Δευτέρα 31 Οκτωβρίου 2022

Recurrence of symptoms following cryptococcal meningitis - characterizing a diagnostic conundrum with multiple etiologies

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Abstract
Background
Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies and outcomes among persons with second-episode symptomatic recurrence.
Methods
We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, ART and cryptococcosis histories, clinical outcomes, and CSF analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as 1: microbiological relapse, 2: paradoxical Immune Reconstitution Inflammatory Syndrome (IRIS), 3: persistent elevated intracranial pressure (ICP) only, or 4: persistent symptoms only; along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal Wallis tests as appropriate.
Results
724 participants wer e included (n = 607 primary episode, n = 81 relapse, n = 28 paradoxical IRIS, n = 2 persistently elevated ICP, n = 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/mcL, IQR 9-76) and lower CSF WBC (4 cells/mcL, IQR 4-85) counts than paradoxical IRIS (CD4 78 cells/mcL, IQR 47-142 and WBC 45 cells/mcL, IQR 8-128). Among those with CSF WBC <5 cells/mcL, 86% (43/50) had relapse. Among those with CD4 counts < 50 cells/mcL, 91% (39/43) had relapse. 18-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS.
Conclusions
Poor immune reconstitution was noted more often in relapse compared to IRIS as evidenced by lower CSF WBC counts and blood CD4 counts. These easily obtained lab values should prompt initiation of antifungal treatment while awaiting culture results.
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Post‐COVID‐19 vaccination arm pain diagnosed as complex regional pain syndrome: a case report

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Abstract

As the vaccination efforts against the coronavirus disease-2019 (COVID-19) continue, more patients are likely to present with complications related to COVID-19 vaccination. We describe the first reported case of complex regional pain syndrome (CRPS), involving the upper extremities, that occurred after COVID-19 vaccination. The patient presented with acute-onset severe arm pain and swelling following vaccine administration. Based on the clinical, electrodiagnostic, and radionuclide three-phase bone scan findings, the patient was diagnosed with postvaccination CRPS. The COVID-19 vaccine possibly elicited an immune-mediated inflammatory response to the injected antigen in the patient, who was predisposed to CRPS due to inflammatory immunity. The COVID-19 vaccine elicited an immune-mediated inflammatory response to the injected antigen, resulting in CRPS following COVID-19 vaccination.

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Total calcium, dairy foods and risk of colorectal cancer: a prospective cohort study of younger US women

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Abstract
Background
Although colorectal cancer (CRC) incidence is declining among adults aged ≥65 years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55 years.
Methods
In the Nurses' Health Study II (1991–2015), 94 205 women aged 25–42 years at baseline were included in the analysis. Diet was assessed every 4 years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model.
Results
We documented 349 incident CRC cases during 2 202 604 person-years of follow-up. Higher total calcium intake was associated with a reduced risk of CRC. Compared with those with <750 mg/day of total calcium intake, the HR of CRC was 0.61 (95% CI, 0.38–0.97) for those who consumed ≥1500 mg/day (P for trend = 0.01). The HR per 300 mg/day increase was 0.85 (95% CI, 0.76–0.95). There was a suggestive inverse association between total calcium intake and CRC before age 55 years (HR per 300 mg/day increase, 0.87; 95% CI, 0.75–1.00), suggesting the importance of calcium intake in the younger population.
Conclusions
In a cohort of younger women, which reflects the birth cohorts, time periods and age ranges paralleling the recent rise in CRC, higher calcium intake was associated with a decreased risk of CRC.
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Κυριακή 30 Οκτωβρίου 2022

Diagnostic efficacy of positron emission computerized tomography scans in suspicious laryngeal findings postorgan preservation treatment

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Abstract

Background

Larynx preservation protocols (LPP) for glottic primary squamous cell carcinoma has gained popularity worldwide. Direct laryngoscopy (DL) with biopsy is mandated when recurrence is suspected. The efficacy of 18Fluoro-deoxy-glucose positron emission computerized tomography (PET-CT) as alternative first-line diagnostic investigation in suspected recurrence was evaluated.

Methods

A retrospective study of patients with suspicious fiber-optic findings at more than 12 weeks after LPP. Sensitivity, specificity, and the negative predictive value (NPV) of DL and PET-CT were compared.

Results

Seventy-two patients presenting 105 cases of suspicious events were included in this study. Fifty-two events were initially investigated by DL and 53 events by PET-CT. The sensitivity of DL and PET-CT was 56.25% and 100%, respectively. The NPV was 84% for DL and 100% for PET-CT (p = 0.015).

