Detecting Progression of Treated Choroidal Melanomas: Is Ultrasonography Necessary?

Prompt detection and treatment of local treatment failure after radiotherapy for choroidal melanoma optimises any opportunities for conserving vision and the eye, possibly reducing an increased risk of metastatic disease. Long-term surveillance is therefore required but is hampered by the perceived need to perform ultrasonography, which may not be available at a patient’s local hospital. The aim of this study was to determine whether local treatment failure can reliably be detected with colour fundus photography alone, and, if so, in which patients. Patients were included in the study if diagnosed with local treatment failure between April 2016 and February 2021 after eye-conserving therapy for choroidal melanoma. Wide-field colour and fundal autofluorescence (FAF) images, optical coherence tomography (OCT), and ultrasonography (US) were analysed by two of the authors (GN and UH). The cohort included 87 patients with local treatment failure. In 75 patients with clear media, tumour progression was detected by colour photography alone in 74 (98.7%) patients. Sensitivity was not increased by the addition of either OCT or AF. One patient with clear media developed extraocular extension detected with US without visible change in the intraocular part of the tumour. In the other 12 patients, US was required because of opaque media and a consequently poor fundal view. Local treatment failure after radiotherapy for choroidal melanoma is detected in 98.7% of cases with colour photography when the media are clear. Ultrasonography is useful when photography is prevented by opaque media or tumours having locations in the far periphery

Survival analysis following enucleation for uveal melanoma

OBJECTIVES: To determine survival outcomes following enucleation for uveal melanoma. To compare these outcomes with the 8th edition AJCC classification and determine the influence of cytogenetics, using Fluorescent in situ Hybridisation (FISH), on survival. To determine whether failure to gain sufficient sample for cytogenetics using Fine Needle Aspiration Biopsy (FNAB) correlates with survival. SUBJECTS/METHODS: All patients undergoing primary enucleation for uveal melanoma at Moorfields Eye Hospital between 2012 and 2015 were included. Clinical, pathological, cytological and survival data were analysed for all patients. RESULTS: In total, 155 subjects were included. Mean age at enucleation was 65.9 years (SD 14.13). 88 (56.8%) patients died at a mean of three (SD 1.9) years following enucleation. Of these, 52 (33.5%) died from metastatic melanoma, 16 (10.3%) from other causes and 20 (12.9%) causes of death were unknown. Cumulative incidence analysis demonstrated AJCC grade, chromosome 8q gain and monosomy three all predict metastatic mortality. The greatest 5-year mortality rate (62%, SD10.1%) was in those with both chromosome abnormalities and AJCC stage III (Stage IV patients excluded due to low numbers). Largest basal diameter and chromosome status, both independently (p = 0.02 and p < 0.001) predicted metastatic mortality on multivariable regression analysis. Those who had an insufficient sample of cells gained during FNAB (n = 16) had no different prognosis. CONCLUSIONS: This study confirms, in this population, the poor survival of patients enucleated for uveal melanomas. It confirms the prognostic utility of adding AJCC grade to cytogenetic information. It demonstrates that the lack of sample in patients undergoing FNAB is not related to prognosis

Adjuvant External Beam Radiotherapy Following Enucleation of Eyes With Extraocular Extension From Uveal Melanoma

