bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective Case Study of TTC Fusion Treated with Carbon Fiber Nail
Authors: Jones Caleb W. , O’Daly Andres , Smith Kenneth S. , Shah Ashish
Published: October 2016

Category:

Ankle

Introduction/Purpose:

Tibiotalocalcaneal arthrodesis is a salvage option reserved for severe ankle and hindfoot deformities, arthritis of the ankle and subtalar joints, avascular necrosis of the talus, failed total ankle arthroplasty, and Charcot arthropathy. Implants have long been made from various metals most commonly stainless steel or titanium alloys. Disadvantages of metal implants include limited fatigue life, mismatch of modulus of elasticity, potential for wear debris, corrosion, and radiodensity that can preclude accurate radiographic visualization. Carbon fiber implants have been available for years. The advantageous properties of carbon fiber for use as orthopaedic implants include a similar modulus of elasticity to bone to decrease stress shielding, biocompatilibity, with minimal cellular response when studied invitro and invivo, ability to withstand prolonged fatigue straining and radiolucency on XR.

Methods:

A Carbofix TM carbon fiber TTC fusion nail was used in 15 patients with for Tibiotalocalcaneal /TC fusion. All patients received preop, intra op xrays, and follow up xrays at weeks 2/6/12. After 12 weeks xrays were taken every 3 months until 1 year. All xrays were read by a radiology attending to assess for consolidation and maintenance of alignment. We also performed CT scan for the nonunion [clinical & Radiological]

Results:

We were able to find comparable results [patients operated with carbon fiber nail] to the historical data of the patients treated with different metal implants. We were also able to check the safety of using the implant [no tissue reaction or reactivity], easily able to see the fusion across the joints secondary to radioluceny and artifact free CT scan or MRI when required. There were no metal related complications noted.

Conclusion:

These studies have shown the usefulness of carbon fiber implants but there are no studies which explicitly review Tibiotalocalcaneal/Tibiocalcaneal fusion. We present a retrospective case series of 15 patients who were treated with carbon fiber tibiotalocalcaneal fusion nail.
Secondary Procedures in Third Generation Total Ankle Arthroplasties
Authors: Gross Christopher E. , Huh Jeannie , Shi Glenn G. , Lampley Alexander J. , Green Cynthia , Nunley James A. , DeOrio James K. , Adams Samuel B. , Easley Mark E.
Published: October 2016

Category:

Ankle Arthritis

Introduction/Purpose:

As surgeons have become more comfortable with performing more complex total ankle replacements (TAR) with larger amounts of deformity, it is unclear whether or not to address additional pathology at the time of surgery. Currently, we address all foot and ankle pathology at time of the index arthroplasty. It is unclear however, how often and for what reasons secondary surgery is performed after TAR. We hypothesize that there were no differences in the type or rate of secondary surgeries performed.

Methods:

We identified a consecutive series of 761 primary TARs performed between January 1998 and December 2014. We identified patients who required a secondary surgery to treat foot and ankle pathology following a STAR, INBONE I/II, or Salto- Talaris. We then analyzed if there were differences between the implants in terms of time to secondary surgery or types of procedures performed.

Results:

193 patients (25.3%) required a secondary procedure with an average time to a secondary procedure of 24.5 months. The rate of second surgery in both the Salto (25/113, HR=0.64 with 95%CI=0.408-0.996; p=0.048) and STAR (81/333, HR=0.694 with 95%CI=0.507-0.949; p=0.022) is less when compared to the INBONE group (87/315). The STAR had a significantly longer time to secondary procedure (33.8 months) versus a Salto-Talaris (12.8 months) or an INBONE (19.2 months, p=001). The number of secondary procedures (p< .001), polyethylene exchanges (p< .001), cyst grafting (p=.036) were similar in INBONE and STAR, but significantly more than the Salto. The INBONE prosthesis had a significantly higher talar component failure rate (p=.038), but similar rate of subtalar, ankle, and TTC fusion.

Conclusion:

Knowledge of the rates and types of secondary surgeries is useful information on the natural history of third generation ankle implants. While there are differences in the rate of failure or revisions between implants, no implant has proven superior to one another.
Surgical Repair of Symptomatic Chronic Achilles Tendon Rupture Using Synthetic Graft Augmentation
Authors: Shoaib Ahmed , Mishra Viren
Published: October 2016

Category:

Other

Introduction/Purpose:

Surgical repair of symptomatic chronic Achilles tendon (TA) rupture is a challenging problem due to the presence of large defect between tendon edges. We report the results of surgical repair of symptomatic chronic TA rupture by synthetic graft augmentation.

Methods:

Seven consecutive patients with a symptomatic chronic TA rupture underwent surgical repair by VY plasty and augmentation with bio-absorbable synthetic graft (Artelon®). In all patients, the intraoperative tendon gap after debridement was more than 5 cm (Myerson Grade 3). Postoperatively, weight bearing on plantigrade foot was allowed at 4 weeks in a plaster cast. The total duration of plaster immobilization was 10 weeks. The complications were recorded prospectively and functional outcome was assessed by AOFAS score and Achilles tendon Total Rupture Score (ATRS).

