Results after laparoscopic fundoplication: does age matter?

Antireflux fundoplications are undertaken with hesitation in older patients because of presumed higher morbidity and poorer outcomes. This study was undertaken to determine if symptoms of gastroesophageal reflux disease (GERD) could be safely abrogated in a high-risk/reward popu lation of older patients. One hundred eight patients more than 70 years of age (range, 70-90 years) underwent laparoscopic Nissen fundoplications undertaken between 1992 and 2005 and were compared with 108 concurrent patients less than 60 years of age (range, 18-59 years) to determine relative outcomes. Before and after fundoplication, patients scored the severity of reflux and dysphagia on a Likert Scale (0 = minor, 10 = severe). Before fundoplication, older patients had lower reflux scores (P < 0.01), but not lower dysphagia scores or DeMeester scores. One patient (86 years old) died from myocardial infarction; otherwise, complications occurred infrequently, inconsequentially, and regardless of age. At similar durations of follow-up, reflux and dysphagia scores significantly improved (P < 0.01) for older and younger patients. After fundoplication, older patients had lower dysphagia scores (P < 0.01) and lower reflux scores (P < 0.01). At the most recent follow-up, 82 per cent of older patients rated their relief of symptoms as good or excellent. Similarly, 81 per cent of the younger patients reported good or excellent results. Ninety-one per cent of patients 70 years of age or more versus 85 per cent of patients less than 60 years would undergo laparoscopic Nissen fundoplication again, if necessary. With fundoplication, symptoms of GERD improve for older and younger patients, with less symptomatic dysphagia and reflux in older patients after fundoplication. Laparoscopic fundoplication safely ameliorates symptoms of GERD in elderly patients with symptomatic outcomes superior to those seen in younger patients.     

Severe osteoporosis: does structural monitoring help?

Vertebral fractures, the most common osteoporotic fractures, are associated with excess mortality even in the absence of symptoms. Presence of at least one radiological or clinical prevalent vertebral fracture increases the risk of incident vertebral fractures not only in untreated patients, but also in treated patients, as established by studies involving routine radiological monitoring. Therefore, whether structural monitoring is indicated on a routine basis deserves discussion. Height measurement is a basic monitoring tool for detecting new vertebral fractures. However, loss of height is nonspecific. Radiography involves radiation exposure levels and financial costs that are not consistent with use for routine monitoring. Vertebral fracture assessment based on dual-energy X-ray absorptiometry (VFA), in contrast, is an inexpensive method that delivers only low radiation levels. VFA used in conjunction with absorptiometry may be well suited to the monitoring of women with severe osteoporosis.     

Lung xenogenic injury: does anticoagulation help?

