Double Immunohistochemical Labelling of PRAME and Melan A in Slow Mohs Biopsy Margin Assessment of Lentigo Maligna and Lentigo Maligna Melanoma.

Introduction: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) predominantly affect the head and neck areas in elderly patients, presenting as challenging ill-defined pigmented lesions with indistinct borders. Surgical margin determination for complete removal remains intricate due to these characteristics. Morphological examination of surgical margins is the key form of determining successful treatment in LM/LMM and underpin the greater margin control provided through the Slow Mohs micrographic surgery (SMMS) approach. Recent assessments have explored the use of immunohistochemistry (IHC) markers, such as Preferentially Expressed Antigen in Melanoma (PRAME), to aid in LM/LMM and margin evaluation, leveraging the selectivity of PRAME labelling in malignant melanocytic neoplasms. Methods: A Novel double-labelling (DL) method incorporating both PRAME and MelanA IHC was employed to further maximise the clinical applicability of PRAME in the assessment of LM/LMM in SMMS biopsies. The evaluation involved 51 samples, comparing the results of the novel DL with respective single-labelling (SL) IHC slides. Results: The findings demonstrated a significant agreement of 96.1% between the DL method and SL slides across the tested samples. The benchmark PRAME SL exhibited a sensitivity of 91.3% in the SMMS specimens and 67.9% in histologically confirmed positive margins. Discussion: This study highlights the utility of PRAME IHC and by extension PRAME DL as an adjunctive tool in the assessment of melanocytic tumours within staged excision margins in SMMS samples.

Synchronous primary malignancies of papillary thyroid carcinoma and Hodgkin lymphoma: Interventions and outcome.

Thyroid carcinoma is uncommon. Papillary thyroid carcinoma (PTC) represents the majority of differentiated thyroid carcinoma and is a recognised complication of prior exposure to ionizing radiation. Even more uncommon is the synchronous occurrence of PTC with Hodgkin lymphoma (HL) as multiple primary malignancies. We report a 33-year-old mother of three who developed asymptomatic thyroid nodule for four years, and neck swelling for the recent ten months. She denied constitutional symptoms or B symptoms, and thyroid profiles were normal. Initially, metastatic thyroid cancer was suspected based on ultrasound scan findings of enlarged left thyroid gland and enlarged supraclavicular lymph nodes (LN). However, fine needle aspiration examinations of the thyroid nodule were inconclusive, and the supraclavicular LN was suspicious of HL. Computerised tomography scan detected a large mass at the thyroid glands and lymphadenopathies in the mediastinal, hilar, subcarinal and axilla with dimensions up to 6 cm. Left hemi-thyroidectomy with left supraclavicular LN biopsy revealed PTC in the left thyroid lobe measuring 38 x 25 x 18 mm, and the left supraclavicular LN was not definitive of HL. Completion thyroidectomy on the right side, bilateral central neck dissection and excision biopsy of the right supraclavicular LN revealed the presence of HL in the right supraclavicular LN, and both HL and metastatic PTC in right central LN. After multidisciplinary discussions, the patient received chemotherapy at four weeks postoperatively and achieved complete remission. This report highlights the importance of patient-centered approach and multidisciplinary consensus within lack of established guidelines, given rarity of the case.

Predictors of Mortality among COVID-19 Patients - A Case Control Study at Tertiary Care Center, Nanded (Maharashtra).

Background: The novel Coronavirus is belonging to the family of SARS & MERS-CoV, the impact of the earlier is more dreadful as demonstrated by the steady increase in morbid cases. The average incubation period of COVID-19 is 1-14 days with a mean of 6 days. Aim - To evaluate predictors of mortality among COVID-19 patients. Objectives - 1. To assess risk predictors associated with mortality among COVID-19 patients 2. To a suggest prediction model for preventing mortality in future outbreaks. Materials and Methods: Study design - A case-control study. Study place -Tertiary care center, Nanded, Maharashtra. The present study included 400 cases that died off due to Covid-19 and 400 controls survived COVID-19 disease in a 1:1 proportion. Results: On admission, a significant difference was observed among cases and controls with reference to the percentage of SpO2 (p < 0.05). The proportion of associated co-morbidities among cases was very high i.e., 75.75% as compared to controls with a proportion of 29.25% co-morbidities. The median days of hospital stay were significantly lower in cases compared to controls (3 days vs 12 days, P < 0.001). Conclusion: Length of hospital stay (in days) was showing a significant difference among cases and control (3 days Vs 12 days); hospital stay was less (median 3 days) for cases, as they reported late and thus died earlier; hence concluded that early hospital admission will decrease chances of death due to COVID-19.

