A 78-year-old lady developed sudden onset severe vaginal pain during her morning walk. On self-examination, she noted some vaginal bleeding and loops of bowel protruding out from her vagina. She was taken to the local emergency department, where the bowel prolapse was reduced with vaginal packing (). She was given intravenous antibiotics and subsequently emergently transferred to a tertiary centre.
Her past history was significant for a locally advanced bladder cancer treated with a radical cystectomy, hysterectomy and ileal conduit 2 years ago, with subsequent adjuvant chemoradiation. Following her surgery, she had known vaginal prolapse that had recurred despite treatment with a pessary. She was currently on immunotherapy treatment for stable, low-volume lung and liver metastases.
On examination, she was haemodynamically stable and had generalized mild abdominal pain. She had not passed any flatus or opened her bowels for 24 h, which was when the bowel evisceration occurred. Laboratory findings revealed mild leucocytosis of 11.9 × 109/L (normal 4.0–11.0), elevated C-reactive protein of 31 mg/L (normal <5) and a normal lactate of 0.4 mmol/L (normal <0.5).
Computed tomography scan of the abdomen revealed small volume of free fluid and inflammatory fat stranding in the pelvis with loops of thick-walled distal small bowel. Packing material was seen in the vaginal vault ().
At operation, the vaginal packs were removed and the bowel had been successfully reduced. There was a palpable defect in the superior vaginal vault, just posterior to the pubis, which prolapsed out easily, bringing the vaginal defect into view (). There was a small amount of simple serous fluid, with no evidence of blood stained or purulent fluid. As tissue quality was good, the defect was primarily repaired with continuous 0 Vicryl ().
Her post-operative course was unremarkable, and she was discharged home after return of normal bowel function with regular topical oestrogen cream. She is due to follow-up with gynaecology to discuss other options to treat her vaginal prolapse.


A 70-year-old Asian Indian male, after recovery from COVID-19 40 days ago, presented with decreased visual acuity in the right eye (OD) since 1 week, associated with floaters and redness. During the active COVID-19 phase, he was hospitalized for 10 days and treated with oral steroids, remdesivir, favipiravir, doxycycline, and cefpodoxime. He is a known diabetic, hypertensive, and asthmatic with hypothyroidism. On examination, best-corrected visual acuity OD was counting fingers 2 m, and 20/60 in left eye (OS) with pseudophakia in both eyes (OU). Anterior segment showed mild circumciliary congestion in OD and mild posterior capsular opacity in OS. Right eye showed moderate vitreous haze (grade 3) and vitreous cells (grade 3+), spheroid vitreous clumps, a subretinal yellowish well-defined placoid lesion supero-nasally measuring 3 × 3 × 1 mm, and optic disc hyperemia []. It was unremarkable in OS.


An 8-year-old male child with congestive heart failure presented with respiratory distress, bilateral pedal edema, and ascites.
Respiratory distress was present for the past 2.5 years with insidious onset. Dyspnea aggravated in the last 4 months. Gradual swelling of the whole body starting from feet was noted by his mother for the same duration. He had no previous febrile episodes and no family history of cardiac illness. On physical examination, his pulse rate was 112 bpm, irregular, and of low volume and blood pressure was 96/60 mmHg. Jugular venous pressure was raised with absent a wave and prominent v wave and y descent. He had mild cardiomegaly, a loud pulmonary component of S2 (P2), and a grade 3/6 pansystolic murmur, most prominent at the left parasternal area. Liver was palpable up to 7 cm below the right costal margin. There was also moderate splenomegaly (3 cm along the splenic axis).
Electrocardiography showed atrial fibrillation at the time of presentation. Laboratory investigations revealed – hemoglobin 12.6 gm% and total leukocyte count 10,800/mm3 with 75% neutrophils and platelet count 95,000/mm3. Serum electrolytes including calcium, blood glucose, and liver and renal function test were within normal limits. Antistreptolysin O titer and C-reactive protein reports were also normal. Echocardiography was done, which demonstrated biatrial enlargement, moderate mitral and tricuspid regurgitation, pulmonary regurgitation, and moderate pulmonary arterial hypertension (mean pulmonary arterial pressure 41.9). Pulse Doppler at mitral valve showed increased E velocity (E/A = 3.11, E/E’ >10) []. Mitral inflow variation was <25% []. Hepatic venous Doppler showed inspiratory flow reversal during diastole. All these findings suggested restrictive cardiomyopathy rather than constrictive pericarditis.
Patient was treated with bed-rest, diuretics, angiotensin-converting enzyme inhibitor (enalapril), and metoprolol. Gradually, the child improved respiratory distress and arrhythmia resolved after 6 days of treatment. However, hepatosplenomegaly remained of same degree and relatively low platelet count persisted.
The patient underwent bone marrow aspiration (BMA) study with the presumptive diagnosis of infiltrative disorder causing the red cell mass (RCM) and organomegaly. BMA revealed numerous Gaucher cells with hypocellular marrow (myelopoiesis: erythropoiesis = 2.5:1) []. Quantitative enzyme assay showed deficient beta-glucosidase enzyme activity in serum – 1.5 nmol/h/mg (normal activity >4), confirming the diagnosis of Gaucher disease.
The patient was discharged in stable condition after 18 days. The boy is now referred to higher center for possible cardiac transplantation.


A 29-year-old woman presented to the hospital for an elective excision on a soft, mobile mass located on her right lower back. The patient stated that the mass had been causing her discomfort and had been present for quite some time. The mass was excised and during the procedure was noted to be intramuscular. Upon biopsy results, the gross specimen was partially capsulated measuring 11.0 × 10.0 ×5.5 cm, tan-pink to brown in color with a smooth outer surface. The tumor extended into the margins of the excision. The mass consisted of mainly hypocellular, vaguely lobulated, proliferation of small ovoid to spindle cell admixed with scattered lipoblasts, in a background of abundant myxoid material and arborizing vascularity. At the periphery of the lobules, increased cellularity was noted with moderately increased cytological atypia. Mitotic activity was very rare and areas of round cell composed less than 5% of the total tumor. In many of the tumor cells, stain with p53 showed evidence of p53 overexpression. Stain with Ki-67 showed a proliferation index of 2-8%. Fluorescence in situ hybridization (FISH) analysis was positive for detection of rearrangements of the DDIT3 (CHOP) gene at the 12q13 locus, consistent with the diagnosis of myxoid liposarcoma. Following the diagnosis, the patient had a computed tomography (CT) scan of the chest, abdomen and pelvis, which revealed a resection scar along the right paraspinal musculature with no evidence of lymphadenopathy, lesions or pathology. Due to evidence of the tumor extension into the margins, the patient underwent re-excision at the previous resection site of the mass. The patient tolerated the procedure well and will be followed up for subsequent post-operative visits. The biopsy results of the re-excision revealed no evidence of residual myxoid liposarcoma.