The shortage of human organ donors remains a major limitation to the field of transplantation [1], and can potentially be solved using xenografts. During the past decade, many advances have been made to address the major initial immunological obstacle to “discordant” pig‐to‐human solid organ transplantation: hyperacute rejection (HAR). As organs from unmodified pigs were evaluated in animal models, HAR was found to be primarily a consequence of the recipient's preformed anti‐pig antibodies binding on porcine vascular endothelial cells leading to subsequent complement activation, thrombosis and graft failure [2]. This process occurs within minutes to hours of human blood perfusion in porcine organs. Since the carbohydrate structure Galactose‐α(1,3‐Galactose (Gal) is recognized by over 80% of anti‐pig antibodies found in man, genetically modified galactosyl transferase knock‐out (GalTKO) pig organs have been developed [3,4]. Endothelium and parenchymal cells from GalTKO animals lack the Galα1,3Gal epitope. As predicted, heart and kidney transplant studies in baboons showed that the GalTKO phenotype is associated with decreased antibody binding, reduced activation of the complement cascade and prolonged graft survival [5–8]. However, delayed xenograft rejection, consumptive coagulopathy and microangiopathy limit long‐term outcomes. Xenogenic lungs are even more sensitive to xenogenic injury [9, 10], even with additional expression of complement regulatory protein human CD46 [Burdorf et al]. Immunohistology and biochemical evidence and work by others implicated inflammation and coagulation cascade activation as residual xenogenic injury pathways. To determine the role of these pathways in lung xenogenic injury, our group is evaluating new transgenic pigs [11] and various pharmacologic approaches. New transgenes include human thrombomodulin (hTM), endothelial protein C receptor (EPCR) and ectonucleoside triphosphate diphosphohydrolase‐1 (CD39). Pharmacologic interventions consist in targeting platelet receptors (GPIb, GPIIbIIIa), thrombin (hirulog) and adding exogenous activated protein C to perfused human blood and administering desmopressin to lung donor pigs. The differential effects of these interventions on lung physiological parameters, platelet and coagulation activation will be summarized. Future work will place emphasis on combined targeting of these pathways. Acknowledgments: Funded in part by NIH (IU19A1090959, 1U01AI066335) and by gifts from Revivicor and United Therapeutics. References 1. Cooper DKC. Xenografting: how great is the clinical need? Xeno 1993; 1: 25–26. 2. Pierson RNIII. Antibody‐mediated xenograft injury: mechanisms and protective strategies. Transpl Immunol 2009; 21: 65–69. 3. Phelps CJ, Koike C, Vaught TD et al.Production of alpha 1,3‐galactosyltransferase‐deficient pigs. Science 2003; 299: 411–414. 4. Kolber‐ Simonds D, Lail L, Watt SR et al. Production of alpha‐1,3‐galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations. Proc Natl Acad Sci U S A 2004; 101: 7335–7340. 5. Tseng YL, Kuwaki K, Dor FJ et al. alpha1,3‐Galactosyltransferase gene‐knockout pig heart transplantation in baboons with survival approaching 6 months. Transplantation 2005; 80: 1493–1500. 6. Kuwaki K, Tseng YL, Dor FJet al. Heart transplantation in baboons using alpha1,3‐galactosyltransferase gene‐knockout pigs as donors: initial experience. Nat Med 2005; 11: 29–31. 7. Yamada K, Yazawa K, Shimizu Aet al. Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3‐galactosyltransferase gene‐knockout donors and the cotransplantation of vascularized thymic tissue. Nat Med 2005; 11: 32–34. 8. Mohiuddin MM, Corcoran PC, Singh AK, et al. B‐cell depletion extends the survival of GTKO.hCD46Tg pig heart xenografts in baboons for up to 8 months. Am J Transplant. 2012; 12:763–71. 9. Nguyen BN, Azimzadeh AM, Zhang T, et al. Life‐supporting function of genetically modified swine lungs in baboons. J Thorac Cardiovasc Surg 2007; 133: 1354–1363. 10. Nguyen BN, Azimzadeh AM, Schroeder C et al. Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection. Xenotransplantation. 2011; 18:94–107. 11. Cooper DK, Ekser B, Burlak C et al. Clinical lung xenotransplantation – what donor genetic modifications may be necessary? Xenotransplantation. 2012; 19:144–58.     

Backpack and spinal disease: myth or reality?

