A young male with non-resolving consolidation and hepatosplenomegaly.

ABSTRACT: Non-resolving consolidation refers to the persistence of radiographic abnormalities beyond the anticipated timeframe. Conditions such as infection, malignancy, inflammatory disorders, and connective tissue diseases can all manifest as non-resolving consolidation. We share a clinicopathological case study involving a 30-year-old male who exhibits non-resolving consolidation accompanied by hepatosplenomegaly.

Dosimetric Comparison of Dedicated Radiosurgery Platforms for the Treatment of Essential Tremor: Technical Report.

Essential tremor (ET) is one of the most common adult movement disorders. As the worldwide population ages, the incidence and prevalence of ET is increasing. Although most cases can be managed conservatively, there is a subset of ET that is refractory to medical management. By virtue of being "reversible", deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is one commonly accepted intervention. As an alternative to invasive and expensive DBS, there has been a renaissance in treating ET with lesion-based approaches, spearheaded most recently by high-intensity focused ultrasound (HIFU), the hallmark of which is that it is non-invasive. Meanwhile, stereotactic radiosurgical (SRS) lesioning of VIM represents another time-honored lesion-based non-invasive treatment of ET, which is especially well suited for those patients that cannot tolerate open neurosurgery and is now also getting a "second look". While multiple SRS platforms have been and continue to be used to treat ET, there is little in the way of dosimetric comparison between different technologies. In this brief technical report we compare the dosimetric profiles of three major radiosurgical platforms (Gamma Knife, CyberKnife Robotic Radiosurgery, and Zap-X Gyroscopic Radiosurgery (GRS)) for the treatment of ET. In general, the GRS and Gamma Knife were shown to have the best theoretical dosimetric profiles for VIM lesioning. Nevertheless the relevance of such superiority to clinical outcomes requires future patient studies.

Modified Neuropixels probes for recording human neurophysiology in the operating room.

Neuropixels are silicon-based electrophysiology-recording probes with high channel count and recording-site density. These probes offer a turnkey platform for measuring neural activity with single-cell resolution and at a scale that is beyond the capabilities of current clinically approved devices. Our team demonstrated the first-in-human use of these probes during resection surgery for epilepsy or tumors and deep brain stimulation electrode placement in patients with Parkinson's disease. Here, we provide a better understanding of the capabilities and challenges of using Neuropixels as a research tool to study human neurophysiology, with the hope that this information may inform future efforts toward regulatory approval of Neuropixels probes as research devices. In perioperative procedures, the major concerns are the initial sterility of the device, maintaining a sterile field during surgery, having multiple referencing and grounding schemes available to de-noise recordings (if necessary), protecting the silicon probe from accidental contact before insertion and obtaining high-quality action potential and local field potential recordings. The research team ensures that the device is fully operational while coordinating with the surgical team to remove sources of electrical noise that could otherwise substantially affect the signals recorded by the sensitive hardware. Prior preparation using the equipment and training in human clinical research and working in operating rooms maximize effective communication within and between the teams, ensuring high recording quality and minimizing the time added to the surgery. The perioperative procedure requires ~4 h, and the entire protocol requires multiple weeks.

Clinical outcomes of bronchiectasis in India: data from the EMBARC/Respiratory Research Network of India registry.