Conclusion

Negative PET scans after LPP are highly accurate in ruling out recurrent/persistent disease and may spare the patient from negative biopsies.

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The evolution of fertility preservation care models in a large pediatric cancer and blood disorders center

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Abstract

Background

Children and adolescents who receive gonadotoxic treatments are at risk for future infertility. While there is a growing focus on integrating fertility preservation (FP) within pediatric cancer and blood disorder centers, wide variations in care models and methods exist across institutions. The purpose of this work is to describe the evolution of FP care models within a large pediatric hematology/oncology center.

Methods

Models of care and associated timeframes are described, including a pre-FP program model, establishment of a formal FP program, integration of nurse navigators, and the addition of FP consult stratification based on urgency (urgent/nonurgent). The number of patient consults within each model, patient sex, diagnosis (oncologic/hematologic), and consult timing (pre-gonadotoxic treatment/posttreatment completion) were abstracted from the clinical database.

Results

The number of annual consults increased from 24 during the pre-FP program model (2015) to 181 during the current care model (2020). Over time, the proportion of consults for females and patients with nonmalignant hematologic disorders increased. Patient stratification reduced the proportion of consults needing to be completed urgently from 75% at the advent of the FP program to 49% in the current model.

Conclusions

The evolution of care models within our FP program allowed for growth in the number of consults completed, expansion of services to more patients with nonmalignant hematologic disorders, and more consults for female patients. Nurse navigators play a critical role in care facilitating referrals, coordination, and patient education. Urgency stratification has allowed FP team members to manage increasing FP-related encounters.

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Off‐label pharmacological treatment for neuropathic pain: A Delphi study by the Spanish Pain Society Neuropathic Pain Task Force

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Abstract

Objectives

The use of off-label pharmacotherapies for neuropathic pain (NP) is growing relating to the many unmet needs of patients. However, clinical guidelines fail to address it, and the available evidence is sparse and fragmented. We arranged a formal expert consensus to address this controversial issue and provide some guidance on judicious use.

Methods

A two-round standard Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 40-item questionnaire prepared by the authors. Consensus on each statement was defined as at least either 80% endorsement or rejection after the second round.

Results

Forty-three and thirty-seven panelists participated in the first and second round, respectively. Consensus was reached in 34 out of 40 statements. Endorsed alternatives for unresponsive patients include non-gabapentinoid antiepileptics (oxcarbazepine and eslicarbazepine), venlafaxine, intravenous lidocaine (when doses can be optimized), and some vaporized cannabinoids (under appropriate surveillance). In addition, lacosamide, low-dose naltrexone, propofol or ketamine could prove beneficial if subjected to more research. Other options were rejected, and there was controversy about the usefulness of topical preparations.

Discussion

For patients who do not respond to standard NP treatments, some other viable pharmacological options can be attempted before advancing to other therapeutic stages. This may help patients who are reluctant to or have some contraindication for interventional therapies.

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Παρασκευή 28 Οκτωβρίου 2022

Diagnostic performance of magnetic resonance imaging for degenerative temporomandibular joint disease

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Abstract

Background

Degenerative joint disease (DJD) of the temporomandibular joint (TMJ) is an important type of temporomandibular disorders (TMDs) potentially leading to orofacial pain and jaw dysfunction. Magnetic resonance imaging (MRI) is important in TMD diagnosis; however, its diagnostic ability for DJD remains unknown.

Objective

To explore the utility of MRI in diagnosing DJD according to the latest diagnostic criteria for TMD and detecting condylar bone abnormalities and their severity.

Methods

Overall, 122 participants were examined using cone-beam computed tomography (CBCT) and MRI. The sensitivity, specificity, and accuracy of MRI for detecting DJD and different types of TMJ condylar bone abnormalities were calculated (considering CBCT as gold standard); in addition, we tested MRI and CBCT's consistency in scoring five types of condylar bone abnormalities.

Results

The sensitivity and specificity of MRI for DJD were 95.3% and 43.1%, respectively.The MRI sensitivities for condylar flattening, erosion, osteophytes, sclerosis, and cysts were 98.6%, 96.2%, 79.4%, 50%, and 79.2% (specificity, 53.6%, 48.3%, 81.6%, 83.3%, and 88.2%, respectively), respectively. The consistency between MRI and CBCT in assessing the severity of condylar bone abnormalities was fair-to-moderate (kappa coefficient: 0.278-0.491). The inter-observer consistency for CBCT was good, whereas for MRI it was relatively poor.

