High Rate of Return to Sporting Activity Among Overhead Athletes With Subpectoral Biceps Tenodesis for Type II SLAP Tear.

PURPOSE: To evaluate the functional and athletic outcomes after primary subpectoral biceps tenodesis for type II SLAP tear in overhead athletes. METHODS: All competitive elite athletes with type II SLAP tears undergoing biceps tenodesis by a single surgeon were isolated between 2007 and 2015. Exclusion criteria were applied to individuals not involved in overhead athletics, clinical follow-up <24 months, adjacent rotator cuff or labral repair, concomitant SLAP repair, and/or previous arthroscopic shoulder surgery. Patient-reported outcome measures included visual analog scale (VAS), Kerlan Jobe Orthopaedic Clinic shoulder score, and Single Assessment Numerical Assessment. Clinical and sporting outcomes were recorded using a sports-specific questionnaire. RESULTS: Of 22 identified patients, 16 competitive overhead athletes (72.7%; 11 men, 5 women) with a mean age of 21.0 years were available at mean 4.5-year follow-up. Baseball or softball comprised the majority of patients (n = 9; 56.3%), followed by gymnastics (n = 2), swimming (n = 2), and other sports (n = 3). At mean 4.1 months postoperatively, 13 patients (81.3%) returned to previous level of athletic activity, whereas 2 patients (12.5%) failed to return to sporting activity and 1 (6.3%) returned at a lower level of competition. VAS pain significantly decreased from an average of 4.4 preoperatively to 1.7 postoperatively (P = .002), and mean Single Assessment Numerical Assessment scores also demonstrated significant improvement (55.4-76.7; P = .008). Final mean Kerlan Jobe Orthopaedic Clinic score was 74.0 (standard deviation 25.9), including 2 patients with suboptimal outcomes due to persistent pain. There were no significant differences in mean forward flexion or rotation in either the adducted or throwing position (P > .05), although small, significant decreases in postoperative active abduction were noted (165° vs 155°; P = .003). CONCLUSIONS: In the current series of competitive overhead athletes, 81% of patients returned to previous level of play at an average of 4.1 months postoperatively after subpectoral biceps tenodesis for symptomatic SLAP tear. Athletes reliably experienced significant decreased activity-related pain with athletic function. LEVEL OF EVIDENCE: IV, case series.

Clinical Outcomes of Shoulder Stabilization in Females With Glenoid Bone Loss.

BACKGROUND: Nearly all studies describing shoulder stabilization focus on male patients. Little is known regarding the clinical outcomes of female patients undergoing shoulder stabilization, and even less is understood about females with glenoid bone loss. PURPOSE: To assess the clinical outcomes of female patients with recurrent anterior shoulder instability treated with the Latarjet procedure. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All cases of female patients who had recurrent anterior shoulder instability with ≥15% anterior glenoid bone loss and underwent the Latarjet procedure were analyzed. Patients were evaluated after a minimum 2-year postoperative period with scores of the American Shoulder and Elbow Surgeons form, Simple Shoulder Test, and pain visual analog scale. RESULTS: Of the 22 patients who met our criteria, 5 (22.7%) were lost to follow-up, leaving 17 (77.2%) available for follow-up with a mean ± SD age of 31.7 ± 12.9 years. Among these patients, 16 (94.1%) underwent 1.6 ± 0.73 ipsilateral shoulder operations (range, 1-3) before undergoing the Latarjet procedure. Preoperative indications for surgery included recurrent instability with bone loss in all cases. After a mean follow-up of 40.2 ± 22.9 months, patients experienced significant score improvements in the American Shoulder and Elbow Surgeons form, Simple Shoulder Test, and pain visual analog scale (P < .05 for all). There were 2 reoperations (11.8%). There were no cases of neurovascular injuries or other complications. CONCLUSION: Female patients with recurrent shoulder instability with glenoid bone loss can be successfully treated with the Latarjet procedure, with outcomes similar to those of male patients in the previously published literature. This information can be used to counsel female patients with recurrent instability with significant anterior glenoid bone loss.

Vulvar Crohn disease: Diagnostic challenges and approach to therapy.

