Search

For patients with rectal cancer, the standard approach of chemotherapy, radiation therapy, and surgery (trimodality therapy) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality of life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. Cochrane and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between January 1, 2012, and June 15, 2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). The search process yielded 197 articles that advised voting. Increasing data have shown that nonoperative management (NOM) and primary surgery result in QOL benefits noted over trimodality therapy without detriment to oncologic outcomes. For patients with rectal cancer for whom total mesorectal excision would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment approximately 8 to 12 weeks after completion of radiation therapy/chemoradiation therapy was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near-complete or complete response. In the setting of NOM, 54 to 56 Gy in 27 to 31 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for which low anterior resection and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. Recent data support NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multidisciplinary management, patients should be discussed in a multidisciplinary setting, and therapy should be tailored to individual patient goals/values., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In patients with symptomatic severe aortic stenosis (SAS), who are at high surgical risk and who require transcatheter aortic valve implantation (TAVI), anatomic factors can determine if patients are suitable for this technique. A very large aortic annulus is a technical challenge given the limited options of adequate valve sizes, and, in most of them, using them in this type of patient is an off-label indication. We present the case of a 59-year-old man with symptomatic ASOS with surgical risk secondary to chronic liver damage referred for TAVI with an aortic annulus greater than 900 mm2. A Myval #32 valve was implanted with overexpansion without complications and early discharge.

Tricuspid regurgitation (TR) is the most frequent valvular complication after heart transplantation with different clinical sequelae. In its most severe form, it can cause right heart failure with a poor long-term prognosis. Its management is complex, both medical, surgical, and percutaneous. The TricValve system, a bicaval system with two self-expanding valves (superior vena cava and inferior vena cava), dedicated to treating symptomatic IT refractory to medical therapy, is safe and effective in improving quality of life. We present the first heart transplant patient with severe symptomatic TR who underwent successful bicaval valve (TricValve) implantation.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively ( P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group ( P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

Background: Patients with atrial fibrillation (AF) undergoing transcatheter aortic valve implantation (TAVI) have been associated with worse short-term outcomes compared with patients in sinus rhythm but data on long-term outcomes are limited. The aim of our study was to evaluate the association between AF and short- and long-term outcomes in patients undergoing TAVI., Methods: We retrospectively evaluated patients undergoing TAVI between 2012 and 2022 in four tertiary centres. Two different analyses were conducted: (i) in-hospital and (ii) postdischarge analysis. First, we evaluated the association between preexisting AF and short-term outcomes according to VARC-3 criteria. Second, we analyzed the association between AF at discharge (defined as both preexisting and new-onset AF occurring after TAVI) and long-term outcomes at median follow-up of 3.2 years (i.e. all-cause death, hospitalization and major adverse cardiovascular events)., Results: A total of 759 patients were initially categorized according to the presence of preexisting AF (241 vs. 518 patients). The preexisting AF group had a higher occurrence of acute kidney injury [odds ratio (OR) 1.65; 95%confidence interval ( CI) 1.15-2.38] and major bleeding (OR 1.86, 95% CI 1.06-3.27). Subsequently, the population was categorized according to the presence of AF at discharge. At the adjusted Cox regression analysis, AF was independently associated with an increased risk of all-cause death and cardiovascular hospitalization [adjusted hazard ratio (aHR) 1.42, 95% CI 1.09-1.86], all-cause death and all-cause hospitalization (aHR 1.38, 95% CI 1.06-1.78) and all-cause hospitalization (aHR 1.59, 95% CI 1.14.2.22)., Conclusions: In a real-world cohort of patients undergoing TAVI, the presence of AF (preexisting and new-onset) was independently associated with both short- and long-term adverse outcomes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Italian Federation of Cardiology.)

Posterior cruciate ligament (PCL) injury is a rare ligamentous knee injury which most commonly occurs due to direct trauma; it represents only 0.65% of knee injuries. On the basis of magnetic resonance imaging (MRI), PCL injury is divided into surgical and non-surgical. In the last few years we have witnessed an increasing interest in regenerative medicine. The use of innovative techniques allow the reduction of rehabilitation times in sports injuries. Platelet-Rich-Plasma (PRP) is a plasma-derived which stimulate the tissue repair. The objective of our work is to compare the rehabilitation times in PCL non-operative injuries treated with standard conservative treatment and PCL injuries treated with autologous PRP followed by rehabilitation program. We divided patients into two different groups: Group A formed by patients who underwent a standard conservative rehabilitation program and Group B which included patients treated by ultrasound guided PRP injection and following physiotherapy program. Both groups of patients resumed sports activities; however the rehabilitation times for patients which had undergone treatment with autologous PRP injection were reduced compared to patients who underwent a standard conservative treatment.

Chest pain is one of the most frequent reasons for consultation in the emergency department. The most severe pathologies must be quickly ruled out within the diagnostic hypotheses: myocardial infarction (MI), aortic dissection, pulmonary thromboembolism, and pneumothorax. A frequent scenario is ST elevation MI due to a plaque accident. However, there are infrequent cases of aortic dissection associated with a deficit in coronary perfusion (malperfusion syndrome) that triggers a MI. The diagnosis of a double artery is difficult, with higher mortality and surgical complexity. We present the case of a 59-year-old man who presented chest pain and an electrocardiogram with inferior and anterior ST-segment elevation who was referred for primary angioplasty. The angiographic study confirmed the presence of a coronary ostium defect and suggested aortic dissection. Computed tomography angiography confirmed the diagnosis, showing the dissection of the ascending aorta with the compromise of both coronary ostia, which was subjected to surgical treatment.

