Metformin-associated lactic acidosis and temporary ileostomy: a case report

Lactic acidosis is a well-known complication of the anti-hyperglycemic biguanide agent metformin, especially in peculiar but not rare clinical conditions. Attempts to reduce the incidence of this adverse reaction have been enforced by national agencies over the years. The Italian Medicines Agency recently released a safety recommendation on prescribing the drug and with regard to the existence of several conditions that contraindicate drug continuation, such as dehydration, infection, hypotension, surgery or hyperosmolar contrast agent infusion, but the recommendation does not mention the increased risk related to stoma. The present case report is, to our knowledge, the first in the literature of metformin-associated lactic acidosis in a patient with a recently created ileostomy and low anterior resection for rectal cancer. CASE PRESENTATION: A 70-year-old Caucasian man who had undergone low anterior resection with total mesorectal excision and temporary loop ileostomy creation at our institution returned to our department 30 days later because of nausea, vomiting, diffuse abdominal pain and anuria of about 24 hours' duration. During his physical examination, the patient appeared dehydrated and had tachypnea and a reduced level of consciousness. His laboratory tests showed that he had acute kidney injury and severe lactic acidosis. CONCLUSION: An ileostomy puts patients at high risk for output losses that can lead to dehydration and electrolyte abnormalities. The assessment of the losses through the stoma, especially the ileostomy, should be added to the recommendations issued by pharmacovigilance societies. The present clinical case illustrates the need for clinicians on surgical wards to carefully evaluate patients before resuming metformin therapy and to provide appropriate information at discharge to patients with type 2 diabetes mellitus who have undergone ileostomy. Furthermore, this case report highlights the increasing need for more training of general physicians regarding both surgical and internal medicine problems that may arise in the post-operative course after major surgery in patients with co-morbidities

Urinary 1H-NMR Metabolic Signature in Subjects Undergoing Colonoscopy for Colon Cancer Diagnosis

Metabolomics represents a promising non-invasive approach that can be applied to identify biochemical changes in colorectal cancer patients (CRC) and is potentially useful for diagnosis and follow-up. Despite the literature regarding metabolomics CRC-specific profiles, discrimination between metabolic changes specifically related to CRC and intra-individual variability is still a problem to be solved. This was a preliminary case-control study, in which 1H-NMR spectroscopy combined with multivariate statistical analysis was used to profile urine metabolites in subjects undergoing colonoscopy for colon cancer diagnosis. To reduce intra-individual variability, metabolic profiles were evaluated in participants’ urine samples, collected just before the colonoscopy and after a short-term dietary regimen required for the endoscopy procedure. Data obtained highlighted different urinary metabolic profiles between CRC and unaffected subjects (C). The metabolites altered in the CRC urine (acetoacetate, creatine, creatinine, histamine, phenylacetylglycine, and tryptophan) significantly correlated with colon cancer and discriminated with accuracy CRC patients from C patients (receiver operator characteristic (ROC) curve with an area under the curve (AUC) of 0.875; 95% CI: 0.667–1). These results confirm that urinary metabolomic analysis can be a valid tool to improve CRC diagnosis, prognosis, and response to therapy, representing a noninvasive approach that could precede more invasive tests

Colorectal cancer early detection in stool samples tracing CPG islands methylation alterations affecting gene expression

Colorectal cancer (CRC) is a major cause of cancer mortality. Early diagnosis is relevant for its prevention and treatment. Since DNA methylation alterations are early events in tumourigenesis and can be detected in cell-free DNA, they represent promising biomarkers for early CRC diagnosis through non-invasive methods. In our previous work, we identified 74 early altered CpG islands (CGIs) associated with genes involved in cell cross-talking and cell signalling pathways. The aim of this work was to test whether methylation-based biomarkers could be detected in non-invasive matrices. Our results confirmed methylation alterations of GRIA4 and VIPR2 in CRC tissues, using MethyLight, as well as in stool samples, using a much more sensitive technique as droplet digital PCR. Furthermore, we analysed expression levels of selected genes whose promoter CGIs were hypermethylated in CRC, detecting downregulation at mRNA and protein levels in CRC tissue for GRIA4, VIPR2, SPOCK1 and SLC6A3. Most of these genes were already lowly expressed in colon normal tissues supporting the idea that cancer DNA methylation targets genes already barely expressed in the matched normal tissues. Our study suggests GRIA4 and VIPR2 as biomarkers for early CRC diagnosis using stool samples and confirms downregulation of genes hypermethylated in CRC

Is the inversion in the trend of the lethality of the covid-19 in the two hemispheres due to the difference in seasons and weather?

