Voluntary ambulation using voluntary upper limb muscle activity and Hybrid Assistive Limb® (HAL®) in a patient with complete paraplegia due to chronic spinal cord injury: A case report

Context: We sought to describe our experience with the Hybrid Assistive Limb® (HAL®) for active knee extension and voluntary ambulation with remaining muscle activity in a patient with complete paraplegia after spinal cord injury.

Findings: A 30-year-old man with complete paraplegia used the HAL® for 1 month (10 sessions) using his remaining muscle activity, including hip flexor and upper limb activity. Electromyography was used to evaluate muscle activity of the gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in synchronization with the Vicon motion capture system. A HAL® session included a knee extension session with the hip flexor and voluntary gait with upper limb activity. After using the HAL® for one month, the patient’s manual muscle hip flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the left knee, and from 0/5 to 1/5 for the extension of both knees.

Conclusion/clinical relevance: Knee extension sessions with HAL®, and hip flexor and upper-limb-triggered HAL® ambulation seem a safe and feasible option in a patient with complete paraplegia due to spinal cord injury.     

A multicenter,open‐label,phase II study of tirabrutinib (ONO/GS‐4059) in patients with Waldenström’s macroglobulinemia

Tirabrutinib is a second‐generation Bruton’s tyrosine kinase inhibitor with greater selectivity than ibrutinib. Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment‐naïve (Cohort A) or with relapsed/refractory (Cohort B) Waldenström’s macroglobulinemia (WM). Patients were treated with tirabrutinib 480 mg once daily. The primary endpoint was major response rate (MRR; ≥ partial response). Secondary endpoints included overall response rate (ORR; ≥ minor response), time to major response (TTMR), progression‐free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71 y, and the median serum immunoglobulin M level was 3600 mg/dL. Among the patients, 96.2% had the MYD88^L265P mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87 mo. PFS and OS were not reached with a median follow‐up of 6.5 and 8.3 mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade ≥ 3 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug‐related atrial fibrillation or hypertension. Although the follow‐up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed/refractory WM with a manageable safety profile. (JapicCTI‐173646).     

Dynamic high-spatial-resolution MR imaging of invasive ductal carcinoma: influence of histological scirrhous component on MR descriptors.

PURPOSE: The purpose of this study was to assess the relationship between the amount of scirrhous component in invasive ductal carcinoma and its MR characteristics. MATERIALS AND METHODS: We retrospectively reviewed 71 consecutive patients with invasive ductal carcinoma smaller than 25 mm (average, 16.6 mm) in diameter. The scirrhous component was defined as invasive foci in small clusters of cancer cells showing desmoplasia. Invasive ductal carcinoma was subclassified into 3 groups in accordance with the amount of the scirrhous component (scirrhous component degree; SCD): SCD I (scirrhous component less than 20%), SCD II (intermediate), and SCD III (more than 80%). Dynamic magnetic resonance (MR) imaging was performed using volumetric interpolated sequence. Prior to dynamic study, T2*-weighted first-pass perfusion images were obtained before, during, and after bolus injection of 0.1 mmol Gd-DTPA/kg. RESULTS: Twenty-eight lesions were classified as SCD I, 14 as SCD II, and 29 as SCD III. Mass margin and signal intensity loss in the perfusion study were significantly different among the 3 SCD groups (P<0.001). The kinetic patterns were significantly different among the 3 SCD groups (P=0.04), and between SCD I/II and SCD III (P=0.03). The presence of enhancing internal septations was significantly different between SCD I/II and SCD III carcinomas (P=0.05). Central enhancement was only observed in SCD I carcinoma (4%; 3/71). CONCLUSION: The histological predominance of the scirrhous component in invasive ductal carcinoma may be one explanation for the differences in morphologic and kinetic patterns on MR imaging.     

Platinum levels in various tissues of a patient who died 181 days after cisplatin overdosing determined by electrospray ionization mass spectrometry

Platinum (Pt) levels were determined in various tissues and body fluids obtained from a patient who died 181 days after cisplatin overdosing. The symptoms of cisplatin overdose, however, might have almost disappeared by day 40, and the patient’s death was ascribed to the recurrence of malignant lymphoma. Determination of Pt derived from cisplatin was performed by electrospray ionization mass spectrometry (ESI-MS) using silver (Ag) as internal standard. Pt and Ag complexed with diethyldithiocarbamate (DDC) in wetashed blood, and tissue solutions were extracted into isoamyl alcohol, and then acidified with oxalic acid. By injecting an aliquot of the isoamyl alcohol layer into a mass spectrometer in the direct flow injection mode, the quantitation was performed using the signals of Pt(DDC)₃ ⁺ and Ag(DDC)₂ ⁺ at m/z 639 and 403, respectively. The Pt levels ranged from 25ng/ml in blood to 2050ng/g wet weight in the liver of the patient, indicating that Pt remained at high levels in tissues, even after a period as long as 181 days after cisplatin overdosing.     

