Metalloproteinases and their Tissue Inhibitors in Multiple Sclerosis

Matrix metalloproteinases (MMPs) comprise a family of proteolytic enzymes. MMPs are capable of disrupting the blood-brain barrier (BBB), mediating the destruction of extracellular matrix and myelin components. MMPs are also involved in the processing of a variety of cell surface molecules, including the proinflammatory cytokine TNF-alpha. Each of these mechanisms are thought to be important in the pathogenesis of multiple sclerosis (MS). We investigated mRNA expression of MMP-3, MMP-9 and two tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in parallel in blood mononuclear cells (MNC) from patients with MS and controls, using in situ hybridization. Numbers of MMP-9 mRNA-expressing cells in blood were higher in patients with MS compared to other neurological diseases (OND), other inflammatory neurological diseases (OIND) and healthy subjects (P<0.0001 for all comparisons). Patients with MS had also higher levels of MMP-3 and TIMP-1 mRNA expressing blood MNC compared to patients with OND and healthy subjects. A positive correlation was observed for MMP-9 and TIMP-1 mRNA expression in MS. These results demonstrate that MMPs and TIMPs are upregulated in MS and may contribute to the pathogenesis of the disease.     

Comparing the effectiveness of home visiting paraprofessionals and mental health professionals delivering a postpartum depression preventive intervention: a cluster-randomized non-inferiority clinical trial

To determine whether pregnant women receiving the Mothers and Babies group–based intervention exhibited greater depressive symptom reductions and fewer new cases of major depression than women receiving usual community-based services, and to examine whether groups run by paraprofessional home visitors and mental health professionals yielded similar depressive symptom reductions and prevention of major depression. Using a cluster-randomized design, 37 home visiting programs were randomized to usual home visiting, Mothers and Babies delivered via home visiting paraprofessionals, or Mothers and Babies delivered via mental health professionals. Baseline assessments were conducted prenatally with follow-up extending to 24 weeks postpartum. Eligibility criteria were ≥ 16 years old, ≤ 33 gestation upon referral, and Spanish/English speaking. Depressive symptoms at 24 weeks postpartum was the primary outcome. Eight hundred seventy-four women were enrolled. Neither intervention arm was superior to usual care in decreasing depressive symptoms across the sample (p = 0.401 home visiting paraprofessional vs. control; p = 0.430 mental health professional vs. control). Post hoc analyses suggest a positive intervention effect for women exhibiting mild depressive symptoms at baseline. We have evidence of non-inferiority, as the model-estimated mean difference in depressive symptoms between intervention arms (0.01 points, 95% CI: −0.79, 0.78) did not surpass our pre-specified margin of non-inferiority of two points. Although we did not find statistically significant differences between intervention and control arms, non-inferiority analyses found paraprofessional home visitors generated similar reductions in depressive symptoms as mental health professionals. Additionally, Mothers and Babies appears to reduce depressive symptoms among women with mild depressive symptoms when delivered by mental health professionals. This trial is registered on ClinicalTrials.gov (initial post: December 1, 2016; identifier: NCT02979444).

     

Analyzing the learning curves of a novice and an experienced urologist for transrectal magnetic resonance imaging-ultrasound fusion prostate biopsy

BackgroundThe aim of the current study was to evaluate and compare the learning curves of transrectal magnetic resonance imaging-ultrasound fusion biopsy for two urologists with different backgrounds (Operator 1: experienced, self-trained and Operator 2: novice, trained by a mentor/MRI reading courses).MethodsA cohort of 400 patients who underwent fusion prostate biopsy in our department was analyzed. The learning curves were assessed in terms of overall and clinically significant prostate cancer (PCa) detection rates, percentage of positive biopsy cores/targeted and the percentage of PCa tissue on positive targeted cores.ResultsIncreasing trends were observed for both urologists in terms of all biopsy outcomes during the study time. For the novice urologist, a significant increase was observed for overall PCa detection rate, but not for clinically significant disease (25.44%, P=0.04/15%, P=0.145). Operator 1 showed an increasing diagnosis yield of clinically significant disease up to 104 cases. Similar cancer detection rates were observed when comparing the first and last biopsies performed by both operators. Multivariate analysis adjusted for age, PSA, prostate volume, lesion diameter and PIRADS score showed an increase of PCa detection with 51% for every 52 biopsies performed (P=0.022).ConclusionsWhen starting with magnetic resonance imaging-ultrasound fusion prostate biopsy, mentoring and prostate magnetic resonance imaging reading training allow a novice urologist to demonstrate a good initial PCa detection rate. After about 52 cases, he reached a stable PCa and clinically significant PCa detection rate, that was similar to that of an experienced urologist.     