BACKGROUND: Identifying risk factors for poor outcomes can help with risk stratification and targeting of treatment. Risk factors for mortality and exacerbations have been identified in bronchiectasis but have been almost exclusively studied in European and North American populations. This study investigated the risk factors for poor outcome in a large population of bronchiectasis patients enrolled in India. METHODS: The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India (EMBARC-India) registry is a prospective observational study of adults with computed tomography-confirmed bronchiectasis enrolled at 31 sites across India. Baseline characteristics of patients were used to investigate associations with key clinical outcomes: mortality, severe exacerbations requiring hospital admission, overall exacerbation frequency and decline in forced expiratory volume in 1 s. RESULTS: 1018 patients with at least 12-month follow-up data were enrolled in the follow-up study. Frequent exacerbations (≥3 per year) at baseline were associated with an increased risk of mortality (hazard ratio (HR) 3.23, 95% CI 1.39-7.50), severe exacerbations (HR 2.71, 95% CI 1.92-3.83), future exacerbations (incidence rate ratio (IRR) 3.08, 95% CI 2.36-4.01) and lung function decline. Coexisting COPD, dyspnoea and current cigarette smoking were similarly associated with a worse outcome across all end-points studied. Additional predictors of mortality and severe exacerbations were increasing age and cardiovascular comorbidity. Infection with Gram-negative pathogens (predominantly Klebsiella pneumoniae) was independently associated with increased mortality (HR 3.13, 95% CI 1.62-6.06), while Pseudomonas aeruginosa infection was associated with severe exacerbations (HR 1.41, 95% CI 1.01-1.97) and overall exacerbation rate (IRR 1.47, 95% CI 1.13-1.91). CONCLUSIONS: This study identifies risk factors for morbidity and mortality among bronchiectasis patients in India. Identification of these risk factors may support treatment approaches optimised to an Asian setting.

Bronchiectasis in India: results from the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) and Respiratory Research Network of India Registry.

BACKGROUND: Bronchiectasis is a common but neglected chronic lung disease. Most epidemiological data are limited to cohorts from Europe and the USA, with few data from low-income and middle-income countries. We therefore aimed to describe the characteristics, severity of disease, microbiology, and treatment of patients with bronchiectasis in India. METHODS: The Indian bronchiectasis registry is a multicentre, prospective, observational cohort study. Adult patients (≥18 years) with CT-confirmed bronchiectasis were enrolled from 31 centres across India. Patients with bronchiectasis due to cystic fibrosis or traction bronchiectasis associated with another respiratory disorder were excluded. Data were collected at baseline (recruitment) with follow-up visits taking place once per year. Comprehensive clinical data were collected through the European Multicentre Bronchiectasis Audit and Research Collaboration registry platform. Underlying aetiology of bronchiectasis, as well as treatment and risk factors for bronchiectasis were analysed in the Indian bronchiectasis registry. Comparisons of demographics were made with published European and US registries, and quality of care was benchmarked against the 2017 European Respiratory Society guidelines. FINDINGS: From June 1, 2015, to Sept 1, 2017, 2195 patients were enrolled. Marked differences were observed between India, Europe, and the USA. Patients in India were younger (median age 56 years [IQR 41-66] vs the European and US registries; p<0·0001]) and more likely to be men (1249 [56·9%] of 2195). Previous tuberculosis (780 [35·5%] of 2195) was the most frequent underlying cause of bronchiectasis and Pseudomonas aeruginosa was the most common organism in sputum culture (301 [13·7%]) in India. Risk factors for exacerbations included being of the male sex (adjusted incidence rate ratio 1·17, 95% CI 1·03-1·32; p=0·015), P aeruginosa infection (1·29, 1·10-1·50; p=0·001), a history of pulmonary tuberculosis (1·20, 1·07-1·34; p=0·002), modified Medical Research Council Dyspnoea score (1·32, 1·25-1·39; p<0·0001), daily sputum production (1·16, 1·03-1·30; p=0·013), and radiological severity of disease (1·03, 1·01-1·04; p<0·0001). Low adherence to guideline-recommended care was observed; only 388 patients were tested for allergic bronchopulmonary aspergillosis and 82 patients had been tested for immunoglobulins. INTERPRETATION: Patients with bronchiectasis in India have more severe disease and have distinct characteristics from those reported in other countries. This study provides a benchmark to improve quality of care for patients with bronchiectasis in India. FUNDING: EU/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis Consortium, European Respiratory Society, and the British Lung Foundation.

Spontaneous massive hemopneumothorax: Double trouble with a twist.

