Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagus.

BACKGROUND: Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ). METHODS: BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined. RESULTS: 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma. CONCLUSION: Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.

Mpox vaccination for men who have sex with men and their differential risk of exposure and infection.

Following the post-COVID-19 reopening of the society with enhanced traveling between countries, people at risk of mpox infection, notably men who have sex with men (MSM) and people living with HIV, are facing increasing threat of virus exposure. Mpox vaccination is an important public health strategy which is provided free in Hong Kong to people at higher risk of infection. Between October 2022 and January 2023, 326 and 184 MSM vaccinees from vaccination sites and HIV specialist clinics in Hong Kong, respectively, were recruited for assessing their infection risks. Apart from the urge to protect one's significant others (68%), 45% were worried about the stigmatizing mpox symptoms if infected. Compared with MSM vaccinees at vaccination site, a lower proportion of MSM vaccinees in HIV care were sexually active in the past 6 months (88% vs 97%), but a higher proportion had recent sexually transmitted infection diagnoses (19% vs 10%) and perceived considerable exposure risk in the following 6 months (40% vs 22%). There were no differences in the perceived effectiveness of mpox vaccination. If optimal supplies of mpox vaccines can be secured, a low threshold approach at vaccination site could enable MSM with different levels of behavioral risks to become protected.

Assessment of the role of the Edinburgh dysphagia score in referral triage in a national service evaluation of the urgent suspected upper gastrointestinal cancer pathway.

BACKGROUND: The British Society of Gastroenterology has recommended the Edinburgh Dysphagia Score (EDS) to risk-stratify dysphagia referrals during the endoscopy COVID recovery phase. AIMS: External validation of the diagnostic accuracy of EDS and exploration of potential changes to improve its diagnostic performance. METHODS: A prospective multicentre study of consecutive patients referred with dysphagia on an urgent suspected upper gastrointestinal (UGI) cancer pathway between May 2020 and February 2021. The sensitivity and negative predictive value (NPV) of EDS were calculated. Variables associated with UGI cancer were identified by forward stepwise logistic regression and a modified Cancer Dysphagia Score (CDS) developed. RESULTS: 1301 patients were included from 19 endoscopy providers; 43% male; median age 62 (IQR 51-73) years. 91 (7%) UGI cancers were diagnosed, including 80 oesophageal, 10 gastric and one duodenal cancer. An EDS ≥3.5 had a sensitivity of 96.7 (95% CI 90.7-99.3)% and an NPV of 99.3 (97.8-99.8)%. Age, male sex, progressive dysphagia and unintentional weight loss >3 kg were positively associated and acid reflux and localisation to the neck were negatively associated with UGI cancer. Dysphagia duration <6 months utilised in EDS was replaced with progressive dysphagia in CDS. CDS ≥5.5 had a sensitivity of 97.8 (92.3-99.7)% and NPV of 99.5 (98.1-99.9)%. Area under receiver operating curve was 0.83 for CDS, compared to 0.81 for EDS. CONCLUSIONS: In a national cohort, the EDS has high sensitivity and NPV as a triage tool for UGI cancer. The CDS offers even higher diagnostic accuracy. The EDS or CDS should be incorporated into the urgent suspected UGI cancer pathway.

A 5-Year Follow-Up of Study Patients With Asymptomatic Iron-Deficiency Anemia Using a Nurse-Led Pathway.