Crohn disease (CD) may be complicated by contiguous, metastatic, or associated inflammatory cutaneous lesions. Vulvar CD is a rare phenomenon characterized by granulomatous genital inflammation that occurs independently from fistulizing CD. Left untreated, vulvar CD can result in debilitating lymphedema, disfiguring anatomic changes, secondary abscesses, cellulitis, and squamous cell carcinoma. We present a series of cases to highlight the clinical presentation of vulvar CD, the diagnostic testing required to distinguish complicating conditions, the asynchronous courses of skin and intestinal disease, and the complexities in the management of this disease and associated conditions. We review our multidisciplinary approach to care, aimed at reducing morbidity and improving patient quality of life.

Management of Failed Proximal Biceps Surgery: Clinical Outcomes After Revision to Subpectoral Biceps Tenodesis.

BACKGROUND: The preferred surgical technique to manage biceps-superior labral pathology is often debated, and rates of revision and persistence of pain vary widely according to surgical technique and patient characteristics. PURPOSE: To evaluate the clinical and functional outcomes of patients undergoing revision subpectoral tenodesis after failed primary tenodesis or tenotomy of the long head of the biceps. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All patients undergoing revision biceps management by the senior surgeon between 2006 and 2016 and with a minimum 24-month follow-up were retrospectively identified. Patients being treated with concomitant rotator cuff repair or capsular release were excluded. Patient characteristic variables were recorded. Patient-reported outcomes including the functional score, Single Assessment Numeric Evaluation (SANE), visual analog scale (VAS), Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons were obtained, and range of motion, strength, and complications were quantified. RESULTS: In total, 25 patients with revision biceps tenodesis were identified at a mean follow-up of 76.5 ± 31.5 months. The average age was 44.4 ± 14.3 years, and the surgical indications included failure of index suprapectoral biceps tenodesis (56%), subpectoral biceps tenodesis (36%), and patient dissatisfaction after tenotomy (8%). There was a significant improvement in the VAS score (P < .001), SANE (P = .001), SST (P = .035), functional score (P < .001), and forward elevation (P = .028), whereas postoperative strength (P = .440), abduction (P = .100), and external rotation (P = .745) improvement failed to achieve statistical significance after revision surgery. There was no difference in postoperative outcome measures between modes of failures, concomitant procedures, and sex. Twenty-two (88%) patients reported high satisfaction and stated they would have this revision surgery again. The overall complication rate was 48%, with half of these reporting pain of >3 on a scale of 10 and 4% of patients requiring additional surgeries. CONCLUSION: The current study demonstrates high patient satisfaction (88%) and significant improvement in functional outcomes with revision biceps tenodesis, a mini-open subpectoral technique, after previous failed tenodesis or tenotomy. Although this may be an effective strategy to address failed prior biceps surgery, the potential complication of persistent pain must be emphasized. Patients should be counseled on the high complication rate (48%), with persistent pain being the most common complaint.

Effective involvement: a report on the evaluation of a research awareness training package for public involvement in health research.

BACKGROUND: As the role of Patient and Public Involvement contributors expands to all stages of the research cycle, there is increasing demand for training that meets the needs of this diverse population. To help meet this demand the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care, Yorkshire and Humber, worked with members of the public to develop a bespoke training package. The University of Huddersfield's Public Partnership Group were invited to host the training and undertake an independent evaluation. METHODS: Participatory action research was used to structure the evaluation, such that participants in the training and public members of the evaluation team were co-collaborators with a robust, significant and visible share in the process. This is evidenced by public team members' roles in undertaking the majority of data gathering, including surveys, non-participant observation and interviews, and analysis, engaging in all reflective discussions, leading on producing a formal report and contributing significant sections of this paper.The evaluation was approved by a University ethics panel.Public involvement consisted of the 13 participants who received the training, and 3 of the 6 members of the evaluation team. Data collection took place between November 2017 and March 2018. RESULTS: The evaluation found that participants understood more about the research process from attending the training, gaining greater confidence in their ability to volunteer to get involved. It also highlighted the difficulties of meeting the training needs of a diverse group with varying experiences and expectations. Skilful facilitation was needed to maintain pace, whilst engaging people with different levels of interest and knowledge. The management of the environment to maximise comfort and involvement was important. Early feedback to the delivery team enabled timely updating of the package.Involvement in the evaluation was initially daunting for the three public members of the team, but hugely enjoyable and fulfilling, as well as enriching the process and outcomes. In particular, public involvement in the analysis and interpretation stages increased the authenticity of the evaluation findings. CONCLUSIONS: This evaluation validated the training package and demonstrated the value and impact of Public Involvement at all levels in research.

