Elective lower limb orthopedic arthroplasty surgery in patients with pulmonary hypertension.

Patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (PH) are at increased risk when undergoing anesthesia and major surgery. Data on outcomes for elective orthopedic surgery in patients with PH are limited. A patient pathway was established to provide access to elective lower limb arthroplasty. This included assessment of orthopedic needs, fitness for anesthesia, preoperative optimization, and intra- and postoperative management. Patient data were retrospectively retrieved using patient's hospital records. Between 2012 and 2020, 29 operations (21 total hip replacements [THRs], 7 total knee replacements [TKRs], 1 total hip revision) were performed in 25 patients (mean age: 67 years). Perioperatively, 72% were treated with low-dose intravenous prostanoid. All had arterial lines, and central access and perioperative lithium dilution cardiac output monitoring was used in 86% of cases. Four patients underwent GA, 21 spinal anesthesia, and 4 CSE anesthesia. Supplemental nerve blocks were performed in all patients undergoing general, and 12 of 21 undergoing spinal anesthesia. All were managed in high dependency postoperatively. Hospital length of stay and complication rates were higher than reported in non-PH patients. Perioperative complications included hypotension requiring vasopressors (n = 10), blood transfusion (n = 7), nonorthopedic infection (n = 4), and decompensated right heart failure (n = 1). There was no associated mortality. All implants were functioning well at 6 weeks and subsequent follow-up. EmPHasis-10 quality of score decreased by 5.5 (±2.1) (p = 0.04). A dedicated multiprofessional pathway can be used to safely select and manage patients with PH through elective lower limb arthroplasty.

Characterization of colorectal mucus using infrared spectroscopy: a potential target for bowel cancer screening and diagnosis.

Biological materials presenting early signs of cancer would be beneficial for cancer screening/diagnosis. In this respect, the suitability of potentially exploiting mucus in colorectal cancer was tested using infrared spectroscopy in combination with statistical modeling. Twenty-six paraffinized colon tissue biopsy sections containing mucus regions from 20 individuals (10 normal and 16 cancerous) were measured using mid-infrared spectroscopic imaging. A digital de-paraffinization, followed by cluster analysis driven digital color-coded multi-staining segmented the infrared images into various histopathological features such as epithelium, connective tissue, stroma, and mucus regions within the tissue sections. Principal component analysis followed by supervised linear discriminant analysis was carried out on pure mucus and epithelial spectra from normal and cancerous regions of the tissue. For the mucus-based classification, a sensitivity of 96%, a specificity of 83%, and an area under the curve performance of 95% was obtained. For the epithelial tissue-based classification, a sensitivity of 72%, a specificity of 88%, and an area under the curve performance of 89% was obtained. The mucus spectral profiles further showed contributions indicative of glycans including that of sialic acid changes between these pathology groups. The study demonstrates that infrared spectroscopic analysis of mucus discriminates colorectal cancers with high sensitivity. This concept could be exploited to develop screening/diagnostic approaches complementary to histopathology.

Interactions Between Pseudomonas Immunotoxins and the Plasma Membrane: Implications for CAT-8015 Immunotoxin Therapy.

Acute Lymphoblastic Leukemia (ALL) remains the most frequent cause of cancer-related mortality in children and novel therapies are needed for the treatment of relapsed/refractory childhood ALL. One approach is the targeting of ALL blasts with the Pseudomonas immunotoxin CAT-8015. Although CAT-8015 has potent anti-leukemia activity, with a 32% objective response rate in a phase 1 study of childhood ALL, haemolytic-uremic syndrome (HUS) and vascular leak syndrome (VLS), major dose-limiting toxicities, have limited the use of this therapeutic approach in children. Investigations into the pathogenesis of CAT-8015-induced HUS/VLS are hindered by the lack of an adequate model system that replicates clinical manifestations, but damage to vascular endothelial cells (ECs) and blood cells are believed to be major initiating factors in both syndromes. Since there is little evidence that murine models replicate human HUS/VLS, and CAT-8015-induced HUS/VLS predominantly affects children, we developed human models and used novel methodologies to investigate CAT-8015 interactions with red blood cells (RBCs) from pediatric ALL patients and ECs of excised human mesenteric arteries. We provide evidence that CAT-8015 directly interacts with RBCs, mediated by Pseudomonas toxin. We also show correlation between the electrical properties of the RBC membrane and RBC susceptibility to CAT-8015-induced lysis, which may have clinical implication. Finally, we provide evidence that CAT-8015 is directly cytototoxic to ECs of excised human mesenteric arteries. In conclusion, the human models we developed constitutes the first, and very important, step in understanding the origins of HUS/VLS in immunotoxin therapy and will allow further investigations of HUS/VLS pathogenesis.

