North African Patients Research Articles

#228 APOL1 variants and chronic kidney disease in Morocco: case control study

Abstract Background and Aims APOL1 genetic variants account for much of the excess risk of chronic and end stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. These genetic variants were never tested in north African patients and this is the first study aimed to search the existence of this variants in general Moroccan people and patients with chronic kidney disease. Method This is a case control multi center study including Moroccan adult with GFR less than 60 ml per min secondary to unknown etiology or nephroangiosclerosis. Patients with known nephropathy or diabetes were excluded. Between July 2014 and June 2017, patients and 100 controls were enrolled for testing APOL1 variants. ADN extraction was done by isolate II Blood DNA kit and nucleic acid concentration by spectrophotometry. The allele frequency was calculated by PCR TaqMan. Results During the inclusion period 117 patients with chronic kidney disease from unknown etiology and 8 patients with nephroangiosclerosis were included from all the twelve Moroccan regions. There mean age was 49 years and more than 60% were males. The age of end stage renal disease was 42 years. Testing APOL1 variants did not find G1 or G2 classic mutations but we find a G2 deletion and a new mutation GAT to AAT in two patients. We find also a silent mutation AGA to AGG that we are exploring in a family investigation. Conclusion APOL1 genetic variants as described in the literature are not significantly present in Moroccan patient with chronic kidney disease and cannot be yet used as a risk factor in our context. However we find a new mutation needing a wide exploration in a bigger cohort

Validation of the follicular and ovarian thresholds by an 18-MHz ultrasound imaging in polycystic ovary syndrome: a pilot cutoff for North African patients.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrinopathies among young women. Ultrasound evidence of polycystic ovaries is one of its crucial diagnostic criteria. Our main objective is to study the contribution of ultrasound data in diagnosing PCOS. In addition, we aim to establish a new cutoff point for the use of ultrasound and to determine its sensitivity as well as its specificity. It was a prospective study, including all patients presenting with clinical hyperandrogenism. The ultrasound examination of these patients was performed using a novel ultrasound machine (18 MHz) compared to an older ultrasound machine (2 Hz-8 MHz). Inclusion criteria encompassed adult female patients over 18 years presenting symptoms suggestive of PCOS, particularly hyperandrogenism and oligo-anovulation, meeting Rotterdam's diagnostic criteria. Prior to inclusion, assessments were conducted to eliminate other potential causes explaining hyperandrogenism or menstrual disorders in both groups. We examined 92 patients diagnosed with PCOS. Menstrual disorders were the main symptoms, with amenorrhea being more frequent in the PCOS group (G1) (48.9% vs the control group (G2): 11.1%). The follicle number was significantly lower in the control group, as assessed by both ultrasound machines (p < 10-3). The accuracy of the new ultrasound device was evaluated compared to the old one using the receiver operating characteristic (ROC) curve, revealing a cutoff of 18 follicles (sensitivity of 68.1%, specificity of 100%) and an area under the curve of 0.955. We found a significant difference between the median values of the number of follicles (NF) by both ultrasound machines (18 vs 12). It was positively correlated with an index of r = 0.916. For the volume, it was distinctively higher in G1 (p < 10-3). ROC curve analysis revealed an ovarian volume cutoff of 9.25 ml with a sensitivity of 48.9% and a specificity of 100%. Both ultrasound machines were positively correlated with an index of r = 0.979 (p < 10-3). In conclusion, we were able to establish significant correlations between the new and the old ultrasound devices for both the NF and ovarian volume. Our study is distinctive as it represents the first on the African continent to re-evaluate the ultrasound criterion for PCOS.