Qualitative exploration of a targeted school-based mindfulness course in England.

BACKGROUND: Mindfulness-based training has been shown to provide benefits for adults with numerous conditions such as cancer, chronic pain, and depression. However, less is known about its impact for young people. Early adolescence (typically 10-14 years) is a time fraught with challenges such as cognitive changes, social, and academic pressures in the form of exams, all of which can provoke anxiety. While there is a lack of effectiveness studies, there is growing interest in the potential for school-based mindfulness programmes to help young people cope with the pressures of modern life. METHODS: This study outlines a qualitative exploration of a school-based targeted mindfulness course. We interviewed 16 young people who had taken part in a 10-week mindfulness course, and held a focus group with three members of teaching staff who delivered the programme. Interviews and focus groups were analysed using applied thematic analysis. RESULTS: While young people felt that they had to take part, once they started the programme they enjoyed it. Young people felt that they learned a range of coping skills, and it had a positive impact on their behaviour. However, the targeted approach of the intervention could lead to young people being stigmatised by their peers. Teaching staff could see the potential benefit of mindfulness courses in schools but felt there were some barriers to be overcome if it were to be implemented in the long term. CONCLUSIONS: Young people were willing to engage in mindful practice and felt it better equipped them to deal with stressful situations.

Good functional outcomes expected after shoulder arthroplasty irrespective of body mass index.

BACKGROUND: This study evaluated how body mass index (BMI) factors into functional outcomes and complications after shoulder arthroplasty. METHODS: A retrospective analysis was performed of age-matched patients with a minimum 2-year follow-up after total shoulder arthroplasty (TSA), reverse total shoulder arthroplasty (RTSA), or hemiarthroplasty (HA). Patient-reported outcome (PRO) scores, range of motion (ROM), and complications were assessed. Forty-nine patients were classified into the following groups: normal (BMI <24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), class I obese (BMI 30-34.9 kg/m2), class II obese (BMI 35-39.9 kg/m2), and class III morbid obese (BMI ≥40 kg/m2). RESULTS: A total of 245 patients (134 women, 111 men; average age, 64 ± 8 years) were evaluated at an average follow-up of 48 ± 18 months. TSA was performed in 122 patients (50%), RTSA was performed in 103 (42%), and HA was performed in 20 (8%). No significant difference was found among the 5 BMI groups in arthroplasty type (P = .108) or in complications, including reoperations (P = .27). All groups had significant postoperative improvements in PROs and ROM (P < .001 for both). There were no significant differences among the BMI groups in postoperative ROM or PROs. DISCUSSION: This study demonstrates that patients undergoing TSA, RTSA, and HA can expect good functional outcomes, with improvements in pain, function and outcome scores, irrespective of BMI.

Non-modifiable Risk Factors Associated with Sternoclavicular Joint Dislocations in the U.S. Military.

INTRODUCTION: Sternoclavicular joint (SCJ) dislocations, although uncommon, are observed in patients with ligamentous laxity as well as those who experience traumatic injuries. The incidence and epidemiology of this costly and debilitating injury to our relatively young and active military population have not previously been reported. The purpose of this study is to consider and quantify the non-modifiable risk factors associated with this injury. METHODS: Using Defense Medical Epidemiological Database, first-time occurrences, from 2006 to 2015 for the ICD-9-CM code 839.61 (closed dislocation of the SCJ), were obtained and further categorized by gender, race, age, rank, and branch of service. Race was classified based on self-reporting of patients into White, Black, or other categories. Age was divided into the categories of less than 20 yr, 20-24 yr, 25-29 yr, 30-34 yr, 35-39 yr, and greater than 40 yr. Rank was categorized as junior enlisted (E-1 to E-4), senior enlisted (E-5 to E-9), junior officer (O-1 to O-3), and senior officer (O-4 to O-10). Branch of service includes Army, Navy, Air Force, and Marines. Multivariate data analysis was performed to obtain rate per 1,000 person-years as well as adjusted rate (adjusted for age group, gender, race, rank, and service) to isolate risk factors. RESULTS: Between 2006 and 2015, 427 cases of closed SCJ dislocations occurred among an at-risk population of 13,772,342 person-years for an unadjusted incidence rate (IR) of 0.031 per 1,000 person-years. The annual unadjusted IR ranged from 0.017 in 2006 to 0.059 in 2014 with the greatest increase occurring between 2006 and 2007 representing 61% increase in the rate of injuries. Males were almost twice as likely to sustain these injuries compared with females (adjusted rate ratio 1.73; 95% confidence interval [CI] 1.23, 2.43). Age was not found to be a risk factor for the development of these injuries with IRs for each age group overlapping with 95% CI for all other age groups. Similarly, the other category for race was also not found to be a statistically significant risk factor. Junior Officers (adjusted rate 0.017; 95% CI 0.011, 0.025) were found least likely to suffer from these injuries with Junior Enlisted (0.034; 95% CI 0.030, 0.040) and Senior Enlisted (0.032; 95% CI 0.028, 0.037) most at risk. Being in the Navy (0.019; 95% CI 0.015, 0.025) was found to be most protective compared with Air Force (0.032; 95% CI 0.026, 0.039), Army (0.036; 95% CI 0.031, 0.041), and Marines (0.036; 95% CI 0.028, 0.045). DISCUSSION and CONCLUSION: Annual unadjusted IR of SCJ dislocations readily increased from 2006 to 2014. Statistically significant risk factors, for suffering a closed SCJ dislocation, identified by our study, were male sex, enlisted rank, and branch of service other than Navy. Age and race were not found to have a statistically significant risk. These results can shed light on non-modifiable risk factors for dislocations of the SCJ and can be used in other studies to aid in reducing injury burden on the U.S. Military.