Spontaneous hemopneumothorax (SHP) is observed in 3%-7% cases of spontaneous pneumothorax where the tear of an adhesion can lead to bleeding with associated hemothorax. This condition has been reported in patients with hemophilia, sarcoidosis, congenital cystic adenomatoid malformation, systemic lupus erythematosus, etc., Here, we describe an unusual case of acute massive SHP in a 62-year-old male who underwent a percutaneous transluminal coronary angioplasty (PTCA) and presented with worsening dyspnea over the next 3 days. On evaluation, he had a massive hemopneumothorax which was considered to be secondary to the use of anticoagulants during the PTCA procedure. Pleural fluid analysis revealed frank blood and was consistent with the diagnosis of hemothorax. Surprisingly, the pleural fluid cytology revealed malignant cells. As the patient had a normal chest X-ray 3 days ago, thoracoscopic pleural biopsy was taken which confirmed the diagnosis of an epithelioid mesothelioma. Although post-PTCA or mesothelioma-associated hemothorax has been rarely reported, these two conditions have not been associated with SHP. Since the patient had no prior clinicoradiological features of mesothelioma, the procedure, and the anticoagulants probably contributed to the massive and rapid accumulation of blood. The presence of small amount of air added further confusion to the dual etiology and has not been described earlier.

Pulmonary mucormycosis diagnosed by convex probe endobronchial ultrasound-guided fine needle aspiration of cavity wall.

Pulmonary mucormycosis is an opportunistic fungal infection in immunocompromised individuals. It is difficult to diagnose as it requires tissue biopsy, and generally these patients are unfit to undergo invasive lung biopsies. We describe a novel technique in a case with uncontrolled diabetes mellitus with nonresolving pulmonary cavitary disease where convex probe endobronchial ultrasound (EBUS)-guided aspiration of lung cavity wall showed classical histopathological picture establishing the diagnosis of mucorale infection. EBUS being real-time, minimally invasive technique with minimal risk of complications, led to early diagnosis, and prompt treatment. This appears to be a novel diagnostic modality in pulmonary mucormycosis with minimal complications as compared with other biopsy methods with very high complication risk.

Endobronchial Ultrasound: A New Technique of Pericardiocentesis in Posterior Loculated Pericardial Effusion.

Diagnostic and therapeutic pericardiocentesis is traditionally carried out via the transthoracic route under ultrasound or echocardiographic guidance. Posteriorly located loculated pericardial effusion cannot be safely drained using the standard subxiphoid or apical, intercostal approach. In the presence of clinically significant loculated effusion or effusion requiring diagnostic pericardiocentesis where an echocardiographic approach is not feasible, patients are usually referred for surgery. We here present a novel minimally invasive endobronchial ultrasound-guided approach for the aspiration of posteriorly loculated pericardial effusion that may obviate the need for surgery and its related complications.

Tombs of Aspergillus: A missed cause of recurrent respiratory infections in allergic bronchopulmonary aspergillosis.

Broncholithiasis is an often overlooked condition and has been associated with symptoms such as cough, hemoptysis, and recurrent respiratory infections. The most common mechanism of a broncholith formation is the enlargement and subsequent erosion of a lymph node into an adjacent airway. Here, we describe this entity in a patient with advanced allergic bronchopulmonary aspergillosis, with chronic hypercapnic respiratory failure, and with frequent infective exacerbations. These frequent exacerbations were initially attributed to the poor lung function of the patient and the inability to cough out the secretions. The diagnosis of broncholithiasis was eventually established on bronchoscopy, when the patient was intubated and mechanically ventilated. In this patient, the mixed broncholiths were not associated with mediastinal lymphadenopathy and with biopsy showing Aspergillus with no lymph node tissue indicating its bronchial origin. A high index of suspicion should be kept in patients with recurrent infective exacerbations of pulmonary diseases, especially when computed tomography images show calcifications in the vicinity of airways even in the absence of lymphadenopathy, as most of these can be treated with routine bronchoscopic interventions.

Effect of intraoperative navigation on operative time in 1-level lumbar fusion surgery.

