Long‐term follow‐up of negative pressure wound therapy with instillation: a limb salvage procedure?

Negative pressure wound therapy (NPWT) is a treatment to reduce oedema, stimulate granulation tissue formation, remove wound exudate and diminish wound area, thus preparing it for secondary healing, skin grafting or coverage with flaps. The association of instillation to NPWT (NPWTi) is a new method for treating severe wounds, in particular, limb lesions at high risk for amputation. This therapy helps to deliver instillation fluid automatically into the contaminated wound, before application of negative pressure. These steps, repeated cyclically, help to remove infectious material, leading to a better moist environment, a necessary condition for wound healing. We report our experience of treating three patients with complex wounds and associated noble structure exposition conservatively with NPWTi and flap coverage. In a long‐term follow‐up (5 years), we were able to achieve a stable surgery reconstruction on preserved limbs, without evidence of chronic infection and other sequelae or complications. Despite the fact that our experience is limited , as it is based on only a few cases, it suggests how NPWTi could be considered useful in a conservative approach to the treatment of acute complex wounds of the lower extremities. In these patients with high risk of amputation, a long‐term follow‐up becomes fundamental in order to evaluate wound bed status after NPTWi.     

Positive urine cytology but negative white‐light cystoscopy: an indication for fluorescence cystoscopy?

OBJECTIVE

To evaluate the possible benefit of fluorescence cystoscopy (FC) in detecting cytologically ‘confirmed’ lesions when assessing urothelial carcinoma of the bladder, as negative white‐light cystoscopy in cases of a positive cytological finding represents a diagnostic dilemma.

PATIENTS AND METHODS

From January 1996 to December 2006, 348 patients, who had cystoscopy for surveillance or due to suspicion of urothelial carcinoma, presented with an entirely negative white‐light cystoscopy at our hospital. However, 77 of the 348 patients (22.2%) were diagnosed with a positive cytological finding. All patients had white‐light cystoscopy first and a bladder‐wash cytological specimen was obtained, then FC, followed by cold‐cup biopsies and/or transurethral resection of the bladder tumour.

RESULTS

In the 77 patients with a positive cytological specimen FC enabled the detection of the precise site of malignancy within the bladder in 63 (82%). As malignant or premalignant lesions, there were 18 moderate dysplasias, 27 carcinoma in situ (CIS), and 18 pTa‐1/G1‐3 tumours. Moreover using FC, malignant or premalignant lesions were detected in 43 of 271 patients (15.9%) who had a negative cytological specimen (15 moderate dysplasias, six CIS, 22 pTa‐1/G1‐3).

CONCLUSION

This study shows that FC is beneficial in the detection of malignant and premalignant lesions, if there is negative white‐light cystoscopy but positive urine cytology. The immediate identification of the exact site of a malignant lesion during FC enables the physician to diagnose and treat these patients more accurately and with no delay.     

Does use of axillary ultrasound in clinically node‐negative patients receiving neo‐adjuvant systemic therapy for breast cancer lead to surgical overtreatment?

Increased use of neo‐adjuvant chemotherapy (NAC) for breast cancer has raised uncertainty regarding staging of the axilla, particularly for patients with a clinically negative axillary physical examination (PE). We sought to determine whether axillary ultrasound (AUS) prior to NAC to identify occult nodal disease is beneficial in patients with a clinically negative examination by evaluating the difference in nodal burden on final pathology in those with abnormal vs normal AUS. A retrospective review of an institutional cancer registry identified patients who underwent NAC for breast cancer and had a pretreatment AUS. Differences in the number of positive lymph nodes (PLN) in patients with a normal axillary PE and abnormal vs normal AUS prior to NAC were determined. A total of 120 patients who received NAC had a negative axillary PE prior to treatment. Fifty‐three had an abnormal AUS and biopsy‐proven lymph node (LN) involvement. In patients with an abnormal AUS, median number of PLNs at surgery was 1 vs 0 for those with a normal AUS (mean difference of 2.12, P < .0001). Of those patients with an abnormal AUS and biopsy‐proven LN involvement, 87% underwent axillary lymph node dissection (ALND) and nearly half had no PLN on final pathology (N = 23, 43%). Patients with a clinically negative axilla and an abnormal AUS were more likely to have PLN at the time of surgery. However, almost half of those patients had no residual LN involvement. Routine AUS prior to NAC may lead to more extensive surgical management of the axilla.     