Outcomes of Latarjet Versus Distal Tibia Allograft for Anterior Shoulder Instability Repair: A Matched Cohort Analysis.

BACKGROUND: Anterior glenoid reconstruction with fresh distal tibia allograft (DTA) has been described for management of recurrent shoulder instability, with encouraging early outcomes; however, no comparative data with the Latarjet procedure are available. PURPOSE: The purpose of this study was to compare the clinical outcomes between patients undergoing DTA and a matched cohort of patients undergoing Latarjet. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A review was conducted of prospectively collected data for patients with a minimum 15% anterior glenoid bone loss who underwent shoulder stabilization via either the DTA or Latarjet procedure and had a minimum follow-up of 2 years. Consecutive patients undergoing DTA were matched in a 1-to-1 format to patients undergoing Latarjet by age, body mass index, history of contact sports, and number of previous shoulder operations. Patients were evaluated pre- and postoperatively with a physical examination and the following outcome assessments: Simple Shoulder Test, visual analog scale, American Shoulder and Elbow Surgeons, Western Ontario Shoulder Instability Index, and Single Assessment Numeric Evaluation. Complications, reoperations, and episodes of recurrent instability were analyzed. Statistical analysis was performed with Student t tests, with P < .05 considered significant. RESULTS: A total of 100 patients (50 Latarjet, 50 DTA) with a mean ± SD age of 25.6 ± 6.1 years were analyzed at 45 ± 20 months (range, 24-111) after surgery. Thirty-two patients (64%) in each group underwent prior ipsilateral shoulder surgery (range, 1-3). Patients undergoing DTA had significantly greater glenoid bone loss defects when compared with patients undergoing Latarjet (28.6% ± 7.4% vs 22.4% ± 10.3%, P = .001). Patients in both groups experienced significant improvements in all outcome scores after surgery ( P < .05 for all). No significant differences were found in postoperative scores between the Latarjet and DTA groups: visual analog scale (0.67 ± 0.97 vs 1.83 ± 2.31), American Shoulder and Elbow Surgeons (91.06 ± 8.78 vs 89.74 ± 12.66), Western Ontario Shoulder Instability Index (74.30 ± 21.84 vs 89.69 ± 5.50), or Single Assessment Numeric Evaluation (80.68 ± 7.21 vs 90.08 ± 13.39) ( P > .05 for all). However, patients in the Latarjet group had superior Simple Shoulder Test outcomes ( P = .011). There were 10 complications (10%) for the entire cohort, including 5 in the Latarjet group (3 of which required reoperation) and 5 in the DTA group (3 of which required reoperation). The overall recurrent instability rate was 1% (1 patient). CONCLUSION: Fresh DTA reconstruction for recurrent anterior shoulder instability results in a clinically stable joint with similar clinical outcomes as the Latarjet procedure. Longer-term studies are needed to determine if these results are maintained over time.

Evaluation of a pilot police-led suicide early alert surveillance strategy in the UK.