The climate has an influence on the COVID-19 virus lethality. The aim of this study is to verify if the summer weather coincided with the decrease of the Case Fatality Ratio (CFR) in Europe and if, on the contrary, an inverse trend was observed in Australia and New Zealand. To verify our hypothesis, we considered the largest European countries (Germany, UK, France, Italy, and Spain), plus Belgium and the Netherlands. Furthermore, we compared these countries with Australia and New Zealand. For each country considered, we have calculated the CFR from the beginning of the pandemic to May 6th and from May 6th to September 21st (late summer in Europe, late winter in the southern hemisphere). The CFRs were calculated from the John Hopkins University database. According to the results, in all European countries, a progressive decrease in CFR is observed. A diametrically opposite result is found in Australia where, on the contrary, the CFR is much higher at the end of September (at the end of winter) than on May 6th (mid-autumn), and the risk of dying if we count the infection is higher in September. In New Zealand, there are no statistically significant differences between the two surveys. The present study was based on public access macro data

Clustered protocadherins methylation alterations in cancer

Background: Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: \u3b1-, \u3b2- and \u3b3-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation. Results: In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become hypomethylated in this type of cancer. On the other hand, in tissues where PCDHs are lowly expressed, these CpG islands are targeted by DNA methylation. In fact, PCDH-associated CpG islands resulted hypermethylated in gastrointestinal tumours. Conclusions: Our study highlighted a strong alteration of the clustered PCDHs methylation pattern in the analysed solid cancers and suggested these methylation aberrations in the CpG islands associated with PCDH genes as powerful diagnostic biomarkers

Day and night surgery: is there any influence in the patient postoperative period of urgent colorectal intervention?

Background Medical activity performed outside regular work hours may increase risk for patients and professionals. There is few data with respect to urgent colorectal surgery. The aim of this work was to evaluate the impact of daytime versus nighttime surgery on postoperative period of patients with acute colorectal disease. Methods A retrospective study was conducted in a sample of patients with acute colorectal disease who underwent urgent surgery at the General Surgery Unit of Braga Hospital, between January 2005 and March 2013. Patients were stratified by operative time of day into a daytime group (surgery between 8:00 and 20:59) and the nighttime group (21:00–7:59) and compared for clinical and surgical parameters. A questionnaire was distributed to surgeons, covering aspects related to the practice of urgent colorectal surgery and fatigue. Results A total of 330 patients were included, with 214 (64.8 %) in the daytime group and 116 (35.2 %) in the nighttime group. Colorectal cancer was the most frequent pathology. Waiting time (p?<?0.001) and total length of hospital stay (p?=?0.008) were significantly longer in the daytime group. There were no significant differences with respect to early or late complications. However, 100 % of surgeons reported that they are less proficient during nighttime. Conclusions Among patients with acute colorectal disease subjected to urgent surgery, there was no significant association between nighttime surgery and the presence of postoperative medical and surgical morbidities. Patients who were subjected to daytime surgery had longer length of stay at the hospital

Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden

<p/> <p>Background</p> <p>Acute surgery in the management of malignant colonic obstruction is associated with high morbidity and mortality. The use of self-expanding metal stents (SEMS) is an alternative method of decompressing colonic obstruction. SEMS may allow time to optimize the patient and to perform preoperative staging, converting acute surgery into elective. SEMS is also proposed as palliative treatment in patients with contraindications to open surgery. Aim: To review our experience of SEMS focusing on clinical outcome and complications. The method used was a review of 75 consecutive trials at SEMS on 71 patients based on stent-protocols and patient charts.</p> <p>Findings</p> <p>SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months.</p> <p>Conclusion</p> <p>Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.</p