The prevalence of chiropractic-related terminology on South African chiropractors' webpages: a cross-sectional study.

BACKGROUND: Effective communication is imperative for successful interprofessional collaborative interactions that augment both patient-centred and evidence based care. Inquiry into the prevalence of chiropractic-related terminology on South African chiropractor's webpages has not been explored to date. The implications of such analysis could indicate the professions' ability to effectively communicate in interdisciplinary settings. METHOD: From 1 to 15 June 2020, Google search was used to identify the webpages (excluding social media accounts) of South African private practice chiropractors registered with the Allied Health Professions Council of South Africa (AHPCSA). Webpages were word-searched for eight chiropractic terms with context: subluxation; manipulate(-ion); adjust(-ing/-ment); holism(-tic); alignment; vital(-ism/-istic); wellness; and innate intelligence. Data collected was transferred to an Excel spreadsheet. Accuracy of information was verified by the researchers through a process of double checking. The number of instances each term was used, and certain socio-demographic data were recorded. Descriptive statistics and bivariate analyses were used to summarise and analyse the data. RESULTS: Among 884 AHPCSA-registered South African chiropractors, 336 webpages were identified and analysed. From 1 to 15 June 2020, the most commonly found terms on 336 South African chiropractic webpages were 'adjust(-ing/-ment)', 'manipulate/manipulation', and 'wellness', with prevalence estimates of 64.1% (95% confidence interval [CI], 59.0% to 69.2%), 51.8% (95% CI, 46.5% to 57.1%), and 33.0% (95% CI, 28.2% to 38.2%), respectively. The least commonly found terms were 'innate intelligence' and 'vital(-ism/-istic)', with prevalence estimates of 0.60% (95% CI, 0.16% to 2.1%) and 0.30% (95% CI, 0.05% to 1.7%), respectively. Manipulate(-ion) was used more by male chiropractors (p = 0.015). The longer a chiropractor was in practice the more likely they were to use profession-specific terms (p = 0.025). The most frequently occurring combination of terms were adjust(-ing/-ment) and manipulate(-ion), found in 38 out of 336 webpages (11.3%; 95% CI, 8.4% to 15.1%). CONCLUSION: The use of chiropractic-related terminology on South African chiropractic webpages was common, with the prevalence of term use varying by type of terms, by gender of the chiropractor, and by clinical practice experience. Better understanding of the effects of chiropractic terminology use on interprofessional and patient interactions and communication is warranted.

Evaluating the efficacy of ovulation stimulation with intrauterine insemination in women with diminished ovarian reserve compared to women with normal ovarian reserve.

OBJECTIVE: To assess the efficacy of ovulation induction and intrauterine insemination (IUI) in couples with diminished ovarian reserve (DOR). METHODS: Women aged 20-39 years and men younger than 50 years were included. Four "ovarian reserve groups" were created according to anti-Müllerian hormone (AMH) and the partner's age. Gestational sac finding on ultrasound examination was the primary outcome measure. RESULTS: The study was carried out on a total of 770 cycles of 362 women in an infertility cohort that consisted of 75 women with DOR treated by 153 cycles and 287 women without DOR treated by 617 cycles. The pregnancy rate was similar in the four ovarian reserve groups in terms of first, second, third plus fourth, and total attempts of IUI cycles. Moreover, the pregnancy rate, miscarriage rate, and multiple pregnancy rate were similar. We found no difference in the cumulative pregnancy rate among the groups after four IUI cycles. Multivariate logistic regression analysis of the entire cohort revealed that infertility duration, post-wash sperm count, and follicle number greater than 11 mm on the day of human chorionic gonadotropin trigger were independent predictors of pregnancy (P < 0.001). Neither age nor AMH predicted pregnancy after ovulation stimulation and IUI. CONCLUSIONS: Ovulation stimulation and IUI are equally effective in women with DOR and in women with normal ovarian reserve in terms of pregnancy rate, multiple pregnancy rate, and miscarriage rate per IUI cycle or cumulative pregnancy rate after four cycles of IUI.

