgeons). One hundred and eighteen surgeons (88%) reported only neck pain, 16 surgeons (11.9%) had neck pain with radicular arm pain. Only 20.5% of surgeons used a loupe, 18% of surgeons used a microscope, and 24% of surgeons used operating table height at umbilicus during surgery. There was no significant difference between the mean age (p = 0.65), work experience (p = 0.8), time spent in surgery (p = 0.7), and operating table height preference (p = 0.4) when symptomatic and asymptomatic groups were compared. However, a significantly greater percentage of surgeons had a sedentary lifestyle (p = 0.002) & used loupes as compared to microscopes (p = 0.04) in the symptomatic group. There was significant correlation between the surgeon's lifestyle & use of loupe and the incidence of neck pain. Conclusion: Spine surgeons have a higher prevalence of neck pain than general populations and surgeons from other specialties. Considering the high prevalence of neck pain, general health, work, and ergonomic guidelines and recommendations must be formulated to help prevent and decrease the burden of neck pain among spine surgeons.

Outcomes of patients presenting with Guillain-Barre Syndrome at a tertiary care center in India.

BACKGROUND: The Guillain-Barre Syndrome (GBS), also known as acute idiopathic polyneuritis, is a critical acquired condition associated with preceding nonspecific infection or triggering factors like trauma, surgery, or vaccination. GBS is currently the most frequent cause of acute flaccid paralysis in India. This study evaluates the short-term and in-hospital outcomes in different subtypes of GBS. METHODS: A prospective observational study was conducted at V.S. Hospital, Ahmedabad, from September 2015 to December 2017. Patients above the age of 12 were included. Patients having other underlying neurological conditions, as well as immunodeficiency disorders, were excluded. The patients were classified into different subtypes of GBS, and functional outcomes were recorded on admission and discharge according to Hughes Scoring System. All statistical analyses were performed by using SPSS software. RESULTS: Out of 50 patients, 35 (70%) were males. The mean age was of 37.18 +/- 18.35 years. 25 (50%) patients had a preceding infection. 88% of patients presented with cranial nerve (CN) involvement had a Hughes Score of >/= 3 (p = 0.0087). They had less improvement of Hughes Score on discharge (0.13 +/- 0.04) as compared to the patients without cranial nerve involvement (0.38 +/- 0.08) (p = 0.008). Respiratory involvement was associated with a higher Hughes Score (p = 0.005) on admission. 85% of patients diagnosed with an axonal subtype of GBS had a Hughes Score of >/= 3 (p = 0.06) compared to 74% patients with demyelinating subtype. Axonal subtype required double period (11 +/- 2.34) to show improvement as compared to demyelinating subtype (6 +/- 1.2) (p = 0.020). Irrespective of the subtypes, in two different treatment cohorts (PLEX vs IVIG), there was no difference in short term functional outcomes measured by improvement in the Hughes scores (p = 0.89). CONCLUSIONS: Early cranial nerve and respiratory involvement in patients presenting with GBS are associated with poor outcomes warranting immediate critical care involvement. In our study, amongst all the subtypes, axonal had poor clinical outcomes. Further clinical trials on the Indian subpopulation will help us evaluate the impact of different treatment modalities on this disease.

A 2-Year Outcomes and Complications of Various Techniques of Lumbar Discectomy: A Multicentric Retrospective Study.

OBJECTIVES: Various techniques of performing lumbar discectomy are prevalent, each having its rationale and claimed benefits. The authors ventured to assess the perioperative factors, outcomes, and complications of each procedure and compare among them with 946 patients contributed by 10 centers and operated by experienced surgeons. METHODS: This was a retrospective study of patients operated using open discectomy, microdiscectomy, microendoscopic discectomy, interlaminar endoscopic lumbar discectomy, transforaminal endoscopic lumbar discectomy, and Destandau techniques with a follow-up of minimum 2 years. The inclusion criteria were age >18 years, failed conservative treatment for 4-6 weeks, and the involvement of a single lumbar level. RESULTS: There was a significant improvement in the visual analog scale score of back, leg, and Oswestry Disability Index scores postoperatively across the board, with no significant difference between them. Minimally invasive procedures (microendoscopic discectomy, interlaminar endoscopic lumbar discectomy, transforaminal endoscopic lumbar discectomy, and Destandau techniques) had shorter operation time, hospital stay, better cosmesis, and decreased blood loss compared with open procedures (open discectomy and microdiscectomy). The overall complication rate was 10.1%. The most common complication was recurrence (6.86%), followed by reoperation (4.3%), cerebrospinal fluid leak (2.24%), wrong level surgery (0.74%), superficial infection (0.62%), and deep infection (0.37%). There were minor differences in incidence of complications between techniques. CONCLUSION: Although minimally invasive techniques have some advantages over the open techniques in the perioperative factors, all the techniques are effective and provide similar pain relief and functional outcomes at the end of 2 years. The various rates of individual complications provide a reference value for future studies.