INTRODUCTION: Those bereaved by suicide are at increased risk of psychological harm, which can be reduced with the provision of timely support. This paper outlines an evaluation of a pilot police-led suicide strategy, in comparison to a coroner-led suicide strategy looking at the number, and length of time it takes for deaths to be recorded for each strategy. Additionally, the police-led strategy offers timely contact from support services for bereaved individuals. We examined what impact this offer of support had on the capacity of support services. METHODS: A mixed methods evaluation compared how long it took for suspected suicides to be recorded using both strategies. The number of referrals received by support services during the pilot strategy were compared with those from previous years. A feedback focus group, and interviews, were held with key stakeholders. RESULTS: The coroner strategy was more consistent at identifying suspected suicides; however, reports were filed quicker by the police. Bereaved individuals were willing to share contact details with police officers and consent for referral to support services which lead to increased referrals. The focus group and interviews revealed that the pilot police strategy needs better integration into routine police practice. CONCLUSIONS: This strategy has the potential to deliver a real benefit to those bereaved by suicide; however, there are still aspects which could be improved.

Walking energetics, fatigability, and fatigue in older adults: the study of energy and aging pilot.

BACKGROUND: Slow gait speed increases morbidity and mortality in older adults. We examined how preferred gait speed is associated with energetic requirements of walking, fatigability, and fatigue. METHODS: Older adults (n = 36, 70-89 years) were categorized as slow or fast walkers based on median 400-m gait speed. We measured VO2peak by graded treadmill exercise test and VO2 during 5-minute treadmill walking tests at standard (0.72 m/s) and preferred gait speeds. Fatigability was assessed with the Situational Fatigue Scale and the Borg rating of perceived exertion at the end of walking tests. Fatigue was assessed by questionnaire. RESULTS: Preferred gait speed over 400 m (range: 0.75-1.58 m/s) averaged 1.34 m/s for fast walkers versus 1.05 m/s for slow walkers (p < .001). VO2peak was 26% lower (18.5 vs 25.1ml/kg/min, p = .001) in slow walkers than fast walkers. To walk at 0.72 m/s, slow walkers used a larger percentage of VO2peak (59% vs 42%, p < .001). To walk at preferred gait speed, slow walkers used more energy per unit distance (0.211 vs 0.186ml/kg/m, p = .047). Slow walkers reported higher rating of perceived exertion during walking and greater overall fatigability on the Situational Fatigue Scale, but no differences in fatigue. CONCLUSIONS: Slow walking was associated with reduced aerobic capacity, greater energetic cost of walking, and greater fatigability. Interventions to improve aerobic capacity or decrease energetic cost of walking may prevent slowing of gait speed and promote mobility in older adults.

The role of combined assessment in preoperative axillary staging.

BACKGROUND: Axillary lymph node status is the most significant single prognostic factor in breast cancer, and preoperative axillary staging is essential in determining lymph node status. Axillary ultrasound scan (AUS) is the gold standard modality in preoperative staging. However, triple assessment-including clinical examination and radiological assessment with fine needle aspiration (FNA) with or without core biopsy-ensures high sensitivity. METHODS: Our study included 219 women diagnosed with invasive breast cancer between 2009 and 2010. All patients underwent a preoperative staging AUS that was graded from normal (U1) to malignant (U5). All patients with ultrasound scans graded U3 (indeterminate) and above underwent FNA that was graded from C1 (inadequate for diagnosis) to C5 (malignant). Patients diagnosed preoperatively with metastatic lymph nodes were offered axillary lymph node clearance. The rest of the patients were offered sentinel lymph node biopsy. RESULTS: The 219 women were diagnosed with 228 invasive breast cancers. The mean age was 60 years (range 29-90 years). The final histology report showed metastatic axillary lymph nodes in 49 (21.5%) cases. Of these 49 cases, 22 were diagnosed preoperatively with metastatic axillary lymph node and were elected for axillary lymph node clearance, and 27 were elected for sentinel lymph node biopsy that revealed metastatic lymph nodes. AUS showed abnormal (U3/U4/U5) axillary lymph nodes in 30 of 49 (61.2%) cancer cases with an overall accuracy of 91.6%. CONCLUSION: Combined triple assessment increases the sensitivity, negative predictive value, and overall accuracy of preoperative staging of the axilla.

VEGF inhibition and renal thrombotic microangiopathy.

