Variant rs4149584 (R92Q) of the TNFRSF1A gene in patients with familial multiple sclerosis.

INTRODUCTION: Genomic studies have identified numerous genetic variants associated with susceptibility to multiple sclerosis (MS); however, each one explains only a small percentage of the risk of developing the disease. These variants are located in genes involved in specific pathways, which supports the hypothesis that the risk of developing MS may be linked to alterations in these pathways, rather than in specific genes. We analyzed the role of the TNFRSF1A gene, which encodes one of the TNF-α receptors involved in a signaling pathway previously linked to autoimmune disease. METHODS: We included 138 individuals from 23 families including at least 2 members with MS, and analyzed the presence of exonic variants of TNFRSF1A through whole-exome sequencing. We also conducted a functional study to analyze the pathogenic mechanism of variant rs4149584 (-g.6442643C > G, NM_001065.4:c.362 G > A, R92Q) by plasmid transfection into human oligodendroglioma (HOG) cells, which behave like oligodendrocyte lineage cells; protein labeling was used to locate the protein within cells. We also analyzed the ability of transfected HOG cells to proliferate and differentiate into oligodendrocytes. RESULTS: Variant rs4149584 was found in 2 patients with MS (3.85%), one patient with another autoimmune disease (7.6%), and in 5 unaffected individuals (7.46%). The 2 patients with MS and variant rs4149584 were homozygous carriers and belonged to the same family, whereas the remaining individuals presented the variant in heterozygosis. The study of HOG cells transfected with the mutation showed that the protein does not reach the cell membrane, but rather accumulates in the cytoplasm, particularly in the endoplasmic reticulum and near the nucleus; this suggests that, in the cells presenting the mutation, TNFRSF1 does not act as a transmembrane protein, which may alter its signaling pathway. The study of cell proliferation and differentiation found that transfected cells continue to be able to differentiate into oligodendrocytes and are probably still capable of producing myelin, although they present a lower rate of proliferation than wild-type cells. CONCLUSIONS: Variant rs4149584 is associated with risk of developing MS. We analyzed its functional role in oligodendrocyte lineage cells and found an association with MS in homozygous carriers. However, the associated molecular alterations do not influence the differentiation into oligodendrocytes; we were therefore unable to confirm whether this variant alone is pathogenic in MS, at least in heterozygosis.

Retrieval of the gastric specimen following laparoscopic sleeve gastrectomy. Experience on 275 cases.

Severe obesity leads to a high incidence of complications and a decrease in life expectancy, especially among younger adults. Laparoscopic sleeve gastrectomy (LSG) first intended as the first step of biliopancreatic diversion with duodenal switch is gaining a per-se procedure role because of its effectiveness on weight loss and comorbidity resolution. Different techniques have been described for specimen extraction in LSG. In this article we report the technique adopted in 275 LSGs performed in our department. In the first 120 LSGs performed from 2007, the specimen was extracted through a mini laparotomy. In the following 155 cases the technique has been simplified: the grasped specimen has been withdrawn through the 15 mm trocar site. We registered in the fist group six cases of wound infection (5%), ten cases of hematoma (8.3%) and four cases of port site hernia (3.3%). In the second group only one case of hematoma (0.6%, p = 0.01) but no cases of wound infection (p = 0.01) or port site hernia, (p = 0.03) although we registered a specimen perforation during retrieval in 16 patients, were reported. The technique described in the 155 cases of the control group has shown to be more effective than the technique we used in the case group, allowing significantly lower operative time (112.9 ± 1.0 vs 74.9 ± 9.1 p < 0.001) and complications, and providing unchanged costs.

Great saphenous vein stripping and nerve injury: the role of stripping direction.

AIM: Although saphenous nerve (SN) injury represents a complication of great saphenous vein (GSV) stripping, little is know about the techniques to minimize the risk of nerve injury. This is still controversial if the stripping direction could be related to the incidence of nerve injury. METHODS: A prospective comparative study to compare upwards and downwards total GSV stripping during saphenectomy with regard to the occurrence of postoperative SN injury has been designed. Electroneurogram measurement and clinical identification of nerve injury have been performed 1 day before surgery, 1 week, 12 weeks and 1 year after surgery. RESULTS: Although clinical evaluation of nerve injury was found to be similar among upwards and downwards stripping both at one and 12 weeks after surgery, ENG measurement showed a higher incidence of lesions after the downwards stripping both at one and 12 weeks after surgery. No clinical or ENG findings of nerve injury was found 1 year after surgery. CONCLUSION: Upwards method is less traumatic than downwards total GSV stripping in terms of incidence of SN injury, as confirmed by electrophysiological nerve studies.

An early onset of acute renal failure in a young woman with obesity and infertility who underwent gastric balloon positioning. A case report.