Comparison of non-surgical methods for the treatment of deep partial thickness skin burns of the hand

This paper describes a randomized, controlled, parallel-group, single-center clinical trial designed to compare non surgical treatment methods of deep partial thickness skin burns of the hand.All patients were scanned with the Laser Doppler Imaging device to determine the depth of the burn wound. Viable keratinocytes sites were determined according to the established Perfusion Units (PU) measurement system. The trial enrolled 87 patients with hand burn wounds in the section of 260–600 PU.Hand burn patients were divided into the following four groups: treated with hydrocolloid dressings; treated with mechanical debridement of monofilament polyester fibers pad and then applying silver sulfadiazine; treated with gauze dressings containing enzymatic collagenase preparation. The fourth group of patients was treated with silver sulfadiazine and gauze dressings. This group was considered as the control group. The wound healing status was assessed after 3, 7, 14 and 21 days. Burn scars and injured extremity function were assessed after six months according to the Vancouver Scar Scale and Disabilities of the Arm, Shoulder and Hand Outcome Measure.The fastest epithelialization of hand burn wounds was observed in the patients group treated with hydrocolloid dressings (15, 7 days, p < 0,05). The patients of this group also had less scars and a better hand function.     

Cryoablation treatment of benign breast lesions with 12-month follow-up

OBJECTIVE: Eighty percent of all breast biopsies reveal benign findings. The most common benign tumor is a fibroadenoma. Despite their benign nature, many women eventually choose to have their bothersome lumps surgically removed. We report the use of cryoablation to treat these benign breast lesions with minimum 12-month follow-up. METHODS: After receiving Institutional Review Board approval, a prospective nonrandomized trial was initiated in June 2000. Ultrasound-guided cryoablation of core biopsy-proven benign fibroadenomas, other benign breast nodules, or nodular fibrocystic change was performed on 78 lesions in 63 patients. Eighty-five percent of lesions treated were benign fibroadenomas. The cryoablation procedure consisted of a double freeze-thaw cycle that lasted between 6 and 30 minutes and was performed most often in an office setting. Each patient was serially evaluated for treatment efficacy, complications, and patient satisfaction. RESULTS: Sixty-four of 78 lesions (mean size 2.0 cm [range 0.8 to 4.2]) were followed-up for at least 12 months after cryoablation per protocol, which included 53 fibroadenomas. At 1 year, ultrasound tumor volume resorption was 88.3% overall (87.3% for fibroadenomas), and 73% of the entire group became nonpalpable to both clinician and patient (75% for fibroadenomas). Two of the fibroadenoma patients had their palpable residual nodule excised, both revealing necrotic debris and no viable tumor in the treated volume. Serial mammograms showed resorption of the lesion leaving minimal residual density without calcifications. Cosmesis was excellent with only a small scar remaining at the probe insertion site. There was no report of visual or palpable volumetric deficit. Patient satisfaction was good to excellent in 92% of cases. CONCLUSIONS: Cryoablation was successful in treating core biopsy-proven benign breast lesions in 63 patients. At 12 months, we found gradual resorption of treated tissue with no cosmetic deficit. Ultrasound-guided cryoablation is an effective and safe treatment for benign breast lesions, as seen at 12-month follow-up, and offers an office-based, minimally invasive alternative to surgical excision.     

Lipopolysaccharide delays demyelination and promotes oligodendrocyte precursor proliferation in the central nervous system

Systemic infection can influence the course in many diseases of the central nervous system (CNS) such as multiple sclerosis (MS), yet the relationship between infection outside the CNS and potential damage and/or protection within the CNS is still not understood. Activation of microglia is a characteristic feature of most CNS autoimmune disorders, including MS, and both protective and degenerative functions of microglia have been proposed. Hence, we analyzed the effects of a systemic inflammatory reaction induced by peripheral treatment with lipopolysaccharide (LPS) on microglial reaction and cuprizone induced de- and remyelination. We found that LPS administration delayed demyelination, which was linked with inhibition of microglial proliferation and reduced numbers of activated microglia. The phenotype of microglia changed as an increase of Toll-like receptor 4 was found. During remyelination, LPS treatment delayed the onset of myelin protein re-expression, but later there was a beneficial effect via an increase of proliferating oligodendrocyte precursor cells (OPC) and mature oligodendrocytes. Moreover, the expression of ciliary neurotrophic factor was increased in response to LPS, a growth factor known to mediate OPC proliferation. Additional experiments showed that the time window to induce LPS effects was limited and associated with the presence of microglia. In conclusion, LPS delayed demyelination and caused beneficial effects on remyelination via increasing the proliferation of OPC. These differences seem to be an effect of LPS induced microglial modulation and indicate that exposure to certain infectious agents within a given time window may be beneficial in promoting tissue repair.     