Cutaneous metastasis as a first presentation of lung carcinoma: a case series

IntroductionCutaneous metastases (CM) revealing lung carcinoma are extremely rare, accounting for 0.8%. The diagnosis is guided by histology and immunohistochemistry. Treatment is palliative. The prognosis is poor.Case presentationThis is a retrospective study of the available clinical and histological records of four North African patients with CM revealing lung cancer treated at our institute between 2004 and 2010. Three men and one woman were registered. The mean age was 54.5 years (38–74 years). Two patients had primary adenocarcinoma, one patient had small cell carcinoma and one had squamous cell carcinoma. Treatment was based on chemotherapy in two cases and antalgic radiotherapy in two cases, one patient underwent surgical resection as the lesion was infected. The overall survival after diagnosis was between one and four months.ConclusionsA skin nodule can be the first symptom revealing lung cancer. A rare clinical presentation that should not be taken for a benign nodule, the biopsy and histological study with immunohistochemistry confirm the diagnosis.

Evaluation of muscle strength and quality in North African patients with chronic hepatitis B: A pilot case control study

ABSTRACT Early detection of alteration of muscle strength, quantity, and quality, and sarcopenia is useful in non-cirrhotic chronic hepatitis B (NC-CHB) patients. Studies, which explored the handgrip strength (HGS) are scarce with questionable results, and no previous case-control study explored the presence of sarcopenia. The aim of this study was to assess the muscle strength [i.e.; HGS absolute (HGSA), HGSA/body mass index (BMI)], muscle quantity [i.e.; appendicular skeletal muscle (ASM), ASM/height2, ASM/total body weight (TBW), ASM/BMI], and muscle quality [i.e.; HGSA/total muscle mass (TMM), HGSA/ASM] of NC-CHB patients. This was a case-control study. Cases (n = 26) were untreated NC-CHB patients, and controls (n = 28) were ‘apparently’ healthy participants. Muscle mass was estimated via the TMM (kg) and ASM (kg). Muscle strength was evaluated via the HGS data [i.e.; HGSA (kg), HGSA/BMI (m2)]. Six variants of HGSA were determined: highest values for the dominant and non-dominant hands, highest value between the two hands, averages of the three measurements for the two hands, and the average of the highest values of the two hands. Muscle quantity was expressed in three relative variants (ASM/height2, ASM/TBW, and ASM/BMI). Muscle quality was evaluated via relative HGS data adjusted by muscle mass (i.e.; HGSA/TMM, HGSA/ASM). Probable and confirmed sarcopenia were retained in front of low muscle strength, and low muscle strength and muscle quantity or quality, respectively. There were no significant differences between controls and NC-CHB patients in values of muscle i) Strength whatever the HGS’ mode of expression (e.g.; HGSA/BMI: 1.59 ± 0.54 vs. 1.53 ± 0.54 m2, p = 0.622, respectively), ii) Quantity (e.g.; ASM/BMI: 0.79 ± 0.24 vs. 0.77 ± 0.23 m2, p = 0.883), and iii) Quality (e.g.; HGSA/ASM: 2.00 ± 0.25 vs. 2.01 ± 0.41, p = 0.952, respectively). One NC-CHB participant had a confirmed sarcopenia. To conclude, both controls and NC-CHB patients had similar HGS values. Only one NC-CHB patient had a confirmed sarcopenia.

Targeted Next-Generation Sequencing in Children With Bilateral Sensorineural Hearing Loss: Diagnostic Yield and Predictors of a Genetic Cause.

To investigate the diagnostic yield of targeted next-generation sequencing using hearing loss panels and to identify patient-related factors that are associated with a definite genetic cause. Retrospective chart review. Tertiary referral center. Children with congenital or late-onset, bilateral sensorineural hearing loss. Diagnostic. The number of patients with a definite genetic diagnosis. We report on 238 patients with hearing loss: 130 were male and 108 were female. About 55% had congenital hearing loss. A genetic cause was identified in 94 of the patients (39.5%), with 72.3% of these showing nonsyndromic and 27.6% showing syndromic hearing loss. The diagnostic yield was highest among North African patients (66.7%). A multiple linear regression model shows that profound hearing loss, family history of hearing loss, congenital hearing loss, and North African ethnicity are significantly related to identifying a genetic cause. Targeted next-generation sequencing using a panel of hearing loss genes identified a genetic diagnosis in almost 40% of children with bilateral sensorineural hearing loss. We describe the predictors of a genetic diagnosis, and this information may be used during genetic counseling.

