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Filarial lymphedema (LE) remains a significant global problem despite the progress made toward elimination of lymphatic filariasis (LF). In Ghana, the main approach to LF is preventive chemotherapy, but this has minimal impact on individuals who have already developed LE. In 2018-2020, a 24-month randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of stringent hygiene measures using the Essential Package of Care with or without additional administration of doxycycline (DOX) to improve filarial leg LE. This study enrolled 356 participants with LE stages 1-3 from two districts in the Upper East Region of Ghana. In addition to regular training on appropriate care for their affected legs, participants were randomized to receive 6 weeks of either 200 mg/day DOX (n = 117), 100 mg/day DOX (n = 120), or matching placebo (n = 119). Participants were seen every 2 months, with clinical measurements done at 6, 12, 18, and 24 months to assess the status of affected legs. There was a trend toward later appearance of acute attacks after DOX, but surprisingly, DOX showed no effect on LE stage progression. In all groups, leg LE improvement was more common (DOX 200 mg: n = 23 [20%]; DOX 100 mg: n = 23 [19.5%]; placebo: n = 32 [27.4%]) than LE worsening (DOX 200 mg: n = 2 [1.7%]; DOX 100 mg: n = 3 [2.5%]; placebo: n = 2 [1.7%]). Overall, these data show a strong benefit from adherence to a strict hygiene protocol, with some added potential benefit for DOX in preventing acute attacks.

Background: Onchocerciasis causes chronic systemic inflammation. Several studies have used markers such as haemato-biochemical indices to predict the occurrence of systemic inflammation. This study assessed the variability and predictability of haemato-biochemical indices and blood composite ratios (BCRs) in microfilariae positive (MF+) and microfilariae negative (MF-) subgroups of onchocercomata participants., Methods: One hundred and five (105) MF + and 34 MF- participants were retrospectively recruited into the study. Screening for the presence of O. volvulus microfilariae was done from skin snips taken from the left and right iliac crests of participants using established and approved protocols. Haematological and biochemical indices were measured using standard laboratory automated analyzers. Blood composite ratios (BCRs) were calculated as ratios of the absolute parameters involved., Results: A significantly increased total WBC, absolute eosinophil, eosinophil percent and absolute basophil were observed in the MF + participants compared to MF- participants. Reduced gamma-glutamyl transferase (GGT) with increased estimated glomerular filtration rate (eGFR) was significantly associated with MF + participants compared to MF- participants. BCRs were significantly higher for eosinophil-to-neutrophil ratio (ENR), eosinophil-to-monocyte ratio (EMR), eosinophil-to-basophil ratio (EBR) and eosinophil-to-lymphocyte ratio (ELR) in MF + participants compared to MF- participants. After multivariate adjustment, onchocercomata participants with increased eosinophil counts (aOR = 13.86, 95% CI [2.07-92.90], p = 0.007), ENR x10 (aOR = 1.42, 95% CI [1.05-1.93], p = 0.025), EMR (aOR = 2.64, 95% CI [1.25-5.60], p = 0.011), EBR (aOR = 1.07, 95% CI [1.01-1.10], p = 0.020) and ELR x10 (aOR = 1.69, 95% CI [1.14-2.51], p = 0.009) were more likely to have microfilaridermia., Conclusions: Elevated eosinophil counts with higher ENR, EMR, EBR and ELR levels are significantly associated with microfilaridermia in onchocercomata participants. Combining BCRs with eosinophil count significantly led to an improvement in the conventional model for predicting microfilaridermia., (© 2024. The Author(s).)

Chronic lymphedema caused by infection of Wuchereria bancrofti is a disfiguring disease that leads to physical disability, stigmatization, and reduced quality of life. The edematous changes occur mainly on the lower extremities and can progress over time due to secondary bacterial infections. In this study, we characterized participants with filarial lymphedema from Ghana and Tanzania as having low (stage 1-2), intermediate (stage 3-4), or advanced (stage 5-7) lymphedema to determine CD4 + T cell activation patterns and markers associated with immune cell exhaustion. A flow cytometry-based analysis of peripheral whole blood revealed different T cell phenotypes within participants with different stages of filarial lymphedema. In detail, increased frequencies of CD4 + HLA-DR + CD38 + T cells were associated with higher stages of filarial lymphedema in patients from Ghana and Tanzania. In addition, significantly increased frequencies of CCR5 + CD4 + T cells were seen in Ghanaian participants with advanced LE stages, which was not observed in the Tanzanian cohort. The frequencies of CD8 + PD-1 + T cells were augmented in individuals with higher stage lymphedema in both countries. These findings show distinct activation and exhaustion patterns in lymphedema patients but reveal that immunological findings differ between West and East African countries.