Undiagnosed comorbidities among individuals hospitalised with COVID-19 in South African public hospitals.

BACKGROUND: Previous studies have reported comorbid disease, including hypertension, diabetes mellitus, chronic cardiac and renal disease, malignancy, HIV, tuberculosis (TB) and obesity, to be associated with COVID­19 mortality. National demographic surveys have reported a high proportion of undiagnosed and untreated comorbid disease in South Africa (SA). OBJECTIVES: To determine the number of individuals with previously undiagnosed HIV, TB and non-communicable diseases (NCDs) among patients hospitalised with COVID­19, and the level of medical control of these chronic diseases. METHODS: We conducted a sentinel surveillance study to collect enhanced data on HIV, TB and NCDs among individuals with COVID­19 admitted to 16 secondary-level public hospitals in six of the nine provinces of SA. Trained surveillance officers approached all patients who met the surveillance case definition for inclusion in the study, and consenting patients were enrolled. The data collection instrument included questions on past medical history to determine the self-reported presence of comorbidities. The results of clinical and laboratory testing introduced as part of routine clinical care for hospitalised COVID­19 patients were collected for the study, to objectively determine the presence of hypertension, diabetes, HIV and TB and the levels of control of diabetes and HIV. RESULTS: On self-reported history, the most prevalent comorbidities were hypertension (n=1 658; 51.5%), diabetes (n=855; 26.6%) and HIV (n=603; 18.7%). The prevalence of self-reported active TB was 3.1%, and that of previous TB 5.5%. There were 1 254 patients admitted with COVID­19 (39.0%) who met the body mass index criteria for obesity. On clinical and laboratory testing, 87 patients were newly diagnosed with HIV, 29 with TB, 215 with diabetes and 40 with hypertension during their COVID­19 admission. There were 151/521 patients living with HIV (29.0%) with a viral load >1 000 copies/mL and 309/570 (54.2%) with a CD4 count <200 cells/µL. Among 901 patients classified as having diabetes, 777 (86.2%) had a glycated haemoglobin (HbA1c) level ≥6.5%. CONCLUSION: The study revealed a high prevalence of comorbid conditions among individuals with COVID­19 admitted to public hospitals in SA. In addition, a significant number of patients had previously undiagnosed hypertension, diabetes, HIV and active TB, and many and poorly controlled chronic disease, as evidenced by high HbA1c levels in patients with diabetes, and high viral loads and low CD4 levels in patients with HIV. The findings highlight the importance of strengthening health systems and care cascades for chronic disease management, which include prevention, screening for and effectively treating comorbidities, and ensuring secure and innovative supplies of medicines in primary healthcare during the COVID­19 pandemic.

Concomitant behavior of arsenic and selenium from the karst infillings materials of the fractured carbonate Dogger Aquifer (Hydrogeological Experimental Site, Poitiers, France).

Petrographic and mineralogical analyses combined with sequential extractions and leaching experiments as a function of pH were performed on black clayey sediments fulfilling karsts in the Hydrogeological Experimental Site (HES) of Poitiers (France) to investigate the behavior of arsenic and selenium in a fractured limestone aquifer. Sequential extractions showed that arsenic is mainly associated with pyrite (about 35%) and secondary iron oxyhydroxides (around 13%), along with a substantial exchangeable fraction (about 13%). The soluble fraction and the fraction associated to organic matter are âˆ¼2% and ∼5%, respectively. The distribution of selenium is mainly pyritic (around 39%) or associated with organic matter (about 18%). Its association to secondary iron oxyhydroxides minerals is low (around 2%), whereas its soluble fraction is around 5%. SEM analyses revealed the presence of arsenic "hot spots" into euhedral pyrite crystals surrounded by a halo of iron oxyhydroxides resulting from their alteration, and both are enriched with arsenic. Selenium has a similar pyritic origin but after alteration, it is predominantly associated with organic matter. Despite different distributions, the leaching experiment as a function of pH showed that the mobilization of arsenic and selenium overlapped below pH 2 and above pH 8. The main differences were observed between pH 2 and 8 with a plateau at 5% of released selenium, whereas the amount of mobilized arsenic continuously decreased. The pH-dependence of both elements is attributed to the partial dissolution of pyrite in acidic conditions combined with desorption processes at higher pH values.