A 40-year-old man was referred to the department of cardiology of our hospital for difficulty breathing. The patient had been in his normal state of health until approximately 2 weeks before presentation, when exertional dyspnea developed and gradually progressed. His previous medical history included hypertension, dyslipidemia and gout. He did not take any medications. The patient did not drink, smoke, or use illicit drugs, and had no known allergies. There was no family history of cardiovascular diseases.
On examination, he was alert and well. His vital signs were normal except for a blood pressure of 130/111 mm Hg. The jugular venous pressure was not high, but gallops were audible at the apex. No pulmonary rales were heard on auscultation and there was no edema in the legs. Electrocardiography demonstrated left ventricular hypertrophy and left atrial dilation. Chest radiography revealed cardiomegaly with a cardiothoracic ratio of 55% without pleural effusion. The complete blood cell counts were normal. Levels of total bilirubin, aspartate aminotransferase, alanine aminotransferase, creatinine, uric acid and C-reactive protein were 1.7 mg/dL, 110 U/L, 132 U/L, 1.67 mg/dL, 33 mg/dL and 0.43 mg/dL, respectively. Although the creatinine kinase level was 540 U/L, the MB enzyme level was 20 U/L and the high-sensitivity cardiac troponin T level was 0.020 ng/mL (reference value < 0.100). The level of brain natriuretic peptide was high at 734.9 pg/mL (reference value ≤ 18.4).
On echocardiography, the left ventricle was diffusely hypokinetic with an ejection fraction of 22% and enlarged with an end-diastolic diameter of 56 mm, accompanied by mild mitral regurgitation, findings consistent with dilated cardiomyopathy. The transmitral E/A ratio was 2.73 and the E/early diastolic mitral annular velocity ratio of the intraventricular septum was 22.77. The peak velocity of the tricuspid regurgitant was 3.7 m/s and the systolic pulmonary artery pressure was estimated to be 63 mm Hg. The left atrial volume index was high at 48 mL/m2 (reference: 17 - 32).
A diagnosis of heart failure was made, and diuretics, enalapril, bisoprolol and warfarin were administered. The contractility of the left ventricle improved to an ejection fraction of 52% and pulmonary hypertension disappeared. Warfarin was discontinued. Coronary angiography demonstrated no trace of the ostium of the LMCA in the sinuses of Valsalva; the middle to distal part of the LMCA was visualized by rich collateral flow from the right coronary artery to the left anterior descending coronary artery and left circumflex coronary artery (). No trace of the ostium of the LMCA from the aorta or main pulmonary artery was detected on computed tomography (CT) angiography () or echocardiography.
Myocardial imaging with thallium (Tl)-201 (111 MBq) and iodine-123 beta-methyl-p-iodophenyl-pentadecanoic acid (I-123 BMIPP) (111 MBq) was performed. A total of 36 images over a 180° anterior arc were acquired 5 min and 3 h after tracer injection. The acquisition lasted 50 beats per projection, was stored in a matrix of 64 × 64 pixels and the images were reconstructed using a Hanning filter without attenuation or scatter correction. Bull’s eye maps demonstrated mild tracer defect of Tl-201 and I-123 BMIPP in the apex on the initial images, with complete redistribution on the images 3 h later (), suggesting myocardial damage, but not infarction, on the apex in the left ventricle. Of note, the tracer uptake was milder in Tl-201 than in I-123 BMIPP.
The patient underwent coronary artery bypass grafting via an in situ left internal thoracic artery to the mid-left anterior descending artery at another hospital. This surgery was performed through an off-pump approach via left mini-thoracotomy with no signs of myocardial ischemia during the surgery and a final diagnosis of congenital atresia of LMCA was made. The clinical course was uneventful and CT angiography, which was performed at 5 days post-surgery, demonstrated a patent bypass graft and no LMCA with collateral arteries from the right coronary artery ().


A 79-year-old woman applied to the hospital with the complaints of severe pain and discoloration on her nose tip and the distal parts of the toes following persistent fever and cough about 10 days. She had rale sounds on the lungs. Bilateral common consolidation was found in the lungs on thorax computed tomography (CT). According to the history of the patient, the discoloration was emerged after about 10 days by the beginning of the fever and cough. The venous obstruction was observed with venous Doppler ultrasonography on the plantar digital area of the feet (, ). The patient was hospitalized with anticoagulant treatment and antibiotherapy. After antibiotherapy (moxifloxacin) and anticoagulant (enoxaparin) treatment, the nose and distal toe area were healed. Three months after the treatment, the patient was observed in a healthy status and did not have a recurrent thrombosis or thromboembolism complication ascertained by the telephone interview with her family.


A 48-year-old Caucasian man with a history of G6PD deficiency presented to the emergency department with 2 days history of sustained penile erection. He reported a sudden onset of erection non-related to sexual stimulation, which remained sustained, associated 10/10 pain. He tried gabapentin and acetaminophen for pain at home with no relief. He had one prior similar episode a year ago, and the erection lasted for 6 h but resolved in the hospital without intervention. The patient denied urogenital trauma. He reported no use of any triggering medication such as a phosphodiesterase inhibitor, intracavernosal agent or any other medication. He reported a chronic history of hemolysis and anemia since childhood, which required multiple transfusion, and stabilized during adulthood. But he required splenectomy 2 years ago, and he was not sure about the reason for procedure. He also reported same hematological condition, G6PD deficiency in a male cousin.
On examination, patient was in pain, and his penis was erect, with no color changes suggestive of ischemia or necrosis, as well as no temperature change. Initial laboratory results showed macrocytic anemia (hemoglobin (Hb) 9.9 g/dL and mean corpuscular volume (MCV) 123 fL), leukocytosis with white blood cell (WBC) 34,000/µL (Diff Bands 10%, Metas 1%, Myelos 1%, three nucleated RBCs), reticulocytosis, Ret 14.5%; indirect hyperbilirubinemia, total bilirubin 2.6 mg/dL, indirect bilirubin 1.0 mg/dL; lactate dehydrogenase (LDH) 177 IU/L, and haptoglobin 162 mg/dL. Direct antiglobulin test (DAT) was negative. Peripheral blood smear showed presence of Howell jolly bodies and anisocytosis, and no blasts were seen. Toxicology test was negative except for opioids (urine morphine), and urine was collected after patient received morphine in the emergency department.
In the emergency department, patient had three rounds of drainage from either side of his cavernosum; during the second and third rounds, he was given 1 mg of phenylephrine bilaterally. After procedure with persistent priapism, he was admitted for further urology management. During first day of admission, he was taken to operating room (OR) and underwent drainage of stagnant blood from the corpora cavernosa, injection of three syringes of epinephrine with saline into corpora cavernosa and manual reduction of priapism, with some pain relief and reduction of priapism, but after few hours of procedure, patient had persistent priapism. Hematology was consulted to evaluate for possible hematological conditions causing persistent priapism. No hemoglobinopathies were found, and hemoglobin electrophoresis showed no hemoglobin variants. No myeloproliferative process was identified, JAK 2 mutation was not detected, and BCR-ABL was negative. No other causes for hemolysis were recognized: paroxysmal nocturnal hemoglobinuria (PNH) and cold agglutinin were negative, and no reduction in RBC surface band 3 fluorescence for hereditary spherocytosis was detected. G6PD level was found to be low, and folate levels were depleted (12.9 ng/mL).
Patient was taken to OR on day 5 of admission for bilateral spongio-cavernosum shunts, and procedure was uneventful. Patient had clinical improvement, with resolved priapism, and controlled pain. He was discharged from hospital on day 6.


A 24-year-old male college student complained of 11 months of low back pain and 8 months of left lower extremity radicular pain in an L5 distribution. Neurological examination demonstrated a positive straight leg raising sign at 40° on the left side. There was an objective weakness of the left tibialis anterior and extensor pollicis longus graded as 4. Lumbar radiographs were normal, with no spinal segmental instability and deformity. Magnetic resonance imaging (MRI) revealed a cystic lesion adjacent to the L4-L5 intervertebral disc on the left side, with marked compression of the spinal cord thecal sac and left L5 root. The lesion showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, suggesting a cystic lesion (). The CT scan showed disc bulging with no calcification. Before he was admitted, he had received conservative treatment including bed rest, pain control with analgesic and physical therapy for more than half a year. The symptoms had not improved after conservative treatment, and the patient and his family were willing to undertake minimally invasive treatment. We performed a percutaneous transforaminal endoscopic surgery for the discal cyst. The symptoms were relieved immediately after surgery, and there were no intraoperative and postoperative complications. Postoperative MRI showed no remnant of the discal cyst (). Histopathological examination identified the cyst wall that revealed fibrous connective tissue without lining cells. There were no recurrent lesions during a follow-up period of 12 months.


