Exposure to mild blast forces induces neuropathological effects,neurophysiological deficits and biochemical changes

Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces below the level that causes macroscopic neuropathological changes. We found that mild blast forces induced neuroinflammation in cerebral cortex, striatum and hippocampus. Moreover, mild blast triggered microvascular damage and axonal injury. Furthermore, mild blast caused deficits in hippocampal short-term plasticity and synaptic excitability, but no impairments in long-term potentiation. Finally, mild blast exposure induced proteolytic cleavage of spectrin and the cyclin-dependent kinase 5 activator, p35 in hippocampus. Together, these findings show that mild blast forces can cause aberrant neurological changes that critically impact neuronal functions. These results are consistent with the idea that mild blast forces may induce subclinical pathophysiological changes that may contribute to neurological and psychiatric disorders.     

Clinical characteristics and therapeutic outcome of patients with febrile neutropenia who present in shock: need for better strategies

OBJECTIVE: To study the frequency of neutropenic febrile patients who present in shock, to evaluate the influence of this presenting feature on response to antibiotic therapy, morbidity, and mortality and to identify discriminating demographic features and clinical characteristics of these individuals. METHODS: Prospectively collected data on all episodes of fever and neutropenia observed in cancer patients who were hospitalized for parenteral antibiotic therapy. RESULTS: Five hundred and seventy-six patients were evaluated; 22 (3.8%) presented in shock. This group of individuals was compared with the remainder. Patients presenting in shock were more likely to be older (P< 0.01) and have progressive unresponsive cancer (P< 0.01). They were also more likely to present with septic appearance (P< 0.01), dehydration (P< 0.01), diarrhoea (P< 0.01), altered mental status (P< 0.01) clinical bleeding (P= 0.02) and dyspnoea (P< 0.01). They more often had anaemia (P< 0.01), thrombocytopenia (P= 0.02) and abnormal liver function tests (P< 0.01). Eight of the 22 patients presenting in shock had documented bacteraemia. Non-bacteraemic microbiological infections were observed in three patients. Five patients had clinical evidence of infection and another five were severely dehydrated and volume depleted. One patient had cardiogenic shock. Three patients were managed with monotherapy, 19 received combination antibiotics as initial empirical therapy. Overall outcome of these patients was extremely poor, particularly those with infectious aetiology. Eighteen (82%) patients expired. CONCLUSION: Neutropenic febrile patients who present in shock have extremely poor outcomes irrespective of type of initial antibiotic therapy. Intense efforts are required to improve their outcome.     

Association of hospital and surgeon volume of total hip replacement with functional status and satisfaction three years following surgery

OBJECTIVE: To evaluate whether hospital volume and surgeon volume of total hip replacements (THRs) are associated with patient-reported functional status and satisfaction with surgery 3 years postoperatively. METHODS: We performed a population-based cohort study of a stratified random sample of Medicare beneficiaries who underwent elective primary or revision THR in Ohio, Pennsylvania, or Colorado in 1995. The primary outcomes were the self-reported Harris hip score and a validated scale measuring satisfaction with the results of surgery. Both outcomes were assessed 3 years postoperatively. Hospital volume was defined as the aggregate number of elective primary and revision THRs performed on Medicare beneficiaries in the hospital in 1995. High-volume hospitals were defined as those in which >100 such procedures are performed annually, and low-volume centers were defined as those in which 12 procedures per year. CONCLUSION: Hospital volume and surgeon volume have little effect on 3-year functional outcome following THR, after adjusting for patient sociodemographic and select clinical characteristics. However, satisfaction with primary THR is greater among patients who underwent surgery in high-volume centers, and satisfaction with revisions is greater among patients whose operations were performed by higher-volume surgeons. Referring clinicians should incorporate these findings into their discussion of referral choices with patients considering THR. Conclusions regarding the effect of volume on longevity of the implants must await longer-term followup studies. Finally, further research is warranted to better understand the association between hospital and surgeon procedure volume and patient satisfaction with surgery.     