Background: Strategies for blood conservation, coupled with a careful preoperative assessment, may be applied to Jehovah's Witnesses (JW) patients who are candidates for cardiac surgery interventions. There is a need to assess clinical outcomes and safety of bloodless surgery in JW patients undergoing cardiac surgery., Methods: We performed a systematic review and meta-analysis of studies comparing JW patients with controls undergoing cardiac surgery. The primary endpoint was short-term mortality (in-hospital or 30-day mortality). Peri-procedural myocardial infarction, re-exploration for bleeding, pre-and postoperative Hb levels and cardiopulmonary bypass (CPB) time were also analyzed., Results: A total of 10 studies including 2,302 patients were included. The pooled analysis showed no substantial differences in terms of short-term mortality among the two groups (OR 1.13, 95% CI 0.74-1.73, I 2 =0%). There were no differences in peri-operative outcomes among JW patients and controls (OR 0.97, 95% CI 0.39-2.41, I 2 =18% for myocardial infarction; OR 0.80, 95% CI 0.51-1.25, I 2 =0% for re-exploration for bleeding). JW patients had a higher level of preoperative Hb (Standardized Mean Difference [SMD] 0.32, 95% CI 0.06-0.57) and a trend toward a higher level of postoperative Hb (SMD 0.44, 95% CI -0.01-0.90). A slightly lower CPB time emerged in JWs compared with controls (SMD -0.11, 95% CI -0.30-0.07)., Conclusions: JW patients undergoing cardiac surgery, with avoidance of blood transfusions, did not have substantially different peri-operative outcomes compared with controls, with specific reference to mortality, myocardial infarction, and re-exploration for bleeding. Our results support the safety and feasibility of bloodless cardiac surgery, applying patient blood management strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endomyocardial biopsy (EMB) is an invasive procedure and a diagnostic tool used mainly on the follow-up of post-heart transplant rejection in the past years. Currently, it has an important role in the diagnosis of non-ischemic cardiomyopathies. EMB is frequently performed through a venous access to enter the right ventricle. Diagnostic performance has improved with advances in pathology analysis. Its complications risk, close to 1% in high-volume interventional centers, can be justified considering the potential benefit of an accurate diagnosis and prognosis.

Background: Transcatheter aortic valve implantation (TAVI) has developed as an alternative to surgery for symptomatic high-risk patients with aortic stenosis (AS). An important complication of TAVI is acute kidney injury. The purpose of the study was to investigate if the Mehran Score (MS) could be used to predict acute kidney injury (AKI) in TAVI patients., Methods: This is a multicenter, retrospective, observational study including 1180 patients with severe AS. The MS comprised eight clinical and procedural variables: hypotension, congestive heart failure class, glomerular filtration rate, diabetes, age >75 years, anemia, need for intra-aortic balloon pump, and contrast agent volume use. We assessed the sensitivity and specificity of the MS in predicting AKI following TAVI, as well as the predictive value of MS with each AKI-related characteristic., Results: Patients were categorized into four risk groups based on MS: low (≤5), moderate (6-10), high (11-15), and very high (≥16). Post-procedural AKI was observed in 139 patients (11.8%). MS classes had a higher risk of AKI in the multivariate analysis (HR 1.38, 95% CI, 1.43-1.63, p < 0.01). The best cutoff for MS to predict the onset of AKI was 13.0 (AUC, 0.62; 95% CI, 0.57-0.67), whereas the best cutoff for eGFR was 42.0 mL/min/1.73 m 2 (AUC, 0.61; 95% CI, 0.56-0.67)., Conclusions: MS was shown to be a predictor of AKI development in TAVI patients.

Purpose: Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited., Methods: In this prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival., Results: Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates., Conclusion: Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.

Acute Coronary Syndrome with ST segment elevation requires rapid reperfusion, which is why the timely identification of these conditions, based on the patient's symptoms and the correct interpretation of the EKG, is essential for therapeutic decisions. We report three patients with True Posterior Infarction and their difficult EKG diagnosis. The classic 12-lead EKG method is often not capable of supporting the diagnosis, so we recommend the use of posterior leads and mirror images observing inverted V1-V2-V3 leads on the classic EKG.

