Treatment Challenges in a Severe Case of Syphilitic Myelitis With a Longitudinally Extensive Spinal Cord Lesion.

Syphilitic myelitis is an unusual manifestation of neurosyphilis, rarely reported in the literature. The best management approach remains unclear in severe cases with longitudinally extensive spinal cord lesions. We describe a 29-year-old man with a history of incompletely treated syphilis after a high-risk sexual encounter, who presented two years later with several weeks of progressive numbness and weakness in both legs. MRI spine showed significant cord expansion from the craniocervical junction to T6 with patchy cord enhancement. He was diagnosed with syphilitic myelitis given his history of inadequately treated syphilis, positive serum rapid plasma reagin at a high titer, and CSF pleocytosis with elevated protein along with a reactive CSF Venereal Disease Research Laboratory test. Alternative infectious or immunological etiologies were excluded. He was treated with IV penicillin and pulse steroid therapy with IV methylprednisolone 1 g daily for 3 days with improvement. However, he was soon readmitted with recurrent weakness requiring an additional course of pulse steroid therapy followed by a short prednisone taper. Afterward, his symptoms recurred with worsened cord expansion on imaging. He was re-treated with IV penicillin and pulse steroid therapy with a more prolonged prednisone taper. The patient subsequently improved and had no further recurrent symptoms on extended outpatient follow-up. This report illustrates the importance of keeping syphilitic myelitis on the differential as a treatable cause of longitudinally extensive myelopathy. The patient may have benefited from high-dose IV steroids with a prolonged taper while waiting for the full treatment effect of antibiotics.

Neurological Considerations for the Care of Patients With Severe Obesity.

Patients with severe obesity tend to have higher rates of morbidities which can complicate and even lengthen their hospital admission course. Hospitals which do not have the resources to efficiently manage bariatric patients due to equipment weight-restrictions should be proactive in their care and knowledgeable about their options to avoid long delays in treatment. Amid this obesity epidemic, the neurologist plays a role in the inpatient management of patients with severe obesity and could serve as a channel to improve the quality of care and reduce the length of stay. We present a case of a patient with severe obesity who presented with visual loss secondary to idiopathic intracranial hypertension. The patient's treatment was delayed several weeks from the time of admission until his weight decreased enough to safely undergo CT imaging in the operating room, developing complications throughout the course of his stay. This paper highlights the identified barriers of care and potential solutions to ensure improvement in the quality of care of patients with severe obesity, in order to reduce preventable complications.

Priorities for family physician and general practitioner recruitment and retention in Singapore: a PRIORITIZE study.

BACKGROUND: A shortage of primary care physicians has been reported in many countries. Primary care systems are diverse and the challenges leading to a decline in workforce are at times context-specific and require tailored solutions. Inviting frontline clinicians to share their insights can help identify optimal strategies for a particular setting. To determine priorities for family physicians' and general practitioners' recruitment and retention in Singapore, we invited primary care physicians to rank pertinent strategies using PRIORITIZE, a transparent, systematic priority-setting approach. METHODS: The study advisory board, consisting of representatives of Singapore's key primary care stakeholders, determined the criteria for prioritising of general practitioners (GPs) and family physicians (FPs) recruitment and retention strategies in Singapore. A comprehensive list of GPs and FPs recruitment and retention strategies was extracted from a recent systematic review of the relevant literature. A questionnaire listing the strategies and the scoring criteria was administered online to doctors practicing in public and private sector in Singapore. Respondents' scores were combined to create a ranked list of locally most relevant strategies for improving GPs and FPs recruitment and retention. RESULTS: We recruited a diverse sample of 50 GPs and FPs practicing in a variety of primary care settings, many with a range of additional professional responsibilities. Around 60 and 66% of respondents thought that there was a problem with recruitment and retention of GPs and FPs in Singapore, respectively. Strategies focusing on promoting primary care by emphasizing the advantages and enhancing the status of the profession as well as training-related strategies, such as sub-specialisation and high-quality rotations were considered priorities for improving recruitment. For retention of GPs and FPs, improving working conditions by increasing GPs' and FPs' salary and recognition, as well as varying or reducing time commitment, were seen as the most important strategies. The ranking between physicians working in public and private sector was mostly similar, with nine out of the top ten recruitment and retention strategies being the same. CONCLUSION: Primary care physicians' ranking of recruitment and retention strategies for GPs and FPs in Singapore provide important insight into the challenges and the solutions as seen by the members of the profession themselves. This information can guide future policy and decision making in this area.