Is radiation indicated for young women with early stage,node‐negative breast cancer after mastectomy? A multi‐institution,retrospective review

The role of post‐mastectomy radiation for women with node negative, early stage disease is not well‐defined. The purpose of this study is to more clearly define a subset of women who are ≤40 years of age with T1‐T2, node negative breast cancer who may benefit from post‐mastectomy radiation. Using tumor registries at two institutions, we identified 219 women ≤40 years of age with T1‐T2, node negative breast cancer treated with mastectomy. Of these 219 patients, 38 received post‐mastectomy radiation and 181 did not. Kaplan–Meier methods and cox proportional‐hazards regression models were employed for statistical analysis. There were no locoregional failures in the women receiving post mastectomy radiation, which lead to a nonsignificant increase in freedom from locoregional recurrence (P=.08). For women not receiving post‐mastectomy radiation, freedom from locoregional recurrence was 94.7% and 89.7% at 5‐ and 10‐years. Lymphovascular space invasion (LVSI) was the only factor predictive of locoregional recurrence. For women without LVSI, freedom from locoregional recurrence was 96.0% and 93.3% at 5‐ and 10‐years respectively. For women with LVSI who did not receive post mastectomy radiation, freedom from locoregional recurrence was 89.1% at 5‐years. There were no failures in the women with LVSI who received post mastectomy radiation. For women ≤40 years of age with T1‐2, node negative breast cancer treated with mastectomy and no post‐mastectomy radiation, locoregional control is excellent in the absence of LVSI, regardless of other risk factors. In the presence of LVSI (regardless of other risk factors), the risk of locoregional recurrence is high and appears to be decreased with post‐mastectomy radiation.     

Does 18fluoro‐fluorodeoxyglucose positron emission tomography improve recurrence detection in patients treated for head and neck squamous cell carcinoma with negative clinical follow‐up?

BACKGROUND: The aim of this study was to determine the benefits of 18fluoro-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the detection of head and neck squamous cell carcinoma (HNSCC) recurrence in patients with negative clinical follow-up. METHODS: Whole-body 18FDG-PET was performed in 30 patients treated for HNSCC without any clinical element for recurrence. RESULTS: Twenty-one negative PET and 9 positive results were seen. One patient with abnormal 18F-FDG uptake in the laryngeal area did not have recurrent HNSCC (false positive). Eight had proven recurrence. The sensitivity and specificity of 18F-FDG PET for the diagnosis of HNSCC recurrence were 100% (8/8) and 95% (21/22), respectively. The positive predictive value was 89% (8/9). The negative predictive value was 100% (21/21). The overall accuracy was 97% (29/30). CONCLUSION: The results of our study confirm the high effectiveness of 18F-FDG PET in assessment of HNSCC recurrence and suggest that it is more accurate than conventional physical examination follow-up alone.     

Does DCD Donor Time‐to‐Death Affect Recipient Outcomes? Implications of Time‐to‐Death at a High‐Volume Center in the United States

For donation after circulatory death (DCD), many centers allow 1 h after treatment withdrawal to donor death for kidneys. Our center has consistently allowed 2 h. We hypothesized that waiting longer would be associated with worse outcome. A single‐center, retrospective analysis of DCD kidneys transplanted between 2008 and 2013 as well as a nationwide survey of organ procurement organization DCD practices were conducted. We identified 296 DCD kidneys, of which 247 (83.4%) were transplanted and 49 (16.6%) were discarded. Of the 247 recipients, 225 (group 1; 91.1%) received kidneys with a time to death (TTD) of 0–1 h; 22 (group 2; 8.9%) received grafts with a TTD of 1–2 h. Five‐year patient survival was 88.8% for group 1, and 83.9% for group 2 (p = 0.667); Graft survival was also similar, with 5‐year survival of 74.1% for group 1, and 83.9% for group 2 (p = 0.507). The delayed graft function rate was the same in both groups (50.2% vs. 50.0%, p = 0.984). TTD was not predictive of graft failure. Nationally, the average maximum wait‐time for DCD kidneys was 77.2 min. By waiting 2 h for DCD kidneys, we performed 9.8% more transplants without worse outcomes. Nationally, this practice would allow for hundreds of additional kidney transplants, annually.     

Engaged,Workaholic, Burned‐Out or Just 9‐to‐5? Toward a Typology of Employee Well‐being

The aim of this study was to establish a typology of employee well‐being, together with its psychosocial antecedents and consequences. Results obtained with a sample of 786 full‐time employees from different occupational sectors show four types of employee well‐being: 9‐to‐5 or relaxed, work engaged or enthusiastic, workaholic or tense, and burned‐out or fatigued, each having different relationships with job and personal characteristics. This study provides evidence of a parsimonious, theory‐based classification of employee well‐being and contributes to the existing literature about work investment because meaningful relations were found between various types of employee well‐being, and heavy and soft work investors. Copyright © 2013 John Wiley & Sons, Ltd.     

