Biomedical subjects

L Lema

Publications and source records attributed to L Lema.

4 recordsLinked to original sources

PubMed2026

Impact of BRCA2 pathogenic variants on outcomes to first-line CDK4/6 inhibitors plus endocrine therapy in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Currently, three cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are approved in combination with endocrine therapy (ET) as first-line treatment of patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The impact of homologous recombination repair (HRR) pathogenic variants (PV) on outcomes with first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC remains uncertain. PATIENTS AND METHODS: We conducted a multicenter, real-world, case-control study including 233 patients with HR-positive/HER2-negative MBC treated with first-line CDK4/6i and ET. Among them, 116 presented HRR PVs and 117 were matched controls with negative germline testing. The primary objective was to compare progression-free survival (PFS) and overall survival among germline-BRCA2 PV carriers, other HRR PV carriers, and controls. To minimize baseline differences in prognostic factors between PV carriers and controls, inverse probability of treatment weighting was applied. Molecular analyses in pre-CDK4/6i samples among patients with BRCA2 PV were carried out, including RAD51-foci, PAM50 intrinsic subtype, and RB1 loss of heterozygosity (LOH). RESULTS: Among the included 233 patients, median age at diagnosis was 45 years (interquartile range 39-56) and 33% had de novo metastatic disease. Primary resistance to adjuvant ET was present in 10% and secondary resistance in 27%. After a median follow-up of 44 months, patients with germline-BRCA2 PVs (n = 67) had significantly shorter PFS [11 versus 27 months; adjusted hazard ratio (aHR) 2.73, 95% confidence interval (CI) 1.65-4.51, P < 0.001] compared with controls. Among patients with endocrine-sensitive disease, germline BRCA2 PV carriers had markedly shorter PFS (median PFS 12 versus 39 months; aHR 4.04; 95% CI 1.82-8.98, P < 0.001). Exploratory analyses revealed RB1 LOH before CDK4/6i-treatment in most evaluable BRCA2 tumors. CONCLUSIONS: BRCA2 PVs were independently associated with poorer outcomes to first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC compared with controls, especially relevant among patients with endocrine-sensitive disease. These findings suggest that patients with a germline PV in BRCA2 may require alternative first-line strategies.

Humans↗

PubMed1992

Spindle cell ploidy and proliferation in endemic and epidemic African Kaposi's sarcoma.

Comparative studies of ploidy and proliferative activity of spindle cells in sections of 20 (skin, 17; lymph node, 3) biopsy specimens from African patients, 10 with endemic Kaposi's sarcoma (EKS) and 10 with AIDS-associated Kaposi's sarcoma (AKS) were performed by histopathology, feulgen-based DNA measurement and proliferating cell nuclear antigen (PCNA)/cyclin immunohistochemistry, respectively. All specimens were classified as nodular lesions with basically the same histology. In 17 cases immunostained for cyclin/PCNA, the percentage of proliferating spindle cells range between 2-18, with a higher mean rate in AKS although this was not statistically significant. In situ measurement of DNA showed no significant values greater than the diploid level of control cells indicating that spindle cells in both EKS and AKS have euploid DNA content. Our findings indicate that both EKS and AKS represent the same type of euploid low rate cell proliferations. This corroborates previous suggestions that KS could represent a reactive process to yet undefined stimulus rather than a clonal proliferation, of transformed malignant cells.

Adult↗

PubMed1992

High HIV seroprevalence and increased HIV-associated mortality among hospitalized patients with deep bacterial infections in Dar es Salaam, Tanzania.

OBJECTIVES: To correlate deep bacterial infections with HIV infection and evaluate the influence of HIV on clinical picture and outcome in patients with meningitis, pneumonia or pyomyositis. DESIGN: Case-control comparison of HIV seroprevalence between patients and an age- and sex-matched control group in a prospective cross-sectional study of hospitalized patients. PARTICIPANTS: One hundred and sixty-five patients admitted to hospital with either purulent meningitis, pneumonia or pyomyositis and 165 age- and sex-matched controls from orthopaedic/trauma wards. SETTING: University Hospital, Dar es Salaam, Tanzania. OUTCOME MEASURES: Differences in HIV seroprevalence and mortality. RESULTS: Of 78 patients with purulent meningitis, 19 (24%) were HIV-seropositive, compared with 13 (17%) in the control group (P = 0.345). Of 36 patients with meningitis seen before a meningococcal epidemic affected Dar es Salaam, there was a statistically significant association with HIV infection (P = 0.013). Ten out of 19 (53%) HIV-seropositives died, compared with nine out of 59 (15%) seronegatives (P = 0.028). Of patients with pneumococcal meningitis, five out of six (83%) seropositives died, compared with two out of 12 (17%) seronegatives (P = 0.013). Fifteen out of 45 (33%) patients with pneumonia were HIV-seropositive, compared with four (9%) in the control group (P = 0.001). There was no difference in mortality between seropositive and seronegative patients with pneumonia. HIV seroprevalence was 62% among 42 patients with pyomyositis and 12% among 42 controls (P less than 0.0001). Eighteen out of 25 (72%) seropositive patients with pyomyositis fulfilled the World Health Organization (WHO) clinical case definition for AIDS. Response to recommended antibiotic treatment was satisfactory among patients with pneumonia and pyomyositis. CONCLUSIONS: These results show a strong association between pyomyositis, pneumonia and HIV infection. They also indicate an increased mortality associated with HIV infection in patients with pyogenic meningitis, especially pneumococcal meningitis. Pyomyositis should be considered an indicator of stage III HIV disease in the proposed WHO clinical staging system.

AIDS-Related Opportunistic Infections↗

PubMed1990

The management of empyema thoracis by thoracoscopy and irrigation.

A technique of irrigation for the management of empyema thoracis is described. Initial thoracoscopy using a laparoscope under general anaesthesia enabled adequate debridement and breakdown of loculi within the empyema cavity under direct vision. Following this procedure irrigation of the cavity with two tubes was started and continued until three consecutive cultures of drained irrigation fluid became sterile. The procedure was then discontinued. The results in 14 patients are presented using this method, irrigation was required for an average of 14 days. Patients remained in hospital for an average of 4.8 weeks. Tuberculous empyema was not found to be a contra-indication to the irrigation technique.

Adult↗