Global and regional prevalence and outcomes of COVID-19 in people living with HIV: A systematic review and meta-analysis

BackgroundThe relationship between HIV infection and COVID-19 clinical outcome is uncertain, with conflicting data and hypotheses. We aimed to assess the prevalence and risk of severe COVID-19 and death in people living with HIV (PLWH) on the global and continental level. MethodsElectronic databases were systematically searched in July 2021. Studies were screened and then extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Narratives were synthesised and data pooled for global and continental prevalence and relative risk of severity and mortality in HIV-infected COVID-19 patients using random-effect model. Risk of bias was assessed using the Newcastle-Ottawa score, Eggers test and presented as funnel plots. ResultsA total of 46 studies were included involving 18,034,947 COVID-19 cases of which 31,269 were PLWH. The global prevalence of PLWH with SARS-CoV-2 infection was 1% (95% CI = 0.9% -1.1%) with the highest prevalence observed in sub-Saharan Africa. The relative risk (RR) of COVID-19 severity was significant only in Africa (RR, 95% CI = 1.14, 1.08 - 1.24) while risk of COVID-19 mortality was 1.53% (95% CI = 1.45 - 2.03) globally. The prevalence of PLWH in COVID-19 cases was significantly low, and the calculated global risk ratio show that HIV infection may be linked with increased COVID-19 death. The between-studies heterogeneity was significantly high while risk of publication bias was not significant. ConclusionThere is low prevalence of HIV-SARS-CoV-2 co-infection. HIV infection was linked with severe COVID-19 in Africa and increased risk of death globally.

Vaccine serologic responses among transplant patients associate with COVID-19 infection and T peripheral helper cells

BackgroundTherapeutically immunosuppressed transplant recipients exhibit attenuated responses to COVID-19 vaccines. To better understand the immune alterations that determined poor vaccine response, we correlated quantities of circulating T and B cell subsets at baseline with longitudinal serologic responses to SARS-CoV-2 mRNA vaccination in heart and lung transplant recipients. MethodsSamples at baseline and at approximately 8 and 30 days after each vaccine dose for 22 heart and lung transplant recipients with no history of COVID-19, four heart and lung transplant recipients with prior COVID-19 infection, and 12 healthy controls undergoing vaccination were analyzed. Anti-spike protein receptor binding domain (RBD) IgG and pseudovirus neutralization activity were measured. Proportions of B and T cell subsets at baseline were comprehensively quantitated. ResultsAt 8-30 days post vaccination, healthy controls displayed robust anti-RBD IgG responses, whereas heart and lung transplant recipients showed minimally increased responses. A parallel absence of activity was observed in pseudovirus neutralization. In contrast, three of four (75%) transplant recipients with prior COVID-19 infection displayed robust responses at levels comparable to controls. Baseline levels of activated PD-1+ HLA-DR+ CXCR5- CD4+ T cells (also known as T peripheral helper [TPH] cells) and CD4+ T cells strongly predicted the ability to mount a response. ConclusionsImmunosuppressed patients have defective vaccine responses but can be induced to generate neutralizing antibodies after SARS-CoV-2 infection. Strong correlations of vaccine responsiveness with baseline TPH and CD4+ T cell numbers highlights a role for T helper activity in B cell differentiation into antibody secreting cells during vaccine response.

Gastrointestinal Symptoms and Lactic Acidosis in a Chronic Marijuana User.

A patient presented with diffuse abdominal pain and a history of frequent cannabis use, a diet lacking in meat and fish, and an increase in consumption of simple carbohydrates in the past year.

Conus involvement and leptomeningeal enhancement in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: A case report.

There are a variety of clinical phenotypes and radiological features that continue to make a diagnosis of neuromyelitis optica spectrum disorder (NMOSD) challenging. We present an atypical case of an adult woman who presented with flaccid paralysis of all extremities with unusual neuroimaging features, including extensive enhancing lesions in the upper cervical cord and conus medullaris with associated leptomeningeal enhancement. She was ultimately found to have AQP4 antibody-positive NMOSD. We discuss the factors that complicated a timely diagnosis, including her atypical radiographic features and an initially negative cell-based assay for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies. Despite the rarity of conus medullaris involvement or leptomeningeal enhancement in AQP4 antibody-positive NMOSD, it is important to maintain a high level of clinical suspicion to avoid diagnostic and therapeutic delays. Though cell-based assays have high sensitivities, testing should be repeated on negative values in these scenarios.