Offering patients the opportunity to choose their hospital for total knee replacement: impact on satisfaction with the surgery

OBJECTIVE: To describe the extent to which patients were offered a choice between 2 or more hospitals for total knee replacement (TKR); to examine the association between having a choice of hospital for TKR and satisfaction with the surgery; and to identify population groups less likely to be offered a choice. METHODS: We studied a population-based sample of 932 Medicare beneficiaries who underwent elective TKR in 2000. We surveyed patients about their participation in choosing a hospital and their satisfaction with surgery. We examined whether lack of hospital choice influenced satisfaction with surgery after adjusting for age, sex, preoperative function, and socioeconomic status. RESULTS: Among 932 TKR recipients (mean age 74 years, 67% women), more than half (53%) reported having a lack of hospital choice. After adjusting for socioeconomic status, patients reporting lack of choice were approximately twice as likely to be dissatisfied with the results of surgery as patients who reported choosing among 2 or more hospitals for TKR (odds ratio [OR] 2.09, 95% confidence interval [95% CI] 1.13-3.87). Results of logistic regression revealed that patients reporting lack of choice were more likely to be women (OR 1.52, 95% CI 1.14-2.04), >80 years of age (as compared with 65-70 years; OR 1.63, 95% CI 1.03-2.57), living in suburban areas (OR 1.68, 95% CI 1.23-2.30), nonwhite (OR 1.57, 95% CI 0.86-2.87), and were less likely to have TKR performed by a high-volume surgeon (OR 0.71, 95% CI 0.53-0.96). CONCLUSION: More than half of the patients did not have a choice in selecting the hospital where they had TKR. Patients reporting lack of choice were more likely to be dissatisfied with surgery. Interventions to address preferences for hospital may improve satisfaction with care for patients with advanced knee arthritis.     

Thalidomide for the treatment of resistant cutaneous lupus: efficacy and safety of different therapeutic regimens

PURPOSE: Thalidomide is effective for the treatment of severe cutaneous lupus. Our aim was to study the safety and efficacy of different doses of thalidomide in this condition. METHODS: We studied patients with severe cutaneous lupus that was unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n = 17), or 50 mg on alternate days (n = 15) were compared. The response to thalidomide was categorized as complete remission, partial remission, or no visible improvement. All patients received a baseline electromyogram (EMG) followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms developed. RESULTS: Forty-eight patients (46 female; mean [+/- SD] age, 44 +/- 12 years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24) were included. The response rate was 81%, including 29 patients (60%) in complete remission and 10 (21%) in partial remission. Nine patients (19%) failed to respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG-proven in 11, including 4 patients in the 50-mg alternate-day group. Other side effects included drowsiness, constipation or abdominal pain, and amenorrhea. The relapse rate after stopping thalidomide was 67% (26/39). There was no association between a positive response to the drug and either starting doses or cumulative dose. Similarly, no association was found between peripheral neuropathy and the starting or cumulative dose. CONCLUSION: Thalidomide is effective for the treatment of severe cutaneous lupus. There were no clear dose-dependent effects. However, the high incidence of neurotoxicity, even at low doses, suggests that it may be most useful as a remission-inducing drug.     

Incidence and review of sessile serrated polyp reporting in a district general hospital in the UK

The aim of this 4-year audit was to establish whether sessile serrated polyps/adenomas (SSP/A) were diagnosed in a district general hospital in the UK. The study also explored whether SSP/A in the right colon were misdiagnosed as hyperplastic polyps. A retrospective search of the computer records from 2009 to 2012 inclusive for all lesions diagnosed and coded as SSP/A and/or hyperplastic polyps proximal to the splenic flexure was undertaken. All slides were reviewed and a diagnosis of SSP/A made using the criteria recently suggested by the American College of Gastroenterology. Over the study period, no cases of SSP/A were made. On review of all hyperplastic polyps proximal to the splenic flexure, 13/31 in 2009, 17/40 in 2010, 19/48 in 2011 and 16/48 in 2012 were re-classified as SSP/A. The most likely reason for the under-diagnosis of SSP/A is lack of awareness of the lesion both clinically and by pathologists. Adequate biopsies and deeper sections are important to help make the diagnosis of SSP/A. This study shows that SSP/A are reasonably frequently encountered in non-specialist practice settings and that both clinicians and pathologist in this setting need to be aware of its existence.