PURPOSE: To report local disease control and all-cause mortality in patients with extraocular extension (EOE) of uveal melanoma undergoing enucleation followed by observation or external beam radiotherapy (EBRT). METHODS: Charts of patients enucleated between January 1, 1997 and December 31, 2019, with histopathological evidence of EOE of uveal melanoma were reviewed. RESULTS: The cohort comprised 51 patients with a mean age of 67 ± 15 years, 22 (43%) of whom underwent adjuvant postenucleation EBRT. Risk factors for metastasis included presence of epithelioid cells (29/45; 88%), closed loops (20/43; 47%), monosomy 3 (16/25; 64%), and gain of 8q (20/22; 91%). Patients undergoing EBRT had more extensive EOE (median: 5.1 mm vs. 2.6 mm, p = 0.008) and surgical excision was less likely to be histologically complete (2/20; 10% vs. 14/25; 56%, p = 0.002). Local side effects following EBRT were seen in 64% (14/22). At latest follow up, 59% of patients (30/51) were alive, with a median follow up of 1.8 years (interquartile range: 2.9; range: 0.1-6.5]. By Kaplan-Meier survival analysis, the 5- and 10-year overall survival rates were 56% and 12%, respectively. There was no difference in all-cause mortality between those receiving adjuvant EBRT and those who were observed (log rank, p = 0.273). No cases of orbital recurrence were documented. CONCLUSIONS: Orbital EBRT causes significant morbidity. Cases with relatively small EOE undergoing enucleation can be safely observed, without adjuvant EBRT. Multicenter studies are required to better assess the role of EBRT when EOE is more extensive

Immediate implant placement and provisionalization:Aesthetic outcome 1 year after implant placement. A prospective clinical multicenter study

Contains fulltext : 220439.pdf (Publisher’s version ) (Closed access)BACKGROUND: Prospective aesthetic outcomes on a high number of patients after immediate implant placement and provisionalization (IIPP) are lacking. PURPOSE: To analyze the aesthetic outcome after IIPP. MATERIALS AND METHODS: One hundred consecutive patients with a failing maxillary incisor were provided with an immediately placed and provisionalized nonloaded implant using a flapless procedure and palatal implant positioning. The remaining gap buccally was filled with a bone substitute. Preoperatively (T0), 2 weeks postoperatively (T1), direct after placement of the permanent crown (T2), and 1 year after IIPP (T3), standardized light photographs were made. Change in aesthetic score was the primary outcome measure. Both the white aesthetic score (WES) and pink aesthetic score (PES) were used. RESULTS: In the first year postsurgery, the mean total-WES and total-PES scores raised from 4.5 to 8.2, and from 9.9 to 12.1, respectively. The mean PES scores for mesial and distal papilla, soft tissue marginal level, contour, color, and texture, raised significantly (P < .05), while the alveolar process contour, on average, remained stable from T0 to T3. CONCLUSIONS: Within the limitations of this 1-year research, it may be concluded that, following this minimal invasive IIPP procedure, a high aesthetic outcome was achieved

A Fibreoptic Endoscopic Study of Upper Gastrointestinal Bleeding at Bugando Medical Centre in Northwestern Tanzania: a Retrospective Review of 240 Cases.

Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Phenotypic differences between dermal fibroblasts from different body sites determine their responses to tension and TGFβ1

BACKGROUND: Wounds in the nonglabrous skin of keloid-prone individuals tend to cause large disordered accumulations of collagen which extend beyond the original margins of the wound. In addition to abnormalities in keloid fibroblasts, comparison of dermal fibroblasts derived from nonwounded glabrous or nonglabrous skin revealed differences that may account for the observed location of keloids. METHODS: Fibroblast apoptosis and the cellular content of α-smooth-muscle actin, TGFβ1 receptorII and ED-A fibronectin were estimated by FACS analysis. The effects of TGFβ1 and serum were examined. RESULTS: In monolayer cultures non-glabrous fibroblasts were slower growing, had higher granularity and accumulated more α-smooth-muscle actin than fibroblasts from glabrous tissues. Keloid fibroblasts had the highest level of α-smooth-muscle actin in parallel with their expression level of ED-A fibronectin. TGFβ1 positively regulated α-smooth-muscle actin expression in all fibroblast cultures, although its effects on apoptosis in fibroblasts from glabrous and non-glabrous tissues were found to differ. The presence of collagen I in the ECM resulted in reduction of α-smooth-muscle actin. A considerable percentage of the apoptotic fibroblasts in attached gels were α-smooth-muscle actin positive. The extent of apoptosis correlated positively with increased cell and matrix relaxation. TGFβ1 was unable to overcome this apoptotic effect of matrix relaxation. CONCLUSION: The presence of myofibroblasts and the apoptosis level can be regulated by both TGFβ1 and by the extracellular matrix. However, reduction of tension in the matrix is the critical determinant. This predicts that the tension in the wound bed determines the type of scar at different body sites

