Bilateral ulna hemimelia with humeroradial synostosis and oligodactyly: A case report.

Hemimelia denotes the partial or complete absence of the distal half of a limb. Ulna hemimelia, a rare congenital anomaly, involves the complete or partial absence of the ulna in the upper limb, with an incidence of 1 in 150,000. This condition has been classified into 4 types, with the rare Type 4 variant involving humeroradial synostosis. We present a unique case of bilateral complete ulna hemimelia, humeroradial synostosis, and oligodactyly, in an 11-month-old female with bilateral upper limb shortening and restricted elbow movement since birth. Clinical examination revealed bilateral upper limb shortening, medial deviation of both wrist joints, fixed extension of both elbow joints, and bilateral absence of the cubital fossa. Radiographs confirmed bilateral micromelia, absence of ulna, humeroradial synostosis, and oligodactyly. This case, exhibiting bilateral Type 4 ulna hemimelia with Class 1 humeroradial synostosis, is a complex variant, rarely reported, and the first documented in Ghana. It also highlights the importance of radiological assessment in ensuring accurate diagnosis. Long-term follow-up and potential surgical interventions are crucial for optimizing upper limb function in such cases.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.

Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for patients with BRCA1/2 mutations, but patients with other mutations may benefit from PARPi treatment. Another mutation that is present in more cancers than BRCA1/2 is mutation to the TP53 gene. In 2D breast cancer cell lines, mutant p53 (mtp53) proteins tightly associate with replicating DNA and Poly (ADP-ribose) polymerase (PARP) protein. Combination drug treatment with the alkylating agent temozolomide and the PARPi talazoparib kills mtp53 expressing 2D grown breast cancer cell lines. We evaluated the sensitivity to the combination of temozolomide plus PARPi talazoparib treatment to breast and lung cancer patient-derived tumor organoids (PDTOs). The combination of the two drugs was synergistic for a cytotoxic response in PDTOs with mtp53 but not for PDTOs with wtp53. The combination of talazoparib and temozolomide induced more DNA double-strand breaks in mtp53 expressing organoids than in wild-type p53 expressing organoids as shown by increased γ-H2AX protein expression. Moreover, breast cancer tissue microarrays (TMAs) showed a positive correlation between stable p53 and high PARP1 expression in sub-groups of breast cancers, which may indicate sub-classes of breast cancers sensitive to PARPi therapy. These results suggest that mtp53 could be a biomarker to predict response to the combination of PARPi talazoparib-temozolomide treatment.

Spontaneous resolution of tuberculosis related Rasmussen aneurysm in a young West African: A case report.

Rasmussen aneurysm (RA) is an uncommon cause of hemoptysis in pulmonary tuberculosis, first described in 1868 by Rasmussen. It is often treated with surgery or endovascular coiling. A few cases of spontaneous resolution with conservative management have been recorded in literature. We present the case of a 44-year old patient who reported with hemoptysis, weight loss, chronic cough and night sweats and was diagnosed of pulmonary tuberculosis on the basis of clinical assessment and chest X-ray. Subsequently, chest CT scan done showed a giant left RA, treated conservatively with antituberculous chemotherapy with complete radiological resolution of aneurysm after 18-month follow-up. We conclude that conservative management of RA is a good alternative in a low resource setting for hemodynamically stable patients.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

A case of spontaneous intramural duodenal hematoma in a young African man: Imaging findings.

Intramural duodenal hematoma has been reported as a rare condition first described by McLauchlan in 1838. It is now thought to be an uncommon condition due to the increase in the number of reported cases in the medical literature. It has been reported to usually occur secondary to blunt trauma mainly in young men and children, with 82% of the patients being younger than 30 years. Association between spontaneous intramural duodenal hematoma and coagulopathy, coagulating drugs, endoscopic procedures, acute pancreatitis, and pancreatic malignancy has been made. We present the case of a 35-year-old African male lumberjack with no known previous history of trauma, risk factors, or associated predisposing condition that presented to our facility with acute abdominal pain and vomiting and diagnosed as spontaneous intramural duodenal haematoma on CT scan and MR imaging with a complete resolution on conservative management.

Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort.

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case-control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

Use of Magnetic Resonance Imaging (MRI) in the Management of Diagnostic Uncertainty in Low-Resource Settings: A Case Report of Cesarean Ectopic Pregnancy in a Tertiary Hospital in Ghana.

