A 75-year-old woman with diabetes mellitus, hypertension, and hyperlipidemia came to the emergency department with generalized and upper-extremity weakness; she had experienced a fall 2 months earlier. On admission, her drug therapy included lovastatin 40 mg/day, controlled-release diltiazem 240 mg/day, and glimepiride 1 mg/day. Nineteen days earlier, sitagliptin 100 mg/day had been started; it was discontinued 2 weeks later, and glimepiride was begun. A cardiology consultation performed on the day of admission determined that a markedly elevated creatine kinase-myocardial band isoenzyme level and borderline-high troponin I level were diagnostic of rhabdomyolysis secondary to statin use. Because the patient had been taking lovastatin for the past 12 years, the possibility that the rhabdomyolysis may have been caused by a drug interaction between lovastatin and a concomitant drug was evaluated. As it had been 10 months since her last dosage adjustment of diltiazem, it was unlikely that the statin-induced rhabdomyolysis was precipitated by diltiazem. Use of the Drug Interaction Probability Scale to determine the strength of a lovastatin-sitagliptin interaction indicated a possible association (score of 4). Multiple drug interactions have been reported with lovastatin. To our knowledge, however, this is the first case report of a possible sitagliptin-lovastatin interaction that may have caused rhabdomyolysis. Studies must be performed to further evaluate the in vivo effect of sitagliptin on the cytochrome P450 3A4 enzyme system and to elucidate other mechanisms that may potentiate such a drug-drug interaction. In the meantime, however, clinicians should be aware of this possible drug interaction.

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.

Diarrhea is common in transplant recipients. While the majority of cases are mild and transient, some are severe and prolonged, which can threaten graft survival through dehydration. While it is known that some immunosuppressive agents can elicit diarrhea, there does not appear to be any consensus on the role that other nonimmunosuppressive causes can play in transplant patients. The aim of the present open, nonrandomized, multicenter study was to identify nonimmunosuppressive factors involved in severe diarrhea in renal transplant patients. Patients (n = 108) with severe diarrhea (>/=3 stools/day for >/=7 days) were enrolled from 16 Belgian transplant centers. Patients were diagnosed according to an agreed flowchart that consisted of identification of possible infections, followed by changes in empirical and immunosuppressive treatment. Approximately 50% of patients experienced resolution of severe diarrhea following treatment for infections, dietary problems or diarrhea-causing concomitant medications. In conclusion, a large proportion of the severe diarrhea observed in renal transplant recipients is not associated with immunosuppressive therapy and can be treated through anti-infectives, changes to concomitant medication and other empirical treatments. Correct diagnosis of the cause of severe diarrhea in such patients should help to protect graft survival in transplant recipients.

Inability to distinguish Crohn's colitis from ulcerative colitis leads to the diagnosis of indeterminate colitis. This greatly effects medical and surgical care of the patient because treatments for the two diseases vary. Approximately 30 percent of inflammatory bowel disease patients cannot be accurately diagnosed, increasing their risk of inappropriate treatment. We sought to determine whether transcriptomic patterns could be used to develop diagnostic biomarker(s) to delineate inflammatory bowel disease more accurately. Four patients groups were assessed via whole-transcriptome microarray, qPCR, Western blot, and immunohistochemistry for differential expression of Human α-Defensin-5. In addition, immunohistochemistry for Paneth cells and Lysozyme, a Paneth cell marker, was also performed. Aberrant expression of Human α-Defensin-5 levels using transcript, Western blot, and immunohistochemistry staining levels was significantly upregulated in Crohn's colitis, p< 0.0001. Among patients with indeterminate colitis, Human α-Defensin-5 is a reliable differentiator with a positive predictive value of 96 percent. We also observed abundant ectopic crypt Paneth cells in all colectomy tissue samples of Crohn's colitis patients. In a retrospective study, we show that Human α-Defensin-5 could be used in indeterminate colitis patients to determine if they have either ulcerative colitis (low levels of Human α-Defensin-5) or Crohn's colitis (high levels of Human α-Defensin-5). Twenty of 67 patients (30 percent) who underwent restorative proctocolectomy for definitive ulcerative colitis were clinically changed to de novo Crohn's disease. These patients were profiled by Human α-Defensin-5 immunohistochemistry. All patients tested strongly positive. In addition, we observed by both hematoxylin and eosin and Lysozyme staining, a large number of ectopic Paneth cells in the colonic crypt of Crohn's colitis patient samples. Our experiments are the first to show that Human α-Defensin-5 is a potential candidate biomarker to molecularly differentiate Crohn's colitis from ulcerative colitis, to our knowledge. These data give us both a potential diagnostic marker in Human α-Defensin-5 and insight to develop future mechanistic studies to better understand crypt biology in Crohn's colitis.

Several pathogenic processes have been implicated in the development of abdominal ascites. Portal hypertension, most usually in the context of liver cirrhosis, can explain about 75% of the cases, whereas infective, inflammatory and infiltrative aetiologies can account for the rest. In this article, we discuss the consensus best practice as published by three professional bodies for the management of ascites, spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). The aim of this study was to compare available clinical guidelines and identify areas of agreement and conflict. We carried out a review of the guidance documentation published by three expert bodies including the British Society of Gastroenterology, the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD), as well as a wider literature search for ascites, SBP and HRS. Abdominal ultrasonography, diagnostic paracentesis and ascitic fluid cultures are recommended by all three guidelines, especially when there is strong clinical suspicion for infection. EASL and AASLD advocate the use of ascitic amylase and mycobacterial cultures/PCR when there is strong suspicion for tuberculosis and pancreatitis, respectively. Ascitic cytology can be useful when cancer is suspected and has a good diagnostic yield if performed correctly. EASL supports the use of urinary electrolytes for all patients; however, the British Society of Gastroenterology and AASLD only recommend their use for therapy monitoring. All three societies recommend cefotaxime as the antibiotic of choice for SBP and large-volume paracentesis for the management of ascites greater than 5 l in volume. For HRS, cautious diuresis, volume expansion with albumin and the use of vasoactive drugs are recommended. There appears to be good concordance between recommendations by the European, American and British guidelines for the management of ascites and the possible complications arising from it.

Polyarteritis nodosa (PAN) is a rare systemic vasculitis affecting multiple organs. Current standard treatment includes the use of glucocorticoids and cyclophosphamide. Unfortunately, some patients do not respond to this treatment and other therapeutic options are needed. We present a case of a young male with refractory PAN and ongoing biopsy evidence of active vasculitis despite optimal standard therapies, who was successfully treated with interleukin-6 antagonist, tocilizumab. A 24-year-old male presented with severe immobilizing polyneuropathy and myalgias. Clinical features included fasciitis, tenosynovitis, early signs of polyneuropathy, and panniculitis, which were largely refractory to the standard therapies. The previous unsuccessful treatments included high-dose glucocorticoids, methotrexate, cyclophosphamide, rituximab, anakinra, and intravenous immunoglobulins. Magnetic resonance imaging showed signs of myositis, with muscle biopsy confirming the diagnosis of PAN. Rapid clinical improvement and sustained remission occurred after interleukin-6 inhibition with tocilizumab at increased dose of 800 mg every 4 weeks. The used search strategy identified 20 publications of which four articles were included for the further analysis. In total, we report the clinical outcome of five PAN cases from the literature and the present one. The present case and the systematic review of literature suggest that tocilizumab is a possible treatment option for, otherwise, refractory hepatitis B virus negative PAN. Randomized-controlled trials are required to evaluate the safety and efficacy of tocilizumab in PAN.