INTRODUCTION: Although intragastric balloons have been in use for several years to achieve weight reduction in obese patients, acute renal failure after gastric balloon positioning is reported in few studies CASE REPORT: A 32-year-old white infertile woman undergone Bioenterics Intragastric Balloon (BIB) positioning in an attempt to weight loss and improve her fertility status. After only six days of persisting vomiting acute renal failure was found. A complete recovery of renal function was obtained after 14 days. CONCLUSION: Acute renal failure was due to persistent vomiting leading to dehydration. Physicians involved in BIB patients management must consider the possibility of major complications in all hyperemetic subjects. BIB removal, with a concomitant intravenous fluid replacement and minerals or vitamins supplementation has to be taken into account as an emergency procedure.

Outpatient surgical procedures: which is the ideal teaching procedure for a resident surgeon?

AIM: The aim of our study is to evaluate which surgical procedures can be considered the ideal teaching procedure for a resident surgeon. MATERIALS AND METHODS: This is a retrospective study. A chart review was performed on all patients who underwent inguinal hernia repair, saphenectomy, excision of pilonidal sinus and hemorrhoidectomy at our institution, between September 2000 and July 2011, and have at least 1 year of follow-up. We evaluated operative time and complications comparing the results obtained by resident or attending surgeon. RESULTS: We obtained a higher operative time among the procedures performed by resident surgeons for all evaluated interventions. Whereas the occurrence of complications after hernia repair and excision and primary closure of pilonidal sinus were similar in case and control subjects (p = 0,1 and p = 0,1), the occurrence of complications after hemorrhoidectomy and saphenectomy was significantly higher in the case group (p = 0,08 and p = 0,1). CONCLUSION: Hernia repair and excision and primary closure of pilonidal sinus have to be considered the ideal teaching procedure in a residency program, giving to the young surgeon the opportunity of reach several skills that he needs to master most difficult surgical procedures. Saphenectomy and hemorrhoidectomy should be considered safe only if performed by a senior resident surgeon.

Safety and efficacy of saphenectomy in elderly patients.

AIM: The aim of this study is to evaluate safety and efficacy of saphenactomy in elderly patients. PATIENTS AND METHODS: A total of 358 patients with varicose veins of the lower limbs treated between January 2001 and December 2011. 213 of these were patients under 65 years old and 145 patients were over this age. We have evaluated short- and long-term complications to compare the results among young and elderly patients. RESULTS: Postoperative complications that occurred were: infection, haematoma, nerve injury (paresthesia and pain) and deep vein thrombosis. Although a trend towards better results was observed among the young patients, no significant differences were shown in our experience. CONCLUSION: Elective saphenectomy has a good outcome also in the elderly patients. The slightly higher rate of complications that occurred in older patients is not significant and does not support advising against the use of this surgical approach in the elderly. So in our opinion saphenectomy is quite safe and feasible also in patients over 65 years.

The role of drainage after excision and primary closure of pilonidal sinus: a meta-analysis.

We carried out a systematic review of the literature to identify the association between the use of drain and the incidence of infections and recurrences after surgery. MEDLINE, SCOPUS and ISI databases were searched up to September 2012. The two outcomes of this meta-analysis were wound infection and recurrence. Postoperative wound infection occurred in 50 of the 604 (8.28 %) patients who underwent drainage and in 68 of the 598 (11.4 %) patients who did not, with a resulting odds ratio (OR) of 0.71 (95 % CI: 0.48-1.03). Recurrence of pilonidal sinus occurred in 41 of the 604 (6.79 %) patients who underwent drainage and in 50 of the 598 (8.36 %) patients who did not, with a resulting OR of 0.80 (95 % CI: 0.52-1.23). The results suggest that, despite a trend toward a reduction in infectious complications and recurrence, drainage was not associated with a better outcome. However, because of the present literature's limitations, further studies are needed to address this issue.

Outpatient inguinal hernia repair under local anaesthesia: feasibility and efficacy of ultrasound-guided transversus abdominis plane block.

BACKGROUND: The aim of this prospective randomized study was to determine the utility of transversus abdominis plane (TAP) block to improve the efficacy of conventional local anaesthesia for hernia repair in order to achieve an adequate anaesthesia and to evaluate its post-operative analgesic effectiveness. METHOD: Hundred and fifty consecutive male patients undergoing outpatient hernia repair (Lichtenstein technique) were enrolled in this study. Patients were randomly allocated to undergo a combined TAP block and local anaesthesia (case group) or single conventional local anaesthesia (control group). The study was designed to obtain a 1:2 case-control ratio. The primary outcome was the evaluation of the proportion of patients achieving an adequate anaesthesia. The secondary outcome was the evaluation of pain on movement, pain at rest, rescue analgesia need, nausea and satisfaction. RESULTS: An adequate anaesthesia was achieved in 8 % case and in 36 % control subjects (p = 0.001). At the 6 and 12 h post-operative evaluations, patients enrolled in the case group reported significantly less pain (evaluated by VAS score) both at rest and on movement (p always = 0.001). Moreover, the need of rescue analgesia resulted significantly higher in the control group (14 vs. 32 %, p = 0.01). CONCLUSION: Our results demonstrated that, as compared with conventional local anaesthesia, the combination of TAP block with local anaesthesia showed a higher efficacy in the obtainment of an adequate anaesthesia and in the post-operative pain control for hernia repair.