BACKGROUND Low- and middle-income countries (LMICs) account for the overwhelming majority of maternal deaths worldwide. Cesarean section rates have increased globally over the last 10 years, including in LMICs, and are an important intervention to decrease neonatal and maternal mortality. However, cesarean sections also contribute to increased complications in subsequent pregnancies, including invasive placentation and cesarean scar ectopic pregnancies (CSEP). Potential CSEP complications include rupture of the uterus, bladder invasion, and maternal mortality. CASE REPORT We present the case of a 35-year-old Ghanaian woman (gravidity 5, parity 3) with a positive urine pregnancy test and 2 months of amenorrhea. Ultrasound scanning demonstrated a gestational sac with a fetal pole and absent cardiac activity located in the lower uterine segment. Myometrium infiltration was present, with only 2 mm of anterior myometrium between the gestational sac and the urinary bladder. Owing to concern for CSEP with uncertain bladder invasion, a pelvic MRI was obtained for preoperative planning. Following the MRI, which demonstrated an intact bladder, the patient underwent an uncomplicated exploratory laparotomy and excision of the CSEP. CONCLUSIONS In LMICs, pelvic ultrasound continues to be the diagnostic tool of choice for CSEP. However, in cases with diagnostic uncertainty or possible bladder invasion, MRI is an additional imaging tool that can optimize preoperative planning and minimize the risk of maternal mortality and potential post-surgical complications.

Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia.

BACKGROUND: Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgVH) mutation in chronic lymphocytic leukemia (CLL), but it is still not clear whether it is an independent prognostic factor. METHODS: The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression, genetic abnormalities detected by fluorescence in situ hybridization (FISH), and the time from diagnosis to first treatment. RESULTS: Fifty-seven patients (28%) were positive for ZAP-70 (> or = 20%). Positive ZAP-70 status was associated with advanced disease stage, atypical morphology, CD38-positive status, trisomy 12, del(6q), or no detectable abnormalities; negative ZAP-70 status was correlated with del(13q) as a sole abnormality. The treatment-free interval (TFI) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients (P < 0.001). Multivariate analysis in 117 patients identified advanced stage, CD38 > or = 7%, and the absence of del(13q) as a sole abnormality as independent factors for short TFI. Excluding FISH, ZAP-70 status acquired independent prognostic value along with CD38 status. The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress. When both markers were positive, the TFI was 12 months; when both were negative, the median TFI was 54 months; a median TFI of 26 months was observed in patients who had discordant results (P < 0.00001). CONCLUSIONS: The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL.

The diagnostic value of CD123 in B-cell disorders with hairy or villous lymphocytes.

BACKGROUND AND OBJECTIVES: CD123 is an antibody that identifies the a chain of the human interleukin-3 receptor and is expressed in a variety of normal hematopoietic cells, acute leukemia and hairy cell leukemia (HCL). The aim of the study was to investigate the diagnostic value of CD123 expression in B-cell disorders with circulating hairy and villous lymphocytes. DESIGN AND METHODS: We investigated the diagnostic value of CD123 expression in neoplastic cells from 59 patients with B-cell disorders with circulating hairy or villous lymphocytes: HCL (n=24), the variant form of HCL (n=11) and splenic lymphoma with villous lymphocytes (SLVL) (n=24). Cells from 12 patients with chronic lymphocytic leukemia were used as controls. Immunophenotypic analysis was performed by flow cytometry on 77 samples from peripheral blood (n=48), bone marrow (n=25) and spleen cell suspensions (n=4). RESULTS: Our findings show that cells from 95% of typical HCL express CD123 with strong to moderate intensity while this molecule is absent in circulating cells from most cases of HCL-variant (91%) and SLVL (97%). INTERPRETATION AND CONCLUSIONS: We conclude that CD123 is a useful new marker for distinguishing B-cell disorders with circulating villous lymphocytes as its expression is characteristic of typical HCL with high sensitivity and specificity. However CD123 does not allow the distinction between HCL-variant and SLVL, as both are CD123 negative.

Diagnostic significance of CD20 and FMC7 expression in B-cell disorders.

We analyzed by flow cytometry the expression of CD20 and FMC7 in cell suspensions from 932 patients, including 630 cases of chronic lymphocytic leukemia (CLL), 23 cases of other B-cell leukemias, and 279 cases of B-cell non-Hodgkin lymphoma (B-cell NHL). CD20 was positive in 94.5% of cases; FMC7 was positive in 35.7%. There was a correlation between CD20 and FMC7 expression in patients with B-cell NHL (P < .001) but not CLL (P = .1). We also tested a scoring system in which FMC7 was replaced by CD20 and compared it with our current scoring system for CLL. With this modification, the accuracy of the scoring system for differentiating CLL from other non-CLL disorders fell from 94.4% to 81.5%. In CD20+ CLL, the intensity of CD20 expression correlated with FMC7 and low scores (P < .001 for both comparisons). We suggest that the particular conformation of CD20 recognized by FMC7 is manifested only in cells with strong CD20 expression, which is not the case for CLL. FMC7 is of greater diagnostic value than CD20 for distinguishing CLL from other B-cell disorders; we recommend its continued use for this purpose.