Er:YAG laser vs. sharp debridement in management of chronic wounds: Effects on pain and bacterial load

Chronic wounds affect roughly 6.5 million patients in the US annually. Current standard of therapy entails weekly sharp debridement. However, the sharp technique is associated with significant pain, while having minimal impact on the bioburden. Our study proposes the Er:YAG laser as an alternative method of debridement that may decrease procedural pain, reduce bioburden, and potentially improve overall healing. This pilot study was performed as a prospective, randomized, controlled, crossover clinical trial, containing two groups: (1) one group underwent single laser debridement session first, followed by single sharp debridement session one week later; and (2) the other group underwent single sharp debridement session first, followed by single laser debridement session one week later. Variables analyzed included pain during debridement, pre‐ and post‐debridement wound sizes, pre‐ and post‐debridement bacterial loads and patient preference. Twenty‐two patients were enrolled (12 patients in Group 1, plus 10 patients in Group 2). The mean pain score for patients undergoing laser debridement was 3.0 ± 1.7 vs. 4.8 ± 2.6 for those undergoing sharp debridement (p = 0.003). The mean percent change in wound size 1‐week post‐laser debridement was ?20.8% ± 80.1%, as compared with ?36.7% ± 54.3% 1‐week post‐sharp debridement (p = 0.6). The percentage of patients who had a bacterial load in the low/negative category increased from 27.3% to 59.1% immediately after laser debridement (p = 0.04), vs. 54.5% to 68.2% immediately after sharp debridement (p = 0.38). Moreover, there was a sustained decrease in bacterial load 1‐week post‐laser debridement, as compared with no sustained decrease 1‐week post‐sharp debridement (p < 0.02). Overall, 52.9% of patients preferred laser debridement vs. 35.3% for sharp debridement. We believe that Er:YAG laser serves as a promising technology in chronic wounds, functioning as a potentially superior alternative to sharp debridement, the current standard of therapy.     

Interdiction of the diabetic state in NOD mice by sustained induction of heme oxygenase: possible role of carbon monoxide and bilirubin

The aims of the present study were to assess whether sustained HO-1 expression could moderate or prevent diabetes in an animal model of the disease and, if so, to examine the possible mechanisms involved. Our results showed that HO-1 expression and HO activity were upregulated in the pancreas of non-obese diabetic (NOD) mice by the weekly administration of cobalt protoporphyrin (CoPP). Blood glucose levels in CoPPtreated mice decreased to normal, but continuously increased in untreated controls. Beta-cell numbers were preserved in the islets of CoPP-treated mice, whereas no beta cells were found in untreated diabetic mice. The number of CD11c(+) dendritic cells was significantly decreased in the pancreas of CoPP-treated NOD mice, but this effect was reversed by the inhibition of HO activity. Increased levels of HO-1 produced a new pancreatic phenotype, as reflected by increases in phosphorylated AKT, BcL-xL and RSK levels, and decreases in O(2)- and 3-NT levels. These novel findings provide a link between the increase in HO-1 activity, with its concurrent enhanced production of carbon monoxide (CO) and bilirubin, a decrease in infiltrated CD11c(+) dendritic cells and an increase in anti-apoptotic proteins, including RSK and BcL-xL, in the interdiction of the diabetic state.     

Human leukocyte antigen may predict outcome of primary recurrent spontaneous abortion treated with paternal lymphocyte alloimmunization therapy

PROBLEM: Recurrent spontaneous abortion (RSA) is defined by at least three consecutive abortions in otherwise healthy couples. Paternal lymphocyte alloimmunization therapy (PLAT) is an effective therapy for RSA in some cases, but there are no predictive markers about the effectiveness of PLAT. METHOD OF STUDY: Forty-two consecutive cases with primary RSA treated by PLAT and 23 controls were the subjects. Polymorphisms of human leukocyte antigen (HLA)-E, HLA-G, HLA-A, HLA-B, HLA-C and HLA-DRB1 were investigated by sequenced based typing. Promoter polymorphism and a 14 bp ins/del polymorphism in exon 8 were also investigated for HLA-G. RESULTS: Thirty-eight RSA wives became pregnant within 1 year after PLAT. Among them, 27 obtained babies (succeeded PLAT cases), while 11 again aborted with no detectable chromosomal abnormalities in the aborted fetuses (aborted PLAT cases). The frequencies of HLA-G*010401, A*2402, B*5201, and DRB1*1502 were significantly increased in the aborted cases than those in the succeeded cases or controls. Of note, HLA-G*010401 was found in all aborted cases whereas it was found in 51.9% of succeeded cases (odds ratio = 21.4, P = 0.006, P(c) = 0.03), and the presence of HLA-G*010401 could predict the abortion after PLAT with sensitivity and specificity of 100% and 48.1%, respectively. CONCLUSION: Human leukocyte antigen testing may be useful for predicting effectiveness of PLAT in RSA.     