Background The coronavirus disease (COVID-19) pandemic affected the prompt diagnosis and treatment of Acute myocardial infarction (AMI)., Aim: To characterize the clinical profile of patients with AMI during the COVID-19 pandemic, comparing them with a historical cohort., Material and Methods: A case-control study of 96 patients with AMI transferred to a high-volume percutaneous coronary intervention (PCI) hospital between March and July 2020, and a historical cohort of 269 patients transferred during the same period in 2019., Results: When comparing patients transferred during the pandemic with those of the historical cohort, the former were younger (63 ± 12 vs 68 ± 12 years, p < 0.01), had a higher frequency of hypertension (66 vs 45%, p < 0.01) and of smoking (40% vs 25%, p < 0.01). Also, during COVID-19 outbreak a higher proportion of patients had ST-elevation AMI consulting > 12 hours from the onset of symptoms (44 vs 0%, p < 0.01), a higher median door-to-device time (4 vs 3 hours, p < 0.01), a higher use of primary percutaneous coronary intervention (97 vs 71%, p < 0.01), and higher frequencies of cardiogenic shock (20 vs 4%, p < 0.01) and mechanical complications (10% vs 2%, p < 0.01). Patients during COVID pandemic had a higher thirty-day overall (20 vs 1.4%, p < 0.01) and cardiovascular mortality (13 vs 1%, p < 0.01). During the outbreak, 40% of patients had positive COVID-19 status, which was a predictor for thirty-day overall mortality (Risk ratio 2.90; 95% confidence intervals 1.14-7.36)., Conclusions: During the pandemic patients with AMI exhibited delays in consultations and treatment, higher morbidity, and increased mortality. COVID-19 positivity was associated to worse thirty-day overall survival.

Background: Cardiogenic shock (CS) is uncommon in the cardiac catheterization laboratory (CCL) among patients undergoing coronary angiography. Periprocedural CS is more frequent in high-risk patients and in technically demanding procedures., Aim: To describe the clinical outcomes of patients who underwent peripheral venoarterial extracorporeal membrane oxygenation (pVA-ECMO) for CS associated with interventional cardiology procedures., Material and Methods: Review of clinical records of seven patients treated between January 2014 and October 2018., Results: pVA-ECMO was implanted within 6 hours of the interventional cardiology procedure. All patients had coronary artery disease and one of them also had symptomatic severe aortic stenosis. One patient entered the CCL in cardiac arrest. Percutaneous coronary intervention (PCI) was performed in all patients; four patients underwent an emergency procedure and five patients experienced PCI complications. One patient undergoing transcatheter aortic valve replacement suffered acute severe aortic regurgitation. An intra-aortic balloon pump was inserted at the CCL in five patients. Six patients experienced cardiac arrest. Mean SAVE score was -4.3 and baseline lactate 55 mg/dl. pVA-ECMO mean duration was 5 ± 4 days. Survival after both hospital discharge and 12 months of follow-up was 85.7% Regarding vascular access complications, we observed one access site hematoma and one episode of cannulation site bleeding requiring surgical repair., Conclusions: pVA-ECMO should be considered in patients with periprocedural CS as a bridge to recovery. Its use was associated with improved clinical outcomes in this series.

Proteolytic starter cultures with intrinsic immunomodulatory activities are desirably features for the development of functional foods, which would significantly reduce the cost of their production (one-strain starter) having an additional beneficial effect on the host. In this work, Lactobacillus delbrueckii strains were selected according to their ability to efficiently hydrolyse β-casein and to modulate the immune system. Among 36 strains evaluated, the highest proteolytic activities were found for L. delbrueckii subsp. lactis CRL581 and L. delbrueckii subsp. bulgaricus CRL656. The immunomodulatory effect of both strains and their β-casein hydrolysates (CRL581 and CRL656 hydrolysates, respectively) were studied in a murine model. Balb/c mice were fed lactobacilli or their hydrolysates for three days. One day after the last lactobacilli or hydrolysate treatments, mice were challenged with the Toll-like receptor 3 (TLR3) agonist poly(I:C) by intraperitoneal injection. Before and after poly(I:C) challenge the phagocytic and microbicidal activity of peritoneal macrophages, intestinal immunoglobulin A (IgA), cytokine profile, and histological analysis of the intestine were analysed. L. delbrueckii subsp. lactis CRL581 significantly increased the activation of peritoneal macrophages as well as the levels of intestinal IgA, interleukin (IL)-10 and interferon (IFN)-γ when compared to untreated controls. In addition, the CRL581 strain was able to significantly reduce the intestinal inflammatory damage triggered by TLR3 activation. L. delbrueckii CRL581 increased the levels of IL-10, IFN-γ and IFN-β, and reduced tumour necrosis factor alpha and IL-6 concentrations in the intestine of poly(I:C)-challenged mice. No immunomodulatory effects were observed for the CRL656 strain or for the CRL581 or CRL656 hydrolysates. The results of this work show that the technologically relevant and high proteolytic strain L. delbrueckii CRL581 is able to beneficially modulate the intestinal innate antiviral immune response. Although further studies with the CRL581 strain are required to corroborate and deepen its immunological effects, this bacterium is an interesting alternative for the development of new functional foods with antiviral capabilities.

