A 35-year-old pregnant woman at 36 weeks of gestation with a 23 × 11-mm mass and multiple lymph nodes in the left axillary up to 23 × 10-mm involvement in ultrasonography was included in this study. After performing core needle biopsy, she had been diagnosed with invasive ductal carcinoma grade II in the upper outer quadrant of her left breast. Accordingly, this tumor was characterized as negative by immunohistochemistry for estrogen and progesterone receptors, but it resulted as positive for HER2 and Ki67 positive in >25% of tumor cells. The patient at 38 weeks of gestation delivered, and then the assessment for metastasis was done. Fortunately, no metastases were found, and her cancer stage was found to be II.\nThe patient included in this study received neoadjuvant chemotherapy with both adriamycin and cyclophosphamide 4 courses. Following the breast ultrasound, clear reductions were observed in the size of the mass and axilla lymph nodes. Thereafter, the patient received paclitaxel and AryoTrust (TH) for a 12-week duration, and then AryoTrust was continued once per 3 weeks. Of note, the generic name of the trastuzumab biosimilar used for the patient was AryoTrust. Afterward, left breast quadrectomy was done, showing no tumor residue, and left axillary sentinel lymph node excisional biopsy also resulted as negative (which is a very good response to neoadjuvant chemotherapy). After performing breast-conserving surgery, radiation therapy to the whole breast and regional lymphatics were considered. This technique contains tangential fields that is performed using the 3-dimensional conformal radiation therapy. The dose provided to the whole breast was between 45 and 50 Gy over 5–6 weeks (1.8–2 Gy tumor dose daily, 5 weekly fractions), with an additional boost dose or 10–16 GY in 2 Gy fractions to the tumor bed with the patient treated with 6-MV photons.\nThe overall treatment was well tolerated by the patient. After performing 5 cycles of AryoTrust (6 mg/kg every 3 weeks), she complained of swollen eyes and urticarial lesions. By conducting the physical examination, periorbital swelling and erythema (heliotrope rash) were revealed (Fig. ). An erythematous rash on the arms (Fig. ) and chest was also observed. Also, muscle strength of the lower limbs decreased (4/5), while it was normal in all upper limbs. The laboratory examination revealed moderately elevated serum muscle enzymes (a creatine phosphokinase value: 492 IU/L with a normal laboratory range of 38–176 IU/L;lactatedehydrogenase value: 510 IU/L with a normal laboratory range of 140–280 IU/L), but fluorescent antinuclear antibody, anti-double-stranded DNA, and antibodies to histidyl tRNA synthetase were negative. Skin lesion biopsy diagnosed papillary edema, epidermal spongiosis with few eosinophilic infiltrations, and a mild interstitial mucin deposition. Since the interval between radiotherapy and the onset of the symptoms was about 6 months and a recent screening for disease recurrence resulted as negative, the observed DM symptoms were attributed to trastuzumab. For this reason, the practitioner discontinued the use of trastuzumab. With Rheumatologic consult, prednisolone and hydroxychloroquine were started. Subsequently, the patient's symptoms improved, and 1 month later, she was free of any related symptom, and CPK was found in the normal range. In the first week, AryoTrust was started with 4 mg/kg, which was then followed by 2 mg/kg weekly for 3 weeks. Afterward, the dose of AryoTrust was increased to 6 mg/kg every 3 weeks. Fortunately, the patient had no complications.
A 45-year-old woman was admitted to our heart center with severe mitral stenosis and left atrial clot. The patient gave a history of shortness of breath on minimal exertion for one week and no cerebral symptoms, including headache, dizziness, transient ischemic attacks, or strokes. She was found to be fully conscious, alert, and oriented with stable vital signs. Blood pressure was 110/80 mmHg, and diastolic murmur was audible over the mitral area. Physical examination revealed intact cranial nerves, motor power, and sensation. There was no evidence of vasculitis such as Osler’s nodes, Jane way pad, palmer erythema, or cyanosis of fingers. Blood investigation showed an erythrocyte sedimentation rate (ESR) of 4 mm with no leukocytosis and a white blood cell (WBC) of 10.000 mm3. The electrolytes and kidney and liver function were within normal limits. Chest X-ray showed prominence of the left cardiac border due to left atrial enlargement. Electrocardiography was indicative of no change, but two–dimensional echocardiography revealed a large bulky non-mobile thrombosis in the left atrium with severe mitral stenosis. The mitral valve area was 0.6 cm2, and the other cardiac valves were normal. Pre- and postoperative laboratory measurements included negative antinuclear antibodies and rheumatoid factor, and elevation of C4 & C3 components of complement; in addition, HBS Antigen (especially in polyarteritis nodosa) was negative.\nThe patient underwent open heart surgery via the ascending aorta and bicaval cannulation. The aorta was cross-clamped, and the heart was arrested with cold cardioplegia by achieving systemic hypothermia at 30 °C on the cardiopulmonary bypass. Intraoperatively, the stenotic mitral valve was found to have a bulky clot attached to the valve and wall of the left atrium. The diseased mitral valve and the clot were excised, and the left atrial cavity was irrigated with copious amounts of normal saline and a valve was thereafter implanted. The left ventricle was then filled completely with saline and blood and fully deaired. The patient was weaned successfully off cardiopulmonary bypass with inotropic support and transferred to the intensive care unit. After 6 hours, blood pressure dropped and central venous pressure elevated and the extremity became cool and cyanotic. Inotropic support was commenced with dobutamine and adrenaline (2 and 1 mic/kg/min, respectively). On the third postoperative day, the inotropic drugs were tapered and blood pressure stabilized. By this point, however, the cyanosis had changed to gangrene and on the 12th postoperative day the acral part of the extremity was amputated and the specimen was sent for histopathological examination. In the histopathological examination, there was only non-specific vasculitis with thrombosis. The patient did not regain full consciousness on the following morning and was found to be quadriplegic with non-voluntary movements of the four limbs and face. The eyes could move only on the vertical plane, with both pupils having become small and fixed. After 72 hours, she managed to respond to questions only by blinking or moving her eyes vertically. Brain MRI revealed multiple infarction of the brainstem. Prolonged ventilatory support was maintained and eventually a tracheostomy was performed to facilitate tracheobronchial suctioning and weaning. Acute renal failure with anemia was managed and the kidneys recovered completely. However, the patient remained in this locked-in state for 4 weeks with no neurological improvement despite all ventilatory, nutritional, and nursing support. She eventually expired from hepatic failure and generalized sepsis.