The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in whom glomerular disease characteristic of thrombotic microangiopathy developed. To show that local reduction of VEGF within the kidney is sufficient to trigger the pathogenesis of thrombotic microangiopathy, we used conditional gene targeting to delete VEGF from renal podocytes in adult mice; this resulted in a profound thrombotic glomerular injury. These observations provide evidence that glomerular injury in patients who are treated with bevacizumab is probably due to direct targeting of VEGF by antiangiogenic therapy.

Evaluation of in vitro in vivo correlations for dry powder inhaler delivery using artificial neural networks.

The aim of these experiments was to investigate the use of artificial neural networks (ANNs) for generating models able to predict the relative lung bioavailability and clinical effect of salbutamol when delivered to healthy volunteers and asthmatic patients from dry powder inhalers (DPIs). ANN software was used to model in vitro, demographic and in vivo data from human subjects for four different DPI formulations containing salbutamol sulfate. In 12 volunteers, a model linking the in vitro aerodynamic characteristics of the emitted dose and volunteer body surface area with the urinary excretion of drug and its metabolite in the 24h period after inhalation was established. In 11 mild asthmatics, a predictive model correlating in vitro data, baseline lung function, body surface area and age with post-treatment improvements in forced expiratory volume in 1s (FEV1) was also generated. Models validated using unseen data from individual subjects receiving the different DPI formulations were shown to give predictions of in vivo performance. The squared correlation coefficients (R2) for plots comparing predicted and observed in vivo outcomes were 0.83 and 0.84 for urinary excretion and lung function data, respectively. It can therefore be concluded that ANN models have the potential to predict the in vivo performance of DPIs in individual subjects.

Determination of the relative bioavailability of salbutamol to the lungs following inhalation from dry powder inhaler formulations containing drug substance manufactured by supercritical fluids and micronization.

PURPOSE: The relative lung bioavailability of salbutamol sulfate particles produced using supercritical fluids (SEDS) and delivered by dry powder inhaler (DPI) was compared with the performance of a conventional micronized drug DPI using the same device design (Clickhaler, Innovata Biomed). MATERIALS AND METHODS: Twelve healthy volunteers and 11 mild asthmatic patients completed separate four-way randomised cross-over studies, assessing the relative bioavailability of salbutamol sulfate (urinary excretion method), formulated as SEDS particles (three batches) and micronized particles (Asmasal inhaler, UCB Pharma Ltd). Post-treatment improvements in patient lung function were assessed by measuring FEV(1). Physicochemical evaluation of the three SEDS batches revealed inter-batch differences in particle size and shape. RESULTS: There was no significant difference in the relative lung bioavailability of salbutamol and its bronchodilator response between the best performing SEDS formulation and the Asmasal inhaler in volunteers and patients, respectively. SEDS salbutamol sulfate showing wafer like morphology gave greater fine particle dose, relative lung bioavailability and enhanced bronchodilation compared to other SEDS batches containing elongated particles. CONCLUSIONS: Active Pharmaceutical Ingredient (API) manufactured using supercritical fluids and delivered by DPI can provide similar lung bioavailability and clinical effect to the conventional micronized commercial product. Product performance is however notably influenced by inter-batch differences in particle characteristics.

Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables. Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.

Expanding the pathologic spectrum of light chain deposition disease: a rare variant with clinical follow-up of 7 years.

We report an unusual histologic manifestation of light chain deposition disease in a 69-year-old female patient, who presented with nephrotic syndrome and an increased serum creatinine. The renal biopsy findings by light and electron microscopy suggested a glomerulonephritis with massive immune-complex deposition, such as lupus nephritis. However, the overall clinical scenario was inconsistent with lupus. Subsequent tests revealed multiple myeloma confirmed by bone marrow biopsy and identification of a monoclonal kappa light chain immunoglobulin by serum and urine immunoelectrophoresis and immunofixation. Additional immunohistochemistry of the first biopsy also demonstrated strong kappa light chain staining of the glomerular capillary walls and mesangium but not lambda light chain or IgG staining. The patient responded well to therapy and was asymptomatic until nearly 7 years later. A repeat biopsy revealed similar findings to the first biopsy with the addition of immunofluorescence microscopy, which confirmed the prominent kappa light chain staining of the glomeruli, tubular basement membranes, and interstitium with corresponding electron-dense deposits visualized by electron microscopy. This case represents an unusual histologic variant of light chain deposition disease, which to our knowledge has not been previously described and further expands the wide clinicopathologic spectrum within the diagnostic entity of light chain deposition disease.