Demonstration of a second rapidly conducting cortico-diaphragmatic pathway in humans

Functional imaging studies in normal humans have shown that the supplementary motor area (SMA) and the primary motor cortex (PMC) are coactivated during various breathing tasks. It is not known whether a direct pathway from the SMA to the diaphragm exists, and if so what properties it has. Using transcranial magnetic stimulation (TMS) a site at the vertex, representing the diaphragm primary motor cortex, has been identified. TMS mapping revealed a second area 3 cm anterior to the vertex overlying the SMA, which had a rapidly conducting pathway to the diaphragm (mean latency 16.7 ± 2.4 ms). In comparison to the vertex, the anterior position was characterized by a higher diaphragm motor threshold, a greater proportional increase in motor-evoked potential (MEP) amplitude with voluntary facilitation and a shorter silent period. Stimulus–response curves did not differ significantly between the vertex and anterior positions. Using paired TMS, we also compared intracortical inhibition/facilitation (ICI/ICF) curves. In comparison to the vertex, the MEP elicited from the anterior position was not inhibited at short interstimulus intervals (1–5 ms) and was more facilitated at long interstimulus intervals (9–20 ms). The patterns of response were identical for the costal and crural diaphragms. We conclude that the two coil positions represent discrete areas that are likely to be the PMC and SMA, with the latter wielding a more excitatory effect on the diaphragm.     

Antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors

BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles.They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.     

Establishment of a formal program for retinoblastoma: Feasibility of clinical coordination across borders and impact on outcome

Retinoblastoma is an ocular tumor that occurs in young children, in either heritable or sporadic manner. The relative rarity of retinoblastoma, and the need for expensive equipment, anesthesia, and pediatric ophthalmologic expertise, are barriers for effective treatment in developing countries. Also, with an average age‐adjusted incidence of two to five cases per million children, patient number limits development of local expertise in countries with small populations. Lebanon is a small country with a population of approximately 4.5 million. In 2012, a comprehensive retinoblastoma program was formalized at the Children's Cancer Institute (CCI) at the American University of Beirut Medical Center, and resources were allocated for efficient interdisciplinary coordination to attract patients from neighboring countries such as Syria and Iraq, where such specialized therapy is also lacking. Through this program, care was coordinated across hospitals and borders such that patients would receive scheduled chemotherapy at their institution, and monthly retinal examinations and focal laser therapy at the CCI in Lebanon. Our results show the feasibility of successful collaboration across borders, with excellent patient and physician adherence to treatment plans. This was accompanied by an increase in patient referrals, which enables continued expertise development. However, the majority of patients presented with advanced intraocular disease, necessitating enucleation in 90% of eyes in unilateral cases, and more than 50% of eyes in bilateral cases. Future efforts need to focus on expanding the program that reaches to additional hospitals in both countries, and promoting early diagnosis, for further improvement of globe salvage rates.     

A Comparative Evaluation of the Strain Transmitted through Prostheses on Implants with Two Different Macro-Structures and Connection during Insertion and Loading Phase: An In Vitro Study

Background: The purpose of this study was to measure and compare the strain levels in the peri-implant bone as generated by the blade-like implant (BLI) and the screw-type implant (STI) with two different internal connections (hexagonal and conical) and with a 1:1 and 2:1 crown/implant (C/I) ratio. Methods: The implants (BLI and STI) were placed into sawbones according to the manufacturer’s protocol. Two strain gauges, horizontal and vertical to the implant axis, were placed around each implant on the bone surface 1 mm from the cervical part. Each implant was loaded by a material testing machine at a force of 100 N. Micro-strains (με) generated in the surrounding bone were measured by a strain gauge and recorded. Results: Recorded micro-strains were not significant in both the insertion and loading phases (p < 0.0625). The average recorded micro-strain values were lower in the horizontal dimension of STI with hexagonal connection when the C/I ratio was 2:1 compared with BLI, 210 με and 443 με, respectively. Conclusion: Within the limitations of this study, implant design, implant-abutment connection and C/I ratio did not influence strain values in bone and there is no statistically significant effect of these parameters on bone.     

