Fatal septic shock due to disseminated coccidioidomycosis: a case series and review of the literature.

BACKGROUND: Coccidioidomycosis is a fungal infection endemic to the southwestern United States and regions of Latin America. Disseminated disease occurs in < 1% of cases. Septic shock is even rarer, with high mortality despite therapy. We describe two cases of coccidioidal septic shock. Both patients were older men of Filipino ancestry presenting with respiratory failure and vasopressor-dependent shock. Antifungal drugs were initiated after failure to improve with empiric antibiotics; in both, Coccidioides was isolated from respiratory cultures. Despite aggressive care, both patients ultimately died of their infections. We provide a review of the published literature on this topic. CONCLUSIONS: Most of the 33 reported cases of coccidioidal septic shock occurred in men (88%) of non-white race and ethnicity (78%). The overall mortality rate was 76%. All survivors received amphotericin B as part of their treatment. Coccidioidomycosis-related septic shock is a rare disease with poor outcomes; delays in diagnosis and treatment are common. Improved diagnostic testing for coccidioidomycosis could enhance recognition of this disease in the future. Although data are limited, early treatment with amphotericin B in cases of coccidioidal septic shock may reduce mortality.

Exertional-Related Sudden Cardiac Death in a Young, Presumed Healthy, and Medically Screened Population: A Military Case Series.

ABSTRACT: Sudden cardiac death (SCD) is defined as death from cardiac causes with loss of consciousness occurring within 1 hour of a change in cardiovascular status. As subset, SCD associated with physical exertion (SCD/E) can be defined as a cardiac event whose symptoms start during or within 1 hour of physical exertion. The US military represents a unique opportunity for studying SCD/E because of medical screening at recruitment, mandatory physical training, an active surveillance system, and centralized autopsy services. Because of medical screening, recruits are presumed healthy, but significant conditions can go undetected. We present 4 diverse cases of SCD/E in the military setting. Sudden cardiac death associated with physical exertion is often the first indication of a serious occult cardiac pathology. Postmortem genetic testing revealed a causative pathogenic mutation in 1 of 4 cases, enabling genetic testing of family members to prevent similar catastrophic loss of life, underscoring the importance of postmortem evaluation including genetic testing. Further investigations will help direct screening and prevention to capture those at risk for SCD. The cases presented in this series are a sample of the diverse etiologies and contexts surrounding SCD/E in the military setting that have been captured by Armed Forces Medical Examiner System.

Sudden Death in Diabetic Ketoacidosis Complicated by Sickle Cell Trait.

ABSTRACT: In a sudden death investigation of a service member with sickle cell trait (SCT), evidence of sickle cell crisis further complicated by coexisting, undiagnosed diabetic ketoacidosis called into question the synergistic effects of diabetic ketoacidosis on red blood cell sickling. Sickle cell trait affects more than 4 million people in the United States (US) with the highest prevalence in non-Hispanic Blacks (7%-9%; Mil Med 2017;182(3):e1819-e1824). The heterozygous state of sickled hemoglobin was previously considered a benign condition causing sickling during hypoxic, high-stress conditions such as exercise and high altitude ( Am Assoc Clin Chem 2017). However, research within the last decade shows evidence of sudden death among SCT patients ( J Forensic Sci 2011;56(5):1352-1360). It has been shown that the presence of sickled hemoglobin artificially lowers levels of hemoglobin A1c making it a less effective biomarker for red blood cell glycosylation over time in sickle cell patients ( JAMA 2017;317(5):507-515). The limited scope of medical understanding of the effects of SCT in combination with other comorbidities requires further investigation and better diagnostic criteria. The uniqueness of the US Military and its screening program for sickle cell disease (SCD) and SCT allows for more detection. Since May 2006, newborn screening for SCD/SCT has been a national requirement; however, anyone older than 14 years may not know their SCD/SCT status ( Semin Perinatol 2010;34(2):134-44). The previous absence of such national screening makes it more challenging to identify SCT and SCD patients even within high-risk populations. Furthermore, patients may not know or understand the results of their SCD/SCT status testing. International standards for the autopsy of decedents with SCD and SCT exist ( R Coll Pathol 2017). Within the US, testing of vitreous electrolytes is a common practice in suspected natural death cases, but a review of the US literature did not demonstrate any autopsy standards or recommendations for persons with SCT or high-risk persons for sickling pathologies. The identification of a new diagnosis of type 2 diabetes mellitus, as the cause of death, is not uncommon; however, this case indicates that type 2 diabetes mellitus was not the sole contributing factor. It further illustrates that the US may be underestimating the impact of SCD and SCT as a cause of death, a contributing factor to death, and its synergistic effects with other pathologic processes. We propose a stringent literature review in conjunction with a review of international autopsy standards to develop national autopsy standards and possible SCT/SCD screening recommendations for high-risk persons at the time of autopsy.