NP-ALT, a Liposomal:Peptide Drug, Blocks p27Kip1 Phosphorylation to Induce Oxidative Stress, Necroptosis, and Regression in Therapy-Resistant Breast Cancer Cells.

Resistance to cyclin D-CDK4/6 inhibitors (CDK4/6i) represents an unmet clinical need and is frequently caused by compensatory CDK2 activity. Here we describe a novel strategy to prevent CDK4i resistance by using a therapeutic liposomal:peptide formulation, NP-ALT, to inhibit the tyrosine phosphorylation of p27Kip1(CDKN1B), which in turn inhibits both CDK4/6 and CDK2. We find that NP-ALT blocks proliferation in HR+ breast cancer cells, as well as CDK4i-resistant cell types, including triple negative breast cancer (TNBC). The peptide ALT is not as stable in primary mammary epithelium, suggesting that NP-ALT has little effect in nontumor tissues. In HR+ breast cancer cells specifically, NP-ALT treatment induces ROS and RIPK1-dependent necroptosis. Estrogen signaling and ERα appear required. Significantly, NP-ALT induces necroptosis in MCF7 ESRY537S cells, which contain an ER gain of function mutation frequently detected in metastatic patients, which renders them resistant to endocrine therapy. Here we show that NP-ALT causes necroptosis and tumor regression in treatment naïve, palbociclib-resistant, and endocrine-resistant BC cells and xenograft models, demonstrating that p27 is a viable therapeutic target to combat drug resistance. IMPLICATIONS: This study reveals that blocking p27 tyrosine phosphorylation inhibits CDK4 and CDK2 activity and induces ROS-dependent necroptosis, suggesting a novel therapeutic option for endocrine and CDK4 inhibitor-resistant HR+ tumors.

Plasma cell leukaemia with t(11;14) not responsive to venetoclax.

A 70-year-old man with medical history of IgG kappa multiple myeloma, initially diagnosed in 2017, underwent induction therapy with carfilzomib, lenalidomide and dexamethasone followed by autologous haematopoietic stem cell transplantation. Nine months following transplant, disease relapsed in the form of plasma cell leukaemia. Fluorescent in situ hybridisation of malignant plasma cells revealed t(11;14). A combination therapy including venetoclax was used based on efficacy data for Bcl-2 inhibitor venetoclax from available early-phase clinical trials in patients with relapsed multiple myeloma with t(11;14) and other published case studies. Unfortunately, the disease was primary refractory, and after further ineffective therapies, the patient did not have a successful outcome.

Does Three-Dimensional Printed Patient-Specific Templates Add Benefit in Revision Surgeries for Complex Pediatric Kyphoscoliosis Deformity with Sublaminar Wires in Situ? A Clinical Study.

STUDY DESIGN: Case-control study. PURPOSE: To evaluate the accuracy of three-dimensional (3D) printed patient-specific templates (PSTs) for placement of pedicle screws (PAs) in patients undergoing revision surgeries for complex kyphoscoliosis deformity with sublaminar wires in situ. OVERVIEW OF LITERATURE: Revision kyphoscoliosis correction surgery in pediatric patients is a challenging task for the treating surgeon. In patients with sublaminar wires in situ, the native anatomical landmarks are obscured, thus making the freehand screw placement technique a highly specialized task. Hence, the concept of using PSTs for insertion of PAs in such surgeries is always intriguing and attractive. METHODS: Five consecutive patients undergoing revision deformity correction with sublaminar wires in situ were included in this study. Patients were divided in two groups based on the technique of PA insertion. A total of 91 PAs were inserted using either a freehand technique (group A) or 3D printed templates (group B) (34 vs. 57). The placement of PAs was classified according to a postoperative computed tomography scan using Neo's classification. Perforation beyond class 2 (>2 mm) was termed as a misplaced screw. The average time required for the insertion of screws was also noted. RESULTS: Mean age, surgical time, and blood loss were recorded. The change in mean Cobb's angle in both groups was also recorded. The difference in rates of misplaced screws was noted in group A and group B (36.21% vs. 2.56%); however, the mean number of misplaced PAs per patient in group A and group B was statistically insignificant (6.5±3.54 vs. 4.67±1.53, p =0.4641). The mean time required to insert a single PA was also statistically insignificant (120±28.28 vs. 90±30 seconds, p =0.3456). CONCLUSIONS: Although 3D printed PSTs help to avoid the misplacement of PAs in revision deformity correction surgeries with sublaminar wires in situ, the mean number of misplaced screws per patient using this technique was found to be statistically insignificant when compared with the freehand technique in this study.