The use of intraoperative image guided navigation (NAV) in spine surgery is increasing. NAV is purported to improve the accuracy of pedicle screw placement but has been criticized for potentially increasing surgical cost, a component of which may be prolongation of total operative time due to time required for setup and intra-operative imaging and registration. In this study, we examine the effect of the introduction of O-Arm conical CT spinal navigation on surgical duration. We retrospectively analyzed consecutive freehand (FH) (n=63) and NAV (n=70) 1-level lumbar transpedicular instrumentation cases at a single institution by a single surgeon. We recorded setup and procedure time for each case. NAV was associated with significantly shorter total operative time for 1-level lumbar fusions compared to FH (4:30+/-0:42 hours vs. 4:53+/-0:39hours, p=0.0013). This shortening of total operative time was realized despite a trend toward slightly longer setup times with NAV. We also found a significant decrease in operative length over time in NAV but not FH cases, indicative of a "learning curve" associated with NAV. The use of NAV in 1-level lumbar transpedicular instrumentation surgery is associated with significantly shorter total operative time compared to the FH technique, and its efficiency improves over time. These data should factor into cost-effectiveness analyses of the use of NAV for these cases.

Bronchocentric granulomatosis with extensive cystic lung disease in tuberculosis: An unusual presentation.

Tuberculosis is known to cause both cystic lung disease and bronchocentric granulomatosis (BCG). However, both are rare manifestations of this common disease. We report a case of BCG with extensive cystic lung disease in a young female who presented with fever, weight loss, and recurrent pneumothoraces with respiratory failure. Early diagnosis and treatment are imperative, as appropriate therapy may be life-saving in such cases.

Spontaneous Improvement of Chiari I Malformation and Syringomyelia in a Patient With Cystic Fibrosis: Case Report.

BACKGROUND AND IMPORTANCE: Syringomyelia is highly associated with Chiari I malformation, but the pathophysiologic mechanism of syrinx formation and its relation to downward cerebellar tonsillar displacement remains elusive. Cough, Valsalva maneuver, and other physiological strains transiently exacerbate the clinical symptoms of these conditions, exert profound effects on the flow dynamics across the craniospinal junction, and are thought to play an important role in the pathogenesis of syringomyelia. CLINICAL PRESENTATION: We report the case of a patient with cystic fibrosis who presented during an exacerbation of bronchiectasis and was found to have a Chiari I malformation with associated syringomyelia. Eight months later, when the patient had returned to baseline pulmonary status, repeat imaging showed interval improvement in both the size of the syrinx and descent of cerebellar tonsils. CONCLUSION: This rare case of spontaneous improvement of syringomyelia and Chiari I malformation attributable to relief from chronic cough offers interesting insight into the mechanism of these disorders. ABBREVIATIONS: FEV1, forced expiratory volume in 1 secondFVC, forced vital capacity.

WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons.

Activation of Cl(-)-permeable γ-aminobutyric acid type A (GABAA) receptors elicits synaptic inhibition in mature neurons but excitation in immature neurons. This developmental "switch" in the GABA function depends on a postnatal decrease in intraneuronal Cl(-) concentration mediated by KCC2, a Cl(-)-extruding K(+)-Cl(-) cotransporter. We showed that the serine-threonine kinase WNK1 [with no lysine (K)] forms a physical complex with KCC2 in the developing mouse brain. Dominant-negative mutation, genetic depletion, or chemical inhibition of WNK1 in immature neurons triggered a hyperpolarizing shift in GABA activity by enhancing KCC2-mediated Cl(-) extrusion. This increase in KCC2 activity resulted from reduced inhibitory phosphorylation of KCC2 at two C-terminal threonines, Thr(906) and Thr(1007). Phosphorylation of both Thr(906) and Thr(1007) was increased in immature versus mature neurons. Together, these data provide insight into the mechanism regulating Cl(-) homeostasis in immature neurons, and suggest that WNK1-regulated changes in KCC2 phosphorylation contribute to the developmental excitatory-to-inhibitory GABA sequence.

Central nervous system lymphoma presenting as trigeminal neuralgia: A diagnostic challenge.