Results:

At a mean follow up of 29 months there was no re-rupture or deep infection. All patients reported good functional outcome as shown by AOFAS and ATRS scores. There were no graft related complications. One patient had an early superficial infection which was treated by a course of oral antibiotic. Two patients reported numbness in the sural nerve territory after surgery,of which one patient developed scar sensitivity and paraesthesia. At final follow up, six patients were able to do single stance heel raise however, calf wasting was noted in all patients.

Conclusion:

Symptomatic chronic TA repair augmented by synthetic graft is a safe and effective technique in Myerson Grade 3 chronic TA ruptures where gap between two tendon edges is more than 5 cm.
Swelling Results in Poor Outcome After Ankle Arthritis Surgery
Authors: Younger Alastair S. , Daniels Timothy R. , Wing Kevin , Penner Murray J. , Glazebrook Mark A. , Veljkovic Andrea , Wong Hubert , Dryden Peter
Published: October 2016

Category:

Ankle Arthritis

Introduction/Purpose:

Patients often comment on swelling after foot and ankle surgery. However the relationship between swelling and outcome has not been defined. Pinsker and Daniels demonstrated that swelling was an important aspect of outcome. The purpose of this paper was to determine the relationship between swelling score and outcome after ankle fusion and replacement. A secondary purpose was to determine how this relationship changed in time, how swelling score changed before and after surgery, and determine differences in swelling score between total ankle replacement (TAR), open ankle arthrodesis (OAA) and arthroscopic ankle arthrodesis (AAA).

Methods:

The MODEMS outcomes package from AAOS was used, with the validated ankle osteoarthritis score (AOS) score being used to assess outcomes in the pain and disability domains. The swelling score was indexed from 1 to 5, 1 being no swelling and five being severe swelling. Outcomes were recorded pre-operatively and annually up to 2010. Statistical analysis was performed using 95% confidence intervals and correlations being determined using Pearson’s correlation and r 2 values.

Results:

The swelling score was correlated with AOS score preoperatively. Postoperatively patients with a swelling score of 1 had an average AOS score of 15.1 (CI 13.3 to 16.9), a swelling score of 2 had an AOS score of 23 (CI 21.7 to 24.9), 3 an AOS of 31 (CI 29.6 to 33.1), 4 an AOS of 33.6 (CI 34.9 to 38.8), and 5 an AOS of 39 (CI 35.3 to 43.0). There was therefore a difference in outcome score for all groups of swelling score (i.e. 1 scored better than 2, 2 better than 3, 3 better than 4 and 4 better than 5). Swelling scores were the same for TAR, OAA and AAA preoperatively. Postoperatively swelling scores were lower for AAA (2.1, CI 1.9 to 2.2) compared to TAA (2.5, CI 2.4 to 2.6) and OAA (2.5, CI 2.4 t0 2.6).

Conclusion:

Swelling has a relationship with outcome. Swelling after surgery may result in poorer outcomes. Strategies to reduce swelling such as patient education about elevation, surgical technique and the use of compression stockings may improve outcomes. Arthroscopic surgery may have better outcomes because of the reduction in postoperative swelling.
Tarsal Tunnel Release
Authors: Rungprai Chamnanni , Phisitkul Phinit , Femino John , Amendola Annunziato , Sittapairoj Tinnart
Published: October 2016

Category:

Ankle

Introduction/Purpose:

Tarsal tunnel release is a standard surgical treatment for patients who have tarsal tunnel syndrome and failure of conservative treatment. However, there remains little evidence demonstrating the medium-term of functional outcomes and complications of tarsal tunnel release. The purpose of this study was to report functional outcomes and complications of tarsal tunnel release.

Methods:

Retrospective chart review with prospectively collected data of 79 consecutive patients with 87 feet (primary surgery = 74/80 and revision surgery = 5/5) who were diagnosed with tarsal tunnel syndrome and underwent tarsal tunnel release between 2008 and 2014. Diagnosis bases on history and physical examination. All patients were failure of conservative treatment at least 6 weeks and the minimum follow up to be included in the study was 12 months (mean, 32.2 months; range, 12 to 80 months). The primary outcome was visual analogue scale (VAS), Short Form-36 (SF-36); physical and mental component scores, and Foot Function Index (FFI); pain, disability, activity limitation, and total score. Pre- and post-operative SF-36, and Foot Functional Index (FFI), pain (Visual Analog Scale) were obtained and compared using pair t-test. The secondary outcomes were operative time, time to return to activity of daily living and work, and complications. Mann-Whitney U-test was used to compare non-parametric data and Wilcoxon signed ranks test was used to compare parametric data.

Results:

The VAS was significantly decrease from 7.6 to 2.0(p = 0.001) and SF-36 was significantly improved from 33.2 to 40.2, for PCS (p= 0.001) and 47.7 to 49.7 for MCS (p = 0.005). The FFI was significantly decreased from 63.0 to 36.0, 61.9 to 35, 72.5 to 34.9, and 65.8 to 35.3 for pain, disability, activity limitations, and total scores(p=0.001, all). Mean operative time was 36.1 minutes for primary surgery and 54.8 minutes for the revision surgery. There 45 of 87 feet (51.7%) had positive Tinel test pre-operatively and 9 of 87 feet (10.3%) post-operatively. Revision surgery demonstrated significantly worse outcomes (VAS,SF-36,and FFI) compared to primary surgery(p < 0.05) but duration >12 months and Tinel sign did not affect the outcomes compared to duration >12 months and Tinel sign negative (p>0.05 all). An average time to return to activity of daily living and work was 8.1 and 9.5 weeks. Complications were painful scar(14.9%), wound infection(6.9%), CRPS(2.3%), and paresthesia on the foot(20.7%).