Recurrent Thymoma-Associated Paraneoplastic Encephalitis Resulting From Multiple Antibodies: A Case Report.

Few reports describe the clinical course and acute-care management of patients with recurrent multi-antibody paraneoplastic encephalitis. We describe a rare case of a patient having thymoma with multiple paraneoplastic syndromes who was found to have antibodies to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) followed by N-methyl-d-aspartate (NMDA) receptor in the setting of residual thymic tissue. He initially presented to the hospital with severe, rapidly progressive encephalitis with simultaneous antibodies to AMPA and voltage-gated potassium channel complex receptor. Brain magnetic resonance imaging revealed scattered white matter hyperintensities and an enhancing lesion adjacent to the left caudate. Computerized tomography showed an anterior mediastinal mass that was resected and revealed to be a thymoma. He was refractory to treatment with intravenous immunoglobulin, high-dose steroids, and plasmapheresis. He was then started on monthly cyclophosphamide. After 3 cyclophosphamide infusions, he began to show improvement in his alertness, ability to speak, and capacity to follow commands. One month later, he was readmitted to the hospital for new and unusual behavioral outbursts and agitation. He was found to have new anti-NMDA receptor antibodies in his cerebrospinal fluid in the setting of residual hyperplastic thymic tissue that required another resection. He was treated with rituximab and then cyclophosphamide (due to an infusion reaction with rituximab) with positive outcomes. The presence of multiple antibodies may be associated with poor prognosis, requiring prompt recognition and aggressive immunosuppressive treatment. New neurological symptoms should prompt a search for residual pathologic tissue or tumor recurrence causing new autoantibodies and additional paraneoplastic syndromes.

Long-term follow-up of vocal fold movement impairment and feeding after neonatal cardiac surgery.

OBJECTIVE: To determine the long-term prognosis of children with vocal fold mobility impairment (VFMI) after cardiac surgery, with respect to time to normal feeding and incidence of admissions for pneumonia and feeding difficulties. METHODS: A retrospective chart review was conducted of all neonates who had otolaryngology exam after cardiac surgery at a tertiary children's hospital from May 2007 to May 2008. Charts were reviewed for demographics, type of cardiac surgery, vocal fold mobility, diet at time of discharge and at last follow-up, time to full oral feeding, and hospital admissions. RESULTS: There were a total of 94 patients included in the study, 17 of whom had VFMI. While significantly more patients with VFMI required modified diet at discharge, 48% compared to 19% of patients with normal vocal fold mobility; there was no statistically significant difference in time to regular diet on long-term follow-up, 0.8 years (VFMI) compared to 0.4 years (normal vocal fold mobility). Of the 25 patients with modified diet or gastrostomy tube at discharge, 52% returned to full feeds within a year. There was no difference in hospitalizations for pneumonia in patients with or without VFMI. However in patients with VFMI, 35% required readmission for feeding difficulty or poor weight gain compared to only 5% in the infants with normal vocal fold mobility. CONCLUSION: After neonatal cardiac surgery, there do not appear to be long-term effects of VFMI with regards to readmission for pneumonia. However, there is an increased risk for hospitalization with respect to feeding difficulties in those neonates with VFMI. The overall prognosis for time to oral feeding is good.

Laser skin treatment in non-Caucasian patients.

The demand for facial rejuvenation and cosmetic procedures is rising among all ethnicities and skin types. The authors present a review of lasers and how to select a laser based on skin type and the treatment goals of laser resurfacing: skin laxity, dyschromia, hair removal, keloid, and hypertrophic scarring. In addition, they discuss preprocedural and postprocedural considerations, potential complications, and their management to maximize patient outcomes and minimize risk.

Early pulmonary cytokine and chemokine responses in mice immunized with three different vaccines against Mycobacterium tuberculosis determined by PCR array.