Vitamin D and Healthcare Service Utilization in Children: Insights from a Machine Learning Approach.

Vitamin D deficiency and insufficiency is a global health issue: an association has been demonstrated between vitamin D deficiency and a myriad of acute and chronic illnesses. Data regarding vitamin D status among children hospitalized with non-critical illnesses are scanty. We aimed to: (1) identify profiles of children hospitalized due to non-critical illnesses, using vitamin D levels as the driving outcome; (2) assess the association between patient profiles and length of stay. The study included 854 patients (1−17 years old) who underwent blood tests for detecting vitamin D levels. A regression tree was used to stratify patients. The relationship between vitamin D levels and length of stay was explored using Poisson regression. The regression tree identified three subgroups. Group A (16%): African, North African, Hispanic, and Indian patients. Group B (62%): Caucasian and Asian patients hospitalized for respiratory, metabolic, ill-defined, infective, and genitourinary diseases. Group C (22%): Caucasian and Asian patients hospitalized for digestive, nervous, and musculoskeletal diseases, blood and skin diseases, and injuries. Mean serum vitamin D level (ng/mL) was 13.7 (SD = 9.4) in Group A, 20.5 (10.0) in Group B, and 26.2 (12.6) in Group C. Group B was associated with the highest BMI z-score (p < 0.001) and the highest frequency of preterm births (p = 0.041). Mean length of stay was longer in Group A than in the other groups (p < 0.001) and decreased significantly by 9.8% (p = 0.024) in Group A and by 5% (p = 0.029) in Group B per 10 ng/mL increase in vitamin D level. We identified three subgroups of hospitalized children, defined according to ethnicity and discharge diagnosis, and characterized by increasing vitamin D levels. Vitamin D levels were associated with length of hospitalization.

External Validation of the Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) in a Large European Solid Organ Transplant Recipient Cohort

The Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool has been developed in the US to facilitate the identification of solid organ transplant recipients (SOTRs) at a higher risk of developing skin cancer. However, it has not yet been validated in populations other than the one used for its creation. To provide an external validation of the SUNTRAC tool in different SOTR populations. This retrospective external validation prognostic study used data from a prospectively collected cohort of European SOTRs from transplant centers at teaching hospitals in the Netherlands (1995-2016) and Spain (2011-2021). Participants were screened and followed up at dermatology departments. Data were analyzed from September to October 2021. The discrimination ability of the SUNTRAC tool was assessed via a competing risk survival analysis, cumulative incidence plots, and Wolbers concordance index. Calibration of the SUNTRAC tool was assessed through comparison of projected skin cancer incidences. Skin cancer diagnoses included squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. A total of 3421 SOTRs (median age at transplant, 53 [quartile 1: 42; quartile 3: 62] years; 2132 [62.3%] men) were assessed, including 72 Asian patients (2.1%), 137 Black patients (4.0%), 275 Latinx patients (8.0%), 109 Middle Eastern and North African patients (3.2%), and 2828 White patients (82.7%). With a total of 23 213 years of follow-up time, 603 patients developed skin cancer. The SUNTRAC tool classified patients into 4 groups with significantly different risks of developing skin cancer during follow-up. Overall, the relative rate for developing skin cancer estimated using subdistribution hazard ratios (SHRs) and using the low-risk group as the reference group, increased according to the proposed risk group (medium-risk group: SHR, 6.8 [95% CI, 3.8-12.1]; P < .001; high-risk group: SHR, 15.9 [95% CI, 8.9-28.4]; P < .001; very-high-risk group: SHR, 54.8 [95% CI, 29.1-102.9]; P < .001), with a concordance index of 0.72. Actual skin cancer incidences were similar to those predicted by the SUNTRAC tool (5-year skin cancer cumulative incidence for medium-risk group: predicted, 6.2%; observed, 7.0%). The findings of this external validation prognostic study support the use of the SUNTRAC tool in European populations for stratifying SOTRs based on their skin cancer risk and also detecting patients at a high risk of developing skin cancer. This can be helpful in prioritizing and providing better screening and surveillance for these patients.