A 29-year-old male construction worker presented with low back pain radiating to the right lower limb after heavy physical work. Neurological examination demonstrated a positive straight leg raising sign at 45° on the right side. Lumbar radiographs were normal, with no spinal segmental instability and deformity. MRI demonstrated an intraspinal extradural space-occupying lesion just caudal to the L4-L5 intervertebral disc on the right side. The lesion showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images (). He was treated conservatively at his first visit because the symptoms were relatively mild. He continued to work while taking non-steroidal anti-inflammatory drugs and physiotherapy. After 6 months of conservative treatment, the patient's symptoms had not improved and worsened gradually, and repeated MRI images showed persistent cystic structures but no change in size. As the patient was a very active worker, we recommend minimally invasive surgery to avoid back muscle injury. At this time, the patient was willing to undertake the percutaneous transforaminal endoscopic surgery for the discal cyst. Under the endoscope, the cyst wall was attached to the disc. Postoperative MRI showed no remnant of the discal cyst (). The symptoms were relieved immediately after surgery, and there were no intraoperative and postoperative complications. Histopathological examination identified dense fibro collagenous connective tissue, no synovial lining cells and no intervertebral disc material. There were no recurrent lesions and complications during the 1-year follow-up period.


A 26-year-old nulliparous lady presented with complaints of chronic pelvic pain for 1 year. It was more toward left lower abdomen, with no relation to her menses. She had a history of laparotomy done twice, appendicectomy in 2003 and right ovarian cystectomy in 2012. On examination, a large midline vertical scar extending from xiphisternum to symphysis pubis was noted. No other masses or tenderness was found on abdominal palpation. Vaginal examination revealed a 10 cm cystic mass occupying left and posterior fornices with significantly restricted mobility of the uterus.
Trans-abdominal ultrasound showed bilateral adnexal cysts and magnetic resonance imaging confirmed well-defined T2 hyperintense lesion with thin wall and thin septa, measuring 13.5 cm × 13.5 cm × 9.3 cm in size and involving both adnexae []. Bilateral ovaries were not seen separately. Uterus was normal. Tumor markers for ovarian malignancies were within the normal limits.
Laparoscopy was planned after counseling and consenting the patient. In view of anticipated adhesions along the previous midline scar, entry through Palmer's point was attempted using Verres needle. Despite two attempts, pneumoperitoneum could not be created, likely due to intra-abdominal adhesions. A direct entry was made in the preperitoneal space using 5mm port at the Palmer's point, and under vision gas was insufflated in this space keeping the pressure at 12 mmHg. Initially blunt dissection was done in this space with 5 mm lens avoiding vessels. Secondary 5 mm port was inserted under vision in the extraperitoneal space once adequate exposure of the intended site of insertion was achieved []. Blunt and sharp dissection was continued taking care not to breach the peritoneum, with the intent that the peritoneal layer will act as safeguard against injury of bowel underneath. On reaching the adnexa, it was noted that the cyst was a large encysted collection due to adhesions from previous surgeries. An area free of the bowel was chosen to open the peritoneum over the encysted collection for deroofing and visualization of pelvic structures intraperitoneally. The fluid was sent for cytology and to rule out tuberculosis. The uterus was densely adherent to the anterior abdominal wall. Right ovarian fossa was empty, possibly owing to previous surgery. Left ovary was also densely adherent posteriorly and to the lateral pelvic wall. It showed a 3-cm simple cyst which was drained. Pneumoperitoneum was released and skin closed [ (This video is also available at )]. The patient had good recovery and was discharged in stable condition on the second postoperative day. The cytology report showed no abnormality and no evidence of tuberculosis, confirming a diagnosis of encysted collection.


A 51-year-old female with a history of depression, presented with a large pigmentary lesion close to the sternum (), 6×3 centimeters in dimension, with dermoscopic features of large converging blue-black ovoid nests, central ulceration and peripheral regression (). She had the lesion for more than 25 years, while multiple facial plaques and papules (), also pigmentary, with blue-gray and blue-black ovoid nests and ulcerations, as seen dermoscopically, and many with a distinct pearl-like edge, appeared during the last three years. No lymphadenopathy was present. Multiple BCC was suspected and a punch biopsy was performed. Pathology results showed a neoplasm with morphological characteristics of either a skin adnexal tumor or a BCC. More specifically, it was characterized as a basaloid epithelial tumor of the epidermis with peripheral palisades, with mitotic crowded centrally located nuclei, presence of various pale cells and few infiltrating strands of atypical epithelium. Histochemistry and immunohistochemistry uncovered a BerEp4+, EMA − phenotype (), in favor of BCC, and surgical excision of the lesion was recommended. Final pathology validated BCC diagnosis, revealing a tumor with microscopic characteristics of BCC, with various sites of focal ulceration, partial infiltration of the subcutaneous nerves and vessels, and minor focal metaplasia to metatypical basal cell carcinoma, with negative excision margins. A thorax computer-assisted tomography scan (CT) for staging revealed a 7-mm nodule () and several “ground glass”-like micronodules in the left lung, representing possible distant metastases. A videoassisted thoracic surgical (VATS) biopsy of the 7-mm nodule was performed followed by histological examination of the specimen, revealing nests of basaloid epithelial cells with peripheral palisading, thus confirming its metastatic nature. Due to disease extent, adjuvant treatment with vismodegib was initiated at 150mg/day and she was discharged. An unaltered CT-thorax () and regression of her facial lesions were observed at 30-days follow-up.


A 25-year-old male patient reported to the Department of Oral Medicine and Radiology with a complaint of incidental finding of swelling with gradual growth on the right lower one-third of the face for 1 year []. The patient denies the previous history of facial trauma. Medical, social, and family history were nonsignificant. General physical examination revealed no remarkable findings. On extraoral examination, well-defined oval-shaped solitary swelling was observed extending from the right body of the mandible to the angle of the mandible anteroposteriorly and from the zygomatic process to the inferior border of mandible supero-inferiorly measuring about 6 cm × 5 cm approx. in its greatest dimensions. The colour of the swelling was normal skin colour with smooth surface and no secondary changes were observed. Surrounding structures appeared to be normal. On palpation, the swelling was nontender, afebrile, firm, noncompressible, nonfluctuant, nonpulsatile []. On intraoral examination, no abnormality was seen with the hard and soft tissues related to the extraoral swelling. Parotid duct orifice was noted to be patent and no signs of xerostomia were evident. Based on history and clinical examination, provisional diagnosis of right masseteric hypertrophy was made and differential diagnosis included fibroma, lipoma, and parotid tumour.
Patient had cosmetic concern due to large size swelling with gradual growth on right masseteric region for 1 year.
Routine hematological investigations revealed all the parameters within normal ranges. USG of the right masseteric region revealed lobulated, hypoechoic mass in the right masseter muscle. In Colour Doppler USG, vascularity was visible within the mass [Figure and ]. On the basis of above radiological investigations, final diagnosis of intramuscular hemangioma of right masseter muscle was made.
After obtaining patients’ consent, IMH was excised by combined Risdon's and preauricular approaches. For the surgical procedure, incision below and behind the angle of the mandible and preauricular skin incision were made on the right side and skin flaps were raised A parotid gland appeared normal and the underlying masseter showed a diffuse bulge but with no surface abnormality. The branches of the facial nerve were identified and a superficial parotidectomy was performed. The nerve fibers were subsequently dissected from its masseteric bed. The underneath masseter muscle exhibited prominent bulge with hemangioma, the facial nerve branches were gently lifted and then the masseter was mobilized from the mandible after severing its attachment with the zygomatic arch. Through the same incision, the external carotid artery was ligated and vascular control was achieved. Anteriorly, the masseteric fascia was preserved along with the fine communications of the facial nerve. Thereafter, complete excision of the masseter muscle along with hemangioma was successfully achieved [Figures and ].
Specimen excised was sent for histopathological examination which revealed connective tissue stroma with numerous skeletal muscle bundles. Large dilated vascular spaces lined by endothelial cells, interspersed between the skeletal muscle bands were observed which is [] suggestive of intramuscular capillary hemangioma.
No recurrence was observed after 6 months of follow-up.