MRI-based brain structural changes following radiotherapy of Nasopharyngeal Carcinoma: A systematic review.

PURPOSE: Nasopharyngeal carcinoma (NPC) radiotherapy (RT) irradiates parts of the brain which may cause cerebral tissue changes. This study aimed to systematically review the brain microstructure changes using MRI-based measures, diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI) and voxel-based morphometry (VBM) and the impact of dose and latency following RT. METHODS: PubMed and Scopus databases were searched based on PRISMA guideline to determine studies focusing on changes following NPC RT. RESULTS: Eleven studies fulfilled the inclusion criteria. Microstructural changes occur most consistently in the temporal region. The changes were correlated with latency in seven studies; fractional anisotropy (FA) and gray matter (GM) volume remained low even after a longer period following RT and areas beyond irradiation site with reduced FA and GM measures. For dosage, only one study showed correlation, thus requiring further investigations. CONCLUSION: DTI, DKI and VBM may be used as a surveillance tool in detecting brain microstructural changes of NPC patients which correlates to latency and brain areas following RT.

Analysis of complications following multidisciplinary functional intervention in paediatric craniomaxillofacial deformities.

Paediatric craniomaxillofacial (CMF) surgery requires a multidisciplinary team approach to ensure the optimal and holistic management of children with craniofacial deformities. The aim of this retrospective study was to analyse the complications following functional interventions among 34 CMF deformity patients in a single multidisciplinary craniofacial centre. Electronic data including patient demographic characteristics and clinical entry were analysed. Inclusion criteria were all paediatric patients with CMF deformities who underwent various functional interventions. A total of 64 interventions (48 intermediate and 16 definitive) were conducted. Based on the Sharma classification of complications, 20.3% were type I, 4.7% were type II, 1.6% were type III, and 4.7% were type IV . Most complications were type I, which included local infection (3.1%) and premature opening of tarsorrhaphy (3.1%). More serious complications (types III and IV) included temporary visual loss (1.6%) and intraoperative haemorrhage (1.6%). Although a low complication rate was observed in intermediate interventions, a higher complication rate was observed in more complex definitive interventions such as monobloc distraction osteogenesis. Although most complications were manageable, effective prevention remains mandatory, as serious complications may lead to permanent damage and mortality. This analysis highlights the importance of a multidisciplinary team approach to optimize the outcomes in CMF patient management.

Antimicrobial susceptibility and serotype distribution of Streptococcus agalactiae rectovaginal colonising isolates from pregnant women at a tertiary hospital in Pretoria, South Africa: An observational descriptive study.

BACKGROUND: Streptococcus agalactiae or group B streptococcus (GBS) is a significant cause of neonatal sepsis. Intrapartum antibiotic prophylaxis is recommended for pregnant women identified to be rectovaginally colonised between 34 and 37 weeks' gestational age to decrease the risk of invasive disease in their newborns. An effective multivalent GBS vaccine may prevent a broader scope of GBS-associated diseases, such as GBS early-onset disease, GBS late-onset disease, spontaneous abortion, stillbirth and maternal bacteraemia. Serotype distribution of GBS isolates is essential to determine the efficacy of such a vaccine. OBJECTIVES: To investigate serotype distribution and antimicrobial susceptibility patterns of GBS isolates cultured from rectovaginal specimens during pregnancy. METHODS: Sixty-nine archived maternal colonising isolates were tested against penicillin, erythromycin, clindamycin, vancomycin and levofloxacin. Minimum inhibitory concentration testing was performed using the ETEST method. Serotyping was performed by the latex agglutination method. RESULTS: The most common serotypes detected were Ia (54%), III (20%), V (16%), II (6%), IV (2%) and Ib (1%). All isolates were fully susceptible to penicillin, vancomycin and levofloxacin. Eight (11%) and 50 (56%) isolates showed intermediate resistance to erythromycin and clindamycin, respectively, and 1 isolate was resistant to erythromycin. The macrolide-lincosamide-streptogramin B (MLSB) phenomenon was noted in 3 (4%) of the isolates. CONCLUSIONS: GBS-colonising isolates remain susceptible to penicillin, which remains the drug of choice for intrapartum antibiotic prophylaxis and treatment of invasive disease in newborns. Macrolides should only be used if clinically indicated due to the high prevalence of intermediate resistance. A pentavalent GBS vaccine currently in phase I trials should provide coverage for 97% of the isolates identified in this study.