A protocol-driven, systematic pathway was developed to allow rapid and coordinated investigation of patients with iron-deficiency anemia (IDA) in a nurse-delivered outpatient setting. The study objective was to assess the safety and efficacy of the pathway by 5-year outcome data for the exclusion of gastrointestinal (GI) malignancy. This is a 5-year follow-up study of 122 patients entered onto the pathway with negative initial upper and lower GI investigations. The study was conducted at Hereford County Hospital NHS Trust (a district general hospital serving 220,00 people). Clinical outcomes of patients at 5 years and service efficiency at detecting relevant pathology were observed. A total of 272 patients were investigated through the pathway, and in 150 patients a GI cause for IDA was found. We established the outcome in 97% of the 122 patients with normal GI investigation at 5 years after their initial investigation. Of the 118 patients followed up, 92 patients were alive and well and 26 had died or developed malignancy. With the exception of diabetes (odds ratio 0.24; 95% confidence interval [0.1, 0.8]; p = .02), no features were found to be a significant risk factor for poor prognosis, including age, gender, hemoglobin level, anemia at 3 months, or other comorbidities. Three patients developed colonic malignancy; two patients had diverticular disease at barium enema and presented 4 years later with colorectal cancer. One patient declined lower GI investigation and presented with metastatic colon cancer on computed tomography scan at 1 year. No other GI cancers were diagnosed. Our nurse-delivered, protocol-driven pathway is a highly effective and safe system for the exclusion of GI cancer within 5 years of follow-up.

Factors Associated with Upper Gastrointestinal Cancer Occurrence After Endoscopy that Did Not Diagnose Cancer.

BACKGROUND AND AIMS: Up to 14 % of upper gastrointestinal cancer (UGIC) subjects underwent esophago-gastro-duodenoscopy (EGD) in the preceding 3 years, which did not detect UGIC. The frequency of such events and associated risk factors was evaluated. METHODS: UGIC subjects were identified from a UK primary care database. Post-EGD upper gastrointestinal cancers (PEUGIC) cases were subjects undergoing EGD 12-36 months prior to UGIC diagnosis. Controls had not undergone EGD during the same period. Logistic regression analysis examined associations with PEUGIC. RESULTS: 4249 gastric cancer (GC) subjects (44.8 %) and 5238 esophageal cancer (EC) subjects (55.2 %) were analyzed. There were 633 (6.7 %) PEUGIC subjects [279 EC and 354 GC]. Multivariate analysis revealed that younger age [OR 1.02, (95 % CI 1.01-1.03), p < 0.0001], female gender [1.39 (1.17-1.64), p < 0.0001], increasing comorbidity [1.35 (1.13-1.61), p < 0.0001], and greater deprivation [1.31 (1.09-1.59), p = 0.005] were associated with PEUGIC. Alarm symptoms on presentation [0.32 (0.26-0.40), p < 0.0001] were less likely to be associated with PEUGIC. GC was more likely to be associated with PEUGIC than EC [1.33 (1.13-1.58), p = 0.001]. PEUGIC EGDs reported findings associated with UGIC (stricture or ulceration) in 8.3 % of cases, and only 60.9 % had a follow-up EGD within 90 days. PEUGIC rate declined from 7.9 to 2.7 % for EC and 9.0-6.5 % for GC during the study period. CONCLUSIONS: PEUGIC occurs in 6.7 % of UGIC. PEUGIC was associated with GC, younger age, female gender, increasing comorbidity and deprivation, and a lack of alarm symptoms.

Factors associated with colorectal cancer occurrence after colonoscopy that did not diagnose colorectal cancer.

