Clinical manifestations and risk factors for COVID-19 and its severity in patients with hematological malignancies.

BACKGROUND: Patients with hematological malignancies (HM) were at a high risk of developing severe disease from coronavirus disease 2019 (COVID-19). We aimed to assess the clinical outcome of COVID-19 in hospitalized patients with HM. METHODS: Adult patients with HM who were hospitalized with a laboratory-confirmed COVID-19 between May, 2021 and November, 2022 were retrospectively identified. Primary outcome was respiratory failure requiring mechanical ventilation or mortality within 60 days after hospitalization. We also analyzed associated factors for de-isolation (defined as defervescence with a consecutive serial cycle threshold value > 30) within 28 days. RESULTS: Of 152 eligible patients, 22 (14.5%) developed respiratory failure or mortality in 60 days. Factors associated with developing respiratory failure that required mechanical ventilation or mortality included receipt of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) (adjusted hazards ratio [aHR], 5.10; 95% confidence interval [CI], 1.64-15.85), type 2 diabetes mellitus (aHR, 2.47; 95% CI, 1.04-5.90), lymphopenia at admission (aHR, 6.85; 95% CI, 2.45-19.15), and receiving <2 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines (aHR, 3.00; 95% CI, 1.19-7.60). Ninety-nine (65.1%) patients were de-isolated in 28 days, against which two hazardous factors were identified: receipt of B-cell depletion therapies within one year prior to COVID-19 (aHR, 0.55, 95% CI, 0.35-0.87) and lymphopenia upon admission (aHR, 0.65; 95% CI, 0.43-1.00). CONCLUSION: We found a high rate of respiratory failure and mortality among patients with HM who contracted the SARS-CoV-2. Factors associated with developing respiratory failure or mortality in 60 days included receipt of allo-HSCT, type 2 diabetes mellitus and lymphopenia upon admission. Having received ≥2 doses of vaccination conferred protection against clinical progression.

Effect of early dexamethasone on outcomes of COVID-19: A quasi-experimental study using propensity score matching.

BACKGROUND: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain. METHODS: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days. RESULTS: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98). CONCLUSION: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19.

Higher serologic responses of early syphilis to single-dose benzathine penicillin G plus doxycycline versus single-dose benzathine penicillin G alone among people with HIV.

BACKGROUND: Single-dose benzathine penicillin G (BPG) is the preferred therapy for early syphilis, but poorer serologic responses have been observed among people with HIV (PWH). No enhanced regimen has previously been shown to improve serologic outcomes of early syphilis. METHODS: We conducted a retrospective study to compare the treatment responses to single-dose BPG combined with 7-day doxycycline versus BPG alone in PWH who presented with early syphilis. Rapid plasma reagin (RPR) titers were determined every 3-6 months for all included PWH. Serologic response was defined as at least a fourfold decline in RPR titers at month 12. RESULTS: During January 2018 to March 2022, 223 PWH with 307 episodes of early syphilis received single-dose BPG plus doxycycline and 347 PWH with 391 episodes received BPG alone. The median age was 36 years and baseline CD4 count was 600 cells/mm3. In the intention-to-treat with last-observation-carried-forward analysis, PWH receiving BPG plus doxycycline had a significantly higher serologic response rate at 12 months of treatment than those receiving BPG alone (79.5% vs 70.3%, respectively; P= .006). The factors associated with 12-month serologic response were RPR titer (per 1-log2 increase, adjusted odds ratio [AOR], 1.25; 95% CI, 1.15-1.35) and receipt of BPG plus doxycycline (AOR, 1.71; 95% CI, 1.20-2.46). In the subgroup analyses, BPG plus doxycycline was consistently associated with a better serologic response than BPG alone at month 12. CONCLUSIONS: Among PWH with early syphilis, single-dose BPG plus doxycycline achieved higher serologic responses than BPG alone during a 12-month follow-up period.

