Ensuring no patient is lost along the way – a single-centre experience of the clinical genetics referral pathways for Lynch syndrome

Lynch syndrome (LS), caused by heterozygous germline mutation in one of the key mismatch repair (MMR) genes, is the primary cause of inherited colorectal cancer (CRC). LS also increases susceptibility to several other cancers. It is estimated that just 5% of patients with LS are aware of their diagnosis. Therefore, in an attempt to increase the identification of cases within the UK population, the 2017 NICE guidelines recommend offering immunohistochemistry for MMR proteins or microsatellite instability (MSI) testing to all people with CRC when first diagnosed. Following identification of MMR deficiency, eligible patients should be assessed for underlying causes, including potential referral to the genetics service and/or germline LS testing (if appropriate). In our regional centre for CRC, we audited local pathways to identify what proportion of patients are being correctly referred, in line with national guidelines. Reflecting on these results, we highlight our practical concerns by identifying the pitfalls and issues faced with the recommended referral pathway. We also propose possible solutions to improve the efficacy of the system for both referrers and patients. Finally, we discuss the ongoing interventions that national bodies and regional centres are implementing to improve and further streamline this process.     

Trends of isolation of intrinsically resistant to colistin Enterobacteriaceae and association with colistin use in a tertiary hospital

The objective of this investigation was to evaluate the association between colistin consumption and the isolation of intrinsically resistant to colistin Enterobacteriaceae (IRCE) in a university hospital in Crete, Greece. The database of the microbiological laboratory was reviewed retrospectively during 2006–2010. All positive cultures for IRCE were retrieved. We assessed the total consumption of colistin in medical, surgical, and intensive care units (ICUs). A total of 1,304 single-patient IRCE isolates were recorded. Of these, 466 (35.7%) were hospital-acquired, while 838 (64.3%) were community-acquired. Proteus spp. accounted for 72% of them, Serratia spp. for 16.6%, Morganella morganii for 8.4%, and Providencia spp. for 3%. Urine (44.8%), pus (20.4%), and lower respiratory tract specimens (12.8%) accounted for the majority of specimens. IRCE isolated during the first half (2006 to 1st semester of 2008) and second half (2nd semester of 2008 to 2010) of the study period accounted for 5.8% and 7.4% of Gram-negative isolates, respectively (p?p?=?0.013). Colistin consumption was associated with the isolation of hospital-acquired IRCE (p?=?0.037); a trend was noted between colistin consumption and the isolation of IRCE in the ICU (p?=?0.057). In this study, colistin consumption was associated with the isolation of hospital-acquired IRCE. The use of colistin increased in the ICU during the study period. Prudent use of colistin is essential for the prevention of nosocomial outbreaks due to resistant IRCE.     

ASO Author Reflections: Minority-Serving Hospitals are Associated with Lower Likelihood of Providing NCCN Guideline Compliant Care to Patients with Resectable Cholangiocarcinoma

Annals of Surgical Oncology -     

LINX■ reflux management system to bridge the “treatment gap” in gastroesophageal reflux disease: A systematic review of 35 studies

BACKGROUND Gastroesophageal reflux disease(GERD) occurs when the reflux of stomach contents causes troublesome symptoms and/or complications. When medical therapy is insufficient, surgical therapy is indicated and, until now, Laparoscopic fundoplication(LF) constitutes the gold-standard method. However, magnetic sphincter augmentation(MSA) using the LINX^® Reflux Management System has recently emerged and disputes the standard therapeutic approach.AIM To investigate the device’s safety and efficacy in resolving GERD symptoms.METHODS This is a systematic review conducted in accordance to the PRISMA guidelines.We searched MEDLINE, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL databases from inception until September 2019.RESULTS Overall, 35 studies with a total number of 2511 MSA patients were included and analyzed. Post-operative proton-pump inhibitor(PPI) cessation rates reached 100%, with less bloating symptoms and a better ability to belch or vomit in comparison to LF. Special patient groups(e.g., bariatric or large hiatal-hernias)had promising results too. The most common postoperative complication was dysphagia ranging between 6% and 83%. Dilation due to dysphagia occurred in 8% of patients with typical inclusion criteria. Esophageal erosion may occur in up to 0.03% of patients. Furthermore, a recent trial indicated MSA as an efficient alternative to double-dose PPIs in moderate-to-severe GERD.CONCLUSION The findings of our review suggest that MSA has the potential to bridge the treatment gap between maxed-out medical treatment and LF. However, further studies with longer follow-up are needed for a better elucidation of these results.     