Use of Zipper Ratcheting Straps as a Bailout for Postoperative Cerebrospinal Fluid Leaks: Our Experience.

STUDY DESIGN: Technical note. OBJECTIVES: Management of postoperative cerebrospinal fluid (CSF) leaks is a challenge. Reexploration increases the morbidity risks. The main objective was to evaluate the outcomes of noninvasive zipper-like system (Zip surgical skin closure system, ZipLine Medical, Inc, Campbell, CA, USA) as a bailout technique for postoperative CSF leaks. METHODS: Retrospective case series. Consecutive patients with postoperative CSF leaks that occurred secondary to spinal surgeries performed between January 2017 and September 2018 were part of the study. All these patients were managed conservatively by reinforcement with zipper ratcheting straps over the sutured surgical wound. Successful clinical outcomes included cessation of CSF leaks and adequate wound healing in the postoperative period and at follow-up. RESULTS: Ten patients underwent the application of zipper ratcheting straps. The mean follow-up was 6 months (range 6 months to 1 year). In 7 cases, the dural tears were recognized postoperatively and in 3 cases, the tears were noted intraoperatively and repaired and reinforced with fibrin sealants. None of the patients developed wound soakage or subsequent CSF leak from the wound after the application of zipper ratcheting straps. CONCLUSIONS: Zipper ratcheting straps as augmentation to sewing of the wound seem to be a good alternative and bailout in treating patients with postoperative CSF leaks. The ease of its application, the ability in minimizing the complications associated with CSF leaks, and negating the need of surgical reexploration makes it a worthy option.

Management of Metastatic Spine and Hip Alveolar Soft Part Sarcoma: Case Report and Review of Literature.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor. Primary or metastatic involvement of the spine is unusual in ASPS. In most case, it is refractory to chemotherapy and radiation. Surgical resection is the most effective intervention. We report the case of a 38-year-old female having ASPS along with metastatic spine and hip involvement treated surgically as a single-stage operation, which is the first of its kind approach to our knowledge. We present the case of a 38-year-old female with simultaneous L4 pathological fracture with symptomatic lumbar canal stenosis without focal neurology and pathological fracture of neck of femur of left hip, secondary to metastatic ASPS. Since both conditions were contributing equally to her disability and demanded early intervention, they were treated simultaneously with intralesional excision of the tumor and posterior stabilization of the spine and left hip proximal femur resection and replaced it with proximal femur endoprosthesis as a single-stage operation. Postoperatively, she had significant relief of radiculopathy and left hip pain. She was mobilized out of bed on the postoperative day 1 and was discharged from hospital on the postoperative day 6. She was given chemotherapy drug sunitib postoperative. At her last follow-up, 20 months' postoperative, she was asymptomatic and was independent in terms of activities of daily living. Metastatic ASPS of the spine and hip is a rare clinical entity. Simultaneous surgical treatment of the spine and hip pathology is technically demanding. If the conditions demands, as in our case, both of them can be managed safely in a single-stage with good midterm outcome.

Management of Proximal Thoracic Kyphoscoliosis with Early Myelopathy in a Young Adult with Neurofibromatosis Type 1: A Case Report and Review of Literature.

