Gastric type adenocarcinoma of the cervix presenting as ovarian neoplasm.

Gastric-type adenocarcinoma of the uterine cervix (GAS) is a rare subtype of mucinous adenocarcinoma, unrelated to HPV infection. It first appeared in the World Health Organization Classification of Tumours of Female Reproductive Organs in 2014. This report discusses a 50-year-old, Caucasian female who presented with new onset abdominal pain, distension, and diffuse ascites. CT scan revealed an ovarian neoplasm later diagnosed as GAS on surgical pathology. Immunohistological stains were positive for PAX8, CK7, CK20 (focally strong), CAIX (strong), CEA (patchy), MUC6 (strong), HNF1b, UBC, RNA, KOC (focal), and P53 (wild type). Tumor cells were negative for p16, PAX2, ER, low-risk 5 HPV, high-risk 18 HPV, and CDX2. The proliferative index (Ki-67) was 20%. The patient is scheduled to receive systemic chemotherapy of cisplatin, paclitaxel, and bevacizumab. Following chemotherapy, she will undergo external beam radiation and vaginal brachytherapy. The prevalence of GAS in the United States is currently unknown. Little is understood about the ideal treatment for this disease, and prognosis is very poor. As more cases are identified and reported, more targeted therapy be developed and trialed in these patients.

Prevalence and Risk Evaluation of Diabetic Complications of the Foot Among Adults With Type 1 and Type 2 Diabetes in a Large Canadian Population (PEDAL Study).

OBJECTIVES: The lower limb complications of diabetes contribute significantly to patient morbidity and health-care costs in Canada. Despite practice guidelines, awareness of and screening for modifiable early pathologies has been inconsistent. Our study objective was to determine the prevalence and types of early foot pathology in a large, Canadian, community care-based diabetes population. METHODS: This study was a retrospective, observational analysis of the LMC Diabetes & Endocrinology foot care program launched in 2017. We examined foot pathologies associated with vascular, nerve, nail and dermatologic complications, as well as foot deformities. Individuals ≥18 years of age with diabetes, assessed by an LMC chiropodist in Ontario between February 2018 and April 2019, were included in the analysis. RESULTS: Of the 5,084 individuals assessed, 470 with type 1 diabetes and 3,903 with type 2 diabetes met the study criteria. Mean age, body mass index and diabetes duration were 61.5 years, 31.3 kg/m2 and 13.9 years, respectively. Reduced pedal pulses, sensory neuropathy and onychomycosis were reported in 8.9%, 16.7% and 14.5% of those in the type 1 diabetes group, and in 19.4%, 26.6% and 28.7% of those in the type 2 group, respectively. Hyperkeratosis was present in 51% and foot deformities were present in 44.5% among both groups. Foot ulcer prevalence was 1.7%, and pedal pulses, sensory neuropathy, hyperkeratosis and onychauxis, adjusted for age, sex, body mass index and diabetes duration, were each significantly associated with ulceration. CONCLUSIONS: In a large foot screening program of community-based adults with diabetes, modifiable early foot pathologies were prevalent and provided further evidence of the value of consistent screening to alleviate the morbidity and economic burden of lower limb complications.

Novel Opioid Safety Clinic Initiative to Deliver Guideline-Concordant Chronic Opioid Therapy in Primary Care.

OBJECTIVE: To develop and evaluate a novel Opioid Safety Clinic (OSC) initiative to enhance adherence to guidelines on the assessment and monitoring of patients prescribed chronic opioid therapy (COT). PATIENTS AND METHODS: The OSC was developed at an urban Federally Qualified Health Center to provide guideline-concordant care for COT, standardize workflows, and efficiently use clinic staff. We evaluated the OSC using a matched cohort study. Five hundred thirty-nine patients participated in the clinic between July 1, 2014, and March 31, 2016. Of these, 472 clinic participants were matched to 472 nonparticipants by sex and age on the date of the OSC visit. The OSC was evaluated by its completion rates of standardized pain assessments, urine toxicology, and naloxone dispensings. We conducted logistic regression comparing OSC participants to OSC nonparticipants. RESULTS: A total of 539 patients attended an OSC visit, representing approximately 53% of patients in the chronic opioid registry. The OSC participants were more likely than nonparticipants to have completed a pain assessment (adjusted odds ratio [aOR], 169.8; 95% CI, 98.3-293.5), completed a urine toxicology (aOR, 46.1; 95% CI, 30.4-69.9), or had naloxone dispensed (aOR, 2.8; 95% CI, 1.9-4.3) over 12 months of follow-up. CONCLUSION: The OSC model improved adherence to guideline-concordant COT in primary care. Future research is needed to assess the impact of these interventions on pain, quality of life, and adverse events from opioid analgesics.