Back pain has become a real public health concern both for adults and children. In general, patients complain of moderate pain. While the topic was long ignored by the scientific community, the number of publications has increased over the last three Years. We reviewed the literature to separate real evidence from speculations. Recognized risk factors for spinal pain are: female gender, poor general status, family history of back pain, particular psychological patterns, time spent sitting watching television, history of spinal trauma, intense physical activity, practicing competition sports, and age (more frequent in adolescents than children). Several recent papers have drawn attention to the role of the weight of the school backpack in children, particularly when its weight exceeds 20% of the child's body weight. Many children carry heavy backpacks which for some may weigh 30% to 40% of their body weight. Several groups have estimated that the maximum should be 10% of the body weight. It appears that time spent carrying the backpack as well as its weight is an important factor favoring back pain. Backpacks can injury the head or face, as well as the hands, the elbow, the wrist, the shoulder, the foot and the ankle. Back trauma is observed as the sixth most common injury. The 'weak point' is the shoulder and not the back. A poorly positioned backpack can modify posture and gait. Carrying the backpack with two shoulder straps affects posture and gait less than carrying it on one shoulder. The posture of the spine changes when the weight of the backpack increases. This is probably one of the reasons why many parents who consult believe that there is a relationship between the weight of the backpack and scoliosis or kyphosis, observed in many of their children. It is proven that adolescents who suffer from back pain will probably have chronic back pain as adults, but there is not evidence to our knowledge demonstrating a relationship between the development of spinal deviation and the weight of the backpack. Recent studies have been conducted to design backpacks allowing a better weight distribution and comfort. This type of backpack appears to have a limited benefit. Furthermore, the question of mode must not be ignored for children and adolescents. Backpacks with one sack in front and one in back certainly provide better weight distribution but are they acceptable for children and adolescents?     

Evaluating inflammatory joint disease: how and when can autoantibodies help?

The diagnosis of inflammatory joint disease rests on a constellation of symptoms, signs, laboratory test results and, occasionally, histological findings. Classification criteria have been developed by national learned societies, international panels of experts or, more rarely, an expert working alone. These criteria are intended to provide a common language for therapeutic trials and international publications. Yet, they are often inappropriately used as diagnostic tools for the individual patient. Identification of an early seroimmunologic marker with high sensitivity and specificity for classifying patients with recent-onset joint disease is a daunting challenge. Test performance characteristics such as sensitivity, specificity, positive and negative predictive values, and the positive or negative likelihood ratio help to assess the diagnostic usefulness of a laboratory test in a specific situation. The difference between the pretest and posttest likelihoods of obtaining a positive or negative result measures the usefulness, or performance, of a laboratory test in a specific situation according to the prevalence of the disease. A higher positive likelihood ratio indicates a more useful test. In a patient with inflammatory joint disease, the diagnosis can be sought by assaying a limited number of autoantibodies according to a decision tree. Thus, IgM rheumatoid factors (latex test or ELISA) and antibodies to filaggrin or other citrullinated proteins (antikeratin antibodies by indirect immunofluorescent assay or anticyclic citrullinated peptides by ELISA) identify more than 70% of cases of early rheumatoid arthritis with greater than 98% specificity. If these markers are negative, testing for antinuclear antibodies by indirect immunofluorescent assay on HEp-2 cells identifies 99% of cases of lupus and progressive systemic sclerosis. Confirmation of the diagnosis can be obtained by characterizing the autoantibodies: thus, presence of antidouble-stranded DNA (dsDNA, by the Farr radioimmunoassay, indirect immunofluorescent assay on Crithidia luciliae, or ELISA (IgG)) or of antinucleosome antibodies (ELISA) indicates lupus, whereas anticentromere, antitopoisomerase I (Scl 70), and antinucleolar antibodies point to progressive systemic sclerosis. A positive test for antibodies to soluble nuclear antigens of the U1 RNP type suggests mixed connective tissue disease or lupus but may indicate scleroderma. Anti-Sm antibodies are found in fewer than 10% of lupus patients but are highly specific. Anti-SSA (Ro) and anti-SSB (La) suggest lupus or primary Sj?gren's syndrome. When tests are negative for ANA, several antibodies to cytoplasmic organelles are valuable diagnostic tools, such as anti-J01 for polymyositis syndromes and antiribosome antibodies for lupus, although their sensitivity is modest (20-25%). Finally antineutrophil cytoplasmic antibodies (ANCAs) ensure the diagnosis of small-vessel vasculitides, which often involve the lungs and kidneys. Thus, in diffuse Wegener's granulomatosis, ANCAs exhibiting the classic cytoplasmic pattern and corresponding by ELISA to anti-PR3 are found. In microscopic polyangiitis the ANCAs are peripheral and correspond by ELISA to antimyeloperoxidase antibodies. Tests for other antibodies are less often needed to evaluate inflammatory joint disease.     