Clinical diagnostic utility of transcranial magnetic stimulation in neurological disorders. Updated report of an IFCN committee.

The review provides a comprehensive update (previous report: Chen R, Cros D, Curra A, Di Lazzaro V, Lefaucheur JP, Magistris MR, et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin Neurophysiol 2008;119(3):504-32) on clinical diagnostic utility of transcranial magnetic stimulation (TMS) in neurological diseases. Most TMS measures rely on stimulation of motor cortex and recording of motor evoked potentials. Paired-pulse TMS techniques, incorporating conventional amplitude-based and threshold tracking, have established clinical utility in neurodegenerative, movement, episodic (epilepsy, migraines), chronic pain and functional diseases. Cortical hyperexcitability has emerged as a diagnostic aid in amyotrophic lateral sclerosis. Single-pulse TMS measures are of utility in stroke, and myelopathy even in the absence of radiological changes. Short-latency afferent inhibition, related to central cholinergic transmission, is reduced in Alzheimer's disease. The triple stimulation technique (TST) may enhance diagnostic utility of conventional TMS measures to detect upper motor neuron involvement. The recording of motor evoked potentials can be used to perform functional mapping of the motor cortex or in preoperative assessment of eloquent brain regions before surgical resection of brain tumors. TMS exhibits utility in assessing lumbosacral/cervical nerve root function, especially in demyelinating neuropathies, and may be of utility in localizing the site of facial nerve palsies. TMS measures also have high sensitivity in detecting subclinical corticospinal lesions in multiple sclerosis. Abnormalities in central motor conduction time or TST correlate with motor impairment and disability in MS. Cerebellar stimulation may detect lesions in the cerebellum or cerebello-dentato-thalamo-motor cortical pathways. Combining TMS with electroencephalography, provides a novel method to measure parameters altered in neurological disorders, including cortical excitability, effective connectivity, and response complexity.

Immune Reconstitution Inflammatory Syndrome in People Living with HIV Who Presented with Interstitial Pneumonitis: an Emerging Challenge in the Era of Rapid Initiation of Antiretroviral Therapy.

Studies on immune reconstitution inflammatory syndrome (IRIS) in people living with HIV (PLWH) and presenting with interstitial pneumonitis (IP) are limited in the era of rapid antiretroviral therapy (ART) initiation, particularly with integrase strand-transfer inhibitor (INSTI)-containing regimens. Adult PLWH presenting with IP in whom ART was initiated within 30 days of IP diagnosis between 2015 and 2021 were retrospectively identified. The primary outcome was the occurrence of IRIS within 30 days after admission. Of 88 eligible PLWH with IP (median age, 36 years; CD4 count, 39 cells/mm3), Pneumocystis jirovecii and cytomegalovirus (CMV) DNA were detected via polymerase-chain-reaction assay in 69.3% and 91.7% of respiratory specimens, respectively. 22 PLWH (25.0%) had manifestations that met French's IRIS criteria for paradoxical IRIS. There were no statistically significant differences in terms of the all-cause mortality (0.0% versus 6.1%, P = 0.24), the occurrence of respiratory failure (22.7% versus 19.7%, P = 0.76), and pneumothorax (9.1% versus 7.6%, P = 0.82) between PLWH with and those without paradoxical IRIS. In a multivariable analysis, the factors associated with IRIS were the decline of the 1 month plasma HIV RNA load (PVL) with ART (adjusted hazard ratio [aHR] per 1 log decrease, 3.45; 95% CI, 1.52 to 7.81), a baseline CD4-to-CD8 ratio of <0.1 (aHR, 3.47; 95% CI, 1.16 to 10.44), and the rapid initiation of ART (aHR, 7.95; 95% CI, 1.04 to 60.90). In conclusion, we found a high rate of paradoxical IRIS among PLWH with IP in the era of rapid ART initiation with INSTI-containing ART and this was associated with immune depletion at baseline, a rapid decline of PVL, and an interval of <7 days between the diagnosis of IP and the initiation of ART. IMPORTANCE Our study of PLWH who presented with IP mainly due to Pneumocystis jirovecii demonstrates that a high rate of paradoxical IRIS and a rapid decline of PVL with the initiation of ART, a CD4-to-CD8 ratio of <0.1 at baseline, and a short interval (<7 days) between the diagnosis of IP and the initiation of ART were associated with paradoxical IP-IRIS in PLWH. Paradoxical IP-IRIS was not associated with mortality or respiratory failure with heightened awareness among the HIV-treating physicians, rigorous investigations to exclude the possibilities of concomitant infections, or the malignancies and adverse effects of medications, including the cautious use of corticosteroids.

