Restoring the glycosaminoglycans layer in recurrent cystitis: Experimental and clinical foundations

Restoring the bladder glycosaminoglycans layer has recently been introduced as prophylactic treatment for recurrent urinary tract infections. Herein, we analyze the latest main clinical and experimental studies to support this therapeutic option. An electronic research was carried out in the most common databases in order to identify any published studies. Retrieved studies were categorized as experimental or clinical according to their setting. For the clinical studies, the evidence level was assigned. A total of 13 laboratory studies showed how bladder glycosaminoglycans instillations act: attenuation of the inflammation process, reduction of bladder contraction amplitude and frequency, reduction of epithelium damage, and lower bacterial growth in urine and tissue samples. Likewise, two randomized clinical trials with grade 2 evidence level and two case series with grade 4 evidence level reported glycosaminoglycans as an alternative to reduce episodes and to prolong recurrence time in patients with recurrent urinary tract infections. At least 12 months of follow up was completed. No serious adverse events were reported. Compared with a placebo, in one randomized study a significantly higher maximum cystometric capacity was obtained, whereas in the other study a significant increase in quality of life scores was reported too. An improvement in the urinary symptoms score was reported by the two randomized trials. Although the clinical use of glycosaminoglycans replacement therapy for recurrent urinary tract infections is supported by a small number of clinical studies with different evidence levels, the laboratory studies show that glycosaminoglycans could have a protective role against inflammatory factors, supporting the idea “to restore the glycosaminoglycans bladder layer to prevent chronic disease course”.     

The influence of fluorescence imaging on the location of bowel transection during robotic left-sided colorectal surgery

Background

Hypoperfusion is an important risk factor for anastomotic leakage in colorectal surgery. This study was designed to evaluate the impact of fluorescence imaging on visualization of perfusion and subsequent change of transection line during left-sided robotic colorectal resections.

Methods

Patients scheduled for robotic left-sided colon or rectal resections were enrolled in this prospective, multicenter study. Resections were performed as per each surgeon’s preference. After complete colorectal mobilization, ligation of blood vessels, and distal transection of the bowel, the mesocolon was completely divided to the planned proximal or distal transection line, which was marked in white light. Indocyanine green was injected intravenously and the transection location(s) and/or distal rectal stump, if applicable, were re-assessed in fluorescent imaging mode. Imaging information, perioperative, and early postoperative outcomes were recorded. An independent video review of the surgeries was performed.

Results

Data for 40 patients (20 female/20 male) with a mean age of 63.9 years and a mean body mass index of 27.6 kg/m² were analyzed. Fluorescence imaging resulted in a change of the proximal transection location in 40 % (16/40) of patients. There was one change in the distal transection location in a patient with benign disease. The use of fluorescence imaging took an average of 5.1 min of the mean overall operative room time of 232 min. Two patients (5 %) with a change in transection line developed an anastomotic leak at postoperative days 15 and 40.

Conclusion

Fluorescence imaging provides additional information during determination of transection location in left-sided colorectal procedures. This results in a significant change of transection location, particularly at the proximal transection site. Further research needs to be conducted with larger patient cohorts and in comparative design to determine actual effect on anastomotic leak rate.     

Laparoscopic repair of perforated peptic ulcer: single-center results

Background

Perforated peptic ulcer (PPU), the most common indication for emergency gastric surgery, is associated with high morbidity and mortality rates. Outcomes might be improved by performing this procedure laparoscopically, but no consensus exists on whether the benefits of laparoscopic repair (LR) of PPU outweigh the disadvantages.

Methods

From January 2002 to December 2012, 111 patients underwent surgery for perforated ulcer. A “laparoscopy-first” policy was attempted and then applied for 56 patients. The exclusion criteria for LR ruled out patients who had shock at admission, severe cardiorespiratory comorbidities, or a history of supramesocolic surgery. The aim of this study was a retrospective analysis of the 56 patients treated laparoscopically.