The effects of adding bovine skin gelatin hydrolysate obtained with subtilisin, on water-holding capacity (WHC), in a thermally processed chicken meat model, were investigated. Hydrolysates with different degrees of hydrolysis (DH) (6.57%, 13.14%, and 26.28%) were prepared. The results showed that all the tested hydrolysates improved water retention in the meat matrix. The hydrolysate with 26.28% DH showed similar behavior throughout the full range of concentrations [0% to 5% w/w] compared to that of the positive control (sodium tripolyphosphate [STPP]). In addition, the other hydrolysates [6.57% DH and 13.14% DH at 3% and 2.5% w/w concentrations, respectively] showed behaviors that coincided with that of STPP at its maximum limit allowed. A correlation was observed between the WHC and the pH of the meat samples treated with each hydrolysate or STPP. In addition, it was found that the WHC of the hydrolysates was due to increases in pH and the specific effects of the hydrolysate beyond the typical effects of pH and ionic strength in meat systems. The solubility of all hydrolysates was high (>90%). In conclusion, bovine skin gelatin hydrolysates could serve as an alternative to polyphosphates to improve water retention and the functional properties of thermally processed meat products. PRACTICAL APPLICATION: This study investigated the effects of adding bovine skin gelatin hydrolysate obtained with subtilisin on water-holding capacity (WHC) in a thermally processed chicken meat model. It was found that the hydrolysis of bovine skin gelatin with subtilisin can replace chemical products harmful to health, such as STPP, in terms of water-holding capacity. Therefore, bovine skin gelatin hydrolysate can be used as an ingredient in the formulation of thermally processed meat products., (© 2020 Institute of Food Technologists®.)

Adenovirus (ADV) is a recognized cause of severe disease among immunocompromised patients. We report a previously healthy 39-year-old female, admitted with influenza pneumonia and evolving with lung hemorrhage and acute renal failure requiring mechanical ventilation and hemodialysis. She received high corticosteroid doses due to an initial suspicion of alveolar hemorrhage. Lymphopenia already present before steroid use (567/μL), was maintained during the whole hospital stay (mean 782/μL). From the second week of admission she presented a high-volume diarrhea (mean 2.5 L/day) associated to intermittent bloody stools. An ulcerative enterocolitis was confirmed by CT images and colonoscopy. ADV was detected in a colonic tissue sample by real time PCR but not by a commercial filmarray test. Cidofovir-probenecid and racecadotril therapy were indicated without changing the clinical course of diarrhea and the patient finally died.

Aims: Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt)., Methods and Results: Data of 67 Ile68Leu ATTRm patients from two Italian referral centres (Bologna and Florence) were retrospectively analysed and compared to those of 82 ATTRwt patients. Fifty-five unaffected mutation carriers were also analysed. Cumulative disease onset was 50% at age 71. A total of 56/67 (84%) patients had a predominantly cardiac phenotype at presentation with concentric increase in left ventricular wall thickness [median 17 mm], and normal or near normal left ventricular ejection fraction (79% of patients). Low QRS voltages were present only in 29% of patients but voltage/mass ratio was low (0.5). Carpal tunnel syndrome was noted in 43%. The overall phenotypic profile was similar to ATTRwt but Ile68Leu ATTRm patients typically presented younger (median 71 vs. 78 years) and were more likely to have (mild) symptomatic neurological involvement (19% vs. 2%). Male prevalence was 44% in unaffected mutation carriers and 78% in affected patients. Age-adjusted survival was comparable between groups., Conclusions: Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Dentistry constitutes the basic nucleus of professionals of higher level of health in Brazil with one of the largest concentrations of dentists per capita in the world. However, the genetic in dentistry in Brazil is explored, basically, in research field. Future actions need to be performed in order to deep the whole knowledge about diagnosis and treatment of diseases with genetic basis in dentistry, in Brazil., (© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Background and Objective: Since oxidative stress plays a pathogenetic role in chronic neck pain (CNP), we investigated whether a combination of α-lipoic acid (ALA) and superoxide dismutase (SOD) might improve pain control and the efficacy of physiotherapy ("multimodal therapy") in patients with CNP., Setting: This study was conducted in the Rehabilitation Unit of the Department of Surgical and Oncological Sciences at the University Policlinic in Palermo, Italy., Design and Patients: This was a prospective, randomized, open study in outpatients., Intervention: Patients randomly received either physiotherapy alone (group 2; n = 45) or a combination of ALA 600 mg and SOD 140 IU daily in addition to physiotherapy (group 1; n = 51), for 60 days. Pain was assessed by a visual analogue scale (VAS) and a modified Neck Pain Questionnaire (mNPQ). Treatment compliance and safety were also evaluated., Results: Both groups experienced a significant reduction in the VAS and mNPQ scores after 1 month; however, while no further improvement was observed in group 2 at 60 days, group 1 showed a further VAS reduction (p < 0.001). In addition, in the mNPQ at 60 days, more patients in group 1 than in group 2 reported that their neck pain was improved (p < 0.01), and they showed greater compliance with prescribed physiotherapy (p = 0.048). No drug reaction was observed., Conclusion: Use of ALA/SOD in combination with physiotherapy may be a useful approach to CNP, being antioxidants that act on nerve inflammation and disease progression., Clinical Rehabilitation Impact: These preliminary observations suggest that some interesting goals (better pain control and physical wellbeing) can be achieved by multimodal therapy in CNP patients.