Conclusion:

Tarsal tunnel release demonstrated significant improvement of functional outcomes and pain relief in medium-term follow-up as measured with SF-36, FFI, and VAS. Revision surgery demonstrated less favorable outcomes while pre-operative Tinel test and duration of symptom more than 12 months did not affect the outcome. This procedure was effective and feasible for tarsal tunnel syndrome with minor complications.
The Evaluation of SPECT-CT in the Early Management of Acute Charcot Osteoarthropathy (CN)
Authors: Ahluwalia Raju S. , Ahmed Bilal , Mullhollad Nicola , Vivian Jill , Kavarthapu Venu , Edmonds Michael
Published: October 2016

Category:

Diabetes

Introduction/Purpose:

Charcot osteooarthropathy (CN) is a debilitating condition afflicting the bone, soft tissue and joints of foot and ankle and is related to pain insensitivity. Its pathogenesis and natural progression is poorly understood. In patients with high clinical suspicion, treatment with immediate off-loading and immobilisation may halt and (help to) reverse or prevent deformity. We aim to establish the role of SPECT CT in the diagnosis of acute charcot osteoarthropathy of the red swollen foot prior to radiographic changes and assess its reliability in diagnostic accuracy and guiding treatment.

Methods:

A prospective, observational review of all patients presenting to the multidisciplinary diabetic foot clinic from 1st Jan 2009 to 1st Jan 2013 with clinically suspected acute active charcot arthropathy was performed. All patients with a high clinical suspicion of acute CN and normal radiographs, underwent SPECT-CT within 10 days of the assessment after emergency off-loading in a TCC. A positive SPECT CT scan for new onset acute CN was diagnosed if radioisotope uptake was seen in all 3 phases of scanning. Further CT fusion images provided localization of ongoing activity. All patients were followed up for 1-year or until treatment ceased and treated in concordance with clinical symptoms and SPECT CT imaging.

Results:

In total 137 patients were referred or self referred with a high suspicion of new onset acute CN. The majority being diabetic (98%), including 116 unilaterally symptomatic feet with normal radiographs; 86 were consequently positively confirmed on SPECT-CT CN; 15 new ‘diabetic’ fractures were diagnosed on the CT component. At 1 year – only 5 patients went on to develop radiological changes consistent with charcot arthropathy even with accepted off loading in TCC. Thirty negative scans were recorded where no triple phase trace response & localisation was uni-focal or not associated with skeletal structures. Differential diagnosis included cellulitis, degenerative changes, old fractures, and planter fasciitis were made. At 1-year none of the patients were found to have developed CN in neither in the form of foot deformity nor radiological evidence of fragmentation or loss of normal bone anatomy.

Conclusion:

A combination of symptoms including swelling, pain and/or heat, positive three phase tracer uptake and localisation on SPECT CT can identify and aid the management of acute active CN in radiographically normal feet. Positive scans seem to identify an intermediate grade of charcot arthropathy where cortical fractures have occurred with significant subchondral bone turnover. A negative scan excludes high-risk feet for CN confidently and thus can direct treatment. We find SPECT CT a valuable addition to the armamentarium of the treating physician in instituting off loading to prevent the possible progression and onset of deformity and avoiding unnecessary treatment.
The Natural History of Charcot Neuroarthropathy
Authors: Kane Justin M. , Brodsky James W. , Daoud Yahya , Rabinovich Alexander
Published: October 2016

Category:

Diabetes

Introduction/Purpose:

There are limited data in the literature regarding natural history of Charcot Neuroarthropathy (CN) of the foot and ankle. The utility of a classification system should be threefold: accurately describe the disease process, guide the appropriate treatment, and predict the long-term prognosis. This study investigates the natural history of CN of foot and ankle, and whether the Anatomic Classification is predictive of outcome and prognosis.

Methods:

A retrospective review of 334 patients treated at a single institution by a single surgeon from January 1986 to June 2010 was conducted. Clinical records, imaging studies, and operative reports were reviewed to tabulate the Anatomic Classification type, patient demographics (age, gender, BMI, diabetes, RA), number and types of surgeries performed, location of surgery, initial and final job status, ulcer status, ambulatory status and shoe wear type. ANOVA and Pearson Chi square were utilized to assess whether the classification was predictive of variables. P-values of < 0.05 were considered statistically significant.

Results:

Outcomes/p-values are listed in table 1. 35.3% of patients presented with a unilateral Type 1 Charcot foot(n=118), 17.1% presented with a unilateral Type 2(n=57), 13.8% presented with a unilateral Type 3(n=46), and 33.8% presented with bilateral disease(n=113). CN due to RA had increased bilateral involvement(12.4%; 14/113) compared to unilateral involvement(5%,11/221)(p=0.026). Comparing bilateral versus unilateral Types 1,2,or 3, a similar trend was noted(p=0.0939). The Anatomic classification predicted location/need for surgical intervention(p < 0.00001). The classification predicted distal disease was associated with increased likelihood to require shoe-wear modifications(p=0.0001). While a statistically significant difference was not detected, a trend for the classification to predict persistent ulceration at final follow-up was noted. Patients with bilateral involvement and more distal disease were more likely to have ulceration(p=0.0968).