In this study, the early pulmonary cytokine and chemokine responses in mice immunized with either BCG vaccine, a DeltasecA2 mutant of Mycobacterium tuberculosis, or a DNA vaccine expressing an ESAT6-antigen 85B fusion protein and then aerogenically challenged with a low dose of M. tuberculosis were evaluated by PCR array. The cellular immune responses at day 10 postchallenge were essentially equivalent in the lungs of mice immunized with either the highly immunogenic BCG vaccine or the DeltasecA2 M. tuberculosis mutant strain. Specifically, 12 immune biomolecules (including gamma interferon [IFN-gamma], interleukin-21 [IL-21], IL-27, IL-17f, CXCL9, CXCL10, and CXCL11) were differentially regulated, relative to the levels for naïve controls, in the lungs of vaccinated mice at this time point. Although the vaccine-related immune responses evoked in mice immunized with the DNA vaccine were relatively limited at 10 days postinfection, upregulation of IFN-gamma RNA synthesis as well as increased expression levels of CXCL9, CXCL10, and CXCL11 chemokines were detected.

Mycobacterium bovis BCG immunization induces protective immunity against nine different Mycobacterium tuberculosis strains in mice.

Recent preclinical and epidemiologic studies have suggested that certain Mycobacterium tuberculosis genotypes (in particular, Beijing lineage strains) may be resistant to Mycobacterium bovis BCG vaccine-induced antituberculosis protective immunity. To investigate the strain specificity of BCG-induced protective responses in a murine model of pulmonary tuberculosis, C57BL/6 mice were vaccinated with BCG vaccine and then challenged 2 months later with one of nine M. tuberculosis isolates. Four of these strains were from the W-Beijing lineage (HN878, N4, NHN5, and ChS) while four were non-Beijing-type isolates (C913, CDC1551, NY669, and NY920). As a control, the WHO standard M. tuberculosis Erdman strain was evaluated in these vaccination/challenge experiments. To assess the protective responses evoked by BCG immunization, organ bacterial burdens and lung pathology were assessed in vaccinated and naïve mice at 4, 12, and 20 weeks postchallenge as well as during the day of infection. At 4 weeks after the aerosol challenge with each of these strains, significantly reduced bacterial growth in the lungs and spleens and significantly improved lung pathology were seen in all vaccinated animals compared to naïve controls. After 12 weeks, reduced organ bacterial burdens were detected in vaccinated animals infected with six of nine challenge strains. Although lung CFU values were lower in vaccinated mice for only three of nine groups at 20 weeks postchallenge, significantly decreased lung inflammation was seen in all immunized animals relative to controls at 20 weeks postchallenge. Taken together, these data demonstrate that BCG vaccination protects against infection with diverse M. tuberculosis strains in the mouse model of pulmonary tuberculosis and suggest that strain-specific resistance to BCG-induced protective immunity may be uncommon.

Protection against an aerogenic Mycobacterium tuberculosis infection in BCG-immunized and DNA-vaccinated mice is associated with early type I cytokine responses.

Although vaccination against tuberculosis (TB) was initiated more than 80 years ago, the correlates of protective immunity against infection by Mycobacterium tuberculosis have still not been well defined. To investigate the vaccine-induced immune responses against TB, we evaluated the early pulmonary cytokine responses elicited by a low dose M. tuberculosis aerogenic challenge in mice that had been immunized with either BCG or a TB DNA vaccine cocktail, two vaccine preparations that induce long-term protection in the mouse model of pulmonary TB. Using three different assays, we showed that specific cytokine responses were elevated in the lungs of vaccinated mice (relative to naïve controls) during the second week post-challenge. By measuring cytokine levels in the bronchoalveolar lavage fluid (BAL) and cytokine mRNA concentrations in pulmonary cells, the levels of IFN-gamma, IL-12, and RANTES were shown to be elevated from days 7-14 post-challenge in the lungs. By intracellular cytokine staining (ICS), increased numbers of lung CD4 and CD8 cells expressing IFN-gamma were also seen at days 10 and 14 after the infection. Moreover, increased post-challenge IFN-gamma levels were detected using the ICS and cytokine mRNA assays in aging BCG-immunized mice that had been effectively boosted with a TB DNA vaccine. Taken together, these data suggest that the post-infection induction of early type 1 cytokine responses correlate with the induction of long-term protective immunity in vaccinated mice.

Vaccination with a Sindbis virus-based DNA vaccine expressing antigen 85B induces protective immunity against Mycobacterium tuberculosis.

