One month maximal electrostimulation for genuine stress incontinence in women

While awaiting surgery for genuine urinary stress incontinence, 51 women with were treated at home for 1 month with vaginal maximal electrostimulation. They were evaluated subjectively, urodynamically, and with two different pad tests. Six patients (12%) were cured and 17 (33%) were much improved, subjectively and objectively. Statistically significant improvement was observed for both pad tests. Successful treatment was significantly more likely in women with milder degrees of incontinence but was unrelated to age or urethral pressure. Patient acceptance was excellent and apart from some vaginal soreness no complications were seen. Sixteen patients (31%) elected not to be operated on. These 16 patients were reevaluated after 1 year and 13 (81%) had maintained their improvement. Three had disimproved but were still better than before treatment; 2 again refused surgery and 1 opted for surgery. Therefore, 15 of 51 (29%) operations were saved after 1 year. This conservative treatment for stress incontinence is safe, simple, inexpensive, and reasonably successful. © 1994 Wiley-Liss, Inc.     

Endoscopic Treatment of Vesicoureteral Reflux with Collagen: Preliminary Report and Cost Analysis

Purpose

We determined therapeutic and operative cost efficacy of endoscopic collagen injection for vesicoureteral reflux.

Materials and Methods

We performed a multicenter study of 10 male and 23 female sequential patients (45 renal units) with vesicoureteral reflux and a surgical indication. Patients were skin tested with collagen and when negative, they underwent endoscopic injection. Renal ultrasound/ cystography was done 3 months after treatment. Cost analysis was performed at 1 institution.

Results

Reflux was grade I in 2 renal units, II in 18, III in 15 and IV in 10. The majority of cases were single systems with primary reflux. We performed 1 treatment in 32 renal units, 2 in 6, 3 in 6 and 4 in 1. Cure was evident in 31 of 38 renal units (81.6 percent) and 21 of 27 patients (78 percent) 3 months after the last injection. Patient morbidity was minimal. Operative cost per renal unit was $1,599.68 for collagen injection and $9,144.47 for reimplantation.

Conclusions

Endoscopic injection of collagen is effective treatment for vesicoureteral reflux. Furthermore, it causes minimal morbidity and may effect cost savings in health care management.     

Prevalence and Incidence of Hypoparathyroidism in the United States Using a Large Claims Database

Hypoparathyroidism is a rare endocrine disorder whose incidence and prevalence have not been well defined. This study aimed to 1) estimate the number of insured adult patients with hypoparathyroidism in the United States and 2) obtain physician assessment of disease severity and chronicity. Prevalence was estimated through calculation of diagnoses of hypoparathyroidism in a large proprietary health plan claims database over a 12‐month period from October 2007 through September 2008 and projected to the US insured population. Incidence was also calculated from the same database by determining the proportion of total neck surgeries resulting in either transient (≤6 months) or chronic (>6 months) hypoparathyroidism. A physician primary market research study was conducted to assess disease severity and determine the percentage of new nonsurgical patients with hypoparathyroidism. Incidence data were entered into an epidemiologic model to derive an estimate of prevalence. The diagnosis‐based prevalence approach estimated 58,793 insured patients with chronic hypoparathyroidism in the United States. The surgical‐based incidence approach yielded 117,342 relevant surgeries resulting in 8901 cases over 12 months. Overall, 7.6% of surgeries resulted in hypoparathyroidism (75% transient, 25% chronic). The prevalence of chronic hypoparathyroidism among insured patients included in the surgical database was estimated to be 58,625. The physician survey found that 75% of cases treated over the past 12 months were reported due to surgery and, among all thyroidectomies and parathyroidectomies and neck dissections performed in a year, 26% resulted in transient hypoparathyroidism and 5% progressed to a chronic state. In conclusion, the two claims‐based methods yielded similar estimates of the number of insured patients with chronic hypoparathyroidism in the United States (～58,700). The physician survey was consistent with those calculations and confirmed the burden imposed by hypoparathyroidism. © 2013 American Society for Bone and Mineral Research.     

Long-term health-related quality of life after pancreatic resection for malignancy in patients with and without severe postoperative complications

Background

Surgery for pancreatic cancer yields significant morbidity and mortality risks and survival is limited. Therefore, the influence of complications on quality of life (QoL) after pancreatic surgery is important. This study compares QoL in patients with and without severe complications after surgery for pancreatic (pre-)malignancy.

Early oral feeding after pancreatoduodenectomy enhances recovery without increasing morbidity

Objective

The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes.

Methods

An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake.

Results

The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien–Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods.

Conclusions

The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity.     

Ouabain Protects against Shiga Toxin–Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL

Hemolytic uremic syndrome, a life-threatening disease often accompanied by acute renal failure, usually occurs after gastrointestinal infection with Shiga toxin 2 (Stx2)–producing Escherichia coli. Stx2 binds to the glycosphingolipid globotriaosylceramide receptor, expressed by renal epithelial cells, and triggers apoptosis by activating the apoptotic factor Bax. Signaling via the ouabain/Na,K-ATPase/IP3R/NF-κB pathway increases expression of Bcl-xL, an inhibitor of Bax, suggesting that ouabain might protect renal cells from Stx2-triggered apoptosis. Here, exposing rat proximal tubular cells to Stx2 in vitro resulted in massive apoptosis, upregulation of the apoptotic factor Bax, increased cleaved caspase-3, and downregulation of the survival factor Bcl-xL; co-incubation with ouabain prevented all of these effects. Ouabain activated the NF-κB antiapoptotic subunit p65, and the inhibition of p65 DNA binding abolished the antiapoptotic effect of ouabain in Stx2-exposed tubular cells. Furthermore, in vivo, administration of ouabain reversed the imbalance between Bax and Bcl-xL in Stx2-treated mice. Taken together, these results suggest that ouabain can protect the kidney from the apoptotic effects of Stx2.Hemolytic uremic syndrome (HUS) is a life-threatening disease, with acute renal failure as one of the most prominent symptoms. HUS generally occurs after a gastrointestinal infection with Shiga toxin 2 (Stx2)–producing Escherichia coli.^1,2 Stx2 penetrates the intestine, enters the circulation, and binds with high affinity to glycosphingolipid globotriaosylceramide receptors (Gb3), which are expressed in many tissues but are particularly abundant in renal epithelial cells. The Stx2/Gb3 complex is endocytosed and then translocated via the Golgi apparatus and the endoplasmic reticulum to the cytosol, where the toxic A subunit will exert its effects by acting on ribosomes.³ Apoptosis is a major manifestation of Stx2 toxicity, as shown in biopsy samples from patients with HUS and in kidneys from mice inoculated with Stx2-producing versus Stx-nonproducing E. coli O157:H7, those treated with Stx2, and Stx2-exposed cells.^1,4,5The mechanism by which Stx2 activates apoptotic pathways is not fully understood, but several lines of evidence suggest that it involves activation of caspase-8 and the intrinsic, mitochondrial pathway. It is well documented that Stx2 increases caspase-8 expression.^6,7 Caspase-8 may trigger a signaling cascade that results in caspase-3 cleavage and cell death without involving the mitochondrial pathway (the extrinsic apoptotic pathway), or it may act by stimulating the apoptotic oligomerizing factors Bax and Bak, which bind to the mitochondrial membrane and make it permeable. This leads to a series of events that also result in caspase-3 cleavage and cell death (the intrinsic apoptotic pathway).⁷ Bax belongs to the Bcl-2 family, which includes both pro- and antiapoptotic factors. Bcl-xL is an antiapoptotic member of the Bcl-2 family and a potent inhibitor of Bax.^8,9 Little is known about the effect of Stx2 on Bax and Bcl-xL expression. Two independent studies found that the overexpression of Bcl-xL by transient transfection protected from Stx2 B subunit–mediated apoptosis.^10,11 HUS was previously more common in children, but the recent large outbreak of food-borne Stx2-producing E. coli O104:H4 infection suggested that severe HUS might affect adults as well as children. No available therapy protects patients from acute toxin-mediated cellular injury, including apoptosis.^12,13 Chronic renal affection or failure occurs in up to 10% of patients who survive the acute manifestations of the disease.¹³Our group has identified a novel signaling system that protects against apoptosis.^14,15 The signal is activated by the cardiotonic steroid ouabain. The signaling pathway involves interaction between Na,K-ATPase and the inositol 1,4,5-triphosphate receptor (IP3R), triggering of slow intracellular calcium oscillations, and activation of the NF-kB p65 subunit (or RelA).^16–19 Because NF-κB p65 is known to increase the expression of Bcl-xL,²⁰ we hypothesized that ouabain-triggered Na,K-ATPase signaling may counteract the apoptotic action of Stx2 by upregulation of Bcl-xL and downregulation of Bax. Here we present a series of studies in support of this hypothesis. We show that ouabain in nM concentrations protects Stx2-exposed rat renal epithelial cells from apoptosis by reversing an imbalance between Bax and Bcl-xL. Studies on mice inoculated with Stx2 provide proof of principle and show that treatment with ouabain protects against apoptosis and reverses the imbalance between Bax and Bcl-xL.     

Surgical treatment of acute pancreatitis

Background

Acute pancreatitis remains an unpredictable, potentially lethal disease with significant morbidity and mortality rates. New insights in the pathophysiology of acute pancreatitis have changed management concepts. In the first phase, characterized by a systemic inflammatory response syndrome, organ failure, not related to infection but rather to severe inflammation, dominates the focus of treatment. In the second phase, secondary infectious complications largely determine the clinical outcome. As infection is associated with increased mortality in acute pancreatitis, numerous prophylactic strategies have been explored in the past two decades.

Purpose

This review describes the strategies that have been developed to lower the infection rate, in an attempt to lower mortality. Antibiotic prophylaxis has been the subject of many RCT’s without showing convincing evidence of their efficacy. Probiotics, although theoretically capable of lowering the rate of infection, also had no effect on infectious complications, and consequently, no effective strategy to lower the rate of infectious complications is currently available. In the second part of this review, new approaches for necrosectomy that have been designed by different centers around the world are discussed. All the interventional techniques have in common their aim to lower the invasive character, hypothesizing that lowering the surgical trauma will improve survival and lower complication rates. Recent advances include postponing intervention as a strategy to facilitate necrosectomy and improve prognosis and the “step-up approach” in case of infected necrosis. The step-up approach includes percutaneous catheter drainage as the first step, to be followed by necrosectomy, either through a minimally invasive approach or by open necrosectomy, as the next step.

Conclusions

All attempts to develop treatment strategies to lower the infection rate in acute pancreatitis have failed. Accumulating evidence is emerging to show that the combination of centralization, the use of catheter drainage as the first step of invasive treatment, and the development of minimally invasive techniques, improve the outlook for patients with infected necrosis. It is uncertain at this point in time as to which of the three effects is dominant in the improvement of prognosis.