Conclusion:

While the Anatomic classification did not predict ambulatory status, and only trended towards statistical significance for ulceration at the time of final follow-up, there is utility in the classification system for predicting location of surgery as well as shoe-wear at final follow-up. Additionally, patients with CN due to RA had an increased likelihood of having bilateral foot involvement. The Anatomic Classification has clinical utility when counseling patients on the overall course of their disease process.
The Preoperative ‘6 Pack’ for Patients With Ankle Arthritis
Authors: Siddique Malik S. , Ramaskandhan Jayasree R. , Chuter Graham S. , Gower Andrew , Murty Aradhyula N. , Patterson Paul R. , Townshend David , Torres Paulo
Published: October 2016

Category:

Ankle Arthritis

Introduction/Purpose:

There is paucity of literature relating to information needs of patients in Orthopaedic Surgery, despite the fact that Orthopaedic Surgeons in the UK welcome the use of patient decision aids for joint replacement surgery. This multi- centre study aimed to study the information needs of patients for surgical treatment of ankle arthritis from 6 different hospitals across the North East region of England.

Methods:

Ethical permissions were obtained for this multi-centre qualitative research study. The study recruited 18 patients from 6 hospitals across the North East of England. They were invited to take part in patient focus group meetings. 3 focus groups were conducted with 4-8 patients/ group. These groups were facilitated by independent researchers using a semi-structured discussion approach. Patients were asked for their views on information needs for surgical treatment of ankle arthritis. The focus group meetings were digitally recorded and transcribed verbatim. Data was analysed using the nVIVO software with framework analysis.

Results:

The analysis highlighted 4 main themes: A) Factors influencing surgical decision making B) Information needs of patients C) Information provision and D) Patient expectations. Theme B is discussed in detail for this abstract. Primary information needs requested by over 70% of patients were: 1. Desire to meet with patients who had undergone similar surgical procedure 2. Information on post-operative rehabilitation 3. Information on return to work and driving 4. Experience of consultant team 5. Written information regarding procedures (advantages, disadvantages, survivorship and outcomes) and 6. Personalized decision support based on individual patient’s lifestyle and preferences. These components form the Preoperative/information ‘6 pack’.

Conclusion:

When developing information materials and decision tools for patients, providing them with the Ankle Arthritis ‘6 pack’ will enable them to make a more informed choice of the surgical options offered by the consultant.
The Use of SPECT-CT in the Diagnosis and Surgical Decision Making for the Treatment of Muller- Weiss Disease
Authors: Li ShuYuan , Zhang JianZhong
Published: October 2016

Category:

Hindfoot

Introduction/Purpose:

Muller Weiss disease (MWD) is an idiopathic avascular necrosis of the navicular, caused by abnormal forces on the immature navicular. The disease is characterized by hindfoot varus, a paradoxical flatfoot deformity, and middle foot pain associated with arthritis. According to Maceira the progress of the disease can be divided into five stages, with the increasing of deformity and fragmentation. However, the stage of disease does not correspond with an increase in symptoms. In addition, neither XR nor CT provides sufficient information to assist with clinical decision making. For early stage cases with minimal clinical and radiological changes, diagnosis is difficult, and for advanced cases, with extensive arthritis and deformity, it is difficult to distinguish which joints are involved in the disease process.

Methods:

We present the use of SPECT-CT in the diagnosis and surgical decision making for the treatment of Muller-Weiss Disease. We propose that it will be helpful to make the diagnosis of early stage disease, and facilitate decision making with respect to the involved joints in advanced disease. The use of SPECT-CT is particularly helpful when the arthritis appears to include both the talonavicular (TN) and navicular-cuneiform (NC) joints, but may isolate one or more joints which require arthrodesis. 5 cases of MWD were prospectively studied with SPECT-CT. There were 4 females and 1 male with a mean age of 52 years, and each with a different stage of the disease process . The clinical outcomes of the treatment were evaluated. We present the unique findings of each patient and the use of SPECT-CT in planning treatment. One patient was successfully treated non operatively with orthotic support.

Results:

One patient was treated with an isolated talonavicular arthrodesis despite radiographs demonstrating arthritis in the NC joint, but with a normal SPECT CT at that joint. One patient was treated with a triple arthrodesis when the SPECT CT did not support the radiographic findings of involvement of the NC joints . One patient who had a postitive uptake of both TN and NC joints on SPECT CT underwent a TN-NC arthrodesis. One patient underwent a triple arthrodesis, but with continued pain, and the SPECT CT was able to clarify the source of pain not as a non union but as arthritis of the NC joint.

Conclusion:

SPECT CT was found to be accurate and predict the course of treatment in these five cases. It is very useful in early diagnosis as well as decision making of advanced stage MWD, with a high sensitivity and ability to specify the clinically involved joints, which had not been possible with plain radiographs in any of these patients.
The Validity of Using ICD-9 Codes for Identifying Venous Thromboembolism Following Below Knee Surgery
Authors: Lubberts Bart , Heijboer Reinout R. , Van Dijk Pim A. , Vopat Bryan G. , Johnson Holly H. , Guss Daniel , DiGiovanni Christopher W.
Published: October 2016

Category:

Other

Introduction/Purpose:

To determine the incidence of venous thromboembolism (VTE) after surgeries performed below the knee, previous studies have used the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes to identify a DVT (deep vein thrombosis) or PE (pulmonary embolism) event. The purpose of this study was (1) to determine the incidence of VTE in a large cohort of patients who had undergone surgery below the knee, and (2) to assess the validity of the ICD-9-CM procedure codes used.