Novel extracellular matrix structures in the neural stem cell niche capture the neurogenic factor fibroblast growth factor 2 from the extracellular milieu

The novel extracellular matrix structures called fractones are found in the lateral ventricle walls, the principal adult brain stem cell niche. By electron microscopy, fractones were shown to contact neural stem and progenitor cells (NSPC), suggesting a role in neurogenesis. Here, we investigated spatial relationships between proliferating NSPC and fractones and identified basic components and the first function of fractones. Using bromodeoxyuridine (BrdU) for birth-dating cells in the adult mouse lateral ventricle wall, we found most mitotic cells next to fractones, although some cells emerged next to capillaries. Like capillary basement membranes, fractones were immunoreactive for laminin beta1 and gamma1, collagen IV, nidogen, and perlecan, but not laminin-alpha1, in the adult rat, mouse, and human. Intriguingly, N-sulfate heparan sulfate proteoglycan (HSPG) immunoreactivity was restricted to fractone subpopulations and infrequent subependymal capillaries. Double immunolabel for BrdU and N-sulfate HSPG revealed preferential mitosis next to N-sulfate HSPG immunoreactive fractones. To determine whether N sulfate HSPG immunoreactivity within fractones reflects a potential for binding neurogenic growth factors, we identified biotinylated fibroblast growth factor 2 (FGF-2) binding sites in situ on frozen sections, and in vivo after intracerebroventricular injection of biotinylated FGF-2 in the adult rat or mouse. Both binding assays revealed biotinylated FGF-2 on fractone subpopulations and on infrequent subependymal capillaries. The binding of biotinylated FGF-2 was specific and dependent upon HSPG, as demonstrated in vitro and in vivo by inhibition with heparatinase and by the concomitant disappearance of N-sulfate HSPG immunoreactivity. These results strongly suggest that fractones promote growth factor activity in the neural stem cell niche.     

Benefits of using the cell block method to determine the discordance of the HR/HER2 expression in patients with metastatic breast cancer

Background

The discordance of the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expressions between primary cancer and metastatic lesions is an important issue when selecting the optimal treatments for patients with metastatic breast cancer. A rebiopsy for the metastatic cancer is recommended before selecting the treatment; however, it is not easy to take a tissue sample for all metastatic lesions. Fine needle aspiration cytology (FNA) for regional lymph nodes and aspiration for pleural effusions or ascites are less invasive procedures to obtain the necessary samples to examine the HR/HER2 expression. These cytologic materials are able to be stained as a tissue sample using the cell block method.

Patients

We examined the HR/HER2 expression of 20 patients with breast cancer (8 with synchronous metastases and 12 with metachronous metastases) using the cell block method. Among 8 patients with synchronous metastases, 7 patients with axillary lymph node (LN) metastasis were examined by fine needle aspiration (FNA), and one patient with pleural metastases was analyzed for the aspirated fluid. While in 12 patients with metachronous metastases, 7 patients were examined for their pleural effusion, 3 patients were examined for regional lymph node metastases, and 1 patient were examined for aspirated ascites. We compared the HR/HER expression between primary cancer and metastatic lesion in 17 patients (5 cases of 8 synchronous metastases, and all of 12 metachronous metastases).

Results

Discordance of HR was seen in 4 of 17 patients (24 %). Three cases with axillary LN metastasis (2 cases with synchronous metastases and one with metachronous metastasis) showed negative change of ER. Negative change of HER2 expression was seen in one patient with ascites caused by peritoneal dissemination.

Conclusions

Cytology materials are easily obtained by FNA for LN metastases and aspiration for malignant effusions and analyzed for HR/HER2 expression using cell block method. We should take advantage of cell block analysis to determine the discordance of the HR/HER2 expression to select the optimal treatment for metastatic breast cancer.

     

Association between Milk Intake and Incident Stroke among Japanese Community Dwellers: The Iwate-KENCO Study

We aimed to evaluate the association between the milk consumption and incident stroke in a Japanese population, where milk consumption is lower than that of Western countries. In total, 14,121 participants (4253 men and 9868 women) aged 40–69 years, free from cardiovascular diseases (CVD) were prospectively followed for 10.7 years. Participants were categorized into four groups according to the milk intake frequency obtained from a brief-type self-administered diet questionnaire. The adjusted HRs of total stroke, ischemic stroke and haemorrhagic stroke associated with milk intake frequency were calculated using the Cox proportional hazards model. During the follow-up, 478 stroke cases were detected (208 men and 270 women). Compared to women with a milk intake of <2 cups/week, those with an intake of 7 to <12 cups/week had a significantly low risk of ischemic stroke in a model adjusting CVD risk factors; the HR (95% CI) was 0.53 (0.32–0.88). No significant associations were found in men. This study suggested that milk intake of 7 to <12 cups/week decreased the risk of ischemic stroke in Japanese women. Milk intake of about 1 to <2 cups/day may be effective in the primary prevention of ischemic stroke in a population with low milk intake.     