Hypothermia predicts mortality in critically ill elderly patients with sepsis

<p>Abstract</p> <p>Background</p> <p>Advanced age is one of the factors that increase mortality in intensive care. Sepsis and multi-organ failure are likely to further increase mortality in elderly patients.</p> <p>We compared the characteristics and outcomes of septic elderly patients (> 65 years) with younger patients (≤ 65 years) and identified factors during the first 24 hours of presentation that could predict mortality in elderly patients.</p> <p>Methods</p> <p>This study was conducted in a Level III intensive care unit with a case mix of medical and surgical patients excluding cardiac and neurosurgical patients.</p> <p>We performed a retrospective review of all septic patients admitted to our ICU between July 2004 and May 2007. In addition to demographics and co-morbidities, physiological and laboratory variables were analysed to identify early predictors of mortality in elderly patients with sepsis.</p> <p>Results</p> <p>Of 175 patients admitted with sepsis, 108 were older than 65 years. Elderly patients differed from younger patients with regard to sex, temperature (37.2°C VS 37.8°C p < 0.01), heart rate, systolic blood pressure, pH, HCO₃, potassium, urea, creatinine, APACHE III and SAPS II. The ICU and hospital mortality was significantly higher in elderly patients (10.6% Vs 23.14% (p = 0.04) and 19.4 Vs 35.1 (p = 0.02) respectively). Elderly patients who died in hospital had a significant difference in pH, HCO₃, mean blood pressure, potassium, albumin, organs failed, lactate, APACHE III and SAPS II compared to the elderly patients who survived while the mean age and co-morbidities were comparable. Logistic regression analysis identified temperature (OR [per degree centigrade decrease] 0.51; 95% CI 0.306- 0.854; p = 0.010) and SAPS II (OR [per point increase]: 1.12; 95% CI 1.016-1.235; p = 0.02) during the first 24 hours of admission to independently predict increased hospital mortality in elderly patients.</p> <p>Conclusions</p> <p>The mortality in elderly patients with sepsis is higher than the younger patients. Temperature (hypothermia) and SAPS II scores during the first 24 hours of presentation independently predict hospital mortality.</p

Pulmonary tuberculosis among people living with HIV/AIDS attending care and treatment in rural northern Tanzania

Tuberculosis is the commonest opportunistic infection and the number one cause of death in HIV/AIDS patients in developing countries. To address the extent of the tuberculosis HIV coinfection in rural Tanzania we conducted a cross sectional study including HIV/AIDS patients attending care and treatment clinic from September 2006 to March 2007. Sputum samples were collected for microscopy, culture and drug susceptibility testing. Chest X-ray was done for those patients who consented. Blood samples were collected for CD4+ T cells count. The prevalence of tuberculosis was 20/233 (8.5%). Twenty (8.5%) sputum samples were culture positive. Eight of the culture positive samples (40%) were smear positive. Fifteen (75%) of these patients neither had clinical symptoms nor chest X-ray findings suggestive of tuberculosis. Nineteen isolates (95%) were susceptible to rifampicin, isoniazid, streptomycin and ethambutol (the first line tuberculosis drugs). One isolate (5%) from HIV/tuberculosis coinfected patients was resistant to isoniazid. No cases of multi- drug resistant tuberculosis were identified. We found high prevalence of tuberculosis disease in this setting. Chest radiograph suggestive of tuberculosis and clinical symptoms of fever and cough were uncommon findings in HIV/tuberculosis coinfected patients. Tuberculosis can occur at any stage of CD4+T cells depletion