Methods:

Current Procedural Terminology codes and ICD-9-CM codes were used to identify patients who had undergone below knee surgery and a reported VTE. The medical records of 21,904 patients were evaluated to assess the validity of the VTE ICD-9-CM code against the documentation of DVT or PE in radiology reports. Positive predictive value (PPV) and sensitivity of ICD-9-CM codes were calculated.

Results:

The incidence of VTE was 2.5% (552/21,904). Of those patients identified as having VTE, 344 (62.3%) had a DVT, 130 (23.6%) had a PE, and 78 (14.1%) were recorded as having both a DVT and PE. The PPV of ICD-9-CM coding were 55.7% (327/587) for DVT, 84.4% (108/128) for PE, 60.2% (59/98) for DVT/PE combined, and 60.8% (494/813) for VTE in total. The resulting sensitivity scores were 95.1% (327/344) for DVT, 83.1% (108/130) for PE, 75.6% (59/78) for DVT/PE combined, and 89.5% (494/552) for VTE in total.

Conclusion:

The overall rate of VTE after below knee surgery was 2.5%. This study found that ICD-9 code use had an 89.5% sensitivity rate for VTE. Using ICD-9 codes to search for a VTE demonstrated a low PPV, however, because only 60.8% could be verified by a radiological study. By comprehensively assessing the incidence of VTE after below knee surgery, we illustrated a potential source of inaccuracy in the use of retrospective ICD-9 based data capture methodologies.
Toe Plantarflexion Exercise for Prevention of Falls
Authors: Amaha Kentaro
Published: October 2016

Category:

Other

Introduction/Purpose:

Toe plantarflexion weakness has been suggested to be associated with a range of disorders and dysfunction. Although toe plantar strength (TPS) clearly contributes to the balance and gait problem, relationship between toe plantarflexion weakness and the prevention of falls is poorly understood. Therefore, we developed a new device that measures toe plantarflexion strength as strength to press the floor. The aim of this study was to assess the hypothesis that toe plantarflexion exercise can be the prevention of falls in elderly persons.

Methods:

A single-blinded randomized controlled trial was conducted in community-dwelling older adults (N = 99, mean age 74.4±6) without major cognitive impairment. The subjects were divided into two groups: 47 females in the toe plantarflexion exercise (Ex) group and 52 in the control (Cr) group by the simple random sampling method. Ex group participated toe exercise program under the supervision of a physiotherapist. The maximum toe plantarflexion forces of all participants were measured by using push-type toe grip strength meter in both upright and sitting position. The number of falls, Timed Up and Go Test (TUGT), one-legged stance time, Functional Reach Test (FRT), Fall Efficacy Score (FES) were assessed at baseline and 2 months, 6 months. All participants were prospectively followed up for one year to count the number of falls.

Results:

There was no difference in the total falls incidence between groups (p = 0.18). Ex group showed significantly improved maximum plantarflexion strength at 6 months assessment (left sitting; p = 0.03, left upright; P = 0.157, right sitting; P = 0.007, right upright; P = 0.047). One-legged stance time, FRT, FES did not differ between groups.

Conclusion:

Although the toe exercise program enhanced toe plantarflexion forces, the total falls incidence, one-legged stance time, FRT, FES did not differ between groups. Future research is needed to determine the role of toe plantarflexion force in the enhancement of strength, balance, and mobility.
Strategies before, during, and after hematopoietic cell transplantation to improve T-cell immune reconstitution
Authors: de Koning Coco , Nierkens Stefan , Boelens Jaap Jan
Published: October 2016

T-cell immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (allo-HCT) is highly variable between patients and may take several months to even years. Patients with delayed or unbalanced T-cell IR have a higher probability of developing transplantation-related morbidity, mortality, and relapse of disease. Hence, there is a need for strategies to better predict and improve IR to reduce these limitations of allo-HCT. In this review, we provide an update of current and in-near-future clinically relevant strategies before, during, and after transplantation to achieve successful T-cell IR. Potent strategies are choosing the right HCT source (eg, donor-recipient matching, cell dose, graft manipulation), individualized conditioning and serotherapy (eg, antithymocyte globulin), nutritional status, exercise, home care, modulation of microbiota, enhancing homeostatic peripheral expansion, promoting thymopoiesis, and the use of adjuvant-targeted cellular immunotherapies. Strategies to prevent graft-versus-host disease are important as well because this complication and the subsequent need for immunosuppression affects T-cell IR and function. These options aim for personalized precision transplantation, where allo-HCT therapy is designed to boost a well-balanced T-cell IR and limit complications in individual patients, resulting in overall lower morbidity and higher survival chances.
Piracy off the coast of Somalia: implications for China’s maritime security
Authors: Venkataraman Manickam
Published: October 2016

