Multistate Outbreak of Salmonella Thompson Infections Linked to Seafood Exposure - United States, 2021.

In July 2021, the Colorado Department of Public Health and Environment (CDPHE) laboratory identified a cluster of five Salmonella enterica serotype Thompson isolates related to one another within one allele difference, using whole genome multilocus sequence typing (wgMLST). These five isolates, submitted to the public health laboratory as is routine process for confirmatory testing of Salmonella, were highly related to those identified in a 2020 multistate investigation, during which traceback was conducted for sushi-grade tuna and salmon; a common supplier was not identified. The 2021 investigation commenced on August 5, 2021, with five patients living in Colorado, and one each in Missouri, Washington, and Wisconsin. During August-December 2021, CDC, CDPHE, public health and regulatory officials in several states, and the Food and Drug Administration (FDA) conducted epidemiologic, environmental, and laboratory investigations of this multistate outbreak of Salmonella Thompson. Isolates were genetically related to one another and to 2020 isolates within zero to one allele difference. Implicated seafood products were traced to a single seafood distributor, in which the outbreak strain was identified through environmental sampling, and in which inspection identified inadequate sanitization and opportunities for cross-contamination of raw fish. The distributor issued a voluntary recall of 16 seafood items with high potential for contamination and completed remediation actions. This outbreak illustrated the importance of effective cleaning and sanitizing procedures and implementation of controls. When multiple products are recalled during an outbreak investigation, collaboration between public health agencies and implicated facilities can help provide food safety information to restaurants, retailers, and consumers, and to ensure disposal of all recalled products.

Case to highlight a rare differential diagnosis of necrotising fasciitis in the presence of a stoma: peristomal pyoderma gangrenosum.

Peristomal pyoderma gangrenosum (PPG) is a rare clinical entity, which can masquerade as the more common and lethal necrotising fasciitis. The authors present a case of PPG in a 65-year-old woman who underwent robotic abdominoperineal resection for low rectal carcinoma and returned 8 days postoperation for peristomal skin ulcerations and pain, accompanied by leucocytosis; thus, she was treated as per necrotising fasciitis and underwent surgical debridement. Thereafter, her wound continued to worsen despite conventional wound care with vacuum-assisted closure and demonstrated signs of pathergy. The case was referred to dermatology where a diagnosis of PPG was made. This case report presents a cautionary tale for fellow clinicians, highlights the diagnostic challenge, and presents an updated literature review on diagnosis and management of this unique condition.

PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein.

Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro. PRL3 antigens are detected on the cell surface and outer exosomal membranes, implying an 'inside-out' externalization of PRL3. PRL3-zumab binds to surface PRL3 in a manner consistent with that in classical antibody-dependent cell-mediated cytotoxicity or antibody-dependent cellular phagocytosis tumor elimination pathways, as PRL3-zumab requires an intact Fc region and host FcγII/III receptor engagement to recruit B cells, NK cells and macrophages to PRL3+ tumor microenvironments. PRL3 is overexpressed in 80.6% of 151 fresh-frozen tumor samples across 11 common cancers examined, but not in patient-matched normal tissues, thereby implicating PRL3 as a tumor-associated antigen. Targeting externalized PRL3 antigens with PRL3-zumab may represent a feasible approach for anti-tumor immunotherapy.

Colonic stenting for malignant large bowel obstruction is safe and effective: a single-surgeon experience.

INTRODUCTION: Self-expanding metal stents (SEMS) can be used as a bridge to surgery (BTS) or for palliation in the treatment of malignant large bowel obstruction. This case series evaluates the short-term outcomes of SEMS and success rates over time. METHODS: A total of 75 consecutive patients who underwent colonic stenting for malignant colonic obstruction over a period of six years were included. This time period was subdivided into two equal parts for analysis. The procedure was carried out by a single surgeon from a tertiary institution in Singapore. RESULTS: Technical success was reported in 93.3% of cases and clinical success in 81.3% of cases, with better success rates in the second half of the study (89.2% vs. 73.7%; p < 0.05). There were seven cases of inadequate decompression and two cases of colonic perforation. The median duration from stent insertion to surgery was ten days, and the median postoperative length of stay was six days. CONCLUSION: SEMS are a safe and effective way of relieving malignant large bowel obstruction, including those that are proximal. The improvement in success over time reflects the importance of having an experienced endoscopist carry out the procedure to ensure optimum success rates.