INTRODUCTION: Neurofibromatosis (NF) 1 is associated with skeletal deformities. Scoliosis is seen in about 10-64% of NF-1 patients. NF-1 may be associated with dystrophic or non-dystrophic type of curve. There are technical difficulties in treating large dystrophic curve with proximal thoracic kyphoscoliosis in NF-1. This case report and subsequent review of literature attempts to provide a line of management for such difficult lesions. MATERIALS AND METHODS: We present a case of 22-year-old male with NF-1 who came to us with gradually progressive upper back deformity and signs of early myelopathy for 2-3 months. The patient had a 100° proximal thoracic kyphosis and 100° scoliosis with no neurological deficit and brisk reflexes. A single stage posterior fixation with three column osteotomy at the apex of the curve was performed. RESULTS: The kyphosis was corrected to 65° from 100, the scoliosis was corrected to 60° from 100. Clinically, the hump in the upper back was visibly reduced. At 1-year follow-up, the patient remained asymptomatic with no loss of correction and implant breakage on X-ray. CONCLUSION: Large dystrophic proximal thoracic kyphoscoliosis is a difficult lesion to treat and can be managed with an all posterior approach, achieving good cosmetic and neurological outcomes, as demonstrated by this case.

Analysis of the Functional and Radiological Outcomes of Lumbar Decompression without Fusion in Patients with Degenerative Lumbar Scoliosis.

STUDY DESIGN: Retrospective study. PURPOSE: This study aimed to analyze the functional and radiological outcomes of lumbar decompression in patients with degenerative lumbar scoliosis (DLS). OVERVIEW OF LITERATURE: Patients with DLS have symptoms related to lumbar canal stenosis (LCS) and those due to compensated spinal imbalance. Whether the deformity is the cause of pain or is an adaptive change for the ongoing LCS remains debatable. The extensive surgery for deformity correction along with spinal fusion is reported to have high perioperative morbidity and complication rate. METHODS: This retrospective analysis involved 51 patients who underwent lumbar decompression for LCS associated with DLS from October 2006 to October 2016. The magnitude of the curve was determined using Cobb's angle and lumbar lordosis (D12-S1) on the preoperative and final follow-up, respectively. The Visual Analog Scale (VAS) and modified Oswestry Disability Index (mODI) scores at the preoperative and final follow-up indicated the functional outcome. Statistical analyses were performed using Student t -test. RESULTS: All 51 patients were included in the statistical analyses. The mean patient age at presentation was 63.88±7.21 years. The average follow-up duration was 48±18.10 months. The average change in the Cobb's angle at the final follow-up was statistically insignificant (1°±1.5°, p=0.924; 20.8°±5.1° vs. 21.9°±5.72°). The mean change in lumbar lordosis at the final follow-up was statistically insignificant (3.29°±1.56°, p=0.328; 30.2°±7.9° vs. 27.5°±7.1°). There was statistically insignificant worsening in the back VAS scores at the final follow-up (4.9±1.9 vs. 6.0±1.2, p=0.07). There was statistically significant improvement in the leg pain component of the VAS score at the final follow-up (5.8±1.05 vs. 2.6±1.2, p<0.001). There was statistically significant improvement in the mODI scores at the final follow-up (p<0.001). CONCLUSIONS: Lumbar decompression in DLS is associated with good functional outcome, especially when the symptoms are related to LCS. Curve progression following lumbar decompression is very less at mid-term and is similar to that in the natural course of the disease.

Osteoid Osteoma of Cervical Spine: A Case Report and Review of Literature.

INTRODUCTION: Osteoid osteoma of cervical spine is a rare clinical entity and accounts for 4% of cases of overall spinal osteoid osteoma. It has predilection for neural arch and complete resection is difficult task due to proximity to important neurovascular structures. Incomplete resection leads to recurrence in about 4.5% of patients. Computed tomography (CT)-based navigation may aid in resection of tumor without compromising stability, but whenever it inevitable fusion is mandatory. CASE REPORT: We report two cases of osteoid osteoma of cervical spine managed with surgical excision. Case1 had recurrence of tumor at the left C6 pedicle after minimally invasive intervention that was later managed by surgical excision with the help of CT-guided navigation. Case 2 had osteoid osteoma of the right C4 lateral mass that was treated with surgical excision and fusion. CONCLUSION: Osteoid osteoma is a rare pathology in cervical spine. Surgical excision of cervical osteoid osteoma is a daunting task due to the proximity to neurovascular structures. Recurrence though less often is the result of inadequate excision.

A Non-Operative Approach to Rectal Cancer after Chemo-Radiotherapy: Case Series and Review.