Piracy off the coast of Somalia in the Gulf of Aden in the Indian Ocean region has become a significant non-traditional security challenge to many nations. The increasing number of such attacks as a result of failure of Somali government to tackle its internal problem drew the attention of international community who lent a drastic response thereby curtailing the number of such incidents significantly now. The intensity of the attacks had its implications on international shipping and maritime security of near and distant countries like China, which has of late become assertive. This article aims to analyze the inter-connection between failed states and piracy and the consequent maritime security implications for China. The article adopts qualitative approach using descriptive and analytical methods depending primarily on secondary sources such as published literatures and archival and internet sources. The article concludes that the implications of Somalia piracy to China’s maritime security was so grave that China was compelled to join the international community by taking part in the multinational naval task force to combating piracy signifying a cooperative role and at the same time utilizing the opportunity to come closer to Somalia by way of reopening its embassy and engaging in bilateral economic ties. This article is divided into seven broad sections. Besides the introduction, the second section provides the conceptual note on piracy and maritime security. The third section highlights the methodology while the fourth section discusses the background on Somalia and its failed status while the fifth section brings out a short glimpse of Somalia piracy and its method of operation. The sixth section analyzes the role of China and its maritime security implications and the last section provides the concluding remarks.
Longitudinal Changes in Depression Symptoms and Survival Among Patients With Lung Cancer: A National Cohort Assessment
Authors: Sullivan Donald R. , Forsberg Christopher W. , Ganzini Linda , Au David H. , Gould Michael K. , Provenzale Dawn , Slatore Christopher G.
Published: October 2016

Purpose

Depression symptoms are common among patients with lung cancer; however, longitudinal changes and their impact on survival are understudied.

Methods

This was a prospective, observational study from the Cancer Care Outcomes Research and Surveillance Consortium from five US geographically defined regions from September 2003 through December 2005. Patients enrolled within 3 months of their lung cancer diagnosis were eligible. The eight-item Center for Epidemiologic Studies Depression scale was administered at diagnosis and 12 months’ follow-up. The main outcome was survival, which was evaluated using Kaplan-Meyer curves and adjusted Cox proportional hazards modeling.

Results

Among 1,790 participants, 681 (38%) had depression symptoms at baseline and an additional 105 (14%) developed new-onset depression symptoms during treatment. At baseline, depression symptoms were associated with increased mortality (hazard ratio [HR], 1.17; 95% CI, 1.03 to 1.32; P = .01). Participants were classified into the following four groups based on longitudinal changes in depression symptoms from baseline to follow-up: never depression symptoms (n = 640), new-onset depression symptoms (n = 105), depression symptom remission (n = 156), and persistent depression symptoms (n = 254) and HRs were calculated. Using the never-depression symptoms group as a reference group, HRs were as follows: new-onset depression symptoms, 1.50 (95% CI, 1.12 to 2.01; P = .006); depression symptom remission, 1.02 (95% CI, 0.79 to 1.31; P = .89), and persistent depression symptoms, 1.42 (95% CI, 1.15 to 1.75; P = .001). At baseline, depression symptoms were associated with increased mortality among participants with early-stage disease (stages I and II; HR, 1.61; 95% CI, 1.26 to 2.04), but not late-stage disease (stages III and IV; HR, 1.05; 95% CI, 0.91 to 1.22). At follow-up, depression symptoms were associated with increased mortality among participants with early-stage disease (HR, 1.71; 95% CI, 1.27 to 2.31) and those with late-stage disease (HR, 1.32; 95% CI, 1.04 to 1.69).

Conclusion

Among patients with lung cancer, longitudinal changes in depression symptoms are associated with differences in mortality, particularly among patients with early-stage disease. Symptom remission is associated with a similar mortality rate as never having had depression.
Randomized Trial Comparing R-CHOP Versus High-Dose Sequential Chemotherapy in High-Risk Patients With Diffuse Large B-Cell Lymphomas
Authors: Cortelazzo Sergio , Tarella Corrado , Gianni Alessandro Massimo , Ladetto Marco , Barbui Anna Maria , Rossi Andrea , Gritti Giuseppe , Corradini Paolo , Di Nicola Massimo , Patti Caterina , Mulé Antonino , Zanni Manuela , Zoli Valerio , Billio Atto , Piccin Andrea , Negri Giovanni , Castellino Claudia , Di Raimondo Francesco , Ferreri Andrés J.M. , Benedetti Fabio , La Nasa Giorgio , Gini Guido , Trentin Livio , Frezzato Maurizio , Flenghi Leonardo , Falorio Simona , Chilosi Marco , Bruna Riccardo , Tabanelli Valentina , Pileri Stefano , Masciulli Arianna , Delaini Federica , Boschini Cristina , Rambaldi Alessandro
Published: October 2016

Purpose

The benefit of high-dose chemotherapy with autologous stem-cell transplantation (ASCT) as first-line treatment in patients with diffuse large B-cell lymphomas is still a matter of debate. To address this point, we designed a randomized phase III trial to compare rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-14 (eight cycles) with rituximab plus high-dose sequential chemotherapy (R-HDS) with ASCT.

Patients and Methods

From June 2005 to June 2011, 246 high-risk patients with a high-intermediate (56%) or high (44%) International Prognostic Index score were randomly assigned to the R-CHOP or R-HDS arm, and 235 were analyzed by intent to treat. The primary efficacy end point of the study was 3-year event-free survival, and results were analyzed on an intent-to-treat basis.