Two-weekly docetaxel in treatment of advanced breast cancer: A preliminary study.

OBJECTIVE: Three-weekly docetaxel causes a high rate of febrile neutropenia, especially in the Asian population. Two-weekly docetaxel has been shown to reduce rate of febrile neutropenia in castrate-resistant prostate cancer patients. We conducted a preliminary study to investigate the safety of two-weekly docetaxel in advanced breast cancer patients. METHODS: We recruited 10 patients with advanced breast cancer with ECOG (Eastern Cooperative Oncology Group) performance status score of zero to two, who needed chemotherapy in the first or second-line setting to receive two-weekly docetaxel for 8 cycles. The primary endpoint was safety and secondary endpoints were response rate and progression free survival. RESULTS: The most reported adverse events were haematological (anaemia 100% and neutropenia 90%). The febrile neutropenia rate was 10%. The overall response rate was 20%. The median progression free survival was 5.0 months. CONCLUSION: Two-weekly docetaxel may be a reasonable alternative treatment regimen for patients with advanced breast cancer in the first or second-line setting. This regimen is yet to be compared with standard 3-weekly schedule in a phase 3 randomised clinical trial.

Chemodiversity and Antiproliferative Activity of the Essential Oil of Schinus molle Growing in Jordan.

The leaves and unripe and fully-grown fruits of Schinus molle were collected from three geographical regions of Jordan: Amman (the Mediterranean), Madaba (Irano-Turanean), and Sahab (Saharo-Arabian). The hydrodistilled volatile oils of fresh and dried leaves and fruits were analyzed by gas chromatography-mass spectrometry (GC/MS). The actual composition of the emitted volatiles was determined using Solid Phase Micro-Extraction (SPME). α- and ß-Phellandrenes were the major components in all the analyzed samples. Quantitative differences were observed in the obtained essential oils (0.62-5.25 %). Additionally, cluster analysis was performed. Biologically, the antiproliferative activity of the essential oil, ethanol, and water extracts of the fruits and leaves was screened on Caco2, HCT116, MCF7, and T47D cell lines. The essential oil and ethanol extracts exhibited a dose-dependent inhibition of cell growth with IC50 ranging between 21 and 65 µg/mL. The water extract did not exhibit any antiproliferative activity against the investigated cell lines.

Semi-automated standardisation of melanin bleaching procedures of heavily pigmented melanocytic lesions for immunohistochemical analysis on an automated platform.

Background: The diagnosis of heavily pigmented melanocytic lesions is problematic. This is often compounded by lack of visibility of nuclear detail of tumour cells due to physical masking by melanin pigment. Similarly, there can be colour merging of chromogenic final reaction products with melanin, making an evidence of antigenic localisation problematic. There are a number of melanin bleaching techniques available for immunohistochemical assessments.Material and methods: All methods to date have involved the bleaching of melanin as a manually performed primary step before loading subsequently bleached slides onto automated immunohistochemical platforms. Here we define a semi-automated bleaching procedure that allows full integration on one of the most widely employed automated IHC staining platforms (Roche Ventana BenchMark Ultra). The bleaching protocol was defined on the BenchMark Ultra and involved the assessment of 24 histological cases of heavily pigmented malignant melanoma lesions (13 cutaneous and 11 metastatic) routinely fixed processed and paraffin wax embedded.Results: Completion of the bleaching was assessed on H&E preparations performed following the semi-automated bleaching step and employing the Roche Ventana BenchMark Ultra machine for 60 min at 42°C. Complete immunohistochemical staining was achieved on the automated platform within 5-6 h including the bleaching step. Results were consistent across all tissue evaluated.Discussion: This data provides evidence that the hydrogen peroxide bleaching procedure can be adapted for integration on one of the most widely employed automated IHC staining platforms and as a result, improve the efficiency and reproducibility of the technique.