A case of aldosterone-producing adrenocortical adenoma associated with a probable post-operative adrenal crisis: histopathological analyses of the adrenal gland.

We describe a case of aldosterone-producing adrenocortical adenoma (APA) associated with a probable post-operative adrenal crisis possibly due to subtle autonomous cortisol secretion. The patient was a 46-year-old female who suffered from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm diameter adrenal mass. The patient's plasma aldosterone level was increased, and her plasma renin activity was suppressed, both of which findings were consistent with APA. Cushingoid appearance was not observed. Morning and midnight serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as measured by an overnight 1-mg dexamethasone suppression test, but was incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone suppression test. In addition, adrenocortical scintigraphy showed a strong uptake at the tumor region and a complete suppression of the contra-lateral adrenal uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and a transient glucocorticoid replacement improved the symptoms. Histopathological studies demonstrated that the tumor was basically compatible with APA. The clear cells in the tumor were admixed with small numbers of compact cells that expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in the zonae fasciculata and reticularis was markedly diminished, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to neoplastic production and secretion of cortisol. Together, these findings suggested that autonomous secretion of cortisol from the tumor suppressed the HPA axis of the patient, thereby triggering the probable post-operative adrenal crisis. Post-operative adrenocortical insufficiency should be considered in clinical management of patients with relatively large APA, even when physical signs of autonomous cortisol overproduction are not apparent.     

The floating hip injury: which should we fix first?

In floating hip injuries, the priority of the steps in fixation has not been well described. We have treated these patients in accordance with the following protocols. In patients with pelvic ring fractures, the external fixation should be performed first, and in patients with acetabular fractures, the femoral fractures should be internally fixated first. The purpose of the present study was to review our experience with these fracture treatments to evaluate our strategy. For 8 years, 31 patients with femoral fractures associated with ipsilateral fractures: 26 unstable pelvic ring fractures and 7 unstable acetabular fractures were surgically treated at our level 1 trauma center. We reviewed the admission, operation, and follow-up records retrospectively and evaluated the order of the fixation and the complications. Two patients with acetabular fractures failed to follow our protocol outlined at the preoperative planning stage. There were no surgical difficulties other than two patients with the hemipelvis dislocated proximally who required traction of the fixated femur. The complications that were thought to be related to our protocol were one fat embolism syndrome and one pubic fracture displacement. One heterotopic ossification seemed to occur due to using a single approach for both fractures. We believe our protocol to be generally effective, however, in patients with acetabular and vertical shear type pelvic ring fractures, the internal or external fixation of the femur should be performed before the internal fixation of the pelvis.     

Severe Graves' ophthalmopathy accompanied by myasthenia gravis]

We report a 53-year-old woman with severe Graves' ophthalmopathy accompanied by uncontrolled myasthenia gravis. She presented remarkable exophthalmos, chemosis, and restriction of eye movement. Despite plasma exchange, steroid pulse therapy, local injection of steroid, and irradiation, ocular symptoms did not ameliorate. Since optic neuropathy was seen, orbital decompression surgery was performed in the left eye. Bilateral chemosis was improved after the surgery. Five years after surgery, there was no ocular palsy in the operated left eye, but in the contralateral eye. For the good prognosis of the eye movement, orbital decompression might be recommended in the severe Graves' ophthalmopathy accompanied by the optic neuropathy and/or ophthalmoplegia with proptosis.     

Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

Congenital quadricuspid aortic valve with tetralogy of Fallot and pulmonary atresia

We report the case of a 4-year-old girl who had quadricuspid aortic valve regurgitation with tetralogy of Fallot and pulmonary atresia. This combination is very uncommon. Aortic valve replacement was performed successfully due to aortic regurgitation which had progressed one year after the total repair. The dilated aortic annulus plus quadricuspid aortic valve may result in progressive aortic regurgitation for a short period.