Modulating motor cortical oscillation with coordinated reset multifocal transcranial magnetic stimulation.

According to the theory of coordinated reset (CR) stimulation, multifocal bursts of stimuli delivered in a random order with a specific interval may reduce the resonance power of the oscillatory generator in the epicenter. We develop a noninvasive coordinated multifocal burst stimulation (COMBS) with three repetitive transcranial stimulation machines based on CR theory to modulate the target frequency in the primary motor cortex and to assess its effect on motor cortical excitability in separate experiments. Electroencephalography and electromyography were recorded in 16 healthy participants during a finger-tapping task, both before and after the intervention. The resting oscillatory power at the targeted frequency was not changed by COMBS. α-Band power was increased in both preparation and movement stages and the low ß-band power was increased in the movement stage of the finger tapping task. The extent of low ß-band event-related desynchronization was reduced by COMBS. There were no changes in reaction time, but there was a trend for a reduced error rate after COMBS. In another 14 healthy participants, there were no significant changes in cortical excitability before and after COMBS measured by rest motor threshold, short interval intracortical inhibition, short interval intracortical facilitation, and cortical silent period. The result indicates that COMBS may modify the cortical oscillatory power and its perturbation within specific movement stage.NEW & NOTEWORTHY This is the first study, to our knowledge, to apply coordinated reset (CR) neuromodulation to the motor cortex with three repetitive transcranial magnetic stimulation (rTMS) stimulators to assess its effect on cortical oscillation. The results revealed enhancement of α-band power specifically in preparation and movement stages and low ß-band power in the movement stage of a motor task. It postulated that CR stimulation may modify the motor cortical oscillation in the specific movement stages.

A difficult-to-treat pleuropulmonary histoplasmosis in a patient with rheumatoid arthritis in Taiwan.

Amphotericin B and itraconazole are the primary agents for treating histoplasmosis. Newer azoles are alternatives for patients refractory to or intolerant of standard therapy. We report an 83-year-old woman with rheumatoid arthritis complicated with pleuropulmonary histoplasmosis who responded to liposomal amphotericin B, but progressed under voriconazole and posaconazole maintenance therapy.

Pyrazinamide related prolonged drug-induced liver injury: A case report.

RATIONALE: Drug induced liver injury (DILI) is a common side effect causing treatment discontinuation during tuberculosis (TB) treatment, and pyrazinamide (PZA) usually leads to a delayed and prolonged abnormal liver function of the 4 standard anti-tuberculosis regimens. However, a prolonged hepatitis lasting more than 4 months is rarely reported. PATIENT CONCERNS: A 78-year-old man presented with general weakness and poor appetite on his seventh week of anti-TB treatment for tuberculosis lymphadenitis. DIAGNOSIS: Drug induced liver injury, PZA-related. NAT2 slow acetylator phenotype was accidentally found during workup of DILI. INTERVENTION: A liver biopsy was performed and PZA-related DILI was suspected. All anti-TB medications were therefore discontinued. OUTCOME: After withholding all anti-TB medications for 4 months, the elevations of aminotransferases and hyperbilirubinemia completely resolved. Anti-TB therapy was switched to ethambutol and levofloxacin for 15 months without adverse events. Long-term ultrasound follow-up was performed and cervical lymphadenopathy completely resolved. CONCLUSION: Our patient presents with PZA related prolonged DILI resolved after drug discontinuation for 4 months. NAT2 slow acetylator phenotype may be related to this condition through unknown mechanisms.