In October 2018, a 54-year-old female patient visited the hospital because a left breast tumor was discovered 10 months prior, and tumor redness and swelling had lasted for more than one month. At the beginning of 2018, the patient discovered a left breast tumor resembling peanut rice without pain and nipple discharge, erosion or other symptoms. There was no special diagnosis or treatment. In September 2018, the patient’s tumor increased significantly in size, accompanied by redness, swelling and bloating pain, and the pain was not related to the menstrual cycle. Subsequently, the tumor broke, and a light red and light yellow liquid outflow was observed. She was sent to our hospital for further diagnosis and treatment.
Physical examination on admission (): The appearance of the breasts was asymmetrical, and the left breast was red and swollen and larger than the right breast. There was a defect in the upper outer quadrant of the left breast, and the gap was approximately 5*4*5 cm. A palpable mass measuring approximately 15*10*8 cm, hard and fixed on the chest wall, was observed in the left breast central region and external quadrant. The right breast was not abnormal, and the bilateral axillary and supraclavicular lymph nodes were not palpable. Auxiliary examination: left breast dressing covered, failed to photograph. Breast ultrasound showed the following: 1, left breast dressing coverage failed to film, right breast no obvious occupation; and 2, left subclavian to left axillary abnormal echo, size 26*11 mm, considering lymph node enlargement, metastasis to be rowed (metastatic?). Mammography, CT, and SPECT showed no abnormalities. As the patient was noncooperative, MRI of the breasts could not be performed.
After completing the relevant examinations and considering the taboo associated with invasive operations, the patient underwent a “left breast tumor puncture”. The postoperative pathological examination (–) showed some lamellar tumor cells, different sized cells, atypia, coarse chromatin, obvious nuclear division, and osteoclast-like cells. Some tumor cells were tubular, while some were fusiform and atypical, with different sizes and in different stages of nuclear division. Cancer and sarcoma components, mostly sarcoma components, overlap and are difficult to distinguish. Necrosis was observed in the center of the tumor. Immunohistochemistry: ER(-), PR(-), HER2(0), Ki-67(40%), Vim(+), GCDFP-15(+), MC(-), P63(+), CK5/6(+), CK8(+), and P53(+). Pathological diagnosis (left breast mass puncture): conforms to metaplastic carcinoma with osteoclast-like giant cells, mostly with sarcoma components, including invasive ductal carcinoma and spindle cell carcinoma. The postoperative pathological examination of the “left axillary and subclavian lymph node puncture” showed inflammation with severe atypical hyperplasia. Based on the pathological results, the mass was clearly diagnosed as left emulsification bioplastic carcinoma, stage cT4N3M0, stage IIIC. Neoadjuvant therapy for breast cancer was proposed.
On October 20, 2018, the patient was given the “EC” chemotherapy regimen (epirubicin 130 mg d1; cyclophosphamide 0.8 mg d1), and its efficacy was evaluated as progressive disease (PD) after 2 cycles (). Considering that the patient had left emulsified metaplastic carcinoma, the molecular classification was triple negative, and the treatment plan was changed to the “PCb” chemotherapy regimen (albumin paclitaxel 150 mg d1/8/15; carboplatin 0.2 g d1/8/15) for 2 cycles. During chemotherapy, the patient’s mass increased significantly (), bleeding was obvious, and the efficacy was still evaluated as PD. At this time, the patient’s physical condition had deteriorated, with a Karnofsky performance status (KPS) score of 60 and severe anemia. Considering that the patient could not tolerate chemotherapy, PARP inhibitor therapy was proposed, but no pathogenic BRCA1/2 gene exon mutation was detected. After communicating with a radiotherapist, palliative radiotherapy was recommended for the patient to stop bleeding. Intensity-modulated conformal radiotherapy (IMRT) was performed, and the total radiation dose and segmentation method were as follows: planning target volume (PTV) DT45 Gy/15 F/21 d for and DT300 cGy/F for chest bone metastases. After 2 rounds of radiotherapy, the left breast tumor spontaneously detached during the dressing change. The exfoliated tissue was sent for a pathological examination. Microscopically, necrotic tissue with inflammatory cell infiltration, local abscess formation, and a small amount of cancer tissue were observed. Immunohistochemistry: ER (-), PR (-), HER-2 (0), and Ki-67 (+, 30%). However, during subsequent radiotherapy, the left breast tumor further increased in size, and at the same time, a mass of approximately 4*10*3 cm in size and soft with a sense of fluctuation was palpated at the sternal stalk. Re-examination of the ultrasound findings showed a mixed cyst-solid space in the subcutaneous soft tissue of the sternum (range: approximately 86*32*27 mm), and metastases were possible. CT findings: sternal destruction with a soft tissue mass, metastasis considered. PET/CT findings: sternal bone destruction with metabolic abnormalities, metastasis considered. PET/CT imaging of other parts of the body showed no obvious abnormalities. At this time, the patient was diagnosed with left breast metaplasia, stage cT4N3M1, stage IV, and left breast cancer with sternal metastasis. After communication, a tissue-based NGS assay was performed, showing a MAP2K1 deletion mutation, along with TP53 p.S183X on exon 5 and TP53 p. S241F on exon 7 mutations, with a low tumor mutational burden (TMB), and microsatellite stability. Drug sensitivity test results showed that the drugs with high sensitivity were carboplatin, taxon, cyclophosphamide, letrozole, and mitomycin. After consultation with the multidisciplinary team (MDT) in our hospital, the patient was diagnosed with left emulsification metaplasia, stage cT4N3M1, stage IV, left breast cancer with sternal metastasis. “Replace chemotherapeutics±antiangiogenic drugs” was recommended. Considering that the patient’s physical condition was still poor, with a KPS score of 70, after communicating with the patient and her family, they indicated that chemotherapy was not an option, and radiotherapy was voluntarily suspended. Finally, a single drug, “anlotinib” (12 mg orally) was administered for two weeks and stopped for one week.
After the administration of anlotinib, the tumor spontaneously detached again and did not increase in size (), and the sternum metastasis was stable. After 2 weeks, the blood pressure of the patients was high (up to 140/90 mmHg). After treatment in the Department of Cardiology, the patient was given oral “nifedipine controlled-release tablets”, and her blood pressure was maintained at 110–120/70–90 mmHg without adjusting the dose of anlotinib. Currently, the patient continues to take anlotinib, the progression-free survival (PFS) duration is up to 25 months, the efficacy is evaluated as PR, the drug is well tolerated, and the patient continues follow-up.