Predictors of difficult pediatric intravenous access in a community Emergency Department.

BACKGROUND: Successful intravenous (IV) placement is important in the care of the acutely ill and injured pediatric patient. There are little data that exist regarding predicators of difficult IV access in pediatric Emergency Department (ED) patients who present to community EDs. METHODS: We retrospectively analyzed all pediatric charts for the calendar year 2012 from a single community teaching hospital. We identified all cases with patients less than 18 years of age in whom an IV or IV medications were ordered. We defined difficult IV access as those requiring more than one attempt, or those where the IV team was required to place the IV. We identified patient, provider, and procedural characteristics. Data were analyzed using descriptive statistics and univariate logistic regression to determine the odds ratio (OR) for predictors of difficult IV access. RESULTS: We identified 652 patients, 607 (93%) without difficult access and 45 with difficult access. Increasing age [OR 0.94 (0.89-0.99) p = 0.017] was associated with decreased odds of difficult IV access. IVs attempted in the hand [OR 3.02 (1.06-8.58) p = 0.039] and lower extremity [OR 7.82 (2.27-26.91) p = 0.001)]) were associated with greater odds of difficult access than the antecubital fossa. Non-black/non-white race [2.37 (1.1-5.12) p = 0.028] was also associated with difficult IV access. Other factors (sex, IV catheter size, and so on) were not associated. CONCLUSIONS: In this retrospective study of pediatric patients in a community ED, decreasing age, non-black/non-white race, and IV attempt location (hand and lower extremity vs. antecubital fossa) were associated with greater odds of difficult IV access.

MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression.

Although deregulated expression of specific microRNAs (miRNAs) has been described in solid cancers and leukemias, little evidence of miRNA deregulation has been reported in ALK-positive (ALK(+)) anaplastic large cell lymphomas (ALCL). These tumors overexpress the major antiapoptotic protein myeloid cell leukemia 1 (MCL-1), a situation that could compensate for the lack of BCL-2. We report that ALK(+) ALCL cell lines and biopsy specimens (n = 20) express a low level of miR-29a and that this down-modulation requires an active NPM-ALK kinase. Murine models (transgenic mice and mouse embryonic fibroblast [MEF] cells), which allow conditional NPM-ALK fusion protein expression, showed an increase of miR-29a expression in the absence of NPM-ALK. Concordant results were observed after the abolition of NPM-ALK kinase activity (siALK or PF-2341066) in NPM-ALK(+) ALCL cell lines. In addition, we showed that low expression of miR-29a, probably through methylation repression, plays an important regulatory role in MCL-1 overexpression that could promote tumor cell survival by inhibiting apoptosis. Enforced miR-29a expression was found to modulate apoptosis through inhibition of MCL-1 expression in ALCL cell lines and in a xenografted model, with a concomitant tumor growth reduction. Thus, synthetic miR-29a represents a potential new tool to affect tumorigenesis in these lymphomas.

The Cm56 tRNA modification in archaea is catalyzed either by a specific 2'-O-methylase, or a C/D sRNP.

We identified the first archaeal tRNA ribose 2'-O-methylase, aTrm56, belonging to the Cluster of Orthologous Groups (COG) 1303 that contains archaeal genes only. The corresponding protein exhibits a SPOUT S-adenosylmethionine (AdoMet)-dependent methyltransferase domain found in bacterial and yeast G18 tRNA 2'-O-methylases (SpoU, Trm3). We cloned the Pyrococcus abyssi PAB1040 gene belonging to this COG, expressed and purified the corresponding protein, and showed that in vitro, it specifically catalyzes the AdoMet-dependent 2'-O-ribose methylation of C at position 56 in tRNA transcripts. This tRNA methylation is present only in archaea, and the gene for this enzyme is present in all the archaeal genomes sequenced up to now, except in the crenarchaeon Pyrobaculum aerophilum. In this archaea, the C56 2'-O-methylation is provided by a C/D sRNP. Our work is the first demonstration that, within the same kingdom, two different mechanisms are used to modify the same nucleoside in tRNAs.