Gender Differences in Melanoma Progression and Survival

__Abstract__ Cutaneous melanoma is developing into a major public health problem worldwide. Incidence differs greatly across the world with high incidence rates in the Unites states, Europe and especially in Australia and New Zealand, but relatively low incidence rates in Central and South America, Asia and Africa. In Europe, melanoma incidence is rising, especially in the Northern and Western European countries. This is also true for the United States, where melanoma is one of the few cancer types which showed continuously increasing incidence rates from 1975 onward. Also in the Netherlands, incidence of melanoma keeps increasing (figure 2). Although incidence in Australia and New Zealand remains the highest in the world1, incidence has been observed to stabilize in younger individuals in both Australia5, as well as in Canada. Differences across gender in melanoma incidence have been noted for a long time

Correlation of Isotope Count With Sentinel Node Positivity in Vulvar Cancer

Objective: Sentinel node biopsy (SNB) has become standard of care in early stage vulvar cancer. As the correlation of isotope count with the presence of metastases remains unclear, often several active nodes are excised per groin. This can result in increased morbidity in node-negative disease despite of SNB. In the current analysis, we assess whether resection of the hottest node could be sufficient to detect sentinel lymph node (SLN) metastasis. Methods: Patients with primary vulvar cancer receiving an SNB with radioactive tracer at the University Medical Center Hamburg-Eppendorf between 2008 and 2015 were evaluated. Results: A total of 145 patients with SNB were analyzed;thereof, 144 underwent bilateral SNB, resulting in 289 analyzed groins. A median of 2 SLNs (range, 1-7) per groin were removed. From 94 (32.5%) of 289 groins, more than 2 SLNs were excised. Median overall SLN isotope count was 1400 cps. In 50 groins, a positive SLN was detected (unilateral in 38 patients, bilateral in 6). The median number of positive SLN per groin was 1 (range, 1-4). The SLN with the highest isotope count carried metastases in 36 (78.3%) of 46 groins (in 4 cases, the highest count was unknown). In 10 (21.7%) of 46 positive groins, the SLN with the highest count was not the metastatic SLN (9/10 second highest count). Median count of these 10 SLN was 60% of the highest count with a range from 11.0% to 74.0%. Conclusions: The highest isotope count does not reliably detect the positive SLN in vulvar cancer. To prevent mostly fatal groin recurrences, surgeons should continue to remove all SLN accumulating relevant radioactive tracer over background activity

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease: A Systematic Review and Revised Dosing Considerations

OBJECTIVES: Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which i

Applications of Nanopore sequencing in precision cancer medicine

Oxford Nanopore Technologies sequencing, also referred to as Nanopore sequencing, stands at the forefront of a revolution in clinical genetics, offering the potential for rapid, long read, and real‐time DNA and RNA sequencing. This technology is currently making sequencing more accessible and affordable. In this comprehensive review, we explore its potential regarding precision cancer diagnostics and treatment. We encompass a critical analysis of clinical cases where Nanopore sequencing was successfully applied to identify point mutations, splice variants, gene fusions, epigenetic modifications, non‐coding RNAs, and other pivotal biomarkers that defined subsequent treatment strategies. Additionally, we address the challenges of clinical applications of Nanopore sequencing and discuss the current efforts to overcome them

Statin use and its effect on all-cause mortality of melanoma patients:A population-based Dutch cohort study

Preclinical data showed anticancer effects of statins in melanoma, but meta-analyses could not demonstrate a reduced melanoma incidence in statin users. Rather than preventing occurrence, statins might reduce growth and metastatic spread of melanomas and ultimately improve survival. In this population-based study, we investigated the relationship between statin use and survival of melanoma patients. Patients ≥18 years who were diagnosed with cutaneous melanoma (Breslow thickness >1 mm) and registered in the Eindhoven Cancer Registry and in PHARMO Database Network between 1 January 1998 and 31 December 2010 were eligible. The hazard ratio (HR) of all-cause mortality was calculated by employing adjusted time-dependent and time-fixed Cox proportional hazard models. Disease-specific survival was estimated by means of 3-year relative survival rates (RSR). A control cohort of randomly selected patients using statins from PHARMO Database Network matched on age and gender was used to compare RSR of statin users to the general population. After melanoma diagnosis, 171 of 709 patients used statins. Use of statins showed a nonsignificantly decreased hazard of death (adjusted HR 0.76, 95% confidence interval [CI] 0.50–1.61). After stratification for gender, male but not female statin users showed a favorable outcome compared to nonusers (HR 0.57, 95% CI 0.32–0.99; HR 1.22, 95% CI 0.62–2.38, respectively). Three-year RSR for male statin users tended to be higher than for nonusers (91% vs. 80.5%, P = 0.06), no differences were observed in women (87.1% vs. 92.5%, P = 0.76). Statin use was not associated with an improved survival of melanoma patients. The trend for better survival of male in contrast to female statin users warrants further research