A review of genetic factors underlying craniorachischisis and omphalocele: Inspired by a unique trisomy 18 case.

Very few cases of craniorachischisis (CRN) with concomitant omphalocele (OMP) in the setting of trisomy 18 are reported in literature. Solitary midline closure defects are estimated to be more prevalent in trisomy 18 compared to the general population. Neurulation defect comparisons include anencephaly 0-2% versus 0.0206%, spina bifida 1-3% versus 0.0350%, and encephalocele 0-2% versus 0.0082% [Parker et al. (2010); Birth Defects Research. Part A: Clinical and Molecular Teratology, 88:1008-1016; Springett et al. (2015); American Journal of Medical Genetics. Part A, 167A:3062-3069]. The solitary anterior malformation OMP has been reported as high as 6% with trisomy 18 [Springett et al. (2015); American Journal of Medical Genetics. Part A, 167A:3062-3069]. We report the third published case of CRN with concomitant OMP observed in a likely trisomy 18 fetus that screened positive by noninvasive prenatal screening. Furthermore, we review and analyze the current literature to augment understanding of the genetic basis for anterior and posterior closure defects such as CRN and OMP. Although the current genetic lexicon lacks any definitive association with the simultaneous defects presented, previous research elucidated various genes related to anterior or posterior closure interruption individually. By consolidating current research, the authors advance knowledge of interconnected genetic pathology and direct future genetic mapping efforts.

Recurrent idiopathic painless shoulder weakness in a Navy F/A-18 aviator.

Brachial plexopathies of various etiologies are commonly discussed in the literature; however, recurrent painless shoulder weakness is an uncommon event, especially in an otherwise healthy adult man. A designated Naval F/A-18 E/F aviator presented with acute right-sided, painless shoulder girdle weakness that initially presented 2 yr earlier in a similar fashion. Extensive medical workups during both episodes did not reveal any identifiable cause. This case report discusses the most common etiologies of shoulder weakness. Additionally, we discuss the aviator's most recent presentation and evaluation for acute shoulder weakness. Lastly, we propose a hypothesis as to the cause of the patient's symptoms based on a review of the literature.

Increased duration of viral suppression is associated with lower viral rebound rates in patients with previous treatment failures.

OBJECTIVE: We investigated whether the rate of viral rebound decreases with increasing duration of viral suppression and, if so, whether rebound rates in patients previously failing antiretroviral regimens ultimately decline to levels as low as those seen in patients who have never experienced virological failure. METHODS: All patients from the UK CHIC Study (n = 21 256) who achieved a viral load (VL) of < or = 50 copies/ml while receiving HAART were followed until viral rebound (two consecutive VL > 400 copies/ml). Patients could re-enter the analysis if they experienced a subsequent VL < or = 50 copies/ml. Rebound rates were calculated according to the number of regimens previously failed and duration of viral suppression. RESULTS: Of 12 648 patients on HAART 10 237 (80.9%) achieved a VL < or = 50 copies/ml. During 26 494 person-years (PY) of follow-up, 1853 (18.1%) patients experienced at least one viral rebound 'event', with 2460 events in total [rebound rate, 9.3 (range, 8.9-9.7)/100 PY). Within the first year of viral suppression, the rate of viral rebound was 8.3 (7.5-9.1)/100 PY in patients who had not previously failed treatment, increasing to 32.7 (27.6-37.8)/100 PY in patients who had failed more than four regimens. Irrespective of previous treatment failure, rebound rates in those who remained suppressed for > 4 years were similar to those in patients who had at no time experienced treatment failure. CONCLUSION: After around 4 years of viral suppression rebound rates in individuals with multiple prior treatment failures approach those of individuals with no prior treatment failure.

Myeloid Sarcoma: Presenting with Massive Cervical and Inguinal Lymphadenopathy.

A 21 year old Active Duty Marine presented with acute onset of diffuse lymphadenopathy and B-symptoms. Biopsy was conducted which demonstrated myeloid sarcoma. Myeloid sarcoma is diagnostic for AML but is only present in 2-8 % of patients with AML. Our article presents a classic presentation and histologic appearance and discusses the current status of the literature.