Clinical Significance of Somatic Mutations in RAS/RAF/MAPK Signaling Pathway in Moroccan and North African Colorectal Cancer Patients.

Mutations in RAS (KRAS, NRAS) and BRAF genes are the main biomarker predicting response to anti-EGFR monoclonal antibodies in targeted therapy in colorectal cancer (CRC). Our study aims to evaluate the frequencies of KRAS, NRAS and BRAF mutations and their possible associations with clinico-pathological features in CRC patients from Morocco. DNA was extracted from 80 FFPE samples using the QIAamp DNA FFPE-kit. RAS and BRAF mutations were assessed by pyrosequencing assays using Qiagen, KRAS Pyro®kit 24.V1, Ras-Extension Pyro®kit 24.V1 and BRAF Pyro®Kit 24.V1, respectively, and carried out in the PyroMark-Q24. RAS mutations were identified in 57.5% (56.2% in KRAS, 8.8% in NRAS). In KRAS gene, exon 2 mutations accounted for 93.3% (68.9% in codon 12, 24.4% in codon 13). Within codon 12, G12D was the most prevalent mutation (37.7%), followed by G12C (13.4%), G12S (8.9%) and G12V (6.6%). Within codon 13, the most frequently observed mutation was G13D (22.3%). The mutation rates of exon 3 and 4 were 15.6% and 13.3%, respectively. In exon 3 codon 61, 2.3% patients were detected with two concurrent mutations (Q61R, Q61H), and 4.4% with three concurrent mutations (Q61R, Q61H, Q61L). In NRAS gene, the mutation rates of exon 2, 3 and 4 were 57.1%, 28.6%, and 14.3%, respectively. G13A and Q61H were the most common mutations, accounting for 42.9% and 28.5%, respectively. There were 13% patients with concurrent KRAS/NRAS mutation and 4.3% wt KRAS with NRAS mutations. No mutations were identified in BRAF gene. In both sexes, KRAS codon 12 mutations were associated with higher stage III/IV tumors. Moreover, Patients whose tumor is in the proximal colon (56.3%) are more likely to harbor KRAS mutations than those tumor located in rectum (25%). RAS mutations could be useful in future target anti-EGFR therapy and molecular CRC screening strategy in Morocco.

Predictive factors of nebulized morphine failure in North-African patients with chest trauma: a prospective pilot study

ABSTRACT Objective To determine the predictive factors of nebulized morphine (nMOR) failure in patients with chest trauma. Research design and methods This was an interventional clinical study. Patients admitted with isolated chest trauma with a pain visual analog score > 4 were included. Each patient received 10 mg nMOR. If pain was still > 4 after 10 minutes of nebulization, the latter was repeated every 10 minutes until pain was relieved (i.e. ≤ 4). If pain was > 4 at 30 minutes, nMOR was considered a failure. Patients were divided into two groups: MOR (+) and MOR (-) (good response to and nMOR failure, respectively). Results Seventy-five patients were included. Analysis of the risk factors revealed that road traffic accidents (relative risk (RR): 0.117 [0.031–0.443]; p = 0.002), number of fractured ribs > 4 (RR: 0.317 [0.092–0.543]; p = 0.006), bilateral injury (RR: 0.114 [0.037–0.349]; p < 0.001), flail chest (RR: 0.120 [0.037–0.386]; p < 0.001), hemothorax (RR: 0.203 [0.062–0.660]; p = 0.008), pulmonary contusion (RR: 0.202 [0.069–0.589]; p = 0.003), and pain at admission > 7 (RR: 0.363 [0.147–0.579]; p = 0.004) were predictors of nMOR failure. Conclusion Our results can help optimize the analgesic management of chest trauma patients by identifying the most eligible patients to benefit from nMOR. Clinical trial registration www.clinicaltrials.gov identifier is NCT03580187.

