Thyroid peroxidase autoantibodies obtained from random single chain FV libraries contain the same heavy/light chain combinations as occur in vivo

Three combinatorial libraries were constructed from unpurified, CD19(+), and antithyroid peroxidase (anti-TPO) B cells extracted from thyroid tissue of Graves' disease patients. Fifteen of the 41 randomly derived anti-TPO single chain variable region fragments (scFvs), showed VH1-3/V lambda 1-51 or VH1-69/V lambda 1-40 heavy/light chain pairing similar to that obtained with TPO-specific scFv derived from an in-cell library. One VH1-3/V lambda 1-51 scFv, A16, showed exactly the same nucleotide sequence as in-cell scFv ICB7, demonstrating that in vivo rearrangement can be obtained from a random combinatorial library. The majority of the scFvs used a heavy chain gene derived from the VH1-3 gene segment, whereas the light chain gene segments used were more heterogeneous, with dominance of the V kappa 1-39 and V lambda 1-51 gene segments. The anti-TPO scFvs showed high affinities to TPO, with values between 0.77 and 12.3 nM, and defined seven antigenic regions on the TPO molecule. The anti-TPO fragments, particularly VH1-3/V lambda 1-51 randomly associated scFv B4, which mimic natural H/L pairing, and VH1-3/V lambda 1-40 in-cell-derived scFv ICA5, efficiently displaced the TPO binding of serum autoantibodies from 20 Graves' disease patients. Our study directly demonstrates that antibodies derived from combinatorial libraries are likely to represent in vivo pairing, leading to high affinity antibody fragments mimicking the binding of serum autoantibodies to TPO.     

Clinical characteristics,treatment intent,and outcome in a consecutive 10-year cohort of oral cancer patients aged 75 years and older

The prevalence of oral squamous cell carcinoma (OSCC) in the elderly is expected to increase by nearly a third in the next decade. Its management in older patients is potentially more challenging due to their pre-existing medical comorbidities, frailty, reduced life expectancy, and social issues. The aim of this retrospective review was to report on treatment given to patients aged 75 years and over, case mix, and survival. All patients aged 75 years and over who were diagnosed with OSCC in Merseyside between 1 January 2007 and 31 December 2016, and treated with either curative or palliative intent, were included. Their hospital notes were reviewed. Fisher’s exact test and Kaplan-Meier analysis were used for data analysis. There were 236 patients (median (IQR) age 81 (78-86) years); 67% were treated curatively and 33% palliatively. Factors associated with palliation included older age, advanced tumour stage, cognitive impairment, and residence in a nursing or residential home. Of the 165 patients who were offered curative treatment, six (4%) declined due to personal or family reasons. Overall survival for palliative patients was 12% at one year and 7% at two years, whereas for patients treated curatively it was 74% at one year, 56% at two years, and 34% at five years. Patients over 85 years of age were less likely to have composite free flaps and postoperative radiotherapy. Perioperative mortality was 2.6%. Improvements in surgical techniques and perioperative management have enabled clinicians to offer treatment with curative intent to older frail patients, and with careful case selection outcomes can be very good.     

Extensor pollicis et indicis communis or extensor indicis radialis muscle

Anatomical variations of the fingers extensor tendons are not uncommon and have been described by several authors. Participation of intertendinous band of fascia in this kind of variation can change muscle functionality. However, this element is scarcely described in the literature. In this case report, we describe the finding of an accessory tendon located between the extensor digitorum communis muscle tendon, destined for the index finger, and the extensor pollicis longus tendon. In an anatomical analysis, we observed a connection between the radial portion of the accessory tendon and the ulnar portion of the extensor pollicis longus tendon by intertendinous fascia. This finding corresponds anatomically to the supernumerary muscle denominated extensor indicis radialis, but due to the fascial connections observed with the extensor pollicis longus, this muscle would behave functionally as a supernumerary muscle denominated extensor pollicis et indicis communis. This report suggests that participation of fascia in muscular variation in this anatomical segment is essential to establish the correct morpho-functional denomination of muscular variants.     

Relationship of Quality of Life with Disability Grade in Obsessive Compulsive Disorder and Dysthymic Disorder

Background:

There is paucity of information on the relationship of quality of life (QOL) in obsessive compulsive disorder (OCD) and dysthymic disorder (DD) with disability grade in India.

Aim:

To assess the relation of QOL with disability level in OCD and DD.