Responses to a 1 month self-report on adherence to antiretroviral therapy are consistent with electronic data and virological treatment outcome.

OBJECTIVES: Many questionnaires on adherence to antiretroviral therapy are in use, but the validity of patients' responses has not been tested. The Medication Adherence Self-Report Inventory (MASRI) has been developed and tested for its validity against objective measures and treatment outcome. DESIGN: Prospective study comparing questionnaire responses with MEMS TrackCap (MC, a medication event monitoring system), pill count (PC) and plasma HIV viraemia in a publicly funded specialist HIV clinic. PARTICIPANTS: Patients self-medicating antiretroviral therapy who were not cognitively impaired and were able to read and understand English. RESULTS: Mean adherence by MC of the 78 subjects was 92.9% (SE, 1.8%) and by PC 96.8% (SE, 1.4%). Agreement between MC and responses to items about doses missed 1, 2 or 3 days ago was low (kappa = 0.23 (P < 0.03), 0.44 (P < 0.001) and 0.28 (P < 0.01) respectively). This improved when these responses were summated (kappa = 0.46;P < 0.001) and was similar to that for recall of non-adherence over the preceding 2 weeks (kappa = 0.54; P < 0.001). Mean self-reported adherence by visual analogue scale (VAS) over the preceding month was 93.3% (SE, 1.2%). This was strongly associated with both MC (r = 0.63; P < 0.001) and PC (r = 0.75; P < 0.001). On multivariate analysis, the strongest association between a MASRI item and MC was for the VAS. Both the 2 week recall and VAS items were inversely associated with viral load (P = 0.01). There was no association between dose timing (measured MC or questionnaire) or 3 day self-report and viral load. CONCLUSIONS: The MASRI provides a means of measuring patient adherence that is valid when compared with objective measures.

Case report. Severe cutaneous ulceration secondary to cytomegalovirus inclusion disease during successful immune reconstitution with HAART.

Restoration of the immune system following HAART is not without its adverse effects. We describe a case of severe cutaneous ulceration secondary to cytomegalovirus (CMV) infection in an HIV-1-seropositive man following the initiation of HAART in the absence of active CMV retinitis and discuss the likely mechanisms associated with its development.

A common presentation to an uncommon disease. Penile Mondor's disease: a case report and literature review.

Penile Mondor's disease, or superficial thrombophlebitis of the dorsal vein of the penis, is a relatively uncommon but potentially anxiety-inducing self-limiting condition that should be easily recognizable by any primary care practitioner. It typically presents with a cord-like mass and pain to the dorsal penis and has a myriad of causes, including trauma, excessive sexual activity, excessive exercise, or malignancy. Although Penile Mondor's disease is typically a clinical diagnosis, Doppler ultrasound is the initial imaging modality of choice if there is question or doubt about the diagnosis. Accurate diagnosis and reassurance about the condition's benign and self-limiting nature assuages most patients' fears. Treatment is primarily symptomatic but may vary depending on possible underlying disease processes.

Are previous treatment interruptions associated with higher viral rebound rates in patients with viral suppression?

OBJECTIVE: We investigated whether previous treatment interruptions are associated with a raised risk of viral rebound in individuals who have attained virological suppression. METHODS: All patients achieving an undetectable viral load while on therapy were followed until viral rebound or the time of the last viral load. Poisson regression was used to describe the independent impact of treatment interruptions on rebound rates. RESULTS: A total of 12,977 patients from the United Kingdom Collaborative HIV Cohort (UK CHIC) Study achieved a viral load of less than 50 copies/ml. These patients contributed a total of 37,314 person-years of follow-up. The overall rebound rate was 8.07 (7.78, 8.36) per 100 person-years. In adjusted analyses, rates of viral rebound were up to 64% higher (rate ratio 1.64; 1.43, 1.88) in those who had previously interrupted therapy compared with those who had not. Patients who had interrupted at detectable viral loads had up to a 74% (1.74; 1.42, 2.14) higher chance of rebounding compared with those who had not interrupted with a detectable viral load. We found no evidence to suggest interrupting treatment at an undetectable viral load was associated with viral rebound. CONCLUSION: Among patients with an undetectable viral load, having previously interrupted therapy while the viral load was detectable is associated with a raised risk of rebound.