Initial experience of laparoscopic right hemicolectomy with complete mesocolic excision in Singapore: a case series.

INTRODUCTION: Laparoscopic colorectal surgery is increasingly performed worldwide due to its multiple advantages over traditional open surgery. In the surgical treatment of right-sided colonic tumours, the latest technique is laparoscopic right hemicolectomy with complete mesocolic excision (lapCME), which aims to lower the rate of local recurrence and maximise survival as compared to standard laparoscopic right hemicolectomy (lapS). METHODS: We conducted a retrospective analysis of our initial experience with lapCME in Singapore General Hospital between 2012 and 2015. All procedures were performed by a single surgeon. RESULTS: Nine patients underwent lapCME and 16 patients underwent lapS. Indication for lapCME was cancer in the right colon. None of the patients required conversion to open surgery, and all were discharged well. The number of lymph nodes resected in the lapCME group was significantly greater than in the lapS group (29 ± 15 vs. 19 ± 6; p = 0.02) during the study period, and the mean operation time was significantly longer for lapCME (237 ± 50 minutes vs. 156 ± 46 minutes; p = 0.0005). There were no statistically significant differences in terms of demographics, tumour stage, time taken for bowel to open postoperatively, time taken for patient to resume a solid diet postoperatively and length of hospital stay. Two patients who underwent lapS were re-admitted for intra-abdominal collections - one patient required radiology-guided drainage, while the other patient was managed conservatively. CONCLUSION: Our initial experience with lapCME confirms the feasibility and safety of the procedure.

Colonic stenting for malignant large bowel obstruction is safe and effective: a single-surgeon experience

INTRODUCTION@#Self-expanding metal stents (SEMS) can be used as a bridge to surgery (BTS) or for palliation in the treatment of malignant large bowel obstruction. This case series evaluates the short-term outcomes of SEMS and success rates over time.@*METHODS@#A total of 75 consecutive patients who underwent colonic stenting for malignant colonic obstruction over a period of six years were included. This time period was subdivided into two equal parts for analysis. The procedure was carried out by a single surgeon from a tertiary institution in Singapore.@*RESULTS@#Technical success was reported in 93.3% of cases and clinical success in 81.3% of cases, with better success rates in the second half of the study (89.2% vs. 73.7%; p < 0.05). There were seven cases of inadequate decompression and two cases of colonic perforation. The median duration from stent insertion to surgery was ten days, and the median postoperative length of stay was six days.@*CONCLUSION@#SEMS are a safe and effective way of relieving malignant large bowel obstruction, including those that are proximal. The improvement in success over time reflects the importance of having an experienced endoscopist carry out the procedure to ensure optimum success rates.

Initial experience of laparoscopic right hemicolectomy with complete mesocolic excision in Singapore: a case series

INTRODUCTION@#Laparoscopic colorectal surgery is increasingly performed worldwide due to its multiple advantages over traditional open surgery. In the surgical treatment of right-sided colonic tumours, the latest technique is laparoscopic right hemicolectomy with complete mesocolic excision (lapCME), which aims to lower the rate of local recurrence and maximise survival as compared to standard laparoscopic right hemicolectomy (lapS).@*METHODS@#We conducted a retrospective analysis of our initial experience with lapCME in Singapore General Hospital between 2012 and 2015. All procedures were performed by a single surgeon.@*RESULTS@#Nine patients underwent lapCME and 16 patients underwent lapS. Indication for lapCME was cancer in the right colon. None of the patients required conversion to open surgery, and all were discharged well. The number of lymph nodes resected in the lapCME group was significantly greater than in the lapS group (29 ± 15 vs. 19 ± 6; p = 0.02) during the study period, and the mean operation time was significantly longer for lapCME (237 ± 50 minutes vs. 156 ± 46 minutes; p = 0.0005). There were no statistically significant differences in terms of demographics, tumour stage, time taken for bowel to open postoperatively, time taken for patient to resume a solid diet postoperatively and length of hospital stay. Two patients who underwent lapS were re-admitted for intra-abdominal collections - one patient required radiology-guided drainage, while the other patient was managed conservatively.@*CONCLUSION@#Our initial experience with lapCME confirms the feasibility and safety of the procedure.