Materials and Methods:

This hospital based study was conducted in a medical institution in Davanagere, Karnataka, India. Data was collected by using Diagnostic and Statistical Manual IV Text Revision (DSM IV TR) criteria, WHO QOL BREF and IDEAS. Relationship between disability grade and QOL was assessed by independent sample t test.

Results:

Mild disabled OCD patients had a significantly better QOL in the Q1 domain i.e. perception on quality of life as compared to moderately disabled patients (P < 0.05), while in other domains of QOL, there was no statistically significant difference (P > 0.05). But, QOL score in physical domain showed significant difference across disability grades (56.00, SD = 6.89; 48.50, SD = 12.28) in DD, but not in other domains.

Conclusion:

Perception of QOL is better in those with mild disability in OCD, but in DD, physical domain of QOL score is more in mild disability compared to moderate disability.     

Fatigue-Induced Balance Impairment in Young Soccer Players

Context:

Although balance is generally recognized to be an important feature in ensuring good performance in soccer, its link with functional performance remains mostly unexplored, especially in young athletes.

Objective:

To investigate changes in balance induced by fatigue for unipedal and bipedal static stances in young soccer players.

Design:

Crossover study.

Setting:

Biomechanics laboratory and outdoor soccer field.

Patients or Other Participants:

Twenty-one male soccer players (age = 14.5 ± 0.2 years, height = 164.5 ± 5.6 cm, mass = 56.8 ± 6.8 kg).

Intervention(s):

Static balance was assessed with postural-sway analysis in unipedal and bipedal upright stance before and after a fatigue protocol consisting of a repeated sprint ability (RSA) test (2 × 15-m shuttle sprint interspersed with 20 seconds of passive recovery, repeated 6 times).

Main Outcome Measure(s):

On the basis of the center-of-pressure (COP) time series acquired during the experimental tests, we measured sway area, COP path length, and COP maximum displacement and velocity in the anteroposterior and mediolateral directions.

Results:

Fatigue increased all sway values in bipedal stance and all values except COP velocity in the mediolateral direction in unipedal stance. Fatigue index (calculated on the basis of RSA performance) was positively correlated with fatigue/rest sway ratio for COP path length and COP velocity in the anteroposterior and mediolateral directions for nondominant single-legged stance.

Conclusions:

Fatigued players exhibited reduced performance of the postural-control system. Participants with better performance in the RSA test appeared less affected by balance impairment, especially in single-legged stance.Key Words: postural sway, repeated sprint ability test, athletes

Key Points

• In young soccer players, balance was adversely affected by fatigue.
• A moderate correlation existed between balance impairment and repeated sprint ability performance.

In soccer, as in many other disciplines, researchers continuously attempt to define which anthropometric, physiologic, psychological, and cognitive characteristics are most relevant to identifying talent at an early age. Such features, together with the development of new assessment methods in the laboratory or on the field, are essential to improving the chances of recognizing future top players.In particular, somatotype, aerobic and anaerobic power, agility, joint flexibility, and muscular development are considered essential contributors to achieving high-level performance.¹ Nevertheless, it remains unclear how these factors are to be objectively selected, measured, weighed, and combined with coaches'' subjective perceptions, which are mainly based on personal experience.^1,2Somewhat surprisingly, balance is not included among the most important features in athletic success; this quality is considered important mostly as a cofactor that helps reduce the risk of injuries.³ Also, soccer is a discipline that relies a great deal on single-legged support under unstable conditions. In fact, players use 1 limb (the dominant limb) to control the force and direction of the ball while dribbling, maintaining ball possession, and kicking; the nondominant limb basically ensures the necessary stability to optimally perform the required technical maneuver.⁴ Thus, it appears very important for players to have (and possibly improve during their maturation) excellent balance skills, especially for unipedal stance.Although previous authors^5–7 have shown that soccer players are generally characterized by superior balance performance compared with athletes in other sports (except gymnasts) or nonathletes, few data are available on the relationship between balance variables and functional performance in soccer players.⁸ Similarly, the possibility of improving postural-control performance in healthy athletes using specific balance-training protocols remains partly unexplored. However, recent investigators^9,10 have demonstrated that young athletes may benefit from proper stimulation of the proprioceptive system.