Psychiatric comorbidity among patients attending an addiction treatment center in Morocco

IntroductionThe comorbidity between psychiatric disorders and substance use disorders is more and more common in daily clinical practice. However, only few studies have adressed this subject in north african patients.ObjectivesThe main objective of our study was the estimation of the prevalence and patterns of psychiatric co-morbidities in substance users seeking care.MethodsOur work consisted of a cross-sectional study of a sample of patients attending outpatient substance use treatment at the addiction center in Oujda, Morocco. A hetero-questionnaire was used to collect sociodemographic data and patient history, DSM-IV criteria to assess substance abuse and dependence, and the Mini-International Neuropsychiatric Interview [MINI] to assess psychiatric comorbidities.ResultsOur study involved 100 patients, with a male predominance (89% of users). The main substances used in the last 12 months were tobacco (78%), followed by cannabis (74%), alcohol (50%), and benzodiazepines (44%). Psychiatric comorbidity was identified in 71% of the users, 51% of whom had a depressive disorder, 35% an anxiety disorder and 10% a gambling disorder. The dependence on the substance that initially motivated the consultation was higher in patients with psychiatric comorbidity (p=0.033). The post-traumatic stress disorder was significantly associated with the presence of alcohol dependence (p=0.028). The presence of benzodiazepine dependence (p=0.025) and abuse of cocaine (p=0.028) and Ecstasy (p=0.000) were significantly associated with suicide risk.ConclusionsOur study found a high prevalence of psychiatric comorbidities among substance users seeking treatment, this should prompt clinicians to pay particular attention to this issue in order to adapt and improve their management.DisclosureNo significant relationships.

A recurrent ZP1 variant is responsible for oocyte maturation defect with degenerated oocytes in infertile females.

A female factor is present in approximately 70% of couple infertility, often due to ovulatory disorders. In oocyte maturation defect (OMD), affected patients have a primary infertility with normal menstrual cycles but produce no oocyte, degenerated (atretic) or abnormal oocytes blocked at different stages of maturation. Four genes have so far been associated with OMD: PATL2, TUBB8, WEE2, and ZP1. In our initial study, 6 out of 23 OMD subjects were shown to carry the same PATL2 homozygous loss of function variant and one patient had a TUBB8 truncating variant. Here, we included four additional OMD patients and reanalyzed all 27 subjects. In addition to the seven patients with a previously identified defect, five carried the same deleterious homozygous ZP1 variant (c.1097G>A; p.Arg366Gln). All the oocytes from ZP1‐associated patients appeared shriveled and dark indicating that the abnormal ZP1 protein induced oocyte death and degeneration. Overall ZP1‐associated patients had degenerated or absent oocytes contrary to PATL2‐associated subjects who had immature oocytes blocked mainly at the germinal vesicle stage. In this cohort of North African OMD patients, whole exome sequencing permitted to diagnose 44% of the patients studied and to identify a new frequent ZP1 variant.

Ethnicity and Clinical Outcomes in Patients Hospitalized for COVID-19 in Spain: Results from the Multicenter SEMI-COVID-19 Registry.

(1) Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5–58.9) to 57.1 (44.1–67.1) vs. 71.5 (59.5–81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10–0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17–1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26–2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21–1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often.

Worldwide Differences in Clinical Phenotype of Axial Spondyloarthritis.

This review aims to describe the variations in the clinical presentation of axial spondyloarthritis (axSpA) across the globe. We searched the PubMed database and screened more than 1360 articles; 60 of them were selected based on relevance to the topic being discussed and the goals of the review. Most of the clinical manifestations, including IBP, peripheral arthritis, and extra-articular involvement are seen in different regions of the world, but with appreciable clinical heterogeneity, possibly related to a smaller number of patients from some countries, and global variation in the prevalence of HLA-B27. For example, HLA-B27-positive patients have an earlier age of onset, higher prevalence of acute anterior uveitis, and greater familial occurrence. Peripheral arthritis and enthesitis are most commonly seen among axSpA patients from Latin America and Asia, whereas IBD appears to be slightly more common among Middle Eastern and North African patients. The main weakness encountered while reviewing these data is that some studies were small, and others were cross-sectional and retrospective; hence the inferences may have a selection bias. AxSpA is a very heterogenous disease with varied presentation across the globe, in part related to HLA-B27 positivity. It is imperative to further investigate the key regional differences as they impact timely disease recognition and initiation of early treatment. Therefore, there is a need for a large worldwide systematic study to capture the clinical picture of AxSpA in a more uniform manner.