BACKGROUND AND AIMS: Up to 6% of colorectal cancers (CRCs) are diagnosed within 5 years of a colonoscopy that did not diagnose CRC (post-colonoscopy colorectal cancer, PCCRC). PCCRC and associated risk factors were examined within a national hospital episode database. METHODS: A retrospective case-control study of all colonoscopies performed on adults recorded in Hospital Episode Statistics (HES) between 2003 and 2009 in England. PCCRC cases underwent colonoscopy 6 to 60 months before diagnosis; controls had not undergone colonoscopy 6 to 60 months before diagnosis. Multivariate logistic regression analysis examined associations with PCCRC. RESULTS: A total of 1,439,684 colonoscopies were analyzed, including 67,202 cases of CRC and 8147 cases of PCCRC (12.1%). Multivariate analysis revealed that female sex (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.08-1.19; P < .001), older age (70-74 years) (OR, 1.09; 95% CI, 1.00-1.18; P = .039), increased comorbidity (Charlson index 5+) (OR, 1.16; 95% CI, 1.05-1.28; P < .003), and CRC of the right side of the colon (OR, 1.17; 95% CI, 1.11-1.23; P < .0001) were associated with PCCRC. Emergency colonoscopy (OR, 0.54; 95% CI, 0.59-0.69; P < .0001) was negatively associated with PCCRC. More individuals with PCCRC developed metastases within 12 months and fewer underwent surgery (OR, 0.33; 95% CI, 0.32-0.35; P < .0001) or chemotherapy (OR, 0.66; 95% CI, 0.62-0.69), P < .0001). PCCRC rates varied 2-fold between providers and PCCRC was associated with medium-volume providers compared with high-volume providers (OR, 1.13; 95% CI, 1.01-1.27; P = .035). The PCCRC rate fell from 13.8% in 2003 to 11.9% in 2009. CONCLUSIONS: PCCRC occurred in 12.1% of patients with CRC between 2003 and 2009. PCCRC was associated with female sex, older age, increased comorbidity, CRC of the right side of the colon, elective procedures, and colonoscopy volume. PCCRC was associated with worse outcomes.

A CASE OF ACCIDENTAL OCULAR INJURY FROM COSMETIC LASER BURN.

PURPOSE: To report the clinical course of a patient sustaining a ocular laser injury from 1,064-nm Nd:YAG cosmetic laser machine. METHOD AND PATIENT: A 31-year-old beauty parlor aesthetician was operating an Nd:YAG cosmetic laser machine of 1,064 nm wavelength. However, the probe was held in the opposite direction, and on firing, the laser shot fired into her left eye. The patient heard a "pop" sound followed by immediate floaters and blurring of vision. Her clinical course was followed for 6 weeks, with investigations including optical coherence tomography, fluorescein angiogram, and Humphrey's visual field examination performed. RESULTS: Optical coherence tomography taken over the injured area showed thickened retina and preretinal hyperreflectivities. Fluorescein angiogram showed hypofluorescence superonasal to the disk with late staining of vessels. Humphrey's visual field showed a dense scotoma emanating from the blind spot. The lesion eventually scarred down, and the patient's vision recovered. DISCUSSION: The eye is the most susceptible body part to laser light injury. A review of reported laser accidents revealed the majority to be ocular injuries. The retina is particularly vulnerable, as laser light with wavelength between 400 nm and 1,400 nm is focused by the cornea and lens onto the retina, increasing the retinal irradiance as a result. Most injuries were parafoveal, suggesting that most injuries occurred during laser beam alignment. The prognosis is generally favorable. As laser use becomes more widespread and its application increasingly heterogeneous, regulation of laser use and monitoring of laser safety are crucial but at the same time challenging.

Managing a patient with burning mouth syndrome.

A 64-year-old woman presented with an increasing frequency of symptoms of heartburn and retrosternal pain over the last few months, and a constant and intense burning pain affecting her tongue tip, mouth and lips for the past 5 years. She found consuming hot drinks exacerbated the burning oral pain and chewing gum seemed to alleviate some of her symptoms. She thought these oral sensations were caused by frequently licking her finger tips to separate prints in her work in publishing. She had been previously diagnosed with gastro-oesophageal reflux disease (GORD), and her heartburn symptoms had been controlled until recently with lansoprazole 15 mg daily. Her past medical history included irritable bowel syndrome and depression, for which she had been treated with mebeverine and paroxetine for a number of years. She was a non-smoker and did not consume alcohol. Clinical examination was unremarkable with no oral lesions on examination. Her routine laboratory tests, including autoimmune serology, haematinics and thyroid function tests were all within normal limits. She underwent a gastroscopy, which revealed moderate reflux oesophagitis, and following commencing omeprazole 20 mg twice daily, her heartburn resolved. However, her oral burning symptoms were not affected and a diagnosis of burning mouth syndrome (BMS) was made. Following explanation and reassurance concerning the cause of her BMS symptoms, she chose not to receive treatment for this but to access cognitive behavioural therapy in the future if her symptoms worsened.