A 52-year-old man experienced epigastric discomfort accompanied by a sense of fullness for 3 mo.
Three months prior, the patient developed epigastric discomfort, which was accompanied by a sense of fullness. He did not have fever, cough, chest tightness, or other discomfort.
He had never consumed alcohol or smoked cigarettes. He had no known food or drug allergies. He also had no history of blood transfusion or surgical trauma.
The patient had no specific family history.
A body temperature of 36 °C, blood pressure of 120/94 mmHg, heart rate of 80 beats/min, and respiratory rate of 16 breaths/min were noted upon arrival. The abdomen was flat and soft, and the patient did not have abdominal tenderness or rebound pain.
No obvious abnormalities were found in routine blood tests, liver and kidney function tests, electrolytes or GI tumor indices.
An upper GI endoscopy revealed a submucosal lump located in the gastric antrum (Figure ). Endoscopic ultrasonography identified a 2.4 cm × 1.8 cm lump located in the gastric antrum (Figure ). It originated from the muscularis propria and exhibited both intraluminally and extraluminally growth, with hypoechoicity on the periphery, hyperechoicity in the middle, and unclear boundaries. Computed tomography (CT) showed nodular thickening of 3.0 cm × 2.2 cm in the gastric wall of the gastric antrum, and after enhancement (Figure ), the lesion exhibited obvious enhancement (Figure ).
We suspected that it was a GIST (neither glomus tumor nor schwannoma were excluded).


A 3-year-old male with a history of autism along with cognitive, language, and behavioral delays presented to the emergency department after falling 4 feet from a window. Head computerized tomography (CT) revealed a 5 × 5 × 4 cm AC of the left frontal convexity with subjacent mass effect. Before the fall, he had delays in cognitive advancement with difficulty following commands, naming objects, and making eye contact. He was able to ambulate with assistance but unable to climb stairs. He also banged his head against walls frequently while screaming and it was unclear if this was secondary to headaches. The patient received physical, occupational, and behavioral therapy through early intervention therapies with no real improvement. On neurological examination, he made no eye contact, did not follow commands, was not cooperative, did not speak or verbalize, but did demonstrate symmetric movement. The patient’s family stated that he had undergone neuropsychiatric testing which diagnosed autism but the patient’s family did not provide reliable follow-up with us; we were unable to obtain this report. The patient was lost to follow-up for 6 months, and on representation, a magnetic resonance imaging (MRI) was obtained which demonstrated a 5.6 × 5.2 × 4.5 cm left frontal AC with associated mass effect on the adjacent parenchyma and frontal horn of the left lateral ventricle. Ophthalmological assessment revealed no papilledema. The patient underwent a left frontal craniotomy for microsurgical fenestration of the AC with excision of the cyst wall without complication. At 10-day follow-up, his parents reported much calmer behavior with no further labile outbursts and less head banging. At 1 month follow-up, his parents reported significant improvement in cognitive function whereby he was following instructions in computer games and solving multistep problems. His behavior was completely altered and more appropriate for 3 years old and he was making eye contact and interacting with multiple examiners while playing games with them as well. He was following simple commands and no longer banging his head on walls. He was naming objects and persons at home and in clinic. At 3 months follow-up, his behavior continued to improve, most noticeably, with additional verbalization and interaction and eye contact with family and strangers. Unfortunately, the patient was lost to further follow-up [-].


A 52-year-old gentleman initially presented to our institution with a perianal fistula and abscess in June 2020. The abscess drained spontaneously and he responded to conservative management. Four months later, he returned with perianal pain and suspected recurrent abscess in the left gluteal region. He had no pyrexia or systemic symptoms. White blood cell count was normal at 5.4 × 10.9/L, hemoglobin was also normal at 145 g/L. Pelvic MRI was performed which delineated a left trans-sphincteric fistula leading to a T2 hyperintense ovoid uniformly hyperenhancing focus measuring approximately 2 × 1.5 × 3 cm in the left ischioanal fossa [ and ]. The lesion showed no appreciable fluid component resulting in two main etiological considerations, first, a neoplasm arising from a longstanding perianal fistula and second, a solid inflammatory phlegmon.
An ultrasound-guided biopsy was performed, [] in view of possible malignancy, which showed suppurative inflammation and granulation tissue with no evidence of malignancy []. The surgical team, therefore, went ahead with a simple excision of the lesion and fistula tract. Final excision specimen confirmed an inflammatory phlegmon with dense acute inflammatory infiltrate forming microabscess as well as granulation tissue with reactive endothelial cells. A degenerated hair follicle was also noted at the center of the inflammatory focus. Absence of malignancy was confirmed by pathology.


The patient is a 32-year-old female who presented with 3 days of headache associated with blurring of vision and giddiness. She also had weakness on the left upper and lower limb from 1 day. The family reported history of the patient receiving her first dose of Covishield vaccine 11 days before admission. She was unmarried, an active cigarette smoker, with no history of comorbidities or medications, nor any similar episodes in the past.
On examination, she was conscious and oriented, with heart rate of 76/min, respiratory rate of 22/min, blood pressure of 110/70 mmHg, oxygen saturation of 94% on room air, a normal Glasgow Coma Scale score, and normal pupils. Limb power was 2/5 and 3/5 on the left upper and lower limbs, respectively. A magnetic resonance imaging (MRI) of brain [] showed a large right parietal hemorrhage with mild adjacent peri-focal edema, causing mass effect on adjacent right lateral ventricle and locoregional effacement of sulci and gyri, with a mid-line shift of 5 mm to the left. CT venogram [] and 3D volume rendering technique [] showed thrombosis of the left transverse and sigmoid sinuses and partial thrombosis of superior sagittal sinus. Following neurology review, she was started on 100 ml of 20% mannitol every 6 h, 200 ml of 3% saline every 6 h, intravenous levetiracetam 500 mg twice daily, and therapeutic dose of enoxaparin 40 mg twice daily subcutaneously, with close neuromonitoring in ICU. A work-up for pro-coagulant disorders was sent including factor V Leiden mutation, protein C and S deficiency, vasculitis, and anti-phospholipid antibody syndrome. Her initial coagulation parameters were normal, with platelet count of 120 × 109/L. Vitamin B12 was low at 40 pg/ml (reference range 180–914 pg/ml), which was corrected with intravenous cyanocobalamin 5000 mcg once daily for 5 days.
On day 2 in ICU, her sensorium acutely deteriorated and a CT brain showed significant increase in the right parietal hematoma and worsening midline shift of 10 mm []. She underwent emergency right parietal decompressive hemicraniectomy with evacuation of the intracranial hematoma [], following which she remained intubated, on mechanical ventilation and sedated. The same day, her platelet count was noted to drop to 105 × 109/L, with a further fall to 69 × 109/L on day 3 []. Fibrinogen was normal (2.6 mg/dl and 4.0 mg/dl, on days 2 and 3, respectively). Initial d-dimer was 1105 ng/ml (normal <250 ng/ml) and 1101 ng/ml on day 2. Pro-coagulant work-up returned normal. The possibility of VITT was considered and enzyme-linked immunosorbent assay (ELISA) for platelet factor-4 antibody was sent for, which was found raised at 15.2 IU/ml (reference range 0–12 IU/ml). After hematology review, enoxaparin was substituted with injection fondaparinux 7.5 mg subcutaneously once daily, with instructions to stop it in case of platelet count drop below 50 × 109/L or bleeding manifestations. She was given intravenous immunoglobulin (IVIG) 1 g/kg once daily for 2 days. There was a gradual rise in platelet count over the next few days, increasing up to 252 × 109 on by day 11 of admission.
She underwent percutaneous tracheostomy on day 5 of admission, anticipating prolonged need for airway protection due to slow neurological recovery. Her sensorium started improving by day 6 and she was gradually weaned off ventilator. By day 10, she was conscious, oriented, breathing on room air through the tracheostomy, and communicating by writing. Her left lower limb power had improved to 4/5 although upper limb remained weak with power 3/5. By day 17, the tracheostomy was decannulated after assessing her cough and swallowing reflexes. She was monitored for another 2 days and discharged with home neurorehabilitation services, on tablet dabigatran 150 mg twice daily until the next review.