Deep analysis of the LRTOMTc.242G>A variant in non-syndromic hearing loss North African patients and the Berber population: Implications for genetic diagnosis and genealogical studies.

Autosomal recessive non‐syndromic hearing loss (ARNSHL) is the most common inherited sensory impairment. It is particularly frequent in North African populations who have a high rate of consanguineous marriage. The c.242G>A homozygous variant in LRTOMT gene was previously established as pathogenic and is associated with NSHL in both humans and mice. The aim of this study is to determine the carrier frequency for the LRTOMT c.242G>A variant and also to estimate its age in addition to evaluating its diagnostic potential as a deafness biomarker among various populations and ethnicities in Northern African countries. A total of 179 Tunisian and 34 Libyan unrelated deafness patients were screened for this variant. The homozygous c.242G>A variant was found in 5.02% and 2.94% in Tunisian and Libyan families, respectively. Subsequent screening for this variant in 263 healthy controls of various ethnicities (136 Tunisian Berbers, 32 Andalusian and 95 Tunisian from undefined ethnic origin) revealed higher frequency for the heterozygous state among Tunisians of Berber origin only (19.11%). Genotyping 7 microsatellite markers nearby the variant location in ARNSHL patients who had the homozygous variant revealed the same haplotype suggesting a common founder origin for this variant. The age of this variant was estimated to be between 2025 and 3425 years (this corresponds to 3400 years when the variant rate was set at 10−3 or 2600 years when the variant rate is set at 10−2), spreading along with the Berber population who migrated to North Africa. In conclusion, the LRTOMT c.242G>A homozygous variant could be used as a useful deafness biomarker for North African ARNSHL patients meanwhile the heterozygous variant could be utilized in genealogical studies for tracing those of the Berber ethnic group.

Identification of BRCA2 Cis Double Heterozygous Breast Cancer Cases Using Whole Exome Sequencing: Phenotypic Expression and Impact on Personalized Oncology.

BRCA1 and BRCA2 are the most commonly mutated breast cancer susceptibility genes that convey a high risk of breast and ovarian cancer. Most BRCA1 or BRCA2 mutation carriers have inherited a single heterozygous mutation. In recent years, very rare cases with biallelic or trans double heterozygous mutations on BRCA1 and or BRCA2 have been identified and seem to be associated with distinctive phenotypes. Given that this genotype-phenotype correlation in cancer predisposing hereditary conditions is of relevance for oncological prevention and genetic testing, it is important to investigate these rare BRCA genotypes for better clinical management of BRCA mutation carriers. Here we present the first report on Cis double heterozygosity (Cis DH) on BRCA2 gene identified using Whole exome sequencing (WES) in a Tunisian family with two BRCA2 mutations namely: c.632-1G>A and c.1310_1313DelAAGA that are both reported as pathogenic in ClinVar database. Subsequent analysis in 300 high-risk Tunisian breast cancer families detected this Cis double heterozygous genotype in 8 additional individuals belonging to 5 families from the same geographic origin suggesting a founder effect. Moreover, the observed Cis DH seems to be associated with an early age of onset (mean age = 35.33 years) and severe phenotype of the disease with high breast cancer grade and multiple cancer cases in the family. The identification of unusual BRCA genotypes in this Tunisian cohort highlights the importance of performing genetic studies in under-investigated populations. This will also potentially help avoiding erroneous classifications of genetic variants in African population and therefore avoiding clinical misdiagnosis of BRCA related cancers. Our findings will also have an impact on the genetic testing and the clinical management of North African breast cancer patients as well as patients from different other ethnic groups in regard to several emerging target therapies such as PARP inhibitors.