Noncemented tibial components: does a stem help?

A prospective, nonrandomized study was conducted in an attempt to determine if the addition of a stem to the tibial component in noncemented total knee replacement reduces the incidence of sinkage. A stemmed tibial component was used in 125 cases and an identical artificial knee without a stem was used in 307 cases. Follow-up was two to six years. Sinkage occurred in 0.8% of the cases with stemmed tibial components and in 3.5% of the nonstemmed tibial components, among which two (0.8%) required revision. The clinical results for both groups were similar. A small group of 34 patients who had a stemmed tibial component on one side and a nonstemmed component on the other also were examined. Fifty percent of these patients preferred the stemmed component knee. The results of these studies suggest that the addition of a stem to the tibial component in noncemented total knee replacement is of value in preventing tibial sinkage.     

Wilson disease and IgA nephropathy: accidental or related?

International Urology and Nephrology -     

Laparoscopic surgery for gastroesophageal reflux disease patients with impaired esophageal peristalsis: total or partial fundoplication?

BACKGROUND: It has been proposed that partial fundoplication is associated with less incidence of postoperative dysphagia and consequently is more suitable for patients with gastroesophageal reflux disease (GERD) and impaired esophageal body motility. The aim of this study was to assess whether outcomes of Toupet fundoplication (TF) are better than those of Nissen-Rossetti fundoplication (NF) in patients with GERD and low-amplitude esophageal peristalsis. STUDY DESIGN: Thirty-three consecutive patients with proved GERD and amplitude of peristalsis at 5 cm proximal to lower esophageal sphincter (LES) less than 30 mmHg were randomly allocated to undergo either TF (19 patients: 11 men, 8 women; mean age: 61.7 +/- 8.7 SD years) or NF (14 patients: 7 men, 7 women; mean age: 59.2 +/- 11.5 years), both by the laparoscopic approach. Pre- and postoperative assessment included clinical questionnaires, esophageal radiology, esophageal transit time study, endoscopy, stationary manometry, and 24-hour ambulatory esophageal pH testing. RESULTS: Duration of operation was significantly prolonged in the TF arm (TF: 90 +/- 12 minutes versus NF: 67 +/- 15 minutes; p < 0.001). At 3 months postoperatively, the incidences of dysphagia (grades I, II, III) and gas-bloat syndrome were higher after NF than after TF (NF: 57% versus TF: 16%; p < 0.01 and NF: 50% versus TF: 21%; p = 0.02, respectively), but decreased to the same level in both groups at the 1-year followup (NF: 14% versus TF: 16% and NF: 21% versus TF: 16%, respectively). At 3 months postoperatively, patients with NF presented with significantly increased LES pressure than those with TF (p = 0.02), although LES pressure significantly increased after surgery in both groups, as compared with preoperative values. Amplitude of esophageal peristalsis at 5 cm proximal to LES increased postoperatively to the same extent in both groups (TF, preoperatively: 21 +/- 6 mmHg versus postoperatively: 39 +/- 12 mmHg; p < 0.001, and NF, preoperatively: 20 +/- 8 mmHg versus postoperatively: 38 +/- 12 mmHg; p < 0.001). Reflux was abolished in all patients of both groups. CONCLUSIONS: Both TF and NF efficiently control reflux in patients with GERD and low amplitude of esophageal peristalsis. Early in the postoperative period, TF is associated with fewer functional symptoms, although at 1 year after surgery those symptoms are reported at similar frequencies after either procedure.     

Prostate cancer and coronary heart disease: correlation or coincidence?