The caregiver’s experience of childhood cancer treatment in South Africa

Background: This study explored the treatment-related, financial and psychological experiences of caregivers during cancer treatment of their children in South Africa’s (SA) public and private sectors. Methods: In this exploratory study, three focus groups were conducted with caregivers of children undergoing cancer treatment in SA’s public healthcare sector. A fourth small focus group with two parents in the private sector was conducted online. A mixed-methods approach was employed using a combination of thematic analysis and grounded theory. Results: Of the 20 public sector caregivers, many expressed frustration at the number of visits to primary healthcare clinics before being referred. Caregivers had difficulties coping with and accepting the diagnosis, alongside managing continued care for the child and other children at home. Support received by family and community members was varied. Financial strain was an important concern. The two private sector parents indicated greater levels of support and no financial hardship, but expressed similar levels of emotional stress. Conclusion: These caregiver experiences indicate that improvements are urgently needed in the recognition of childhood cancer symptoms at primary healthcare level in SA. They also highlight a need for increased financial support from government through social grants, travel allowances and nutritional support

Extramedullary versus intramedullary fixation of unstable trochanteric femoral fractures (AO type 31-A2):a systematic review and meta-analysis

Objective: The aim of this systematic review was to compare extramedullary fixation and intramedullary fixation for AO type 31-A2 trochanteric fractures in the elderly, with regard to functional outcomes, complications, surgical outcomes, and costs. Methods: Embase, Medline, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched for randomized controlled trials (RCTs) and observational studies. Effect estimates were pooled across studies using random effects models. Results are presented as weighted risk ratio (RR) or weighted mean difference (MD) with corresponding 95% confidence interval (95% CI). Results: Fourteen RCTs (2039 patients) and 13 observational studies (22,123 patients) were included. Statistically superior results in favor of intramedullary fixation were found for Harris Hip Score (MD 4.09, 95% CI 0.91–7.26, p = 0.04), Parker mobility score (MD − 0.67 95% CI − 1.2 to − 0.17, p = 0.009), lower extremity measure (MD − 4.07 95% CI − 7.4 to − 0.8, p = 0.02), time to full weight bearing (MD 1.14 weeks CI 0.92–1.35, p &lt; 0.001), superficial infection (RR 2.06, 95% CI 1.18–3.58, p = 0.01), nonunion (RR 3.67, 95% CI 1.03–13.10, p = 0.05), fixation failure (RR 2.26, 95% CI 1.16–4.44, p = 0.02), leg shortening (MD 2.23 mm, 95% CI 0.81–3.65, p = 0.002), time to radiological bone healing (MD 2.19 months, 95% CI 0.56–3.83, p = 0.009), surgery duration (MD 11.63 min, 95% CI 2.63–20.62, p = 0.01), operative blood loss (MD 134.5 mL, 95% CI 51–218, p = 0.002), and tip-apex distance &gt; 25 mm (RR 1.73, 95% CI 1.10–2.74, p = 0.02). No comparable cost/costs-effectiveness data were available.Conclusion: Current literature shows that several functional outcomes, complications, and surgical outcomes were statistically in favor of intramedullary fixation when compared with extramedullary fixation of AO/OTA 31-A2 fractures. However, as several of the differences found appear not to be clinically relevant and for many outcomes data remains sparse or heterogeneous, complete superiority of IM fixation for AO type 31-A2 fractures remains to be confirmed in a detailed cost-effectiveness analysis.</p

Extramedullary versus intramedullary fixation of unstable trochanteric femoral fractures (AO type 31-A2):a systematic review and meta-analysis