Results

The patient distribution was 30 men and 26 women, who had a mean age of 59 years (range 19–95 years). The mean ulcer size was 10 mm, and the Mannheim peritonitis index (MPI) was 21. LR was performed for 39 (69.6 %) of the 56 patients and included peritoneal lavage, suturing of the perforation, and omental patching. Conversion to laparotomy was necessary in 17 cases (30.4 %). The “conversion group” showed significant differences in ulcer size (larger ulcers: 1.9 vs 0.7 mm; p < 0.01), ulcer-site topography (higher incidence of posterior ulcers: 5 vs 0; p < 0.01), and MPI score (higher score: 24 vs 20; p < 0.05). The LR group had a mean operating time of 86 min (range 50–125 min), an in-hospital morbidity rate of 7.6 %, a mortality rate of 2.5 %, and a mean hospital stay of 6.7 days (range 5–12 days). None of these patients required reintervention.

Conclusions

The results showed that LR for PPU is feasible with acceptable mortality and morbidity rates. Skill in laparoscopic abdominal emergencies is required. Perforations 1.5 cm or larger, posterior duodenal ulcers, and an MPI higher than 25 should be considered the main risk factors for conversion.     

Emerging biologic therapies for hypercholesterolaemia

Introduction: LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy.

Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed.

Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.     

Italian translation of the VISA-A score for tendinopathy of the main body of the Achilles tendon

Purpose. To translate and adapt the English VISA-A questionnaire to Italian, to perform reliability and validity evaluations of the Italian VISA-A version in patients with tendinopathy of the main body of the Achilles tendon. Methods. The VISA-A English version was translated into Italian by a bilingual orthopaedic surgeon. The back translation of the Italian version into English was performed by another bilingual orthopaedic surgeon. The original version was compared with the back translation. The VISA-A-I questionnaire was then administered to 50 male athletes (average age 26.4, range 18 - 49 years) with a diagnosis of tendinopathy of the main body of the AT. For test-retest evaluation, the 50 patients were asked to complete the questionnaire at first examination, and 30 minutes following the end of this examination. Results. The kappa statistics for 50 patients was 0.80 (range 0.7 - 0.86). There were no significant differences between the scores immediately after the consultation and 30 minutes later. Conclusions. Italian and the English versions of the VISA-A questionnaire evaluate the same aspects of clinical severity in patients with tendinopathy of the main body of the Achilles tendon.     

Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load

The aim of this study was to simultaneously measure in vivo volumes of gray matter (GM), normal white matter (WM), abnormal white matter (aWM), and cerebro-spinal fluid (CSF), and to assess their relationship in 50 patients with relapsing-remitting multiple sclerosis (RR-MS) (age range, 21-59; mean EDSS, 2.5; mean disease duration, 9.9 years), using an unsupervised multiparametric segmentation procedure applied to brain MR studies. Tissue volumes were normalized to total intracranial volume providing corresponding fractional volumes (fGM, faWM, fWM, and fCSF), subsequently corrected for aWM-related segmentation inaccuracies and adjusted to mean patients' age according to age-related changes measured in 54 normal volunteers (NV) (age range 16-70). In MS patients aWM was 23.8 +/- 29.8 ml (range 0.4-138.8). A significant decrease in fGM was present in MS patients as compared to NV (49.5 +/- 3.2% vs 53.3 +/- 2.1%; P < 0.0001), with a corresponding increase in fCSF (13.0 +/- 3.8% vs 9.1 +/- 2.4%; P < 0.0001). No difference could be detected between the two groups for fWM (37.5 +/- 2.6% vs 37.6 +/- 2.2%). faWM correlated inversely with fGM (R = -0.434, P < 0.001 at regression analysis), and directly with fCSF (R = 0.473, P < 0.001), but not with fWM. There was a significant correlation between disease duration and EDSS, while no relationship was found between EDSS or disease duration and fractional volumes. Brain atrophy in RR-MS is mainly related to GM loss, which correlates with faWM. Both measures do not appear to significantly affect EDSS, which correlates to disease duration.