Clinical Profile and Health Disparities in a Multiethnic Cohort of Patients With Hypertrophic Cardiomyopathy.

Clinical studies of hypertrophic cardiomyopathy are over-represented by individuals of European ethnicity, with less known about other ethnic groups. We investigated differences between patients in a multiethnic Australian hypertrophic cardiomyopathy population. We performed a retrospective cohort study of 836 unrelated hypertrophic cardiomyopathy probands attending a specialized clinic between 2002 and 2020. Major ethnic groups were European (n=611), East Asian (n=75), South Asian (n=58), and Middle Eastern and North African (n=68). The minor ethnicity groups were Oceanian (n=9), People of the Americas (n=7), and African (n=8). One-way ANOVA with Dunnett post hoc test and Bonferroni adjustment were performed. Mean age of the major ethnic groups was 54.9±16.9 years, and 527 (65%) were male. Using the European group as the control, East Asian patients had a lower body mass index (29 versus 25 kg/m2, P<0.0001). South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, P=0.024). East Asians were more likely to have apical hypertrophy (23% versus 6%, P<0.0001) and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, P=0.0003). East Asians were less likely to undergo genetic testing (55% versus 85%, P<0.0001) or have an implantable cardioverter-defibrillator implanted (19% versus 36%, P=0.037). East Asians were more likely to have a causative variant in a gene other than MYBPC3 or MYH7, whereas Middle Eastern and North African and South Asians had the highest rates of variants of uncertain significance (27% and 21%, P<0.0001). There are few clinical differences based on ethnicity, but importantly, we identify health disparities relating to access to genetic testing and implantable cardioverter-defibrillator use. Unless addressed, these gaps will likely widen as we move towards precision-medicine-based care of individuals with hypertrophic cardiomyopathy.

Breast tuberculosis: a case series

Background and aimBreast tuberculosis is a rare disease, even in endemic areas. The diagnosis can be challenging, as it can mimic breast cancer. We aim to report our experience and discuss diagnoses and management modalities.ResultsWe encountered twelve cases of breast tuberculosis in our institution from 2004 to 2019. The average age of our Caucasian North African patients was 42 years old (22–63). The classic presentation was a breast lump found in half of the cases. On physical examination, we suspected breast carcinoma in seven patients. The average size of the tumors was 39 mm (15–80 mm). Nine patients had a mammogram. In five cases, there was a suspicious breast mass mimicking a malignant tumor with an average size of 33 mm (25–60 mm). A ultrasonography was performed in 6 cases and revealed a suspicious ill-circumscribed nodule in four patients with an average size of 37.5 mm (10–60 mm). Five patients had a lumpectomy, and seven women underwent drainage of the abscess and the biopsy of its hull. The association of epithelioid cell granulomas and caseous necrosis was mandatory for the histological diagnosis of tuberculosis. All of them had an antitubercular therapy. The median period of follow-up was of 43 months (3–156 months). One patient presented with a recurrent abscess of the breast.ConclusionOur study found that clinical examination and radiological imaging were not specific. Positive cultures for Koch bacillus or histological confirmation are mandatory for the diagnosis. A meta-analysis of the existing cases is needed.

FANCA Gene Mutations in North African Fanconi Anemia Patients.

Populations in North Africa (NA) are characterized by a high rate of consanguinity. Consequently, the proportion of founder mutations might be higher than expected and could be a major cause for the high prevalence of recessive genetic disorders like Fanconi anemia (FA). We report clinical, cytogenetic, and molecular characterization of FANCA in 29 North African FA patients from Tunisia, Libya, and Algeria. Cytogenetic tests revealed high rates of spontaneous chromosome breakages for all patients except two of them. FANCA molecular analysis was performed using three different molecular approaches which allowed us to identify causal mutations as homozygous or compound heterozygous forms. It included a nonsense mutation (c.2749C > T; p.Arg917Ter), one reported missense mutation (c.1304G > A; p.Arg435His), a novel missense variant (c.1258G > A; p.Asp409Glu), and the FANCA most common reported mutation (c.3788_3790delTCT; p.Phe1263del). Furthermore, three founder mutations were identified in 86.7% of the 22 Tunisian patients: (1) a deletion of exon 15, in 36.4% patients (8/22); (2), a deletion of exons 4 and 5 in 23% (5/22) and (3) an intronic mutation c.2222 + 166G > A, in 27.3% (6/22). Despite the relatively small number of patients studied, our results depict the mutational landscape of FA among NA populations and it should be taken into consideration for appropriate genetic counseling.