Universal suprapubic approach for complete mesocolic excision and central vascular ligation using the da Vinci Xi® system: from cadaveric models to clinical cases.

There has been little enthusiasm for performing robotic colectomy for colon cancer in recent years due to multiple factors, one being that the previous robotic systems such as the da Vinci Si® (dVSi) were poorly designed for multi-quadrant surgery. The new da Vinci Xi® (dVXi) system enables colectomy with central mesocolic excision to be performed easily in a single docking procedure. We developed a universal port placement strategy to allow right and left hemicolectomies to be performed via a suprapubic approach and a Pfannensteil extraction site. This proof of concept paper describes the development and subsequent clinical application of this setup. After extensive training on the dVXi system concepts in collaboration with clinical development engineers, we developed a port placement strategy which was tested and adapted after performing experimental surgery in three cadaveric models. Subsequently our port placement was used for two clinical cases of suprapubic right and left hemicolectomy. With some modifications of port placements after the initial cadaveric colectomies, we have developed a potentially universal suprapubic port placement strategy for robotic colectomy with complete mesocolic excision and central vascular ligation using the dVXi robotic system. This port placement strategy was applied successfully in our first two clinical cases. Based on our cadaveric laboratory as well as our initial clinical application, the suprapubic port placement strategy for the dVXi system with its improved features over the dVSi can feasibly perform right and left hemicolectomy with complete mesocolic excision and central vascular ligation. Further studies will be required to establish efficacy as well as safety profile of these procedures.

The number of retrieved lymph nodes needed for accurate staging differs based on the presence of preoperative chemoradiation for rectal cancer.

The aim of this study is to investigate if retrieval of 12 lymph nodes (LNs) is sufficient to avoid stage migration as well as to evaluate the prognostic impact of insufficient LN retrieval in different treatment settings of rectal cancer, particularly in the case of preoperative chemoradiotherapy (pCRT).The data of all patients with biopsy proven rectal adenocarcinoma who underwent curative surgery between January 2005 and December 2012 were analyzed. Univariate and multivariate analyses for oncologic outcomes were performed in LN metastasis or no LN metastasis (LN-) group. Subgroup analyses were performed according to whether a patient had received pCRT.A total of 1825 patients were enrolled into the study. The maximal Chi-square method revealed the minimum number of harvested LNs required to be 12. Univariate and multivariate analyses found LNs ≥ 12 to be an independent prognostic factor for both overall survival (OS) (hazard ratio [HR] = 0.5, 95% confidence intervals [CIs]: 0.3-0.8; P = 0.002) and disease-free survival (DFS) (HR = 0.6, 95% CI: 0.4-0.7; P < 0.001) in the LN- group. In the LN- group, LNs ≥ 12 continued to be a significant prognostic factor both for OS and DFS in the subgroup of patients who did not undergo pCRT. However, in the subgroup of the LN- patients who underwent pCRT, LN ≥ 8 was significant for DFS and OS.Retrieval of LNs ≥ 12 and LNs ≥ 8 should be achieved to obtain accurate staging and optimal treatment for the non-pCRT and pCRT groups in rectal cancer, respectively.

Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia.

Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia.

Bosutinib in the treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia: an overview.

Bosutinib is an orally bioavailable SRC/ABL tyrosine kinase inhibitor with activity against all phases of resistant chronic myeloid leukemia that do not express the T315I or V299L ABL kinase domain mutations. Bosutinib has a unique toxicity profile that is manageable. This paper provides an overview of bosutinib, covering pharmacodynamics and pharmacokinetic properties, results of treatment in newly diagnosed and previously treated chronic myeloid leukemia patients, as well as common side effects.