In November 2020, a 57-years-old woman with no significant medical history was referred to the emergency room for cough and dyspnea, prompting a SARS-COV-2 real-time polymerase chain reaction (RT-PCR) test, which resulted in positive results. Chest CT evidenced bilateral patchy ground-glass opacities, consistent with COVID-19 pneumonia (). Blood tests showed severe neutropenia (neutrophils 0.55 x 109/L), mild thrombocytopenia (platelets 115 x 109/L), and anemia (Hb 50 g/L) (). The patient was admitted to the intensive care unit (ICU), where she was immediately treated with piperacillin/tazobactam 4.5 g QID, posaconazole 300 mg QD, and dexamethasone per institutional guidelines for the treatment of COVID-19 pneumonia. Ventilatory support with continuous positive airway pressure (CPAP) and pronation cycles was also started without the need for intubation. Antibiotic therapy was continued for 41 days.
A bone marrow aspirate was performed to investigate the abnormal blood results, which were diagnostic for AML, with 69% blasts. The immunophenotype was positive for CD34, CD117, human leukocyte antigen DR isotype (HLADR), CD33, and weakly positive for CD13. Cytogenetic revealed a 46, XX normal karyotype and molecular characterization by NGS an isocitrate dehydrogenase 2 (IDH2) mutation with FLT3-ITD, NPM1, CEBPA wild-type, therefore classifying the disease as AML not-otherwise-specified according to the WHO 2016 classification, with an intermediate risk based on ELN 2017 recommendations.
A contrast chest CT was performed due to a marked D-dimer increase on day two after ICU admission, showing bilateral pulmonary emboli and confirmed the bilateral ground-glass opacities already highlighted in the previous CT. Anticoagulant therapy with low-molecular-weight heparin (LMWH) was therefore added.
Upon multidisciplinary review, it was decided to postpone leukemia therapy to enable adequate COVID-19 pneumonia treatment. The patient experienced progressive clinical improvement and requiring gradually decreased oxygen consumption. Oxygen weaning was obtained after 15 days after ICU admission. Despite the clinical improvement, the persistent positivity of the nasopharyngeal swab for RT-PCR for SARS-CoV2 was observed. Therefore, we decided to infuse two cycles of convalescent plasma collected from patients who had recovered from SARS-COV2 disease,– unfortunately without achieving the clearance of the virus. A plausible explanation for the benefit of hyperimmune plasma is to provide immunity by giving patients virus-specific neutralizing antibodies, which might result in immediate clearance of SARS-CoV-2.
Due to the persistent swab positivity for SARS-CoV-2 and the recent severe pneumonia and pulmonary embolism, the risk of a standard intensive chemotherapy induction was deemed unacceptable for this patient. Thus, based on the current data showing that IDH1/2 mutations are responsive to venetoclax-based therapy,– a treatment with Azacytidine-Venetoclax was preferred and started 32 days after diagnosis. 5-Azacitidine was administered subcutaneously at 75 mg/m2 once daily from day 1 to day 7. Venetoclax was administered orally, 100 mg day 1, 200 mg day 2, 300 mg day 3, 400 mg day 4 to be continued till day 28. Due to the well-known pharmacological interference of Venetoclax with azoles, posaconazole was replaced with micafungin at a dose of 50 mg QD. The patient tolerated the treatment exceptionally well, without hemorrhagic or infectious events. Complete recovery of blood counts was observed 46 days after treatment initiation (), and antibiotic and antifungal therapy was suspended.
Notably, on day 18 of the cycle (the seventh week since the onset of COVID-19 infection), the nasal swab became finally negative, and the patient was discharged to complete the 28-day course of venetoclax at home. At the end of the cycle, a bone marrow evaluation showed marrow hypoplasia, with residual 6% myeloid blasts detected by immunophenotype.
After 19 days from the end of the first cycle, the patient received a second cycle of Azacytidine-Venetoclax. After seven days from the end of the second cycle, a bone marrow evaluation showed complete remission, and a post-remission consolidation with alloHSCT was planned. A new chest CT scan repeated four months later showed extensive resolution of lung infiltrates (). An unrelated donor was identified, but the patient refused to undergo allogeneic transplantation. We, therefore, planned to continue Azacitidine-Venetoclax therapy until relapse or development of unacceptable toxicity. After the second cycle of treatment, a bone marrow evaluation was also performed, confirming the complete remission of the disease.


A 49-year-old female was admitted to our department with a chief complaint of coughing and excessive sputum production for more than 1 month. Chest computed tomography (CT) demonstrated a lesion located in the upper lobe of right lung, and multiple nodules scattered in the bilateral lungs, consistent with a diagnosis of primary lung cancer and metastases (–).
She was previously healthy, had no significant medical history, and there was no history of cancer history or any other disease in her family. She was a non-smoker and not exposed to second-hand smoke. Neck and supraclavicular lymph nodes were not enlarged and not palpable on physical examination.
Laboratory examinations showed that blood carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CTFRA21-1) levels were normal. Positron emission tomography-CT (PET-CT) and brain magnetic resonance imaging (MRI) scans showed metastases in the bilateral lungs, and no metastases in the liver, brain, adrenal glands, bone, or other organs. A CT-guided needle biopsy was performed of the right upper lobe lesion. Histopathological examination and immunohistochemical (IHC) staining were consistent with a diagnosis of primary lung adenosquamous carcinoma. Staining for cytokeratin 5/6 (CK5/6), P40, thyroid transcription factor-1 (TTF-1), and Napsin-A was positive. The Ki-67 index was about 70% in the squamous cell carcinoma (SCC) component, and about 30% in the adenocarcinoma (AC) component (–). ARMS-PCR sequencing demonstrated concurrent EGFR exon 21 (L858R) and PIK3CA (H1047R/E545K) mutations in the AC component (–) She was diagnosed with primary lung adenosquamous carcinoma and bilateral lung metastases, disease stage IVA.
She was treated with pemetrexed (500 mg/m2) plus platinum-based chemotherapy every 3–4 weeks, and gefitinib 250 mg, orally, once daily. After 2 cycles, efficacy evaluation indicated a partial response (PR) (). After another 2 cycles of the same therapy evaluation indicated steady disease (SD) (). She was then begun on gefitinib alone as maintenance therapy. After 2 months, she developed an intermittent cough and hemoptysis, chest CT illustrated that the tumor and metastases had increased in size ().
The patient declined a repeat biopsy for next-generation sequencing (NGS), and she was begun on the same chemotherapy regime and osimertinib 80 mg, orally, once daily. After 4 cycles, evaluation indicated a PR (). Adverse events included a grade 1/2 rash and anemia, and grade 1/2 hematological toxicity (decreased white blood cells and platelets). After osimertinib only for maintenance therapy for 2 months, she developed an intermittent cough again and evaluation indicated progressive disease (PD) ().
The time from diagnosis to the second occurrence of PD was about 10 months. A repeat CT-guided needle biopsy was performed, and pathological examination was consistent with adenosquamous carcinoma. The frequency of SCC and AC components in the tumor, and IHC staining results and the Ki-67 index were almost the same as the first evaluations. NGS demonstrated concurrent EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations. No T790M, C797S, or other mutations were identified.
The patient declined further chemotherapy and was treated with anlotinib as the third-line regime (a dose of 12 mg/day for 2 weeks, stop for 1 week, and then repeat). After 2 cycles, evaluation indicated a PR (), and SD after 4 cycles. The only adverse effect was grade 1 hand-foot syndrome. She continues to receive treatment and follow-up.