Purpose: We designed American College of Surgeons Oncology Group (ACOSOG) Z6041, a prospective, multicenter, single-arm, phase II trial to assess the efficacy and safety of neoadjuvant chemoradiation (CRT) and local excision (LE) for T2N0 rectal cancer. Here, we report tumor response, CRT-related toxicity, and perioperative complications (PCs)., Methods: Clinically staged T2N0 rectal cancer patients were treated with capecitabine and oxaliplatin during radiation followed by LE. Because of toxicity, capecitabine and radiation doses were reduced. LE was performed 6 weeks after CRT. Patients were evaluated for clinical and pathologic response. CRT-related complications and PCs were recorded., Results: Ninety patients were accrued; 6 received nonprotocol treatment. The remaining 84 were 65% male; median age 63 years; 83% Eastern Cooperative Oncology Group performance score 0; 92% white; mean tumor size 2.9 cm; and average distance from anal verge 5.1 cm. Five patients were considered ineligible. Therapy was completed per protocol in 79 patients, but two patients did not undergo LE. Among 77 eligible patients who underwent LE, 34 patients achieved a pathologic complete response (44%) and 49 (64%) tumors were downstaged (ypT0-1), but 4 patients (5%) had ypT3 tumors. Five LE specimens contained lymph nodes; one T3 tumor had a positive node. All but one patient had negative margins. Thirty-three (39%) of 84 patients developed CRT-related grade ≥3 complications. Rectal pain was the most common PC., Conclusions: CRT before LE for T2N0 tumors results in a high pathologic complete response rate and negative resection margins. However, complications during CRT and after LE are high. The true efficacy of this approach will ultimately be assessed by the long-term oncologic outcomes.

Objective: To identify a biomarker profile associated with tumor response to chemoradiation (CRT) in locally advanced rectal cancer., Background: Rectal cancer response to neoadjuvant CRT is variable. Whereas some patients have a minimal response, others achieve a pathologic complete response (pCR) and have no viable cancer cells in their surgical specimens. Identifying biomarkers of response will help select patients more likely to benefit from CRT., Methods: This study includes 132 patients with locally advanced rectal cancer treated with neoadjuvant CRT followed by surgery. Tumor DNA from pretreatment tumor biopsies and control DNA from paired normal surgical specimens was screened for mutations and polymorphisms in 23 genes. Genetic biomarkers were correlated with tumor response to CRT (pCR vs non-pCR), and the association of single or combined biomarkers with tumor response was determined., Results: Thirty-three of 132 (25%) patients achieved a pCR and 99 (75%) patients had non-pCR. Three individual markers were associated with non-pCR; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutation (P = 0.0145), cyclin D1 G870A (AA) polymorphism (P = 0.0138), and methylenetetrahydrofolate reductase (NAD(P)H) C677T (TT) polymorphism (P = 0.0120). Analysis of biomarker combinations revealed that none of the 27 patients with both tumor protein p53 (p53) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations had a pCR. Further, in patients with both p53 and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations or the cyclin D1 G870A (AA) polymorphism or the methylenetetrahydrofolate reductase (NAD(P)H) C677T (TT) polymorphism (n = 52) the association with non-pCR was further strengthened; 51 of 52 (98%) of patients were non-pCR. These biomarker combinations had a validity of more than 70% and a positive predictive value of 97% to 100%, predicting that patients harboring these mutation/polymorphism profiles will not achieve a pCR., Conclusions: A specific biomarker profile is strongly associated with non-pCR to CRT and could be used to select optimal oncologic therapy in rectal cancer patients. ClinicalTrials.org Identifier: NCT00335816.

Background: This study aimed to determine the diagnostic yield of colonoscopy 1 year after colorectal cancer (CRC) resection based on whether the index colonoscopy was performed by the operating surgeon., Methods: All patients undergoing surgery for colorectal cancer by two colon and rectal surgeons at a university hospital from 1991 to 2005 were identified from the tumor registry. Those patients with a complete preoperative colonoscopy by any physician and a 1-year follow-up examination by the operating surgeon were selected for the study population. Family history of colorectal cancer, tumor location, endoscopist, presence of synchronous neoplasms, and findings of 1-year colonoscopy were recorded. Fisher's exact test was used to compare the probability of finding any adenoma, advanced adenoma, or invasive cancer based on the index endoscopist., Results: Of the 719 patients who underwent resection during the study period, 432 met the inclusion criteria. The index colonoscopy for 117 of these patients (27.1%) was performed by one of the two surgeons. Overall, 10 patients (2.3%) had a "new" cancer diagnosed at 1 year, and 1 patient (0.2%) had a local recurrence. Patients whose index colonoscopy was performed by their operating surgeon appeared less likely to have an advanced lesion found at 1 year (5.1% vs 11.4%; p = 0.06). The index colonoscopy for 9 of the 10 of cancers found at 1 year was not performed by the operating surgeon., Conclusions: Colonoscopy 1 year after CRC resection is clearly justified. An index colonoscopy by the operating surgeon eliminates a "handoff" and may diminish the incidence of high-risk lesions at 1 year.