Patient preferences for topical treatment of actinic keratoses: a discrete-choice experiment.

BACKGROUND: The treatment of actinic keratosis (AK) is a potentially effective strategy for the prevention of cutaneous squamous cell carcinoma (cSCC). However, the patient perspective on potential benefits of AK treatment in terms of skin cancer reduction has received little attention to date. OBJECTIVES: (i) To investigate patient preferences for topical treatments for AK using a discrete-choice experiment (DCE); (ii) to evaluate patient willingness to trade between clinical benefit and medical burden. METHODS: The DCE was conducted as part of a study to establish the feasibility of a phase III randomized controlled trial evaluating the prevention of cSCC using currently available topical interventions. Preferences were elicited by asking patients to make a series of choices between treatment alternatives with different hypothetical combinations of attribute levels. Willingness to trade between treatment attributes was estimated using a flexible-choice model that allows for the heterogeneity of patient preferences. RESULTS: A total of 109 patients with AK completed the DCE. The majority of patients who expressed valid preferences were willing to accept some reduction in both prophylactic and cosmetic efficacy to reduce the burden of the treatment regimen, the severity of skin reaction and other adverse effects. Patients may reject treatment if the perceived therapeutic benefit is outweighed by the subjective burden of treatment. CONCLUSIONS: Evidence of significant variation in the perceived utility of treatments across patients highlights the importance of taking individual patient preferences into account to improve AK treatment acceptability and adherence.

Frequency of food hypersensitivity in patients with Functional Gastrointestinal Disorders.

BACKGROUND AND STUDY AIMS: Food hypersensitivity (FH), irritable bowel syndrome (IBS) and functional dyspepsia (FD) have many overlapping symptoms, including abdominal discomfort, bloating, and altered bowel habits. We aimed to determine the frequency of FH in patients with IBS and functional FD. PATIENTS AND METHODS: Adult patients of either gender diagnosed with IBS and/or FD as per the Rome III criteria were recruited. Patients underwent serological testing against 6 food allergens: beef, shrimp, egg white, milk, peanut, and soy-bean. Those testing positive were subjected to a food elimination diet for 4 weeks. Those showing improvement on elimination diet were subjected to re-challenge. Changes in symptoms were documented by the Global overall improvement scale (GOS) and Gastrointestinal symptom rating scale (GSRS). RESULTS: Two hundred patients were screened. Average age of the patients was 38.6, and 55 % were male. Nineteen (38%) patients tested positive, and were subjected to a food elimination diet. The most common food hypersensitivity was shrimp (17/89%), followed by 4/21% for egg-white, and peanut. Off these, 8 showed improvement. They were re-challenged, and were evaluated 2 weeks later, when all suffered symptom relapse. These 8 (4%) patients were diagnosed with FH. There was a statistically significant difference in both GSRS (total and component) and GOS scores at baseline between patients testing (+) and (-) on food allergen testing, mainly for diarrhoea (p=0.001), abdominal pain (p=0.001) and indigestion p=<0.001). CONCLUSIONS: FH is present in 4 % of patients with a functional gastrointestinal disorder.

[Unexplained diffuse arteriosclerosis in a 26-year-old patient]. / Artériosclérose diffuse inexpliquée chez une jeune patiente de 26 ans.

Arteriosclerosis is an alteration of the blood vessels whose walls calcify, lose their elasticity and thicken. The result is a decrease in circulating blood flow and ischemic manifestations. Calcification of the arteries is a physiological phenomenon in the elderly but young subjects may also be affected. Indeed, certain risk factors can favor the formation of plaques at the level of the vessels. These include classic cardiovascular risk factors, as well as systemic inflammatory diseases, connective tissue diseases, chronic hypercalcemia… We report the case of a 26-year-old female patient with diffuse arteriosclerosis discovered accidentally, and whose exhaustive etiological investigation remained negative.