We report the case of a 59-year-old male medical doctor living in Guayaquil
with a clinical history of chronic hypertension treated with an angiotensin
receptor blocker (telmisartam). The patient presented to the emergency
department on 23 March with an episode of fever, non-productive cough,
malaise, and diarrhea lasting for 10 days. The episode was accompanied with
abdominal pain localized in the epigastrium and characterized by an intensity of
8/10. The nasopharyngeal swab real-time polymerase chain reaction (RT-PCR)
test for SARS-CoV-2 was positive on the third day. Finally, he reported that
he self-medicated 4 days prior with nitazoxanide 500 mg three times a day
(TID) and azithromycin 500 mg once a day (QD).
He presented the following initial laboratory findings: white cell count 4300
per mm3 (normal range: 4400–10,300), total neutrophils 3410 per
mm3 (normal range: 1780–5380), total lymphocytes 640 per
mm3 (normal range: 1180–3740), total monocytes 180 per
mm3 (normal range: 250–710), total eosinophil count 60 per
mm3 (normal range: 0–6), Ferritin 920 ng/mL (normal range:
30–400), interleukin (IL)-6 13.5 pg/mL (normal range: 0–6.5), D-dimer
2.5 mg/L (normal range: 0–1.9), procalcitonin 0.05 ng/mL (normal range:
<0.046), creatinine 0.5 mg/dL (normal range: 0.80–1.20), and Blood Urea
Nitrogen (BUN) 19 mg/dL (normal range: 5–20 mg/dL). His individualized
prediction of hospitalization risk for a patient with COVID-19 was of 10.5%.
Treatment was started with a continuous infusion of esomeprazole,
hydroxychloroquine 200 mg two times a day (BID), azithromycin 500 mg QD,
ampicillin/sulbactam (3 g intravenous (IV) every 8 h), and
lopinavir/ritonavir 200/50 mg BID. Supplemental oxygen was given via nasal
cannula with a rate of 3 L/min, and oxygen saturation was 97%.
On the fourth day after admission, the patient presented with dyspnea,
tachycardia, and tachypnea. Presenting oxygen saturation of 90% despite the
use of supplemental oxygen via nasal cannula. High flow nasal cannula was
initiated. Tocilizumab was initiated with one dose of 400 mg followed by
200 mg due to blood levels of IL6 of 89 (pg/mL) (normal range: 0–6.5). About
12 h later, hydrocortisone 100 mg TID was added to the therapeutic
regimen.
On the fifth day of hospitalization, the chest x-ray demonstrated multiple
alveolar consolidations in the right inferior lobe and left superior lobe
().
The patient showed tachypnea and use of accessory muscles of respiration, as
well as a deterioration on his level of consciousness. On laboratory
findings, he presented with an arterial blood gas analysis showing
respiratory acidosis with hypoxemia: pH 7.26; PCO2 52.7 mmHg, PO2 45.9 mmHg,
HCO3 20.6 mmHg, and base excess −2.90. Thus, he required endotracheal tube
placement and ICU care. The patient was placed in pronation therapy ().
The antibiotic coverage was changed to piperacillin/tazobactam 4.5 g IV every
6 h. Sedation and muscular relaxation were accomplished with fentanyl
2 µg/kg/h and rocuronium 0.05 µg/kg/min. Enteral feeding was started via
nasogastric tube. Mechanical ventilation parameters at this time were as
follows: volume-controlled mode (AC) with tidal volume (TV) of 6 mL/kg of
predicted body weight (PBW), a constant inspiratory flow of 50 L/min, a
level of positive-end expiratory pressure (PEEP) of 8 cm H2O, and
respiratory rate of 20 breath/min. The expired TV displayed by the
ventilator was reported.
On the sixth day since admission and second day of ICU care, due to the
presence of arterial hypotension of 80/50 mmHg, volume therapy and
vasopressor therapy were started with the administration of 500 mL 0.9%
saline solution and norepinephrine 0.02 µg/kg/min, respectively.
On the eighth day of hospital stay, arterial blood gas analysis showed a pH of
7.40, PCO2 55.2 mmHg, PO2 94.9 mmHg, HCO3
33.9 mEq/L, and SaO2 93%.
On the ninth day since admission, vasopressor therapy was suspended. Propofol
and loop diuretics were added for sedation and improved diuresis,
respectively.
On the tenth day of hospitalization and Day 6 of ICU care, sedation was
removed, and the patient responded positively with an adequate level of
consciousness. Ventilatory parameters were changed to continuous positive
airway pressure (CPAP) mode. The following day, the patient was extubated
and received 45 L high flow nasal cannula with an FiO2 of
50%.
On the eleventh day of ICU care, ambient air and high flow oxygen via nasal
cannula were alternated with good patient tolerance.
On the twelfth day of ICU care, the patient was saturating 100% with nasal
cannula, had adequate diuresis and normal sinusal rhythm. An
electrocardiograph (ECG) was required prior to the continuation of
hydroxychloroquine, and the results were within normal ranges. The patient
was transferred to the hospital ward.
On day 16 since hospital admission, antimicrobial therapy was discontinued. In
addition, the chest computed tomography (CT) scan showed improvement in the
parenchymal and pleural opacities in lung bases and periphery ().
Laboratory results reported normal parameters.
On day 19 since hospital admission, the patient reported an overall improvement
in his clinical condition. He was ambulating and participating in physical
rehabilitation. An antibody test was taken which came back negative for IgM
and positive for IgG.
As of today, the patient has returned to clinical practice. See graphical
representation of timelines ().


A 46-year-old woman was admitted to our department of neurology because of a 2-day history
of paroxysmal slurred speech with numbness of the right upper limb. Two days previously, she
had developed tongue root stiffness and slurred speech without obvious inducement after
meals and simultaneous numbness at the distal end of the right upper limb. These symptoms
were relieved for approximately half an hour, and she experienced no dizziness, headache,
nausea, vomiting, blurriness or rotation of objects, difficulty swallowing, choking or
coughing while drinking water, or limb weakness. In the emergency department of our
hospital, brain computed tomography (CT) showed no obvious hemorrhage. Cerebral infarction
was considered, and the patient was admitted to our department. She had no history of
hypertension, diabetes, or other diseases. She had no history of smoking, drinking, or drug
allergies and had no relevant family history. The patient’s mental condition, sleep habits,
diet, urine, and feces were normal. She had been found to have nephritis, thrombocytopenia,
and elevated rheumatoid factor during physical examination at a local hospital 1 month
previously but was not treated. Because of diagnostic limitations at the local hospital, the
patient visited our hospital to obtain a clear diagnosis and begin appropriate
treatment.
Physical examination after admission revealed a body temperature of 36.6°C, pulse rate of
90 beats/minute, respiratory rate of 19 breaths/minute, and blood pressure of 85/60 mmHg. A
neurological examination revealed slurred speech. Her pupils were equal in size, and her
pupillary reflexes were intact. She exhibited no diplopia or nystagmus, and her eye
movements were normal. Her nasolabial groove was symmetrical, and the oral angle of her
teeth was not skewed. Meningeal stimulation was negative. The muscle strength in her limbs
was grade 5. Distal shallow hypoesthesia of the right upper limb was present. She had a
stable finger-to-nose test, stable heel-knee-tibia test, positive extremity tendon reflexes
(++), and negative bilateral Babinski sign. No obvious abnormalities were observed in the
patient’s abdomen. The skin of her hands and lips was swollen, tight, and hard ().
Laboratory and auxiliary examinations were then performed. Brain CT showed no obvious
abnormalities. Brain magnetic resonance imaging showed an infarction in the left occipital
lobe, left centrum semiovale, and bilateral cerebral parietal lobes (). An electrocardiogram demonstrated sinus
tachycardia, incomplete right bundle branch block, abnormal Q waves in V1 to V4, and right
axis deviation (). No
obvious abnormalities were observed on magnetic resonance angiography (). Thoracic CT showed bilateral
interstitial pneumonia ().
The erythrocyte sedimentation rate was 2800 mm/hour, and routine blood test results were as
follows: hemoglobin, 108 g/L; total protein, 60.3 g/L; albumin, 34.48 g/L; glucose, 3.88
mmol/L; and rheumatoid factor, 156.7 IU/mL. A full set of antinuclear antibodies
(qualitative) was evaluated, revealing the following: anti-Sjogren’s syndrome A, strongly
positive (+++); antiscleroderma 70, strongly positive (+++); antinuclear antibody, positive
(+) at 1:320; anti-RO-52, strongly positive (+++); and anticardiolipin antibody
quantification, 53.71 RU/mL. Normal results were obtained for an antineutrophil cytoplasmic
antibody series (qualitative); immunoglobulins G, A, and M; and anticyclic citrullinate
peptide antibody (quantitative). Normal results were also obtained for HbA1c, routine
urinalysis, novel coronavirus nucleic acid (qualitative) (negative), five coagulation items,
blood lipids, and eight immunity items.
The patient was treated with enteric-coated aspirin tablets (0.1 g once a day), clopidogrel
hydrogen sulfate (75 mg once a day), atorvastatin calcium (20 mg once per night), and
betastastine and triclutin to improve her microcirculation. She was also prescribed a
prednisone tablet (50 mg once a day), cyclophosphamide tablets (0.5 g once a week), and
nifedipine (30 mg once a day).