Objective: The aim of this systematic review was to compare extramedullary fixation and intramedullary fixation for AO type 31-A2 trochanteric fractures in the elderly, with regard to functional outcomes, complications, surgical outcomes, and costs. Methods: Embase, Medline, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched for randomized controlled trials (RCTs) and observational studies. Effect estimates were pooled across studies using random effects models. Results are presented as weighted risk ratio (RR) or weighted mean difference (MD) with corresponding 95% confidence interval (95% CI). Results: Fourteen RCTs (2039 patients) and 13 observational studies (22,123 patients) were included. Statistically superior results in favor of intramedullary fixation were found for Harris Hip Score (MD 4.09, 95% CI 0.91–7.26, p = 0.04), Parker mobility score (MD − 0.67 95% CI − 1.2 to − 0.17, p = 0.009), lower extremity measure (MD − 4.07 95% CI − 7.4 to − 0.8, p = 0.02), time to full weight bearing (MD 1.14 weeks CI 0.92–1.35, p &lt; 0.001), superficial infection (RR 2.06, 95% CI 1.18–3.58, p = 0.01), nonunion (RR 3.67, 95% CI 1.03–13.10, p = 0.05), fixation failure (RR 2.26, 95% CI 1.16–4.44, p = 0.02), leg shortening (MD 2.23 mm, 95% CI 0.81–3.65, p = 0.002), time to radiological bone healing (MD 2.19 months, 95% CI 0.56–3.83, p = 0.009), surgery duration (MD 11.63 min, 95% CI 2.63–20.62, p = 0.01), operative blood loss (MD 134.5 mL, 95% CI 51–218, p = 0.002), and tip-apex distance &gt; 25 mm (RR 1.73, 95% CI 1.10–2.74, p = 0.02). No comparable cost/costs-effectiveness data were available.Conclusion: Current literature shows that several functional outcomes, complications, and surgical outcomes were statistically in favor of intramedullary fixation when compared with extramedullary fixation of AO/OTA 31-A2 fractures. However, as several of the differences found appear not to be clinically relevant and for many outcomes data remains sparse or heterogeneous, complete superiority of IM fixation for AO type 31-A2 fractures remains to be confirmed in a detailed cost-effectiveness analysis.</p

Binocular summation and other forms of non-dominant eye contribution in individuals with strabismic amblyopia during habitual viewing

YesAdults with amblyopia ('lazy eye'), long-standing strabismus (ocular misalignment) or both typically do not experience visual symptoms because the signal from weaker eye is given less weight than the signal from its fellow. Here we examine the contribution of the weaker eye of individuals with strabismus and amblyopia with both eyes open and with the deviating eye in its anomalous motor position. The task consisted of a blue-on-yellow detection task along a horizontal line across the central 50 degrees of the visual field. We compare the results obtained in ten individuals with strabismic amblyopia with ten visual normals. At each field location in each participant, we examined how the sensitivity exhibited under binocular conditions compared with sensitivity from four predictions, (i) a model of binocular summation, (ii) the average of the monocular sensitivities, (iii) dominant-eye sensitivity or (iv) non-dominant-eye sensitivity. The proportion of field locations for which the binocular summation model provided the best description of binocular sensitivity was similar in normals (50.6%) and amblyopes (48.2%). Average monocular sensitivity matched binocular sensitivity in 14.1% of amblyopes' field locations compared to 8.8% of normals'. Dominant-eye sensitivity explained sensitivity at 27.1% of field locations in amblyopes but 21.2% in normals. Non-dominant-eye sensitivity explained sensitivity at 10.6% of field locations in amblyopes but 19.4% in normals. Binocular summation provided the best description of the sensitivity profile in 6/10 amblyopes compared to 7/10 of normals. In three amblyopes, dominant-eye sensitivity most closely reflected binocular sensitivity (compared to two normals) and in the remaining amblyope, binocular sensitivity approximated to an average of the monocular sensitivities. Our results suggest a strong positive contribution in habitual viewing from the non-dominant eye in strabismic amblyopes. This is consistent with evidence from other sources that binocular mechanisms are frequently intact in strabismic and amblyopic individuals

Alignment in the registration, selection, procurement and reimbursement of essential medicines for childhood cancers in South Africa

Introduction The effectiveness of a health system in providing access to medicines is in part determined by the alignment of several core pharmaceutical processes. For South Africa's public health sector, these include the registration of medicines, selection and subsequent procurement through national tenders. Registration, selection and reimbursement are key processes in the private sector. This study assessed the alignment of forementioned processes for essential paediatric oncology medicines in South Africa. Methods A selection of priority chemotherapeutics, antiemetics and analgesics in the treatment of five prevalent childhood cancers in South Africa was compared with those listed in 1) the WHO Essential Medicines List for Children (WHO EMLc) 2021, 2) the registered health products database of South Africa, 3) the relevant South African National Essential Medicines Lists (NEML), 4) bid packs and awarded tenders for oncology medicines for 2020 and 2022 and 5) oncology formularies from the leading Independent Clinical Oncology Network (ICON) and two private sector medical aid schemes. Consistency between these sources was assessed descriptively. Results There was full alignment for 25 priority chemotherapeutics for children between the NEML, the products registered in South Africa and those included on tender. Due to unsuccessful procurement, access to seven chemotherapeutics was potentially constrained. For antiemetics and analgesics, eight of nine active ingredients included on the WHO EMLc were also registered in South Africa and on its NEML. An exploratory assessment of private sector formularies showed many gaps in ICON's formulary and two medical scheme formularies (listing 33% and 24% of the chemotherapeutics, respectively). Conclusion Despite good alignment in public sector pharmaceutical processes, access constraints to essential chemotherapeutics for children may stem from unsuccessful tenders. Private sector formularies show major gaps; however, it is unclear how this translates to access in clinical practice