Evaluation and validation of a PulseNet standardized pulsed-field gel electrophoresis protocol for subtyping Vibrio parahaemolyticus: an international multicenter collaborative study.

The pandemic spread of Vibrio parahaemolyticus is an international public health issue. Because of the outbreak potential of the organism, it is critical to establish an internationally recognized molecular subtyping protocol for V. parahaemolyticus that is both rapid and robust as a means to monitor its further spread and to guide control measures in combination with epidemiologic data. Here we describe the results of a multicenter, multicountry validation of a new PulseNet International standardized V. parahaemolyticus pulsed-field gel electrophoresis (PFGE) protocol. The results are from a composite analysis of 36 well-characterized V. parahaemolyticus isolates from six participating laboratories, and the isolates represent predominant serotypes and various genotypes isolated from different geographic regions and time periods. The discriminatory power is very high, as 34 out of 36 sporadic V. parahaemolyticus strains tested fell into 34 distinguishable PFGE groups when the data obtained with two restriction enzymes (SfiI and NotI) were combined. PFGE was further able to cluster members of known pandemic serogroups. The study also identified quality measures which may affect the performance of the protocol. Nonadherence to the recommended procedure may lead to high background in the PFGE gel patterns, partial digestion, and poor fragment resolution. When these quality measures were implemented, the PulseNet V. parahaemolyticus protocol was found to be both robust and reproducible among the collaborating laboratories.

Rapid pulsed-field gel electrophoresis protocol for subtyping of Streptococcus suis serotype 2.

A rapid pulsed-field gel electrophoresis (PFGE) protocol for subtyping of Streptococcus suis serotype 2 was developed and evaluated using 27 clinical isolates from 22 epidemiologically unrelated patients. Results were matched against antibiogram, virulence genotyping and multi locus sequence typing (MLST). PFGE appeared to be the most discriminatory with numerical index of discrimination (D) equal to 0.87.

Characterization of a Bacillus anthracis isolate causing a rare case of fatal anthrax in a 2-year-old boy from Hong Kong.

We used multiple-locus variable-number tandem repeat analysis (MLVA) and pagA sequencing to genotype a Bacillus anthracis isolate from a fatal case of human anthrax in Hong Kong. The isolate has a unique MLVA genotype, is related to the Sterne and Ames strains, and is consistent with genotypes identified in China.

Routine use of a simple low-cost genotypic assay for the identification of mycobacteria in a high throughput laboratory.

A novel polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene was used for the routine identification of mycobacteria in a high throughput clinical laboratory. A total of 2036 clinical isolates were tested by PRA in conjunction with other methods. The PRA identification of M. tuberculosis complex was 100% sensitive and specific, and 74.5% of nontuberculous mycobacteria (NTM) were correctly identified. It gave highly consistent results for Mycobacterium avium complex (MAC) species and for most isolates of M. fortuitum, M. chelonae, and M. kansasii. It had proven to be highly robust and stable despite usage on such a large-scale and is thus particularly suitable for use in high throughput laboratories in areas with a high incidence of tuberculosis.

Molecular characterization of quinolone-resistant Neisseria gonorrhoeae in Hong Kong.

In Hong Kong, ParC changes among high-level quinolone-resistant Neisseria gonorrhoeae (QRNG) isolates at Ser-87-->Arg were associated with a higher level of resistance than a Ser-87-->Ile alteration. Two previously undescribed mutations in clinical isolates occurring in gyrA, conferring Ala-92-->Pro and Asp-95-->Tyr changes, were detected. Nine different outer membrane lipoprotein (Lip) repeat classes-11 to 19 repeats-were identified, with repeat lengths of 16 and 17 the most common, indicating considerable strain diversity.