INTRODUCTION: Chemotherapy administered concurrently with radiotherapy for locally-advanced rectal cancer prior to surgery is a standard of care approach. A fraction of patients after chemo-radiotherapy achieve pathological complete remission. Our aim was to evaluate patients treated only with a non-operative approach of only chemo-radiotherapy followed by observation at a community cancer center. METHODS: Medical charts of the patients who were treated for locally advanced rectal cancer and treated with chemo-radiation therapy alone from January 1, 2000 through May 1, 2017 at a Midwestern cancer center were reviewed. The clinical course of the patients was followed from the time of the cancer diagnosis through their last available clinical record. RESULTS: A series of three cases were reviewed with locally-advanced distal rectal cancers treated with a non-operative approach. CONCLUSIONS: Watchful waiting for patients with locally advanced distal rectal cancer who have complete clinical response with neoadjuvant chemotherapy and radiation might be an effective treatment strategy.

Tyrosine Phosphorylation of p27Kip1 Correlates with Palbociclib Responsiveness in Breast Cancer Tumor Cells Grown in Explant Culture.

Cdk4-targeting drugs, such as palbociclib, are approved for metastatic ER/PR+, Her2- breast cancer. However, other than loss of retinoblastoma, which is very rare in this subset, there are no biomarkers to predict response. Cyclin D or cdk4 levels are not by themselves indicative, because p27Kip1 is required for cyclin D-cdk4 complex activation. Tyrosine phosphorylation of p27, including modification on residue Y88 (pY88), activates DK4-p27, and the pY88 level correlates with palbociclib responsiveness in cell lines. We developed dual IHC staining for p27 and pY88, and found that benign breast epithelium was negative, while breast cancer biopsies (of varied hormonal status) could be stratified for pY88 status. Lack of pY88 suggested that DK4 was inactive, and that these samples would not have the target required for palbociclib response. Tumor resection material was grown in explant culture, treated with palbociclib, and stained with Ki67 as a marker of response. Explants from the no pY88 group were nonresponsive, while explants from the low or high pY88 group responded to drug. IMPLICATIONS: Use of the pY88 biomarker, as a surrogate for cdk4 activity, may identify patients responsive to cdk4-targeting drugs and expand use of this therapy.Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/3/669/F1.large.jpg.

Severe pneumonitis refractory to steroids following anti-PD-1 immunotherapy.

Anti-programmed death 1 (PD-1) immune checkpoint inhibitors enhance the antitumour activity of the immune system and have produced durable tumour responses in several solid tumours including non-small cell lung cancer (NSCLC). However, PD-1 inhibitors can lead to immune-related adverse events , including pneumonitis, which is typically mild, but can be severe and potentially fatal. Pneumonitis often resolves with steroids, but some cases are steroid refractory, leading to a relapsing and remitting course in milder cases or the need for salvage therapies in more severe cases. Here, we present two patients with NSCLC who developed severe pneumonitis following therapy with nivolumab and pembrolizumab. While one patient improved with steroids and infliximab, the other patient failed to respond to steroids and subsequently died. These cases demonstrate the highly variable presentation and therapeutic responses seen in patients with pneumonitis following anti-PD-1 therapy and illustrate that severe cases can often present refractory to steroid therapy.

Management of Andersson Lesion in Ankylosing Spondylitis Using the Posterior-Only Approach: A Case Series of 18 Patients.

STUDY DESIGN: This retrospective study was conducted including 18 patients who underwent posterior-only stabilization and fusion procedure for pseudoarthrosis in the ankylosed spine from October 2007 to May 2015. PURPOSE: This study aimed to describe the treatment outcomes in 18 patients with Andersson lesion (AL) who were managed using the posterior-only approach. Literature Review: AL is an unstable, localized, vertebral, or discovertebral lesion of the spine. It is observed in patients with ankylosing spondylitis. The exact etiology of this disorder remains unclear, and the treatment guidelines are not clearly described. METHODS: We analyzed 18 patients with AL who were treated with posterior long segment spinal fusion without any anterior interbody grafting or posterior osteotomy. Pre- and postoperative radiography, computed tomography, and recent follow-up images were examined. The pre- and postoperative Visual Analog Scale score and the Oswestry Disability Index score were evaluated for all patients. Whiteclouds' outcome analysis criteria were applied at the follow-up. Moreover, at study completion, patient feedback was collected; all the patients were asked to provide their opinion regarding the surgery and were asked whether they would recommend this procedure to other patients and them self undergo the same procedure again if required. RESULTS: The most common site was the thoracolumbar junction. The symptom duration ranged from 1 month to 10 years preoperatively. Most patients experienced fusion by the end of 1 year, and the fusion mass could be observed as early as 4 months. Pseudoarthrosis void of up to 2.5 cm was noted to be healed in subsequent imaging. In addition, clinically, the patients reported good symptomatic relief. No patient required revision surgery. Whiteclouds' outcome analysis score at the latest follow-up revealed goodto- excellent outcomes in all patients. CONCLUSIONS: ALs can be treated using the posterior-only approach with long segment fixation and posterior spinal fusion. This is a safe, simple, and quick procedure that prevents the morbidity of anterior surgery.

Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation Induces a Potent and Durable Response in Breast Cancer Cells.

Cyclin-dependent kinase 4/6 (CDK4/6)-specific inhibitors, such as palbociclib, have shown clinical efficacy, but primary or secondary resistance has emerged as a problem. To develop more effective therapeutic approaches, investigation is needed into the mechanisms of resistance or adaption. Here, it is demonstrated that CDK2 compensates for loss of CDK4 activity to rescue palbociclib-arrested breast cancer cells, suggesting that inhibition of both kinases is required to achieve durable response. In addition, a novel strategy is described to inhibit tyrosine phosphorylation of p27Kip1 (CDKN1B) and simultaneously inhibit both CDK2 and CDK4. p27Kip1 is a required assembly factor for cyclin-CDK4 complexes, but it must be phosphorylated on residue Y88 to open or activate the complex. The Brk-SH3 peptide, ALT, blocks p27 Y88 phosphorylation, inhibiting CDK4. Nonphosphorylated p27 is no longer a target for ubiquitin-mediated degradation and this stabilized p27 now also inhibits CDK2 activity. Thus, ALT induction inhibits both the kinase that drives proliferation (CDK4) and the kinase that mediates resistance (CDK2), causing a potent and long-lasting cell-cycle arrest. ALT arrests growth of all breast cancer subgroups and synergizes with palbociclib to increase cellular senescence and to cause tumor regression in breast cancer xenograft models. The use of ALT demonstrates that both CDK4 and CDK2 need to be inhibited if long-term efficacy is to be achieved and represents a novel modality to inhibit breast cancer cells.Implications: Modulating tyrosine phosphorylation of p27 impacts both proliferative (CDK4) and resistance (CDK2) mechanisms in breast cancer and suggests that phospho-p27 status may serve as a biomarker for patients that are responsive to CDK4/6 inhibition. Mol Cancer Res; 16(3); 361-77. ©2018 AACR.

A Phase II Trial of Rituximab Combined With Pegfilgrastim in Patients With Indolent B-cell Non-Hodgkin Lymphoma.

BACKGROUND: To explore the role of augmenting neutrophil function in B-cell lymphoma, we conducted a phase II study evaluating the safety and clinical efficacy of pegfilgrastim and rituximab in low-grade CD20+ B-cell non-Hodgkin lymphoma (B-NHL). PATIENTS AND METHODS: Twenty patients with indolent B-NHL were treated with rituximab (375 mg/m2) every other week for 4 doses, followed by every 2 months for 4 additional doses. Pegfilgrastim was administered subcutaneously 3 days before each dose of rituximab. Clinical activity and tolerability were assessed using standard criteria. Biologic monitoring included phenotype characteristics of the host neutrophils, changes in oxidative burst, and functional assays. RESULTS: The patient demographics included median age of 64 years, 70% were male, 70% had follicular lymphoma, and 90% had stage III-IV disease. The median number of previous therapies was 2 (range, 0-5); 90% had received previous anti-CD20 monoclonal antibody therapy. The addition of pegfilgrastim to rituximab did not increase rituximab-related toxicities. The overall response rate was 60% (12 of 20), with a complete response (CR) rate of 35% (7 of 20). The median progression-free survival (PFS) duration was 17.9 months (95% confidence interval, 9.9-27.6 months); the median overall survival was not reached. A shorter time-to-peak oxidative burst after the first dose of pegfilgrastim was associated with greater CR rates (P = .04) and longer PFS (P = .03). CONCLUSION: The pegfilgrastim-rituximab combination was well tolerated, with favorable outcomes compared with historical controls. A shorter time-to-peak oxidative burst was associated with higher CR rates and longer PFS. Our results support further evaluation of strategies that enhance the innate immune system to improve rituximab activity in B-NHL.