To improve DNA vaccination against Mycobacterium tuberculosis, we evaluated the effectiveness of a Sindbis virus-based DNA construct expressing the tuberculosis antigen 85B (Sin85B). The protective efficacy of Sin85B was initially assessed by aerogenically challenging immunized C57BL/6 mice with virulent Mycobacterium tuberculosis. At 1 and 7 months postinfection, the lung bacterial burdens were considerably reduced and the lung pathology was improved in vaccinated mice compared to naive controls. Furthermore, the mean survival period for Sin85B-immunized mice (305 +/- 9 days) after the tuberculous challenge was extended 102 days relative to the naive mice (203 +/- 13 days) and was essentially equivalent to the survival time of Mycobacterium bovis BCG-vaccinated mice (294 +/- 15 days). The essential role of gamma interferon (IFN-gamma) in Sin85B-mediated protection was established by showing that significantly increased levels of IFN-gamma mRNA were present postinfection in lung cells from vaccinated mice relative to control mice and by demonstrating that IFN-gamma depletion prior to challenge abolished the vaccine-induced protection. The substantial antituberculosis protective responses induced by Sin85B immunization of CD4-/- mice strongly suggested that CD8 cells partially mediate Sin85B-induced protective immunity. Interestingly, Sin85B vaccination did not protect RNase L-/- (a key enzyme in the innate antiviral response) mice while significant protection was detected in RNase L-/- mice immunized with either BCG or a conventional DNA plasmid expressing antigen 85B. These data show that immunization with Sin85B offers protection similar to BCG in a murine model of pulmonary tuberculosis and suggest that Sin85B-induced protection is dependent upon both innate and acquired immune mechanisms.

A polyvalent DNA vaccine expressing an ESAT6-Ag85B fusion protein protects mice against a primary infection with Mycobacterium tuberculosis and boosts BCG-induced protective immunity.

In this study, we evaluated the protective efficacy of a DNA vaccine (pE6/85) expressing an ESAT6-Ag85B fusion protein against a primary Mycobacterium tuberculosis infection in mice. In short-term studies, vaccination with pE6/85 protected as well as Mycobacterium bovis BCG immunization with similar lung pathology and bacterial burdens detected 28 days after a low dose aerogenic challenge (>1.0 log(10) reduction relative to naïves). In a survival experiment, the protection induced by pE6/85 immunization was also not significantly different than that elicited by BCG vaccination with the mean-times-to-death (+/-standard error of the mean) being 102+/-20, 271+/-32 and 299+/-14 days for naïve, pE6/85 and BCG-vaccinated mice, respectively. Furthermore, boosting with pE6/85 but not BCG or a DNA vaccine cocktail at 1 year after an initial BCG immunization (when BCG-induced protection was declining), augmented protection in the lung at 15 and 18 months to levels detected at 3 months post-BCG vaccination.

Immunization with a DNA vaccine cocktail protects mice lacking CD4 cells against an aerogenic infection with Mycobacterium tuberculosis.

Tuberculosis (TB) is the most common opportunistic disease and a potentially fatal complication among immunocompromised individuals infected with human immunodeficiency virus (HIV). Effective vaccination against TB in persons with HIV has been considered unlikely because of the central role that CD4 cells play in controlling tuberculous infections. Here we show that the vaccination of CD8(-/-) mice with a TB DNA vaccine cocktail did not significantly enhance protective responses to a Mycobacterium tuberculosis infection. In contrast, immunization with a DNA vaccine cocktail or with the current TB vaccine, Mycobacterium bovis BCG, induced considerable antituberculosis protective immunity in immune-deficient mice lacking CD4 cells. In vaccinated CD4(-/-) animals, substantially reduced bacterial burdens in organs and much improved lung pathology were seen 1 month after an aerogenic M. tuberculosis challenge. Importantly, the postchallenge mean times to death of vaccinated CD4(-/-) mice were significantly extended (mean with DNA cocktail, 172 +/- 7 days; mean with BCG, 156 +/- 22 days) compared to that of naïve CD4(-/-) mice (33 +/- 6 days). Furthermore, the treatment of DNA-vaccinated CD4(-/-) mice with an anti-CD8 or anti-gamma interferon (IFN-gamma) antibody significantly reduced the effect of immunization, and neither IFN-gamma(-/-) nor tumor necrosis factor receptor-deficient mice were protected by DNA immunization; therefore, the primary vaccine-induced protective mechanism in these immune-deficient mice likely involves the secretion of cytokines from activated CD8 cells. The substantial CD8-mediated protective immunity that was generated in the absence of CD4 cells suggests that it may be possible to develop effective TB vaccines for use in HIV-infected populations.