Results

Clinical response (complete response, 78% v 76%; partial response, 5% v 9%) and failures (no response, 15% v 11%; and early treatment-related mortality, 2% v 3%) were similar after R-CHOP versus R-HDS, respectively. After a median follow-up of 5 years, the 3-year event-free survival was 62% versus 65% ( P = .83). At 3 years, compared with the R-CHOP arm, the R-HDS arm had better disease-free survival (79% v 91%, respectively; P = .034), but this subsequently vanished because of late-occurring treatment-related deaths. No difference was detected in terms of progression-free survival (65% v 75%, respectively; P = .12), or overall survival (74% v 77%, respectively; P = .64). Significantly higher hematologic toxicity ( P < .001) and more infectious complications ( P < .001) were observed in the R-HDS arm.

Conclusion

In this study, front-line intensive R-HDS chemotherapy with ASCT did not improve the outcome of high-risk patients with diffuse large B-cell lymphomas.
Phase I/Phase II Study of Blinatumomab in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia
Authors: von Stackelberg Arend , Locatelli Franco , Zugmaier Gerhard , Handgretinger Rupert , Trippett Tanya M. , Rizzari Carmelo , Bader Peter , O’Brien Maureen M. , Brethon Benoît , Bhojwani Deepa , Schlegel Paul Gerhardt , Borkhardt Arndt , Rheingold Susan R. , Cooper Todd Michael , Zwaan Christian M. , Barnette Phillip , Messina Chiara , Michel Gérard , DuBois Steven G. , Hu Kuolung , Zhu Min , Whitlock James A. , Gore Lia
Published: October 2016

Purpose

Blinatumomab is a bispecific T-cell engager antibody construct targeting CD19 on B-cell lymphoblasts. We evaluated the safety, pharmacokinetics, recommended dosage, and potential for efficacy of blinatumomab in children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Methods

This open-label study enrolled children < 18 years old with relapsed/refractory BCP-ALL in a phase I dosage-escalation part and a phase II part, using 6-week treatment cycles. Primary end points were maximum-tolerated dosage (phase I) and complete remission rate within the first two cycles (phase II).

Results

We treated 49 patients in phase I and 44 patients in phase II. Four patients had dose-limiting toxicities in cycle 1 (phase I). Three experienced grade 4 cytokine-release syndrome (one attributed to grade 5 cardiac failure); one had fatal respiratory failure. The maximum-tolerated dosage was 15 µg/m2/d. Blinatumomab pharmacokinetics was linear across dosage levels and consistent among age groups. On the basis of the phase I data, the recommended blinatumomab dosage for children with relapsed/refractory ALL was 5 µg/m2/d for the first 7 days, followed by 15 µg/m2/d thereafter. Among the 70 patients who received the recommended dosage, 27 (39%; 95% CI, 27% to 51%) achieved complete remission within the first two cycles, 14 (52%) of whom achieved complete minimal residual disease response. The most frequent grade ≥ 3 adverse events were anemia (36%), thrombocytopenia (21%), and hypokalemia (17%). Three patients (4%) and one patient (1%) had cytokine-release syndrome of grade 3 and 4, respectively. Two patients (3%) interrupted treatment after grade 2 seizures.

Conclusion

This trial, which to the best of our knowledge was the first such trial in pediatrics, demonstrated antileukemic activity of single-agent blinatumomab with complete minimal residual disease response in children with relapsed/refractory BCP-ALL. Blinatumomab may represent an important new treatment option in this setting, requiring further investigation in curative indications.
Factors Associated With Tyrosine Kinase Inhibitor Initiation and Adherence Among Medicare Beneficiaries With Chronic Myeloid Leukemia
Authors: Winn Aaron N. , Keating Nancy L. , Dusetzina Stacie B.
Published: October 2016

Purpose

There is substantial concern surrounding affordability of orally administered anticancer therapies, particularly for Medicare beneficiaries. We examined rates of initiation and adherence to tyrosine kinase inhibitors (TKIs) among Medicare beneficiaries with chronic myeloid leukemia (CML) with and without cost-sharing subsidies. We selected TKIs given their effectiveness and strong indication for use among patients diagnosed with CML.

Patients and Methods

Using SEER-Medicare data, we identified individuals diagnosed with CML from 2007 to 2011. We used Cox proportional hazards regression to assess time from diagnosis to TKI initiation. We used generalized estimating equations to examine treatment initiation within 180 days and TKI adherence among initiators. We defined adherence as at least 80% of days covered during the 6 months after TKI initiation.

Results

Among 393 individuals diagnosed with CML from 2007 to 2011, 68% initiated TKI treatment within 180 days after diagnosis. In multivariate analysis, individuals with cost-sharing subsidies, younger age, lower comorbidity, and later year of diagnosis were significantly more likely to initiate TKIs. Among TKI initiators, 61% were adherent; adherence was lower for individuals age 80 years or older versus 66 to 69 years.