What is behind phylogenetic analysis of hospital‐, community‐ and livestock‐associated methicillin‐resistant Staphylococcus aureus?

Methicillin‐resistant Staphylococcus aureus (MRSA) has been shown to be the predominant life‐threatening pathogen in Egypt. MRSA is a major cause of severe healthcare‐associated (HA) infections. During the last decades, the incidence of community‐associated (CA) MRSA infections has a complex epidemiology arising from the circulation of different strains in the general population. Moreover, livestock‐associated (LA) MRSA emerged recently becomes an emerging threat to public health. Therefore, it is important to illuminate the differences between CA‐, HA‐ and LA‐MRSA to shed light on their genetic diversity and evolution. This study presents the first data on analysing the correlation between CA‐, LA‐ and HA‐MRSA using antibiogram typing, molecular characteristics and antimicrobial resistance and virulence genes’ profiles. Overall, HA‐MRSA strains tended to be multidrug resistant and less virulent than both LA‐ and CA‐MRSA strains. Importantly, CA‐MRSA strains had a high homology with each of HA‐ and LA‐MRSA. However, no similarity was observed between HA‐ and LA‐MRSA. Our findings suggest that the epidemiological changes in genetic behaviour between HA‐ and LA‐MRSA are due to the presence of CA‐MRSA confirming that CA‐MRSA has created a public health crisis worldwide.     

Are N‐glycolylneuraminic acid (Hanganutziu–Deicher) antigens important in pig‐to‐human xenotransplantation?

BACKGROUND: N-glycolylneuraminic acid (NeuGc) epitopes, so called Hanganutziu-Deicher (HD) antigens, which are widely expressed on endothelial cells of all mammals except humans, are considered to be potential targets for natural and elicited anti-nonGalalpha1-3 Gal (Gal) antibodies in humans. We previously reported that anti-NeuGc antibodies were not detected in healthy humans by enzyme-linked immunosorbent assay (ELISA) using NeuGc-GM3-coated plates, and no antibody production was observed in patients with a history of exposure to pig cells. However, a recent paper has revealed that (i) anti-NeuGc antibodies to porcine red blood cells (PRBC) are detectable in most healthy humans, and (ii) the majority of anti-nonGal antibodies are specific for NeuGc epitopes. The purpose of this study was to reassess whether NeuGc is important as an immunogenic nonGal epitope. METHODS: The binding of antibodies to PRBC and porcine aortic endothelial cells (PAEC) was compared. Cells were treated with (i) alpha-galactosidase, and then (ii) neuraminidase, which digests sialic acids, including NeuGc epitopes. Cells were incubated with human pooled sera, and applied to flow cytometric analysis. After enzyme digestion, almost complete reduction of Gal and NeuGc expression was confirmed by GS-IB4 and HU/Ch2-7 (a chicken monoclonal antibody against HD antigens), respectively. Trypsin, which removes membrane glycoproteins, and endoglycoceramidase which cleaves glycolipids, were used for differentiating between NeuGc-containing glycoproteins and glycolipids. RESULTS: Neuraminidase-treatment reduced the binding of immunoglobulin G (IgG) antibodies to PRBC; about half of the anti-nonGal IgG antibodies to PRBC were directed to NeuGc. In contrast, anti-nonGal antibodies to PAEC were not directed to NeuGc. Trypsin-treatment markedly reduced the expression of NeuGc only on PRBC. Endoglycoceramidase-treatment was followed by a greater reduction in NeuGc epitopes on PAEC than on PRBC. Most NeuGc on PRBC appeared to be linked to proteins, but most NeuGc on PAEC was expressed on glycolipids. CONCLUSIONS: Carbohydrate structures on PRBC are different from those on PAEC. Healthy human sera contain anti-nonGal IgG antibodies to NeuGc expressed on PRBC, but not on PAEC. We speculate that anti-nonGal IgG antibodies to PRBC can recognize both NeuGc and protein, and this may be the reason why such antibodies have not been detected by ELISA. A definite conclusion about the immunogenicity of NeuGc has not been obtained. More sera from patients (not from non-human primates) sensitized with porcine cells or organs need to be studied.     

