Clinical usefulness of telomerase activation and telomere length in head and neck cancer

BACKGROUND: Telomere shortening at every replication cycle is postulated to limit the life span of human somatic cells. In contrast, activation of telomerase is proposed to be an essential step for cancer cell immortalization. Head and neck cancer is the most common malignancy in the Indian population compared with Western countries. However, there are very few reports on telomerase activity and telomere length in head and neck cancer. METHODS: Telomerase activation and telomere length alterations were studied in tumor and adjacent normal tissues in 110 patients with head and neck cancer and 40 patients with precancerous/benign conditions. Telomerase activity and telomere lengths were determined by Telomeric Repeat Amplification Protocol (TRAP assay) and Southern blot analysis, respectively. RESULTS: Telomerase activation was observed in 78.2% of the malignant tissues, 85% of the precancerous tissues, and 53.1% of the adjacent normal tissues. Peak terminal restriction fragment length (TRF) was observed to be significantly lower in malignant tissues compared with the adjacent normal tissues. No significant correlation could be observed between telomerase activation and clinicopathologic characteristics of the patients. Two-year disease-free survival analysis showed that patients showing telomerase activation in the adjacent normal tissues and patients showing higher telomere length in malignant tissues had poor disease-free survival. CONCLUSIONS: Our results demonstrate the significant clinical usefulness of telomerase activation and telomere length for head and neck cancer patients. These markers may be helpful in predicting the clinical course of the disease and thus in identifying the patients in need of a close follow-up and vigorous adjuvant treatment.     

Bilateral Traumatic Intracranial Hematomas and its Outcome: a Retrospective Study

The objective of this study was to evaluate the age distribution, mode of injury, type of hematomas, and their surgical outcome in patients with bilateral traumatic head injuries. The present study included 669 cases of traumatic head injury who presented at the neurosurgery emergency out of which 94 cases had bilateral head injuries from the period of August 2009 to April 2014. The data from the hospital computerized database were retrospectively analysed. Cases of bilateral traumatic head injury included 94 patients out of which 88.29 % (n?=?83) were males and 11.70 % (n?=?11) were females. Commonest mode of injury was road traffic accident in 56.38 % (n?=?53) followed by fall from height in 29.78 % (n?=?28). In our study, 25.53 % patients had epidural hematoma (EDH) with intracerebral hematoma (ICH) or contusion (n?=?24), followed by EDH with subarachnoid hemorrhage (SAH) in 18.08 % (n?=?17). At the time of discharge, all those patients managed conservatively had good Glasgow outcome scale (GOS) while with surgical intervention 58 % patients had good GOS, 19 % had moderate disability, and 9 % remained with severe disability. In cases of bilateral hematomas, EDH is most common and should be managed in neurosurgical emergency. Other combinations of bilateral intracranial hematomas should be managed according to the surgical indication and serial CT imaging.     

In situ reprogramming to transdifferentiate fibroblasts into cardiomyocytes using adenoviral vectors: Implications for clinical myocardial regeneration

Objective

The reprogramming of cardiac fibroblasts into induced cardiomyocyte-like cells improves ventricular function in myocardial infarction models. Only integrating persistent expression vectors have thus far been used to induce reprogramming, potentially limiting its clinical applicability. We therefore tested the reprogramming potential of nonintegrating, acute expression adenoviral (Ad) vectors.

Computer Navigation Helps Reduce the Incidence of Noise After Ceramic-on-Ceramic Total Hip Arthroplasty

Background

Noise after ceramic-on-ceramic (CoC) total hip arthroplasty (THA) is a well-recognized problem. Computer navigation has been shown to achieve desired implant orientation. Our aim was (1) to compare the incidence of noise between navigated and conventional CoC THAs and (2) to determine the factors associated with noise.

Prolapse or incontinence: what affects sexual function the most?

Introduction and hypothesis

Pelvic organ prolapse (POP) and stress urinary incontinence (SUI) adversely affect sexual function in women. Comparative studies of the two subgroups are few and results are conflicting. The aim of this study was to compare the effect of POP and SUI on the sexual function of women undergoing surgery for these conditions.

Methods

The study population comprised women with POP or SUI in a tertiary referral hospital in the UK. Women who underwent SUI surgery had no symptoms of POP and had urodynamically proven stress incontinence. Patients with POP had ≥ stage 2 prolapse, without bothersome urinary symptoms. Pre-operative data on sexual function were collected and compared using an electronic pelvic floor assessment questionnaire (ePAQ). The incidence of sexual dysfunction and comparison of symptoms in both groups were calculated using the Mann–Whitney U test.