Background: Anastomotic leak is a dreaded complication of intestinal surgery and has been associated with a high mortality rate. But it is uncertain exactly which patient populations are at risk of death from the leak. We sought to assess the impact of surgeon volume on leak rate and to better understand the relationship of a leak to postoperative mortality., Study Design: All adult patients having a small or large bowel resection with anastomosis at a university hospital from July 2003 to June 2006 were entered into a prospectively maintained quality database; data were entered by a specially trained nurse practitioner who rounded daily with housestaff. Patients with a postoperative leak based on standardized criteria were identified. Patient characteristics, surgical procedure, and operating surgeon were noted. Overall complication and leak rates by surgeon were compared using Fisher's exact test. Individual case review by a group of peers was performed for all patients with a leak who died, to determine the relationship to mortality., Results: Five hundred fifty-six patients underwent resection with anastomosis during the study period. There were 27 patients with leaks (4.9%), 6 of whom died. Leak rate for the highest-volume surgeons ranged from 1.6% to 9.9% (p <0.01), and overall complication rate varied from 30.5% to 44% (p=0.04). In four of six deaths, leaks occurred in very ill patients undergoing emergency procedures and appeared to be premorbid events. In only one patient did the leak appear to be the primary cause of death., Conclusions: The variability in leak rate by surgeons doing similar operations suggests that many leaks may be preventable. But death after a leak is most often a surrogate for a critically ill patient and was infrequently the actual cause of death.

Background: Administrative databases oversimplify the relationship of factors such as volume or training on surgical outcomes., Methods: A prospective statewide surgeon-initiated database was queried to obtain incident cases of rectal cancer in Vermont from April 1999 to June 2001. Demographics, procedure performed, method of detection, American Society of Anesthesiologists classification, blood transfusions, length of stay, complications, stage, and use of adjuvant therapy were recorded by the operating surgeon. A post hoc analysis was performed on patients operated on for rectal cancer to define the specific impact of specialty training on care patterns., Results: There was a marked difference in the distribution of surgical procedures, with colorectal surgeons using local excision and coloanal anastomosis in addition to anterior and abdominoperineal resection. Although the overall use of adjuvant therapy was similar, patients in the colorectal group were more likely to receive preoperative then postoperative radiation therapy (91% vs 17%, P <.0001) and more likely to receive radiation therapy when stage appropriate (98% vs 67%, P <.001)., Conclusions: Colorectal specialty training in this population was a surrogate for a wider array of surgical options and preoperative radiation. Failure to use radiation when stage-appropriate was related to patient comorbidities and/or refusal and not related to failure of the surgeon to offer adjuvant therapy. Prospective, surgeon-initiated databases provide an excellent opportunity to identify and understand practice variability.

The Salmon Rickettsia syndrome (SRS) remains a major infectious disease in the Chilean aquaculture. A limited number of Piscirickettsia salmonis proteins have been characterized so far for their use as potential candidates for vaccines studies. In this study, we identified and expressed a highly immunogenic protein of P. salmonis extracted by selective hydrophobicity from crude-cell macerates of naturally infected salmonid fish. One and two-D PAGE gels followed by Western blot analysis with a battery of polyclonal anti-P. salmonis antibodies have allowed the isolation of the target protein. Basic local alignment search (BLAST) done after partial sequencing of the pure protein identified it as a member of the heat-shock protein (HSP) family of prokaryotes. The protein, named ChaPs, was cloned as a single open reading frame encoding 545 amino acid residues with a predicted molecular mass of 57.3 kDa. The amplicon representing the entire novel gene was expressed in vitro in different heterologous systems: the PurePro Caulobacter crescentus expression system from where most of the characterization was attained, and also in the Escherichia coli BL-21 CodonPlus model for commercially potential purposes. The immunologic potential of ChaPs was determined with serum from naturally infected fish.

Purpose: The purpose of this study was to assess the safety of subtotal colectomy and outcomes after this procedure in the modern era of immunosuppressive agents and primary pelvic pouch surgery., Methods: All patients undergoing subtotal colectomy with ileostomy for ulcerative colitis or Crohn's colitis from July 1, 1990 to June 30, 2003 were identified from a prospective database. Only patients who were operated on while hospitalized for disease exacerbation were included in the analysis. Age at colectomy, preoperative days in the hospital, postoperative length of stay, and complications were recorded. The medical records were then reviewed for duration of disease, preoperative diagnosis, use of steroids and immunomodulators, parenteral nutrition, endoscopy findings, albumin level, postoperative diagnosis, and ultimate disposition., Results: One hundred one patients underwent subtotal colectomy for inflammatory bowel disease during the study period. Seventy-four patients met all the inclusion criteria. The mean age was 35.9 (range, 18-86) years. Median duration of disease was 36 (0-240) months, but 28 patients had colitis for less than 1 year, whereas 10 patients had disease of greater than 10 years duration at the time of colectomy. Median preoperative hospital stay was 7 (range, 0-43) days and median postoperative length of stay was 6.5 (range, 4-37) days. Sixty-six patients underwent surgery for refractory exacerbation, 5 for free perforation, 2 for abscess, and 1 patient for hemorrhage. Twenty-seven patients (36.5 percent) had a change in diagnosis after surgery. Complications occurred in 17 patients (23 percent), including 8 cases of central venous catheter-associated thrombosis; 7 of these occurred in patients who had been hospitalized for more than a week before surgery. In the ulcerative colitis patients, 31 of 52 ultimately underwent ileal pouch-anal anastomosis, but 20 (39 percent) chose either completion proctectomy or no further surgery., Conclusions: Subtotal colectomy with ileostomy remains a safe and effective treatment for patients requiring urgent surgery for severe inflammatory bowel disease. Because of the substantial incidence of change in diagnosis and satisfaction in many patients with an ileostomy, subtotal colectomy with ileostomy may be preferable to primary ileal pouch-anal anastomosis, even when a pouch is considered safe.