T cell counts and IL-6 concentration in blood of North African COVID-19 patients are two independent prognostic factors for severe disease and death.

The immune system plays a crucial role in the response against severe acute respiratory syndrome coronavirus 2 with significant differences among patients. The study investigated the relationships between lymphocyte subsets, cytokines, and disease outcomes in patients with coronavirus disease 2019 (COVID‐19). The measurements of peripheral blood lymphocytes subsets and cytokine levels were performed by flow cytometry for 57 COVID‐19 patients. Patients were categorized into two groups according to the severity of the disease (nonsevere vs. severe). Total lymphocytes, T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were decreased in COVID‐19 patients and statistical differences were found among different severity of illness and survival states (P ˂ 0.01). The levels of IL‐6 and IL‐10 were significantly higher in severe and death groups and negatively correlated with lymphocyte subsets counts. The percentages of Th17 in the peripheral blood of patients were higher than those of healthy controls whereas the percentages of Th2 were lower. For the severe cases, the area under receiver operating characteristic (ROC) curve of IL‐6 was the largest among all the immune parameters (0.964; 95% confidence interval: 0.927–1.000, P < 0.0001). In addition, the preoperative IL‐6 concentration of 77.38 pg/ml was the optimal cutoff value (sensitivity: 84.6%, specificity: 100%). Using multivariate logistic regression analysis and ROC curves, IL‐6 > 106.44 pg/ml and CD8+ T cell counts <150 cells/μl were found to be associated with mortality. Measuring the immune parameters and defining a risk threshold can segregate patients who develop a severe disease from those with a mild pathology. The identification of these parameters may help clinicians to predict the outcome of the patients with high risk of unfavorable progress of the disease.

HER2 overexpression is a putative diagnostic and prognostic biomarker for late-stage colorectal cancer in North African patients

ABSTRACT Aim: Colorectal cancer (CRC) is one of the leading cancers in the world. Even though its mortality and pathophysiology are well documented in the US and the European countries, it is seldom studied in North African population. Recent studies have shown link of HER2 overexpression in oesophageal and gastric cancers. The aim of this study is to assess the HER2 protein and mRNA expression and its correlation with tumor pathogenesis in Libyan CRC patients. Methodology: A total of 17 FFPE tissue blocks were collected from patients with primary CRC. The HER2 protein expression was assessed by immunohistochemistry and the mRNA expression was assessed using qRT-PCR. Survival analysis of the role of HER2 overexpression on rectal adenocarcinoma was carried out on additional 165 patients. Results: From the CRC cohort, adenocarcinoma was found to be more frequent accounting for 88.2%, and 11.8% for mucinous adenocarcinomas. Almost 47% of the cases were positive for HER2 (score ≥ 2+) and about 50% adenocarcinoma cases with tumor grade II were positive for HER2. Moreover, 57.4% adenocarcinoma patients with grade-II tumor had undergone right hemicolectomy. Furthermore, significant correlation (p = 0.03) between the HER2 mRNA expression with the tumor grade was observed. In addition, poor overall all survival was observed with high HER2 expression in rectum adenocarcinoma. Conclusion: To our knowledge, this is the first study that HER2 overexpression correlates with more aggressive colorectal cancer in North African population. Our study shows that HER2 overexpression associates with right colon surgeries. Also, the correlation of mRNA and protein expression could warrant the implementation of a nationwide screening program for HER2 positivity in CRC patients. Taken together, stratifying patients according to HER2 expression can help in the diagnosis and prognosis of CRC patients from North African origin.