Results

Three hundred and forty-three women undergoing surgery for either SUI or POP were included. Patients were age-matched, with 184 undergoing SUI surgery (age range 33–77 years) and 159 POP surgery (age range 27–78 years; p?=?0.869). The overall impact of POP and SUI was not significantly different in the two subgroups (p?=?0.703). However, both patients (73 % vs 36 %; p?=?0.00) and partners (50 % vs 24 %; p?=?0.00) avoid intercourse significantly more frequently in cases with POP compared with SUI. This did not have a significant impact on quality of life.

Conclusions

The impact of bothersome SUI or POP on sexual function was found to be similar, but patient and partner avoidance in women with POP was greater than those with SUI.

     

Risk factors for recurrent obstetric anal sphincter injury (rOASI): a systematic review and meta-analysis

Objectives

The objective of this study was to estimate the risk of recurrent obstetric anal sphincter injury (rOASI) in women who have suffered anal sphincter injury in their previous pregnancy and analyse risk factors for recurrence through a systematic review and meta-analysis.

Data sources

A review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were made in Ovid MEDLINE (1996 to May 2015), PubMed, EMBASE and Google Scholar, including bibliographies and conference proceedings.

Methods of study selection

Observational studies (cohort/case–control) evaluating rOASI and risk factors were selected by two reviewers who also analysed methodological quality of those studies. Pooled odds ratios (OR) for rOASI and individual risk factors were calculated using RevMan 5.3.

Tabulation, integration and results

From the eight studies assessed, overall risk of rOASI was 6.3 % compared with a 5.7 % risk of OASI in the first pregnancy. The risk in parous women with no previous OASI was 1.5 %. Factors that increased the risk in a future pregnancy were instrumental delivery with forceps [OR 3.12, 95 % confidence interval (CI) 2.42–4.01) or ventouse (OR 2.44, 95 % CI 1.83–3.25), previous fourth-degree tear (OR 1.7, 95 % CI 1.24–2.36) and birth weight ≥4 kg (OR 2.29, 95 % CI 2.06–2.54). Maternal age ≥35 years marginally increased the risk (OR 1.16, 95 % CI 1–1.35).

Conclusion

The overall rate of rOASI and associated risk factors for recurrence are similar to the rate and risk factors of primary OASI. Antenatal decisions could be based on assessment of foetal weight and intrapartum decisions based upon the requirement for an instrumental delivery.

     

Total hip arthroplasty following failed fixation of proximal hip fractures

Background:

Most proximal femoral fractures are successfully treated with internal fixation but a failed surgery can be very distressing for the patient due to pain and disability. For the treating surgeon it can be a challenge to perform salvage operations. The purpose of this study was to evaluate the short-term functional outcome and complications of total hip arthroplasty (THA) following failed fixation of proximal hip fracture.

Materials and Methods:

In a retrospective study, 21 hips in 20 patients (13 females and seven males) with complications of operated hip fractures as indicated by either established nonunion or fracture collapse with hardware failure were analysed. Mean age of the patients was 62 years (range 38 years to 85 years). Nine patients were treated for femoral neck fracture, 10 for intertrochanteric (I/T) fracture and two for subtrochanteric (S/T) fracture of the hip. Uncemented THA was done in 11 cases, cemented THA in eight hip joints and hybrid THA in two patients.

Results:

The average duration of follow-up was four years (2-13 years). The mean duration of surgery was 125 min and blood loss was 1300 ml. There were three dislocations postoperatively. Two were managed conservatively and one was operated. There was one superficial infection and one deep infection. Only one patient required a walker while four required walking stick for ambulation. The mean Harris Hip score increased from 32 preoperatively to 79 postoperatively at one year interval.

Conclusion:

Total hip arthroplasty is an effective salvage procedure after failed osteosynthesis of hip fractures. Most patients have good pain relief and functional improvements inspite of technical difficulties and high complication rates than primary arthroplasty.     

Mechanisms of ENaC regulation and clinical implications

The epithelial Na+ channel (ENaC) transports Na+ across tight epithelia, including the distal nephron. Different paradigms of ENaC regulation include extrinsic and intrinsic factors that affect the expression, single-channel properties, and intracellular trafficking of the channel. In particular, recent discoveries highlight new findings regarding proteolytic processing, ubiquitination, and recycling of the channel. Understanding the regulation of this channel is critical to the understanding of various clinical phenomena, including normal physiology and several diseases of kidney and lung epithelia, such as blood pressure (BP) control, edema, and airway fluid clearance. Significant progress has been achieved in this active field of research. Although ENaC is classically thought to be a mediator of BP and volume status through Na+ reabsorption in the distal nephron, several studies in animal models highlight important roles for ENaC in lung pathophysiology, including in cystic fibrosis. The purpose of this review is to highlight the various modes and mechanisms of ENaC regulation, with a focus on more recent studies and their clinical implications.