Colonic adenocarcinoma has been frequently reported after ureterosigmoidostomy based on carcinogenic substances created when feces and urine are mixed. However, colonic adenocarcinoma has never been reported arising in an Indiana pouch after cystectomy. We report a case of adenocarcinoma arising in a urinary pouch after cystectomy for transitional cell cancer. We believe this to be caused by hereditary nonpolyposis colon cancer (an autosomal dominant syndrome that puts individuals at risk for genitourinary, colonic, and several other cancers) rather than carcinogenic effects of urine on colonic mucosa. When planning urinary reconstruction after cystectomy for malignancy, it is important to consider the possibility that an individual may suffer from hereditary nonpolyposis colon cancer before selecting the colon as a urinary reservoir.

Objectives: The objective of this double-blind randomised, placebo-controlled study was to examine the efficacy and safety intramuscular vitamin B12 (Tricortin 1000) in the treatment of low back pain in patients with mechanical or irritative lumbago., Methods: 60 patients aged between 18 and 65 years with lumbago or sciatic neuritis of mechanical origin without need for surgical procedures were enrolled. Patients had to present with a proven medical history for back pain (lasting from 6 months to 5 years) and a pain intensity [as evaluated with a Visual Analogic Scale (VAS)] equal or greater than 60 mm. Efficacy primary end-point was evaluated by means of a visual analogic scale (VAS) and a Disability Questionnaire (DQ). Consumption of paracetamol during the study period was the secondary efficacy end-point., Results: Both treatment groups experienced a sharp decrease in pain and disability. However, comparison between groups at the end of the treatment period showed a statistically significant difference in favour of the active treatment both for VAS and DQ (p < 0.0001 and p < 0.0002, respectively). Consumption of paracetamol proved significantly higher in the placebo group than in the active treatment (p < 0.0001)., Conclusions: The efficacy and safety of parenteral Vitamin B12 in alleviating low back pain and related disability and in decreasing the consumption of paracetamol was confirmed in patients with no signs of nutritional deficiency.

A case report of an elderly male with multiple medical problems and hemorrhagic, ischemic proctitis is presented. The proctitis was refractory to all other medical options but responded to topical instillation of 4 percent formalin.

Purpose: This study was conducted to report a rare case of anorectal pathology., Methods: We report a case of perianal lymphoma in a nonimmunocompromised, heterosexual patient and review the literature., Results: A 67-year-old white male was found to have an ulcerated posterior anal mass. Biopsy revealed large cell lymphoma, B cell type, immunoblastic. There was no disseminated disease. The patient denied any homosexual activity and was HIV negative. There was complete resolution with chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone), and he remained disease free for six years., Conclusions: Rare anorectal pathology may mimic common conditions. Biopsies should be taken to rule out malignancy.

Purpose: Topical nitrates have been shown to cause nitric oxide-mediated relaxation of the internal anal sphincter. Previous reports have suggested initial efficacy in the treatment of anal fissures. The aim of this study was to assess the longer-term usefulness of this treatment., Methods: Thirty-three patients with an anal fissure were treated with topical 0.3% nitroglycerin ointment, applied to the anoderm three times per day and after bowel movements. Patients were followed up by office visits and telephone calls until symptoms were completely resolved or treatment was noted to be ineffective or intolerable., Results: Thirty-three patients were treated, 16 with acute fissures, and 17 with chronic fissures. Nitroglycerin was effective in 9 of 16 acute fissures (56%), and 7 of 17 chronic fissures (41%). Even when effective, 75% of patients reported an adverse reaction., Conclusions: Topical nitroglycerin was only effective in approximately one-half of patients with an anal fissure. There was a very high incidence of adverse reactions. In our experience nitroglycerin more often causes a headache than treats the symptoms of anal fissure.

Purpose: We report a single case of proctalgia fugax that responded to 0.3 percent nitroglycerin ointment., Methods: Case report., Results: A single case of proctalgia fugax responded to topical application of 0.3 percent nitro glycerin ointment with no significant side effects., Conclusions: Nitroglycerin ointment is a newly described treatment for several painful anal conditions. We describe a single case of levator spasm or proctalgia fugax responding to topical application of nitroglycerin. This is only a single case report, and conclusive evidence awaits completion of a controlled clinical trial.

Objectives: To quantify the HIV-1 load (measured as copies of viral RNA/ml using competitive reverse transcription-polymerase chain reaction) in blood, semen and saliva and to look for relationships between the viral burden, the clinical and immunological status and antiretroviral therapy., Methods: Peripheral blood, semen and whole saliva samples were collected from 26 anti-HIV-1-seropositive patients selected for a cross-sectional study. Nine of the 26 patients provided samples of the three biological fluids for a longitudinal study., Results: HIV-1 RNA was detected in 26 out of 26 samples of plasma, in 25 out of 26 samples of semen and in 24 out of 25 samples of saliva. The median number of HIV-1 copies in plasma was 14 817/ml (range: 167-254 880), in semen was 515/ml (range: 0-196 050) and in saliva was 162/ml (range: 0-72 080). The viral load in semen and in saliva was significantly lower than in plasma (P < 0.0001). The HIV-1 RNA levels in plasma and in saliva were correlated (P < 0.05), but levels in semen were not correlated with either plasma or saliva levels. The HIV-1 copy number in plasma was significantly higher in symptomatic patients than in asymptomatic subjects (P < 0.05). Plasma and saliva HIV-1 RNA levels were higher in subjects with a CD4+ cell count < 200 x 10(6)/l than in subjects with a CD4+ cell count > 200 x 10(6)/l (P < 0.05). The HIV-1 RNA load in either plasma, semen or saliva is not related to antiretroviral therapy., Conclusions: The absence of a correlation between plasma and semen loads suggests that semen and blood are distinct viral compartments. Viral load in semen is not related to the clinical stage of HIV infection or to the CD4+ lymphocyte count. Consequently, HIV-1-infected subjects are potentially infectious at all stages of immuno-deficiency and adequate precautions must always be taken to prevent the sexual transmission of HIV.