Autophagy enhances bacterial clearance during P. aeruginosa lung infection.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen which is the leading cause of morbidity and mortality among cystic fibrosis patients. Although P. aeruginosa is primarily considered an extacellular pathogen, recent reports have demonstrated that throughout the course of infection the bacterium acquires the ability to enter and reside within host cells. Normally intracellular pathogens are cleared through a process called autophagy which sequesters and degrades portions of the cytosol, including invading bacteria. However the role of autophagy in host defense against P. aeruginosa in vivo remains unknown. Understanding the role of autophagy during P. aeruginosa infection is of particular importance as mutations leading to cystic fibrosis have recently been shown to cause a blockade in the autophagy pathway, which could increase susceptibility to infection. Here we demonstrate that P. aeruginosa induces autophagy in mast cells, which have been recognized as sentinels in the host defense against bacterial infection. We further demonstrate that inhibition of autophagy through pharmacological means or protein knockdown inhibits clearance of intracellular P. aeruginosa in vitro, while pharmacologic induction of autophagy significantly increased bacterial clearance. Finally we find that pharmacological manipulation of autophagy in vivo effectively regulates bacterial clearance of P. aeruginosa from the lung. Together our results demonstrate that autophagy is required for an effective immune response against P. aeruginosa infection in vivo, and suggest that pharmacological interventions targeting the autophagy pathway could have considerable therapeutic potential in the treatment of P. aeruginosa lung infection.

ß-Glucosidase 2 (GBA2) activity and imino sugar pharmacology.

ß-Glucosidase 2 (GBA2) is an enzyme that cleaves the membrane lipid glucosylceramide into glucose and ceramide. The GBA2 gene is mutated in genetic neurological diseases (hereditary spastic paraplegia and cerebellar ataxia). Pharmacologically, GBA2 is reversibly inhibited by alkylated imino sugars that are in clinical use or are being developed for this purpose. We have addressed the ambiguity surrounding one of the defining characteristics of GBA2, which is its sensitivity to inhibition by conduritol B epoxide (CBE). We found that CBE inhibited GBA2, in vitro and in live cells, in a time-dependent fashion, which is typical for mechanism-based enzyme inactivators. Compared with the well characterized impact of CBE on the lysosomal glucosylceramide-degrading enzyme (glucocerebrosidase, GBA), CBE inactivated GBA2 less efficiently, due to a lower affinity for this enzyme (higher KI) and a lower rate of enzyme inactivation (k(inact)). In contrast to CBE, N-butyldeoxygalactonojirimycin exclusively inhibited GBA2. Accordingly, we propose to redefine GBA2 activity as the ß-glucosidase that is sensitive to inhibition by N-butyldeoxygalactonojirimycin. Revised as such, GBA2 activity 1) was optimal at pH 5.5-6.0; 2) accounted for a much higher proportion of detergent-independent membrane-associated ß-glucosidase activity; 3) was more variable among mouse tissues and neuroblastoma and monocyte cell lines; and 4) was more sensitive to inhibition by N-butyldeoxynojirimycin (miglustat, Zavesca®), in comparison with earlier studies. Our evaluation of GBA2 makes it possible to assess its activity more accurately, which will be helpful in analyzing its physiological roles and involvement in disease and in the pharmacological profiling of monosaccharide mimetics.

Toxic haemorrhagic colitis: a rare presentation of eosinophilic colitis.

Eosinophilic colitis is a rare condition that usually presents with non specific abdominal symptoms. Very uncommonly it presents with an acute surgical emergency such as peritonitis or haemorrhage. We present a rare presentation of eosinophilic colitis with toxic hemorrhagic colitis and ischaemic bowel requiring laparotomy and bowel resection.

Critical analysis of mucin and signet ring cell as prognostic factors in an Asian population of 2,764 sporadic colorectal cancers.

INTRODUCTION: Conflicting data on the clinicopathological characteristics as well as prognosis and survival of signet ring cell (SRC) and mucinous adenocarcinomas (MA) of the colorectum persist. METHODS: Consecutive patients (2,764) with sporadic colorectal cancer from 1999 to 2005 were evaluated. The clinicopathological characteristics of these patients were reviewed. Univariate analysis was performed, and survival curves were constructed using the Kaplan-Meier method. Multivariate analysis assessed independent prognostic factors. RESULTS: The incidence of MA and SRC is 6% and 1.1%, respectively. MA and SRC tend to occur in patients aged