Electrophysiological assessment of respiratory function.

While the traditional lung function tests are used to assess lung capacity and pulmonary function, they cannot evaluate respiratory driving function and the integrity of the conduction pathway from the central nervous system to the respiratory motor neuron in the spinal cord and to the diaphragm. The inspiratory trigger is sent from the central nervous system through the phrenic nerve and drives the diaphragm to generate inspiratory movement. Therefore, phrenic nerve stimulation and diaphragmatic electromyography are two fundamental methods to assess respiratory function. There are several useful tools to assess respiratory motor system including electrical or magnetic phrenic nerve stimulation, diaphragmatic needle electromyography, and diaphragmatic ultrasound. By these means, physicians can assess current respiratory status in different neurological diseases that affect respiratory muscles, follow-up of the severity of respiratory impairment, help to predict the chance of successfully weaning from ventilatory support, and confirm clinical diagnoses such as diaphragmatic myoclonus. Although some of these tests require special training, applying these neurophysiological assessments in clinical practice is highly recommended.

Clinical neurophysiology of Parkinson's disease and parkinsonism.

This review is part of the series on the clinical neurophysiology of movement disorders. It focuses on Parkinson's disease and parkinsonism. The topics covered include the pathophysiology of tremor, rigidity and bradykinesia, balance and gait disturbance and myoclonus in Parkinson's disease. The use of electroencephalography, electromyography, long latency reflexes, cutaneous silent period, studies of cortical excitability with single and paired transcranial magnetic stimulation, studies of plasticity, intraoperative microelectrode recordings and recording of local field potentials from deep brain stimulation, and electrocorticography are also reviewed. In addition to advancing knowledge of pathophysiology, neurophysiological studies can be useful in refining the diagnosis, localization of surgical targets, and help to develop novel therapies for Parkinson's disease.

Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia.

Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer's disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.

Botulinum Toxin-Associated Prolonged Remission of Idiopathic Cervical Dystonia.

Prolonged remission of dystonia occurs rarely; however, well-documented cases are lacking. We report the clinical characteristics and course of four patients with botulinum toxin (BoNT)-associated prolonged remission of idiopathic cervical dystonia. Mean age at onset was 40 years. All had a relatively short duration of symptoms (mean 10.3 months), and with remission occurring after ≤ 3 treatments with BoNT. At last examination, the remission duration was 2-5 years. In the two cases that subsequently relapsed after 4-5 years, there was an altered phenomenology and worsened severity than at the onset. Recognizing this rare phenomenon has valuable clinical implications.

Systematic examination of low-intensity ultrasound parameters on human motor cortex excitability and behavior.

Low-intensity transcranial ultrasound (TUS) can non-invasively modulate human neural activity. We investigated how different fundamental sonication parameters influence the effects of TUS on the motor cortex (M1) of 16 healthy subjects by probing cortico-cortical excitability and behavior. A low-intensity 500 kHz TUS transducer was coupled to a transcranial magnetic stimulation (TMS) coil. TMS was delivered 10 ms before the end of TUS to the left M1 hotspot of the first dorsal interosseous muscle. Varying acoustic parameters (pulse repetition frequency, duty cycle, and sonication duration) on motor-evoked potential amplitude were examined. Paired-pulse measures of cortical inhibition and facilitation, and performance on a visuomotor task was also assessed. TUS safely suppressed TMS-elicited motor cortical activity, with longer sonication durations and shorter duty cycles when delivered in a blocked paradigm. TUS increased GABAA-mediated short-interval intracortical inhibition and decreased reaction time on visuomotor task but not when controlled with TUS at near-somatosensory threshold intensity.