A prospective study was conducted with 161 human immunodeficiency virus (HIV)-positive patients to investigate the prognostic role of 10 serum-modified nucleosides with regard to some of the most widely used parameters of AIDS progression. Serum concentrations of pseudouridine (> 3.77 nmol/mL) predicted progression to AIDS in CDC stage A2 HIV-infected patients much better than did other widely used parameters (hazard ratio, 2.7; 95% confidence interval, 1.29-6.35; P = .01; median permanence time in stage A2, 17 vs. 30.5 months; P = .03). Serum concentrations of 1-ribosylpyridin-4-one-3-carboxamide (PCNR) and beta 2-microglobulin and the CD4:CD8 cell ratio, in decreasing order and used in combination, differentiated the overall survival time probability of AIDS patients; PCNR was the best and a new independent predictor (overall survival time, > 31 months, no positive parameters; 19.3 months, one positive parameter; and 5.5 months, two positive parameters.

Purpose and Methods: Two hundred fifty-eight consecutive nonsedated colonoscopies were prospectively evaluated over an 18-month period. The cecum was intubated in 250 cases (97 percent). Polypectomies or biopsies were performed in 77 cases (31 percent). Indications for colonoscopy included history of polyps (32 percent), hematochezia (28 percent), family history of colon cancer (16 percent), prior history of colon cancer (9 percent), change in bowel habits (12 percent), abnormal flexible sigmoidoscopy (6 percent), and inflammatory bowel disease (3 percent)., Results: Sedation was withheld for the following reasons: patient preference (57 percent), medical problems (2 percent), prior resection (16 percent), surgeon preference (6.5 percent), lack of intravenous access (3 percent), and age (1 percent). Three patients (1.5 percent) required sedation to complete the procedure. Procedure-related pain was based on a scale from zero to three. One hundred thirty-nine patients (61 percent) rated their pain as either zero (no pain) or one (mild pain), and 217 patients (8 percent) indicated that they would prefer their next colonoscopy to be performed without sedation. One hundred twelve patients had previously undergone sedated colonoscopy. Ninety-two (92 percent) preferred nonsedated to sedated procedures. Average procedure time was 13.7 (range, 0.5 to 85) minutes., Conclusions: Several series have studied nonsedated endoscopic upper and lower gastrointestinal evaluations. None, however, have evaluated patient comfort and satisfaction. In our prospective series of 258 consecutive nonsedated colonoscopies, we found the procedure to be safe, effective, and well accepted.

Background: Endocavitary radiation therapy is an alternative to surgical therapy for some early rectal carcinomas. Careful patient selection is necessary to ensure good results. The purpose of this study was to examine the authors' experience with endocavitary radiation at their institution from 1984 to 1991 to determine which factors were associated with treatment failure to provide for better future patient selection., Methods: Thirty-two patients with carcinoma of the rectum, not apparently involving the muscle wall, underwent 75-120 Gy of endocavitary radiation as potentially curative therapy. Treatment was given as a series of 2-4 doses of 30 Gy at three weekly intervals. Twenty-two patients had polypoid tumors, 5 sessile, and 5 ulcerated., Results: After a mean follow-up of 43 months (range, 6-103 months), 4 of 5 patients (80%) with ulcerated tumors developed local recurrences, compared with only 4 of 27 (15%) with sessile or polypoid lesions. Not only was the incidence of local recurrence greater for patients with ulcerated tumors (P = 0.009), but the time to recurrence was shorter also (P = 0.0001). Tumor size, anterior or posterior location, and dose of radiation received did not affect the rate of recurrence., Conclusions: These results indicate that superficial polypoid and sessile rectal tumors can be managed successfully with endocavitary radiation. Ulcerating tumors are likely to recur locally within a short time and therefore should be considered for surgical treatment initially.

We report the case of a young man, with a previous history of parenteral drug abuse, who developed a Weber's syndrome. Brain computed tomographic scan and nuclear magnetic resonance imaging showed a single ring enhancing lesion in the right mesencephalic site. After the demonstration of seropositivity for human immunodeficiency vims, a presumptive diagnosis of cerebral toxoplasmosis in an AIDS patient was made and a specific treatment was started. A partial neuroradiological and clinical improvement were obtained. Opportunistic cerebral lesions, as first manifestation of AIDS, should be always considered in subjects at risk for AIDS who present a brainstem syndrome., (1995 Lippincott Williams & Wilkins.)