An Evaluation of Introduction of Rapid HIV Testing in a Perinatal Program.

OBJECTIVE: This study was conducted to evaluate the roll-out of rapid HIV testing as part of an emergency Prevention of Perinatal HIV Transmission Program. Specifically, HIV prevalence in this population, the reason(s) for performing the rapid HIV test, and compliance with recommendations for antiretroviral prophylaxis were assessed. METHODS: Since November 2011, all women presenting to a tertiary labour and delivery unit with unknown HIV status or with ongoing risk of HIV infection since their last HIV test were offered rapid HIV testing. Through retrospective chart review, demographic data, HIV risk and prior testing history, and antiretroviral prophylaxis, data were collected and descriptive statistics were performed. RESULTS: One hundred fourteen rapid HIV tests were conducted and there were two preliminary reactive rapid results (one true positive, one false positive). None of the infants was HIV infected. Sixty-three percent of women had multiple risk factors for HIV acquisition, most commonly intravenous drug use (54%). Forty-four percent of women were within the 4-week seroconversion window at the time of delivery; 25% of these women and 52% of their infants received prophylactic drug therapy. CONCLUSION: Rapid HIV testing identified a high-risk cohort and enabled aggressive management of a newly diagnosed HIV-positive pregnancy, successfully preventing perinatal HIV transmission. Risk factors for HIV acquisition were ongoing within the seroconversion window for over half of the women, impacting the utility of the test in eliminating unnecessary antiretroviral prophylaxis in this population because prophylaxis is recommended despite a negative rapid HIV test in these cases.

Unusual skin lesions mimicking bruises caused by Pseudomonas septicemia secondary to undiagnosed peripheral T-cell lymphoma in a young woman.

We present a case of a 30-year-old woman with learning difficulties who was found dead at home by her mother. Her body was partially naked and covered in a number of unusual skin lesions with a targetoid appearance with red erythematous centers and well-delineated halos of pallor. These lesions were initially thought to be bruises by the police and by a forensic postmortem instigated. Postmortem examination also identified hepatosplenomegaly, severe lymphadenopathy, and focal patchy colonic ulceration. Histologic examination of the skin and bowel ulcers showed the lesions to be areas of infarction caused by Pseudomonas aeruginosa vasculitis. Pseudomonas was also cultured from the swabs of the abdomen, the spleen, and the blood cultures. Histologic findings of the lymph nodes showed complete effacement of the normal architecture by a population of pleomorphic small lymphoid cells. Immunohistochemistry confirmed the predominant cell type to be T-cells. The diagnosis of peripheral T-cell lymphoma was made. The cause of death was given as Pseudomonas septicemia secondary to immunocompromise resulting from the undiagnosed peripheral T-cell lymphoma. The pathogenesis of Pseudomonas and its association with malignancy is discussed along with a brief review of peripheral T-cell lymphomas. This case report demonstrates the characteristic macroscopic appearance of cutaneous Pseudomonas-associated lesions and how they can be misinterpreted as bruises.

Nonpigmented intradermal malignant melanoma with cribiform, myxoid, and spindle cell growth patterns.

We describe an unusual variant of intradermal malignant melanoma without any junctional component. The lesion differed from other intradermal melanomas in that it was devoid of pigmentation and was composed of mainly spindle-shaped cells. Within the lesion, there were areas of pseudoglandular and myxoid changes resembling the rare myxoid melanoma. In addition to this, there were areas with an alveolar-like architecture containing nested groups of cells.

Scrotal carcinoma: a reminder of a disappearing occupational disease.

A 55-year-old man presented with a 12 month history of a gradually enlarging eroded lesion on his right scrotum. The patient was a 15-20 cigarettes a day lifelong smoker. Initial histological examination showed a benign squamous lesion. Repeat biopsy at 3 months now showed a poorly differentiated squamous cell carcinoma. Occupational enquiry revealed a long history of exposure to mineral oils. The carcinogenic properties of mineral oils is well recognised and is strongly linked with squamous cell carcinoma (SCC) of the skin, including scrotal carcinoma. This case report highlights the importance of reviewing histology with a second biopsy if clinical manifestations change, and secondly to obtain a thorough occupational history in oddly- presenting lesions.

Warthin tumour of the buccal mucosa.

We report a case of Warthin tumour that arose in the buccal mucosa in a 57-year-old woman. It was treated by excision biopsy. This acts as a reminder particularly to junior clinicians that Warthin tumour may arise outside the parotid.