The role of upper endoscopy in identifying oesophageal involvement in patients with oral pemphigus vulgaris

BACKGROUND AND AIMS: The involvement of oesophagus in pemphigus vulgaris is still debated. The aims of this study were to evaluate the prevalence of oesophageal involvement and the gastro-duodenal mucosa appearance before and after high-dose corticosteroid therapy in a group of patients with oral pemphigus vulgaris. METHODS: We prospectively studied 28 consecutive patients with oral pemphigus by oesophageal symptom standardised questionnaire, upper gastro-intestinal endoscopy, exfoliative cytology and histological biopsy. After clinical remission, all patients underwent new endoscopy. RESULTS: The prevalence of oesophageal symptoms was 57.1%. Endoscopic examination revealed oesophageal involvement with different degrees of severity in 67.8% of patients. After corticosteroid therapy, endoscopy showed normal oesophageal-gastro-duodenal mucosa. No examination-related exacerbations of the oesophageal lesions were seen. CONCLUSIONS: The upper gastro-intestinal endoscopic examination, in oral pemphigus vulgaris patients with oesophageal symptoms, is safe in skilled hands technique and a useful diagnostic tool prior to starting therapy.     

Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration

This report describes the pharmacokinetics of colistin methanesulfonate (CMS) and colistin in five intensive care unit patients receiving continuous venovenous hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma (C_max) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23 liters/h. For colistin, the mean concentration was 0.92 mg/liter and CL/metabolized fraction (f_m) 18.91 liters/h. Colistin concentrations were below the current MIC breakpoints, and the area under the concentration-time curve for the free, unbound fraction of the drug over 24 h in the steady state divided by the MIC (fAUC/MIC) was lower than recommended, suggesting that a dosage regimen of 160 mg CMS every 8 h (q8h) is inadequate.     

Natural immunity to SARS-CoV-2 and breakthrough infections in vaccinated and unvaccinated patients with cancer

Background Consolidated evidence suggests spontaneous immunity from SARS-CoV-2 is not durable, leading to the risk of reinfection, especially in the context of newly emerging viral strains. In patients with cancer who survive COVID-19 prevalence and severity of SARS-CoV-2 reinfections are unknown.Methods We aimed to document natural history and outcome from SARS-CoV-2 reinfection in patients recruited to OnCovid ({"type":"clinical-trial","attrs":{"text":"NCT04393974","term_id":"NCT04393974"}}NCT04393974), an active European registry enrolling consecutive patients with a history of solid or haematologic malignancy diagnosed with COVID-19.Results As of December 2021, out of 3108 eligible participants, 1806 COVID-19 survivors were subsequently followed at participating institutions. Among them, 34 reinfections (1.9%) were reported after a median time of 152 days (range: 40–620) from the first COVID-19 diagnosis, and with a median observation period from the second infection of 115 days (95% CI: 27–196). Most of the first infections were diagnosed in 2020 (27, 79.4%), while most of reinfections in 2021 (25, 73.5%). Haematological malignancies were the most frequent primary tumour (12, 35%). Compared to first infections, second infections had lower prevalence of COVID-19 symptoms (52.9% vs 91.2%, P = 0.0008) and required less COVID-19-specific therapy (11.8% vs 50%, P = 0.0013). Overall, 11 patients (32.4%) and 3 (8.8%) were fully and partially vaccinated against SARS-CoV-2 before the second infection, respectively. The 14-day case fatality rate was 11.8%, with four death events, none of which among fully vaccinated patients.Conclusion This study shows that reinfections in COVID-19 survivors with cancer are possible and more common in patients with haematological malignancies. Reinfections carry a 11% risk of mortality, which rises to 15% among unvaccinated patients, highlighting the importance of universal vaccination of patients with cancer.Subject terms: Oncology, Public health