Conclusion

MRI can detect DJD and condylar bone abnormalities. However, MRI could not efficiently detect the severity of condylar bone abnormalities.

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Broadly Neutralizing Antibodies for HIV Treatment: Broad in Theory, Narrow in Reality

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
In this viewpoint we briefly review the status of antiretroviral therapy, its unmet needs, and the role that broadly neutralizing antibodies (bNAbs) might have in the near future for the treatment of HIV. We summarize advances in the development of bNAbs as antiretroviral therapy, the results of main clinical trials of bNAbs for HIV treatment and prevention, and its role in cure trials. The limitations of broadly neutralizing antibodies are the current need for primary re sistance testing, the still unclear number of antibodies that must be combined, the lack of penetration in anatomical reservoirs and the role they might play in cure studies. We compare the advantages and disadvantages of "classical ART" and therapy based on broadly neutralizing antibodies. We conclude that broadly neutralizing antibodies still need considerable improvements before they can be considered an alternative to "classical ART".
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Τετάρτη 26 Οκτωβρίου 2022

Exhaled Breath Aerosol Shedding by Highly Transmissible Versus Prior SARS-CoV-2 Variants

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Aerosol inhalation is recognized as the dominant mode of SARS-CoV-2 transmission. Three highly transmissible lineages evolved during the pandemic. One hypothesis to explain increased transmissibility is that natural selection favors variants with higher rates of viral aerosol shedding. However, the extent of aerosol shedding of successive SARS-CoV-2 variants is unknown. We aimed to measure the infectivity and rate of SARS-CoV-2 shedding into exhaled breath aerosol (EBA) by individuals during the Delta and Omicron waves and compared those rates with those of prior SARS-CoV-2 variants from our previously published work.
Methods
COVID-19 cases (n = 93, 32 vaccinated and 20 boosted) were recruited to give samples, including 30-minute breath samples into a Gesundheit-II exhaled breath aerosol sampler. Samples were quantified for viral RNA using RT-PCR and cultured for virus.
Results
Alpha (n = 4), Delta ( n = 3), and Omicron (n = 29) cases shed significantly more viral RNA copies into exhaled breath aerosols than cases infected with ancestral strains and variants not associated with increased transmissibility (n = 57). All Delta and Omicron cases were fully vaccinated and most Omicron cases were boosted. We cultured virus from the EBA of one boosted and three fully vaccinated cases.
Conclusions
Alpha, Delta, and Omicron independently evolved high viral aerosol shedding phenotypes, demonstrating convergent evolution. Vaccinated and boosted cases can shed infectious SARS-CoV-2 via EBA. These findings support a dominant role of infectious aerosols in transmission of SARS-CoV-2. Monitoring aerosol shedding from new variants and emerging pathogens can be an important component of future threat assessments and guide interventions to prevent transmission.
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Costs attributable to Clostridioides difficile infection based on the setting of onset

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Although it is established that hospital-onset CDI is associated with significant healthcare costs, the economic burden of CDI with onset in other facilities or the community has not been well studied.
Methods
Incident CDI cases were identified using 2011-2017 Medicare fee-for-service data. Controls were randomly selected in a 4:1 ratio matching to the CDI case surveillance definition. Inverse probability of exposure weights were used to balance on measured confounders. One-, 3-, and 5-year cumulative costs attributable to CDI were computed using a 3-part estimator (parametric survival model and pair of 2-part models predicting costs separately in intervals where death did and did not occur).
Results
60,492 CDI cases were frequency matched to 241,968 controls. One-, 3-, and 5-year adjusted attributable costs were highest for hospital-onset CDI at $14,257, $18,953, and $21,792, respectively compared to hospit alized controls, and lowest for community associated CDI compared to community controls at $1,013, $3,161, and $6,454, respectively. Adjusted 1-, 3-, and 5-year costs attributable to community-onset healthcare facility associated CDI were $8,222, $13,066, and $16,329 and for other health care facility onset CDI were $5,345, $6,764, and $7,125, respectively.
Conclusions
Economic costs attributable to CDI in elderly persons were highest for hospital-onset and community-onset healthcare facility associated CDI. Although lower, attributable costs due to CDI were significantly higher in cases with CDI onset in the community or other healthcare facility than for comparable persons without CDI. Additional strategies to prevent CDI in the elderly are needed to reduce morbidity and healthcare expenditures.
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