Conclusion

Only 68% of Medicare beneficiaries with CML initiated TKI therapy within 6 months of diagnosis. Delayed initiation among individuals without cost-sharing subsidies suggests that out-of-pocket costs may be a barrier to timely initiation of therapy among individuals diagnosed with CML.
Cancer-Related Fatigue in Patients With and Survivors of Hodgkin Lymphoma: The Impact on Treatment Outcome and Social Reintegration
Authors: Behringer Karolin , Goergen Helen , Müller Horst , Thielen Indra , Brillant Corinne , Kreissl Stefanie , Halbsguth Teresa Veronika , Meissner Julia , Greil Richard , Moosmann Peter , Shonukan Oluwatoyin , Rueffer Jens Ulrich , Flechtner Hans-Henning , Fuchs Michael , Diehl Volker , Engert Andreas , Borchmann Peter
Published: October 2016

Purpose

Cancer-related fatigue occurs frequently in patients with Hodgkin lymphoma (HL) and has a major impact on their quality of life. We hypothesized that severe fatigue (sFA) might have an impact on patients’ treatment outcome and social reintegration.

Methods

Of 5,306 patients enrolled in the German Hodgkin Study Group’s fifth generation of clinical trials in HL (HD13, HD14, and HD15; nonqualified and older [> 60 years] patients excluded), 4,529 provided data on health-related quality of life. We describe sFA (defined as a score ≥ 50 on the 0 to 100 scale from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) before and up to 9 years after therapy and analyze its impact on treatment outcome and social reintegration.

Results

The proportion of patients reporting sFA was 37% at baseline and ranged from 20% to 24% during follow-up. Baseline sFA was associated with significantly impaired progression-free survival and a trend to impaired overall survival, which can be overcome in patients receiving highly effective HL therapies as applied in our fifth-generation trials. Our analysis revealed a significant negative association of sFA and employment in survivors: 5 years after therapy, 51% and 63% of female and male survivors, respectively, with sFA were working or in professional education, compared with 78% and 90% without sFA, respectively ( P < .001 adjusted for age, sex, stage, baseline employment status, and treatment outcome). sFA was also associated with financial problems and the number of visits to a general practitioner and medical specialists.

Conclusion

sFA is an important factor preventing survivors from social reintegration during follow-up. This observation underscores the need to address fatigue as a significant diagnosis when treating patients with and survivors of cancer.
Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia
Authors: Etienne Gabriel , Guilhot Joëlle , Rea Delphine , Rigal-Huguet Françoise , Nicolini Franck , Charbonnier Aude , Guerci-Bresler Agnès , Legros Laurence , Varet Bruno , Gardembas Martine , Dubruille Viviane , Tulliez Michel , Noel Marie-Pierre , Ianotto Jean-Christophe , Villemagne Bruno , Carré Martin , Guilhot François , Rousselot Philippe , Mahon François-Xavier
Published: October 2016

Purpose

Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up.

Patients and Methods

IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years. Molecular recurrence (MR) was defined as positivity of BCR-ABL transcript in a quantitative reverse transcriptase polymerase chain reaction assay confirmed by a second analysis point that indicated an increase of one log in relation to the first analysis point at two successive assessments or loss of major molecular response at one point.

Results

The median molecular follow-up after treatment discontinuation was 77 months (range, 9 to 95 months). Sixty-one patients lost UMRD after a median of 2.5 months (range, 1 to 22 months), and one patient died with UMRD at 10 months. Molecular recurrence-free survival was 43% (95% CI, 33% to 52%) at 6 months and 38% (95% CI, 29% to 47%) at 60 months. Treatment was restarted in 57 of 61 patients with MR, and 55 patients achieved a second UMRD with a median time of 4 months (range, 1 to 16 months). None of the patients experienced a CML progression. Analyses of the characteristics of the study population identified that the Sokal risk score and duration of IM treatment were significantly associated with the probability of MR.

Conclusion

With a median follow-up of more than 6 years after treatment discontinuation, the STIM1 study demonstrates that IM can safely be discontinued in patients with a sustained deep molecular response with no late MR.
Is a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy?
Authors: Peterson Sarah J. , McAninch Elizabeth A. , Bianco Antonio C.
Published: October 2016

Context:

Levothyroxine (LT4) monotherapy is the standard of care for hypothyroidism.

Objective:

To determine whether LT4 at doses that normalize the serum TSH is associated with normal markers of thyroid status.

Design:

Cross-sectional data from the US National Health and Nutrition Examination Survey (2001–2012) was used to evaluate 52 clinical parameters. LT4 users were compared to healthy controls and controls matched for age, sex, race, and serum TSH. Regression was used to evaluate for correlation with T4 and T3 levels.

Participants:

A total of 9981 participants with normal serum TSH were identified; 469 were LT4-treated.

Results:

Participants using LT4 had higher serum total and free T4 and lower serum total and free T3 than healthy or matched controls. This translated to approximately 15–20% lower serum T3:T4 ratios in LT4 treatment, as has been shown in other cohorts. In comparison to matched controls, LT4-treated participants had higher body mass index despite report of consuming fewer calories/day/kg; were more likely to be taking beta-blockers, statins, and antidepressants; and reported lower total metabolic equivalents. A serum TSH level below the mean in LT4-treated participants was associated with a higher serum free T4 but similar free and total T3; yet those with lower serum TSH levels exhibited higher serum high-density lipoprotein and lower serum low-density lipoprotein, triglycerides, and C-reactive protein. Age was negatively associated with serum free T3:free T4 ratio in all participants; caloric intake was positively associated in LT4-treated individuals.

Conclusions:

In a large population study, participants using LT4 exhibited lower serum T3:T4 ratios and differed in 12/52 objective and subjective measures.