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia–reperfusion autotransplant model

The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and to evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia–reperfusion autotransplant model. The left kidney of an approximately 40‐kg female Belgian Landrace pig was exposed to 30 minutes of warm ischemia via vascular clamping and randomized to 1 of 6 study groups: (1) 22‐hour static cold storage (SCS) (n = 6), (2) 22‐hour hypothermic machine perfusion (HMP) (n = 6), (3) 22‐hour oxygenated HMP (n = 7), (4) 20‐hour HMP plus 2‐hour normothermic perfusion (NP) (n = 6), (5) 20‐hour SCS plus 2‐hour oxygenated HMP (n = 7), and (6) 20‐hour SCS plus 2‐hour NP (n = 6). Graft recovery measured by serum creatinine level was significantly faster for continuous HMP preservation strategies compared with SCS alone and for all end‐ischemic strategies. The active oxygenated 22‐hour HMP group demonstrated a significantly faster recovery from early graft function compared with the 22‐hour nonactive oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from the time of kidney procurement until transplant might be the best preservation strategy to improve early graft function.     

Outcome analysis of retroperitoneal laparoscopic heminephrectomy in children

PURPOSE: Retroperitoneal laparoscopic heminephrectomy is a relatively new, well tolerated, minimally invasive alternative to open surgery for children with a nonfunctioning moiety in a duplex kidney. We collected data to assess outcomes in our experience with this procedure. MATERIALS AND METHODS: Data were retrospectively gathered on all patients operated on for retroperitoneal laparoscopic heminephrectomy at our institution between February 2001 and November 2004. Followup ultrasound was performed in all patients, and additional imaging was done only when clinically indicated. RESULTS: Retroperitoneal laparoscopic heminephrectomy was performed in 18 girls and 4 boys (18 upper and 5 lower pole moieties). Indications included ureterocele (12 patients), ectopic ureter (9) and vesicoureteral reflux (5). Mean age at surgery was 5 years (range 4 months to 18 years). Four patients required conversion to an open procedure due to inadequate exposure and were excluded from further review. Urine leaks developed postoperatively in 3 patients and were treated with Foley catheter drainage and/or stent placement. Two patients were noted to have large (more than 5 cm) asymptomatic retroperitoneal fluid collections on followup ultrasound. Functional loss of the remaining ipsilateral moiety was confirmed by DMSA scan in 2 children (ages 6 and 7 months). Doppler studies confirmed normal hilar blood flow in both cases. Clinical presentation for this subgroup included fever on postoperative day 3 in 1 patient and hypertension at 32 months postoperatively in 1. Mean followup was 33 months (range 3 to 56). CONCLUSIONS: Although retroperitoneal laparoscopic renal ablative surgery in children appears to be relatively safe and is associated with low morbidity, serious complications may occur with subtle or even late presentation.     

Causes of recurrence in laparoscopic inguinal hernia repair

Purpose

Recurrence after laparoscopic inguinal herniorrhaphy is poorly understood. Reports suggest that up to 13% of all inguinal herniorrhaphies worldwide, irrespective of the approach, are repaired for recurrence. We aim to review the risk factors responsible for these recurrences in laparoscopic mesh techniques.

Methods

A search of the Medline, Embase, Science Citation Index, Current Contents and PubMed databases identified English language, peer reviewed articles on the causes of recurrence following laparoscopic mesh inguinal herniorrhaphy published between 1990 and 2018. The search terms included ‘Laparoscopic methods’, ‘Inguinal hernia; Mesh repair’, ‘Recurrence’, ‘Causes’, ‘Humans’.

Results

The literature revealed several contributing risk factors that were responsible for recurrence following laparoscopic mesh inguinal herniorrhaphy. These included modifiable and non-modifiable risk factors related to patient and surgical techniques.

Conclusions

Recurrence can occur at any stage following inguinal hernia surgery. Patients’ risk factors such as higher BMI, smoking, diabetes and postoperative surgical site infections increase the risk of recurrence and can be modified. Amongst the surgical factors, surgeon’s experience, larger mesh with better tissue overlap and careful surgical techniques to reduce the incidence of seroma or hematoma help reduce the recurrence rate. Other factors including type of mesh and fixation of mesh have not shown any difference in the incidence of recurrence. It is hoped that future randomized controlled trials will address some of these issues and initiate preoperative management strategies to modify some of these risk factors to lower the risk of recurrence following laparoscopic inguinal herniorrhaphy.