Balance and Fatigue

Both localized and whole-body fatigue cause degradation of postural-control performance, which is evident in the form of increased postural sway (ie, constant, slight corrective deviations from vertical when standing upright).¹¹ This phenomenon, which has been extensively reported in the literature, is mainly due to changes in cardiac and respiratory contractions, fluid movement in the body, and release of metabolic products by muscle fibers and is caused by altered sensory information from the proprioceptive system.¹² The magnitude of sway increase is partly influenced by exercise intensity and duration, but it also depends on the muscular groups involved.¹³ From this point of view, localized fatigue and whole-body fatigue are thought to trigger different disturbances of the postural-control system,¹⁴ although the net effect in terms of balance impairment may appear similar.Typical experiments aimed at assessing the effect of fatigue on static balance involve exercise such as the treadmill,^15–17 cycle or rowing ergometer,^14,15,18 isokinetic concentric actions, squat jumps, and heel raises.^14,19 A few authors^20,21 have evaluated the fatiguing effects of actual sport performance in triathletes²² and soccer players. In particular, Zemkova and Hamar²⁰ and Brito et al²¹ analyzed center-of-pressure (COP) velocity of 19- to 21-year-old players (unipedal and bipedal stances with eyes open or closed) before a game, in the break period between the first and second halves, and after a game. When visual input was present, single-legged balance was reduced after the match. Less evident was the effect of fatigue on bipedal standing: changes were observed only when the support surface was unstable and visual input suppressed.The lack of experimental data regarding the effects of fatigue on balance in soccer players is somewhat surprising, considering that fatigue is implicated in injury occurrence²³ and that a deficit in postural control may increase the risk of ankle injuries.²⁴ Thus, it is reasonable to hypothesize that not only may fatigue associated with performance in a match impair balance (and thereby increase the risk of injuries) but also that superior physical fitness in better-trained athletes may limit this effect.Our goal was to assess postural-sway changes induced by fatigue subsequent to a controlled field test (repeated sprint ability [RSA]) representative of actual soccer activity in a cohort of young elite soccer players. We had 2 questions: (1) Is unipedal and bipedal static balance impaired by fatigue? (2) Is there a functional relationship between performance level in RSA and balance alterations?     

Conservative management of post-intubation tracheal tears—report of three cases

Iatrogenic tracheal rupture is a rare complication after intubation. We present three patients with tracheal tears. In all of these patients, a common finding was a lesion of the posterior tracheal wall with postoperative subcutaneous and emphysema as the first clinical sign of the rupture. Diagnosis and follow-up were based on clinical and endoscopic findings and chest computed tomography (CT) scans. In our cases with progressive subcutaneous and mediastinal emphysema or dyspnea, we performed a tracheotomy and bypassed the lesion with a tracheostomy tube to avoid an increase in air leakage into the mediastinum. Under broad-spectrum antibiotic therapy, no mediastinitis occurred and all patients survived without sequelae. Closure of tracheostomy was scheduled for 1-2 months after tracheal injury. Analysis of surgical and anesthesiological procedures revealed no abnormalities and the accumulation of tracheal injuries was considered as accidental. We found that in clinically stable patients with spontaneous breathing and with no mediastinitis, a conservative management of tracheal tears is a safe procedure.     

Intact parathyroid hormone measurement at 24 hours after thyroid surgery as predictor of parathyroid function at long term

Background

There is no consensus about the usefulness of postoperative intact parathyroid hormone (iPTH) determination to predict permanent hypoparathyroidism (pHPP). We evaluated the value of calcium (Ca²⁺) and iPTH concentration at 24 hours after total thyroidectomy (TT) for predicting pHPP.

Methods

Ca²⁺ and iPTH levels from 70 consecutive patients who underwent TT were measured at 24 hours and 6 months after TT.

Results

Five patients (7.1%) developed pHPP. An iPTH concentration ≤5.8 pg/mL at 24 hours after TT identified patients at risk for pHPP (sensitivity, 100%; specificity, 81.5%), but it was not accurate enough to predict its development (positive predictive value, 30%). Conversely, an iPTH level >5.8 pg/mL predicted normal parathyroid function at 6 months (negative predictive value, 100%). Compared with iPTH, a postoperative Ca²⁺ level ≤1.95 mmol/L was 60% sensitive and 78.5% specific to predict pHPP.

Conclusions

An iPTH concentration >5.8 pg/mL on the first postoperative day rules out pHPP with much better diagnostic accuracy than Ca²⁺. Postoperative iPTH could be helpful in identifying patients at risk for developing pHPP.