Background: Lymphatic filariasis (LF) causes chronic morbidity, which usually manifests as lymphedema or hydrocele. Mass drug administration (MDA) began in Kassena Nankana East Municipal (KNEM) and Nabdam, two hotspot districts in the Upper East Region in Ghana, in 2000 and 2005, respectively. This cross-sectional study evaluated the impact of 15 years of MDA on the control of LF as determined by circulating filarial antigen (CFA) and microfilariae assessment in the KNEM and the Nabdam districts., Methodology/principal Findings: A total of 7,453 participants from eight sub-districts in the two hotspot districts (KNEM: N = 4604; Nabdam: N = 2849) were recruited into the study. The overall CFA prevalence as determined by the FTS was 19.6% and 12.8% in the KNEM and Nabdam districts, respectively. Manyoro, a sub-district on the border with Burkina Faso, recorded the highest CFA prevalence of 26% in the KNEM. Assessment of microfilariae and Og4C3 antigen was done from 1009 (KNEM: N = 799 (79.2%); Nabdam: N = 210 (20.8%)) randomly selected FTS-positive (N = 885) and FTS-negative (N = 124) individuals. The Og4C3 antigen was found in 22.6%/23.0% of the selected individuals (KNEM/Nabdam), whereas the night blood revealed microfilariae in only 0.7%/0.5%., Conclusions/significance: Using the WHO endorsed FTS, CFA prevalence exceeded the long-standing <2% threshold-which may need revision and validation. Surprisingly, the Og4C3 ELISA showed positive results in only about one-fifth of the FTS positive samples. However, even this result would not have met the <2% CFA criteria for LF elimination. In contrast, projections from the microfilariae results revealed a halt in LF transmission. The global elimination target was due in 2020 but has been extended to 2030 since this could not be met. Focused MDA intervention intensification on seasonal migrants and non-compliers, and implementation of alternative treatment strategies may suffice for the elimination of the disease., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to assess whether the use of a joint-sparing technique such as curettage and grafting was successful in eradicating giant cell tumours of the proximal femur, or whether an alternative strategy was more appropriate. Between 1974 and 2012, 24 patients with a giant cell tumour of the proximal femur were treated primarily at our hospital. Treatment was either joint sparing or joint replacing. Joint-sparing treatment was undertaken in ten patients by curettage with or without adjunctive bone graft. Joint replacement was by total hip replacement in nine patients and endoprosthetic replacement in five. All 11 patients who presented with a pathological fracture were treated by replacement. Local recurrence occurred in five patients (21%): two were treated by hip replacement, three by curettage and none with an endoprosthesis. Of the ten patients treated initially by curettage, six had a successful outcome without local recurrence and required no further surgery. Three eventually needed a hip replacement for local recurrence and one an endoprosthetic replacement for mechanical failure. Thus 18 patients had the affected joint replaced and only six (25%) retained their native joint. Overall, 60% of patients without a pathological fracture who were treated with curettage had a successful outcome.

The influence of pathological fracture on surgical management, local recurrence and survival was established in patients with high grade, localised, extremity osteosarcoma (n=484), chondrosarcoma (n=130) and Ewing's sarcoma (n=156). Limb salvage was possible in 79% of patients with a fracture compared to 84% of patients without a fracture (p=0.17). No difference in local recurrence was found between fracture and control groups. In univariate analysis, survival in the fracture group was lower than in the control group for osteosarcoma (34% versus 58%, p<0.01) and chondrosarcoma (35% versus 63%, p=0.04), but not for Ewing's sarcoma (75% versus 64%, p=0.80). In multivariate analysis, fracture remained a significant predictor of survival for osteosarcoma, but not for chondrosarcoma, where dedifferentiated subtype appeared to be decisive. Pathological fracture independently predicts worse survival in osteosarcoma, but not chondrosarcoma and Ewing's sarcoma. Limb saving surgery seems safe, if adequate resection margins are achieved.

The prognostic value of alkaline phosphatase (AP) measured before and after chemotherapy, but before surgery was established in a retrospective survey of patients. The patients were 18 years or older, with non-metastatic high-grade osteosarcoma. Pre-chemotherapy AP was available in 89 cases, post-chemotherapy AP in 86 patients, and both in 71 cases. AP was classified as Normal (< 100% upper limit), High (100% < or = AP < 200%) or Very High (AP > or = 200%). Osteosarcoma subtype was predominantly conventional. No correlation was found between subtype and chemotherapy response, local recurrence or survival. Pre-chemotherapy AP was raised more in the osteoblastic subtype. Post-chemotherapy AP and normalisation were the same among different subtypes. AP was not correlated with local recurrence. Normal or High pre-chemotherapy AP correlated with better survival at 10 years (64% and 70%) than Very High pre-chemotherapy AP (37%, P = 0.005). Post-chemotherapy AP correlated with survival (68%, 39% and 25% in the Normal, High and Very High group, P = 0.0007) and response to chemotherapy (P = 0.049). A pre-chemotherapy AP above twice Normal correlated with worse survival. If AP decreased after chemotherapy, but was still raised, survival was better, but still worse than if AP normalised. A raised post-chemotherapy AP predicts poor chemotherapy response.

Aims: To review the oncological and functional outcome in 80 patients who underwent disarticulation of the hip as part of their treatment., Methods: Eighty patients had disarticulation, of whom 46 had a bone sarcoma and 34 a soft tissue sarcoma. In 42 patients the operation was done as the first definitive surgical procedure for that patient. In 38 patients the disarticulation followed local recurrence after unsuccessful limb salvage, three of these patients had palliative amputations already having metastatic disease. All patients had adjuvant therapy when appropriate., Results: The overall survival of the patients following the amputation was 56% at 1 year, 39% at 2 years, 27% at 5 years and 21% at 10 years. The 5-year survival of patients having the amputation as a primary procedure was 32%, for those with local recurrence it was 25% whilst for those with a palliative amputation it was nil. Local recurrence developed in 10 patients following the amputation, and was related to close margins of excision; all of these patients subsequently died. Function was on the whole poor, with only one surviving patient regularly using an artificial limb., Conclusion: Disarticulation of the hip remains a disabling procedure usually carried out for high grade sarcomas with extensive involvement of bone and soft tissues in the thigh. Long term survival is possible if wide margins of excision can be achieved.