Myopathy associated with homozygous PYROXD1 pathogenic variants detected by genome sequencing

Biallelic pathogenic variants in the gene PYROXD1 have recently been described to cause early-onset autosomal recessive myopathy. Myopathy associated with PYROXD1 pathogenic variants is rare and reported in only 17 individuals. Known pathogenic variants in PYROXD1 include missense, insertion and essential splice-site variants. Here we describe a consanguineous family of individuals affected with late-onset myopathy and homozygous PYROXD1 missense variants (NM_024854.5:c.464A>G [p.Asn155Ser]) expanding our understanding of the possible disease phenotypes of PYROXD1-associated myopathy.     

Undiagnosed Acute Viral Febrile Illnesses,Sierra Leone

Sierra Leone in West Africa is in a Lassa fever–hyperendemic region that also includes Guinea and Liberia. Each year, suspected Lassa fever cases result in submission of ≈500–700 samples to the Kenema Government Hospital Lassa Diagnostic Laboratory in eastern Sierra Leone. Generally only 30%–40% of samples tested are positive for Lassa virus (LASV) antigen and/or LASV-specific IgM; thus, 60%–70% of these patients have acute diseases of unknown origin. To investigate what other arthropod-borne and hemorrhagic fever viral diseases might cause serious illness in this region and mimic Lassa fever, we tested patient serum samples that were negative for malaria parasites and LASV. Using IgM-capture ELISAs, we evaluated samples for antibodies to arthropod-borne and other hemorrhagic fever viruses. Approximately 25% of LASV-negative patients had IgM to dengue, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola, and Marburg viruses but not to Crimean-Congo hemorrhagic fever virus.     

Informing efforts to reach UNAIDS’ 90–90–90 targets: a comparison of characteristics of people diagnosed with HIV in health facilities to the general population of people living with HIV in Mozambique

Global targets aim to increase the number of people living with HIV (PLWH) who know their status. Using data from Mozambican facility-based HIV testing and counseling (HTC) and a population-based survey, we compared characteristics of PLWH diagnosed in HTC to the general population of PLWH to identify subgroups that are missing from the health system and may be undiagnosed. Male and female PLWH aged 50+ (PPR?=?0.47, p?=?.0001) and with higher HIV knowledge (PPR?=?0.52, p?=?.004) were underrepresented in HTC. A higher proportion of patients diagnosed in health facilities were aged 25–39 (PPR?=?1.23, p?=?.02). Female PLWH with lower economic (PPR?=?0.70, p?=?.04) and educational status (PPR?=?0.86, p?=?.02) and male PLWH aged 18–24 (PPR?=?0.47, p?=?.03) were underrepresented in HTC. Comparing HTC data to population-based data can inform efforts to increase HIV diagnoses and to ensure that all PLWH know their status.     

Evaluation of undiagnosed solitary lung nodules according to the probability of malignancy in the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines

Background

This study retrospectively investigated the clinical significance of undiagnosed solitary lung nodules removed by surgical resection.

Patients and methods

We retrospectively collected data on the age, smoking, cancer history, nodule size, location and spiculation of 241 patients who had nodules measuring 7 mm to 30 mm and a final diagnosis established by histopathology. We compared the final diagnosis of each patient with the probability of malignancy (POM) which was proposed by the American College of Chest Physicians (ACCP) guidelines.

Results

Of the 241 patients, 203 patients were diagnosed to have a malignant lung tumor, while 38 patients were diagnosed with benign disease. There were significant differences in the patients with malignant and benign disease in terms of their age, smoking history, nodule size and spiculation. The mean value and the standard deviation of the POM in patients with malignant tumors were 51.7 + 26.1%, and that of patients with benign lesions was 34.6 + 26.7%. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.67. The best cut-off value provided from the ROC curve was 22.6. When the cut-off value was set at 22.6, the sensitivity was 83%, specificity 52%, positive predictive value 90%, negative predictive value 36% and accuracy 77%, respectively.

Conclusions

The clinical prediction model proposed in the ACCP guidelines showed unsatisfactory results in terms of the differential diagnosis between malignant disease and benign disease of solitary lung nodules in our study, because the specificity, negative predictive value and AUC were relatively low.