New perspectives on target intraocular pressure

The evidence in support of intraocular pressure (IOP) lowering to reduce risk of glaucoma onset or progression is strong, although the amount and quality of IOP reduction is less well defined. The concept of a target IOP includes a percentage reduction, calculated IOP, or a predetermined IOP figure or range. Yet none of these strategies have been validated. In addition, our understanding of the way IOP influences glaucoma risk is continuously evolving. Examples of this include the data on IOP fluctuation and lamina cribrosa and cerebrospinal fluid pressure differentials. That these variables are not included in target IOP calculation potentially undermines its accuracy and usefulness. We summarize the evidence for target IOP, new developments in our understanding of IOP and glaucoma pathogenesis, as well as emerging strategies for setting targets and assessing response to treatment.     

Long-term efficacy of dexamethasone intravitreal implant in the treatment of Vogt-Koyanagi-Harada disease relapsing posterior uveitis

Purpose:To investigate the efficacy and safety of dexamethasone intravitreal implant in the treatment of relapsing posterior uveitis in patients with chronic recurrent Vogt–Koyanagi–Harada (VKH) disease.Methods: This was a prospective study of 29 eyes of 16 patients with posterior uveitis in chronic recurrent VKH disease. All patients received previous systemic steroid and immunosuppressive regimens. All patients underwent a comprehensive ophthalmic examination, including best-corrected visual acuity (BCVA), Indocyanine green angiography (ICGA), fundus fluorescein angiography (FFA), and spectral-domain optical coherence tomography (SD-OCT). All patients underwent intravitreal injection with sustained-release dexamethasone 0.7 mg implant (Ozurdex®). Primary outcome measures included mean change in BCVA and central foveal thickness (CFT) at 24 months of follow-up compared to the baseline.Results: At 24 month of follow-up, the mean BCVA improved from 0.82 ± 0.13 to 0.38 ± 0.06 logMAR (P < 0.0001). The mean CFT reduced from 505 ± 29 to 244 ± 23 um (P < 0.0001). The mean intraocular pressure (IOP) changed from 15.1 ± 2.2 to 16.9 ± 3.1 mmHg with no significant value (P-value = 0.0955). Twenty-one eyes (72.4%) received one injection, whereas eight eyes (27.6%) required two injections. The mean number of injections was 1.2 ± 0.60. The mean follow-up time was 24.75 ± 0.9 months. No serious ocular or systemic adverse events were noted during the follow-up period. Ocular hypertension was recorded in three (10.3%) eyes and controlled by IOP lowering medications. Cataract progression occurred in 11 (37.9%) eyes.Conclusion: Our cohort highlights the beneficial effects of the dexamethasone implant of 0.7 mg in the treatment of VKH disease relapsing posterior uveitis improving visual acuity, reducing macular edema, and minimizing the burden of systemic steroids in this sample study.     

Treatment Strategies for Residual Disease following Neoadjuvant Chemotherapy in Patients with Early-Stage Breast Cancer

Breast cancer continues to be the most diagnosed cancer among women worldwide. Neoadjuvant chemotherapy is the standard of care for breast cancer patients with locally advanced disease and patients with poor pathological features, such as triple-negative (TN) or human epidermal growth factor receptor-2 (HER2)-positive subtypes. Neoadjuvant therapy offers several advantages, including better surgical outcomes, early systemic treatment for micro-metastases, and accurate tumor biology and chemosensitivity assessment. Multiple studies have shown that achieving pathological complete response (pCR) following neoadjuvant chemotherapy is associated with better prognosis and better treatment outcomes; almost half of such patients may fail to achieve pCR. Tumor proliferative index, hormone receptor (HR) status, and HER2 expression are the major predictors of pCR. Strategies to improve pCR have been dependent on augmenting neoadjuvant chemotherapy with the addition of taxanes and dual anti-HER2 targeted therapy in patients with HER2-positive tumor, and more recently, immunotherapy for patients with TN disease. The clinical management of patients with residual disease following neoadjuvant chemotherapy varies and depends mostly on the level of HR expression and HER2 status. Recent data have suggested that switching trastuzumab to trastuzumab-emtansine (T-DM1) in patients with HER2-positive disease and the addition of capecitabine for patients with HER2-negative and HR-negative subtype is associated with a better outcome; both strategies are incorporated into current clinical practice guidelines. This paper reviews available and ongoing studies addressing strategies to better manage patients who continue to have residual disease following neoadjuvant chemotherapy.