We describe an atypical man with diffuse large B cell lymphoma localized to the sphenoid wing and adjacent cavernous sinus, initially presenting with isolated ipsilateral facial pain mimicking trigeminal neuralgia due to invasion of Meckel's cave but subsequently progressing to intra-axial extension and having synchronous features of systemic lymphoma. Primary central nervous system lymphoma is uncommon, accounting for approximately 2% of all primary intracranial tumors, but its incidence has been steadily increasing in some groups [1]. It usually arises in the periventricular cerebral white matter, and reports of lymphoma in extra-axial regions are rare [2]. This man highlights the importance of maintaining lymphoma in the differential diagnosis of tumors of the skull base presenting with trigeminal neuralgia-like symptoms.

Cost analysis of spinal and general anesthesia for the surgical treatment of lumbar spondylosis.

Lumbar spine surgery is typically performed under general anesthesia, although spinal anesthesia can also be used. Given the prevalence of lumbar spine surgery, small differences in cost between the two anesthetic techniques have the potential to make a large impact on overall healthcare costs. We sought to perform a cost comparison analysis of spinal versus general anesthesia for lumbar spine operations. Following Institutional Review Board approval, a retrospective cohort study was performed from 2009-2012 on consecutive patients undergoing non-instrumented, elective lumbar spine surgery for spondylosis by a single surgeon. Each patient was evaluated for both types of anesthesia, with the decision for anesthetic method being made based on a combination of physical status, anatomical considerations, and ultimately a consensus agreement between patient, surgeon, and anesthesiologist. Patient demographics and clinical characteristics were compared between the two groups. Operating room costs were calculated whilst blinded to clinical outcomes and reported in percentage difference. General anesthesia (n=319) and spinal anesthesia (n=81) patients had significantly different median operative times of 175 ± 39.08 and 158 ± 32.75 minutes, respectively (p<0.001, Mann-Whitney U test). Operating room costs were 10.33% higher for general anesthesia compared to spinal anesthesia (p=0.003, Mann-Whitney U test). Complications of spinal anesthesia included excessive movement (n=1), failed spinal attempt (n=3), intraoperative conversion to general anesthesia (n=2), and a high spinal level (n=1). In conclusion, spinal anesthesia can be performed safely in patients undergoing lumbar spine surgery. It has the potential to reduce operative times, costs, and possibly, complications. Further prospective evaluation will help to validate these findings.

Time interval to surgery and outcomes following the surgical treatment of acute traumatic subdural hematoma.

Although the pre-surgical management of patients with acute traumatic subdural hematoma prioritizes rapid transport to the operating room, there is conflicting evidence regarding the importance of time interval from injury to surgery with regards to outcomes. We sought to determine the association of surgical timing with outcomes for subdural hematoma. A retrospective review was performed of 522 consecutive patients admitted to a single center from 2006-2012 who underwent emergent craniectomy for acute subdural hematoma. After excluding patients with unknown time of injury, penetrating trauma, concurrent cerebrovascular injury, epidural hematoma, or intraparenchymal hemorrhage greater than 30 mL, there remained 45 patients identified for analysis. Using a multiple regression model, we examined the effect of surgical timing, in addition to other variables on in-hospital mortality (primary outcome), as well as the need for tracheostomy or gastrostomy (secondary outcome). We found that increasing injury severity score (odds ratio [OR] 1.146; 95% confidence interval [CI] 1.035-1.270; p=0.009) and age (OR1.066; 95%CI 1.006-1.129; p=0.031) were associated with in-hospital mortality in multivariate analysis. In this model, increasing time to surgery was not associated with mortality, and in fact had a significant effect in decreasing mortality (OR 0.984; 95%CI 0.971-0.997; p=0.018). Premorbid aspirin use was associated with a paradoxical decrease in mortality (OR 0.019; 95%CI 0.001-0.392; p=0.010). In this patient sample, shorter time interval from injury to surgery was not associated with better outcomes. While there are potential confounding factors, these findings support the evaluation of rigorous preoperative resuscitation as a priority in future study.