Prenatal diagnosis of Fukuyama type congenital muscular dystrophy in eight Japanese families by haplotype analysis using new markers closest to the gene

We conducted prenatal diagnosis by haplotype analysis, using newly developed microsatellite markers, in eight Fukuyama type congenital muscular dystrophy (FCMD) families. In addition to six new families, two previously reported families were re-examined by haplotype analysis including detection of an ancestral founder haplotype (138–183–301) for 3 microsatellite markers closest to the FCMD gene, designated D9S2105–D9S2107–D9S172, the distances of which from the FCMD gene are presumed to be ∼140, ∼20, and ∼280 kb, respectively. Five fetuses from five families were diagnosed as nonaffected, and were subsequently confirmed to be healthy. Three fetuses of the other three families were diagnosed as having a high probability of being affected by FCMD. In the prenatal diagnosis conducted for these eight families, the ancestral founder allele was observed in 13 of 16 (81%) FCMD-bearing chromosomes. Detection of the ancestral haplotype facilitated achieving accurate prenatal diagnosis of FCMD. The brains of all three fetuses prenatally diagnosed as FCMD-affected showed the initial stage of cortical dysplasia, strong evidence of FCMD. Am. J. Med. Genet. 77:310–316, 1998. © 1998 Wiley-Liss, Inc.     

Real-world local recurrence rate after cold polypectomy in colorectal polyps less than 10 mm using propensity score matching

BACKGROUNDCold polypectomy (CP) is a simple and safe procedure for polyps less than 10 mm in size; however, there is concern about local recurrence following CP because of unidentified margins of excised specimens and the lack of tumor suppression effect by coagulation. Some clinical trials have evaluated local persistent recurrence; their results suggest that a higher rate of local recurrence has not been documented so far. There were few reports that observed the course over long periods of time after CP in clinical practice.AIMTo evaluate the presence of local recurrence following CP and hot polypectomy (HP) using propensity score matching.METHODSWe analyzed 275 patients who underwent polypectomy for non-pedunculated colorectal polyps less than 10 mm (959 Lesions) between October 2016 and 2017 and underwent follow-up endoscopy subsequently. We divided them into the CP group (706 Lesions), wherein CP was performed, and the HP group (253 Lesions), wherein HP was performed. Using propensity score matching, we extracted 215 Lesions in each group and evaluated the local recurrence and content of CP in the real clinic and adverse events using medical records.RESULTSAfter propensity score matching, there were no significant differences in the patients’ and their endoscopic background (age, use of antithrombotics, indications, size, morphology, location of polyps, and polypectomy device) between the groups. The mean duration between colorectal polypectomy and the next follow-up colonoscopy was 17.5 ± 7.1 (range, 6-39) mo in the CP group and 15.7 ± 6.0 (range, 6-35) mo in the HP group, which was significantly longer in the CP group (P = 0.005). The local recurrence rate was 0.93% in the CP group and 0.93% in the HP group, without a significant difference (P = 0.688). Additionally, no differences were observed in the macroscopic en bloc resection rate, histopathological complete resection rate, and pathological results between the groups. Adverse events did not occur in either group.CONCLUSIONLocal recurrence after CP was equivalent to that following HP in clinical practice. CP is useful and safe in the treatment of non-pedunculated polyps of less than 10 mm.     

Dramatic Inhibition of Retinal and Choroidal Neovascularization by Oral Administration of a Kinase Inhibitor

The most common cause of new blindness in young patients is retinal neovascularization, and in the elderly is choroidal neovascularization. Therefore, there has been a great deal of attention focused on the development of new treatments for these disease processes. Previous studies have demonstrated partial inhibition of retinal neovascularization in animal models using antagonists of vascular endothelial growth factor or other signaling molecules implicated in the angiogenesis cascade. These studies have indicated potential for drug treatment, but have left many questions unanswered. Is it possible to completely inhibit retinal neovascularization using drug treatment with a mode of administration that is feasible to use in patients? Do agents that inhibit retinal neovascularization have any effect on choroidal neovascularization? In this study, we demonstrate complete inhibition of retinal neovascularization in mice with oxygen-induced ischemic retinopathy by oral administration of a partially selective kinase inhibitor that blocks several members of the protein kinase C family, along with vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases. The drug also blocks normal vascularization of the retina during development but has no identifiable adverse effects on mature retinal vessels. In addition, the kinase inhibitor causes dramatic inhibition of choroidal neovascularization in a laser-induced murine model. These data provide proof of concept that pharmacological treatment is a viable approach for therapy of both retinal and choroidal neovascularization.     

Cardiac arrest following cardiac tamponade caused by mycosis fungoides malignant pericarditis

Mycosis fungoides is a low‐grade lymphoma, but on reaching the tumor stage, it can cause cardiac tamponade owing to epicardial infiltration. Myocardial infiltration, even in the absence of abnormal imaging findings, requires attention because it can lead to arrhythmia and cardiac arrest.