A few past clinical and recent case-control studies of statin use, for example, in patients with and without prostate cancer have not demonstrated its potential for reducing or preventing the risk for this disease, and the potential for benefit may have been a confounding coincidence. Data from larger continuing and future studies will be needed to resolve this issue, but the recent data on cholesterol or dyslipidemia and risk increase or reduction with treatment are interesting, especially because of other potential improvements with therapy in nonprostate cancers. In addition, the finding that some available cancer treatments improve some parameters of the lipid profile is fascinating, and some cancer drugs are being used in a specific cardiovascular disease treatment setting to improve outcome. Even if CHD, dyslipidemia, and the treatment of these conditions has no role in preventing prostate cancer or its progression, what has been lost? CVD is still the leading cause of death of men, and a heart-healthy program for the patient concerned about prostate disease would reduce this primary cause of death. Patients would take a step forward in improving all-cause mortality. Recent data from surveys, however, continue to demonstrate that men have an inadequate understanding of cholesterol and heart disease. Crisis creates opportunity, and individuals working in urology have ample reasons not only to discuss the overall benefits of reducing lipid markers, but to improve cholesterol and CHD awareness as much as health professionals working in other fields of medicine. The marriage between general preventive medicine and urology seems to be inevitable, and in the authors' opinion, this merger will provide the foundation for novel research that could affect patients' lives dramatically.     

How can we best prevent or treat postoperative nausea and vomiting?

In pursuit of preventing or rapidly rescuing patients from postoperative nausea and vomiting, new clinical studies provide revised postoperative nausea and vomiting risk prediction tools, risk stratification formulae, comparative trials to identify the most appropriate cost-effective anti-emetics, and several trials recommending the addition of steroids in anti-emetic prophylactic multimodal approaches. Common variables that identify high-risk postoperative nausea and vomiting patients include female sex, a history of postoperative nausea and vomiting or motion sickness, young age, volatile anesthetic agents, nitrous oxide, and the administration of opioids. The most successful approach to the prevention of postoperative nausea and vomiting is multimodal, with combination anti-emetics, dexamethasone, aggressive hydration, the avoidance of opioids, and aggressive pain control.     

Discrepancies in office and ambulatory blood pressure in adolescents: help or hindrance?

The goal of this commentary is to review the most relevant topics concerning the clinical utility of ambulatory blood pressure (BP) monitoring, such as the state of the art “reference BP values”, the importance of the discrepant situations between office and ambulatory BP (white-coat and masked hypertension) and those of the recommended clinical indications to now. From a small number of studies, operational thresholds to define hypertension have been established. They are useful tools even though more studies are necessary to create strong reference values. Ambulatory BP measurement is increasingly recognized as being indispensable to the diagnosis and management of hypertension, and it has contributed significantly to our understanding of hypertension by revealing or “unmasking” BP phenomena that were not readily apparent using traditional techniques of measurement in clinical practice. Ambulatory BP monitoring should be performed in adolescents with either office mild essential hypertension before starting antihypertensive drug treatment or a strong family history of hypertension or an early cardiovascular event. Obese children with normal office BP values will also benefit from ambulatory BP monitoring. Other indications are the assessment of refractory hypertension or drug-induced hypotension. Finally, additional BP information in chronic renal failure, diabetes, and autonomic neuropathy can be obtained by using ambulatory BP monitoring None of the authors has a conflict of interest to declare. The corresponding author had final responsibility for the decision to submit for publication.     

Connecting bar for hip spica reinforcement: does it help?

The purpose of this prospective study was to determine if a connecting bar prevented mechanical failure of hip spicas. Eighty-two hip spicas were applied to 70 patients between April 2000 and June 2001 following open or closed reduction for developmental dysplasia of the hip. Bilateral hip surgery was undertaken in 12 patients. Thirty-six spicas were applied with a bar whilst 46 were without. The technique of application was similar in all patients. Overall nine (11%) hip spicas failed (mechanically) prematurely and had to be replaced in hospital under general anaesthesia. All nine were inpatients whose spica did not have a connecting bar (P < 0.005). The rate of spica revision increased with the age of the patient. All parents of failed spica cases (nine cases) preferred the new spica with a bar to the previous one without, because they agreed that the bar made the spica more secure. The bar did not hamper toileting or handling.