The Challenging Estrogen Receptor‐Negative/ Progesterone Receptor‐Negative/HER‐2‐Negative Patient: A Promising Candidate for Epidermal Growth Factor Receptor‐Targeted Therapy?

While epidermal growth factor receptor (EGFR)-targeted therapy has been very promising in a number of human malignancies, to date these targeted biologic agents have not proven effective in breast cancer. However, the EGFR tyrosinase inhibitors have been used indiscriminately against all types of breast tumors, perhaps missing a subpopulation of patients who may be prime candidates for EGFR-targeted therapy. In this communication we propose that patients with estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/HER-2-negative tumors, which currently present a therapeutic challenge for the oncologist, may be the subgroup of breast cancer patients that might benefit from specific EGFR-targeted therapies.     

Long‐ or short‐acting opioids for chronic non‐malignant pain? A qualitative systematic review

In selected patients with chronic non‐malignant pain, chronic opioid therapy is indicated. Published guidelines recommend long‐acting over short‐acting opioids in these patients. The aim of this systematic review was to investigate whether long‐acting opioids in chronic non‐malignant pain are superior to short‐acting opioids in pain relief, physical function, sleep quality, quality of life or adverse events. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for relevant trials up to July 2012. Reference lists of included trials and relevant reviews were in addition searched by hand. Of the 1168 identified publications, 6 randomised trials evaluating efficacy and safety filled the criteria for inclusion. None of them found a significantly better pain relief, significantly less consumption of rescue analgesia, improved quality of sleep or improved physical function from long‐acting opioids. None of the trials investigated quality of life. None of the trials investigated adverse events properly nor addiction, tolerance or hyperalgesia. Three trials in healthy volunteers with a recreational drug use, found no difference in abuse potential between long‐ and short‐acting opioids. While long term, comparative data are lacking, there is fair evidence from short‐term trials that long‐acting opioids provide equal pain relief compared with short‐acting opioids. Contrary to several guidelines, there is no evidence supporting long‐acting opioids superiority to short‐acting ones in improving functional outcomes, reducing side effects or addiction.     

The prostate cancer gene 3 (PCA3) urine test in men with previous negative biopsies: does free‐to‐total prostate‐specific antigen ratio influence the performance of the PCA3 score in predicting positive biopsies?

Study Type – Diagnosis (exploratory cohort)
Level of Evidence 2b

OBJECTIVE

To determine the performance characteristics of the prostate cancer gene 3 (PCA3) score on the outcome of biopsy relative to different ranges of free‐to‐total prostate‐specific antigen (PSA) ratio (f/tPSA) in men with a previous negative biopsy and a PSA level of 2.5–10 ng/mL, as urine tests like PCA3 are currently under investigation in order to improve prostate cancer diagnosis and to decrease the rate of unnecessary rebiopsies.

PATIENTS AND METHODS

Data from the previous prospective European multicentre study were reviewed. Only patients with a PSA level of 2.5–10 ng/mL were included in the present study. In all, 301 patients had complete data. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity, specificity, negative and positive predictive values. The PCA3 performance was evaluated relative to three different subgroups of f/tPSA, as follows: >20% (group 1), 10–20% (group 2) and <10% (group 3).

RESULTS

The prostate cancer detection rates were 18.8%, 23.9% and 34.8% in groups 1, 2 and 3, respectively. The area under the receiver operating characteristic curve of the PCA3 score, total PSA and f/tPSA was 0.688, 0.553 and 0.571, respectively. The percentage of men with positive biopsies was 30.6%, 37.0% and 44.4% in those with a PCA3 score of >30, vs 10.3%, 15.5% and 28.6% when the PCA3 score was <30, in groups 1, 2 and 3, respectively. The difference was significant only in groups 1 and 2. In men with a f/tPSA of ≤10% the difference in detection rates relative to the PCA3 score was not statistically significant regardless of which PCA3 threshold was used. A high PCA3 score was significantly associated with age, clinical T2 stage and positive biopsy (P < 0.001, 0.013 and <0.001, respectively). In bivariate analysis accounting for the PCA3 score and the f/tPSA, a PCA3 score of >30 was a significant independent predictor of positive biopsies (odds ratio 3.01; 95% confidence interval 1.74–5.23; P < 0.001).

CONCLUSIONS

PCA3 remained a better predictor of prostate cancer than f/tPSA. In men with a f/tPSA of >10%, the use of the PCA3 score was highly correlated with the risk of having cancer on re‐biopsy, and could prevent unnecessary prostate biopsies if the value is low.