Ropivacaine infusion in diabetics subject with peripheral arterial disease. A prospective study.

BACKGROUND: Peripheral arterial disease (PAD) predicts cardiovascular and cerebrovascular ischemic events. PAD treatment is aimed at reducing clinical symptoms, local tissue loss and at preventing complications. AIMS: To evaluated the effect of peridural analgesia on peripheral perfusion and pain control. METHODS: In 280 diabetic subjects with severe limb ischemia (65.7% males and 34.3% females, mean age 59.3±14.4 years) with a failure of medical treatment and contraindications to endovascular and/or surgical reperfusion, we performed a 30-day long peridural ropivacaine infusion, monitoring blood pressure, VAS and ABI periodically. RESULTS: During ropivacaine infusion VAS significantly decreased (from 4.06±0.343 to 1.96±0.413, p<0.001). Furthermore, in the 261 (93.2%) subjects achieving a VAS value ≤2 during infusion, the effect was maintained after infusion withdrawing. ABI significantly improved both during infusion (from 0.30±0.04 at baseline to 0.65±0.05 at T30, p<0.001) and after infusion withdrawing as compared with baseline values. CONCLUSIONS: 30-day peridural analgesia with ropivacaine is a valuable therapeutic option in severe peripheral limb ischemia subjects with contraindication to surgery and with pharmacological therapy failure.

Changes in exercise capacity induced by heart transplantation: prognostic and therapeutic implications.

Survival and exercise performance are key targets of heart transplantation (HT). We designed this study to help in identifying (1) patients with chronic heart failure (CHF) at risk of poor exercise capacity after HT and (2) HT recipients presenting risk factors modifiable with exercise showing a potential impact on outcome. We enrolled 49 HT recipients (age 52 ± 12 years, 84% males) who underwent a cardiopulmonary exercise test before (9 ± 6 months) and after (20 ± 14 months) HT. In the CHF phase, lower peak oxygen consumption (VO(2) ) (odds ratio 0.69, P=0.017) independently predicted peak VO(2) improvement after HT. In the post-HT phase, body mass index (BMI) [adjusted hazard ratio (HR) 1.16, P=0.034] and VE (ventilation)/VCO(2) (carbon dioxide production) slope (adjusted HR 1.07, P=0.031) independently predicted mortality. In conclusion, CHF patients with only a moderate impairment of peak VO(2) are at a risk of failing to achieve a significant improvement of exercise performance after HT. In the post-HT phase, a BMI≥28 and/or a VE/VCO(2) slope ≥47 represent risk factors for death, which are potentially modifiable with exercise. Prospective randomized studies are needed to analyze the effects of training on functional capacity and outcome in the different subsets of HT recipients.

Recurrent varicose veins of the lower limbs after surgery. Role of surgical technique (stripping vs. CHIVA) and surgeon's experience.

BACKGROUND: Surgical treatment of varicose veins of the lower limbs resolves symptoms and improves quality of life. However, the high recurrence (20-80%) is a costly and complex issue. PATIENTS AND METHODS: This is a retrospective review of 1489 patients with varicose vein of the lower limbs seen at our hospital between January 1980 and December 2005. The aim is to evaluate the effect of surgical technique (stripping vs. CHIVA) and surgeon's experience in reducing recurrences. RESULTS: With experienced surgeons, CHIVA appears to be more effective than stripping in reducing the recurrence rate (p <0.05). However, when performed by an inexperienced surgeon the results are far worse than those achieved with stripping. CONCLUSION: There was a clear reduction in recurrences at 5-10 years with CHIVA than with conventional stripping. However, if performed incorrectly, results are far worse with CHIVA. In fact, good results are far more difficult to achieve with CHIVA than with stripping, which is repeatable and easy to perform.

Fine-needle cytology of inflammatory myofibroblastic tumor of the lung. Report of a case.

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) of the lung is a rare condition that may mimic cancer. CASE: We describe a case of inflammatory myofibroblastic tumor discovered by a routine chest X-ray in a 26-year-old male patient, primarily diagnosed by fine needle aspiration biopsy. The clinical, cytopathological and differential diagnostic findings of this rare entity are briefly discussed. CONCLUSION: IMT may be diagnosed accurately on needle cytology samples, provided that other pseudoneoplastic and neoplastic entities can be excluded from its differential diagnosis.