A 63-year-old male with long-term uncontrolled type 2 diabetes presented to our foot and ankle center facility with a 4-year history of DFU and associated episodes of purulent drainage with intermittent chills. The patient’s cardiologic history included three open revascularizations and five endovascular stents within the previous 6 years, and placement of an implantable cardioverter defibrillator (ICD). In addition, he reported an endovascular stent due to arterial stenosis in the affected limb 3 years ago.
Lower extremity physical examination revealed erythema and edema of a midfoot (Lisfranc’s) amputation stump with active purulent drainage from a DFU (). The patient’s left foot amputation stump was plantarflexed, grossly erythematous, and edematous. The associated DFU was actively draining purulent fluid and was associated with wound dehiscence. The wound was probed to bone readily and revealed necrosis of the cuneiforms and cuboid. Dorsalis pedis and posterior tibial pulses were palpable bilaterally, with as no overt signs of peripheral artery disease. After clinical, radiographic (), and ultrasound assessment, patient was diagnosed with a post-operative infection at the amputation stump of midfoot of a neuropathic diabetic foot. Panels 1 and 2 show radiological and clinical presentation of the infected foot over the course of treatment.
Broad-spectrum antibiotic therapy—ertapenem and clindamycin—was initiated with the intention of narrowing based on culture results. Tight blood glucose control was initiated, with a combination of regular, intermediate-acting, and long-acting insulin. Desired levels were 70–130 mg/dL before meals and 180 mg/dL after meals.
Bacterial and fungal growth was only observed in pre-debridement tissue cultures. Right now, the patient’s antibiotic therapy was narrowed following the susceptibility tests. He was treated by the combination of levofloxacin, sulfamethoxazole-trimethoprim, and fluconazole.
All antibiotics therapy was discontinued.
A staged approach to treatment was designed and performed based on clinical and imaging findings.
Surgical irrigation and debridement of the distal stump wound—debridement of all devitalized and infected bones (cuneiforms, cuboid, and navicular) and soft tissue was performed. Pre- and post-debridement tissue samples were collected for cultures of aerobic and anaerobic bacteria, fungi, mycobacteria, and antibiotic susceptibility testing. Achilles tenotomy was performed percutaneously, the wound was primarily closed, and then provisional negative pressure wound therapy (PICO®, Smith & Nephew, London, UK) was installed (80 mm Hg) and set to continuous mode for 72 h ().
A second-look irrigation and debridement were performed with additional tissue samples being sent for cultures. No evidence of progressive infection or necrosis was observed. Negative pressure wound therapy was applied (80 mm Hg) and set for the next 11 days. The result of cultures collected at second-look procedure from remnant tissues was negative.
The wounds were noted to be completely closed with no signs of active infection, blood inflammatory tests—erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)—continued to fall. Based on these criteria and negative cultures at the second-look procedure, the decision was made to proceed with the next stage of treatment. We then performed a tibiotalocalcaneal fusion using lateral transfibular approach and a plantar approach ( and 2). A conventional dressing was maintained for 14 days.
We then performed a total contact casting (TCC_EZ®, Integra, 1100 Campus Road, Princeton – NJ08540) and the patient initiated a weight-bearing rehabilitation protocol (). The TCC was changed every 2 weeks.
Radiographs revealed good bone healing (). Total contact cast was then discontinued. The patient was able to walk independently in a stiff sole shoe with a custom-made orthotic.
The patient was fully weight-bearing in stiff sole sneakers with no gross overt alteration of the gait pattern. During this period, he remained in complete remission and wounds remained completely healed with no signs of infection. Patient demonstrated full range of motion of the hip and knee joints, with a 5+/5+ muscle power for flexion, extension, adduction, and abduction. When assessed by the hindfoot American Orthopaedic Foot and Ankle Society (AOFAS) outcome score, patient reached 79 points ( and 2). We informed patient that the data concerning this case would be considered for publication, and he consented to it.


In July 2018, a 48-year-old Chinese female presented to the Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Health Care Group, Huangshi, Hubei Province, China with a progressive mass on her right mandible over 3 months, which was accompanied by oedema erythema and wheals mainly on the lower limbs. She had seen dermatologists constantly for her rash but did not notice the mass. She reported no fever, night sweats or weight loss. She had no other medical conditions or respiratory symptoms and was otherwise systemically healthy. Her family had no genetic history. Upon physical examination, a nontender and non-erythematous palpable mass with no clear boundary was found in the right submandibular region (). Several enlarged lymph nodes were also observed in the right neck and supraclavicular areas. Wheals were scattered across the trunk and lower limbs, especially on the lower limbs ().
An enhanced computed tomography (CT) scan of the nasopharynx showed a soft tissue mass (1.9 cm × 1.1 cm) in the lateral part of the right submandibular gland (). Chest CT imaging revealed small lymph nodes in the supraclavicular area. Abdominal CT imaging showed no abnormalities. Laboratory tests displayed white blood cells (8.23 × 109/l) and eosinophils (2.15 × 109/l, 11.2%, normal range: 0.02–0.52 × 109/l, 0.40–8.00%). Immunoglobulin (Ig)E levels were elevated at 245 IU/ml (normal range <100 IU/ml). Liver and kidney functions were normal. An incisional biopsy of the mass showed preserved lymph node architecture with hyperplastic lymphoid follicles and patchy expansion of germinal centres (). The interfollicular region contained numerous eosinophils and interstitial fibrosis (). Eosinophilic abscess was noted in some areas (). The patient was finally diagnosed with Kimura’s disease with chronic urticaria.
After surgical resection, the patient underwent four courses of treatment that included the following: 500 mg/day cyclophosphamide intravenously on 1 day, then 100 mg/day prednisone orally for 4 days. The patient then received local radiotherapy (PGTVnd 42.4GY/20F’) for 14 days after 2 days of drug discontinuation. Each course of treatment lasted 21 days. The patient was followed up for 6 months without relapse.


In March 2021, a 23-year-old Chinese female presented to the Department of Dermatology, Huangshi Central Hospital with multiple nodules on the scalp for 2 years, without pain and itching. She denied any history of head trauma and had no other medical conditions or relevant genetic history in her family. Upon physical examination, numerous skin coloured nodules measuring approximately 0.5–3 cm () were found on the occipital area (). No enlarged superficial lymph nodes were observed. Blood count and hepatic and renal function were normal. A biopsy of the lesion showed many irregular hyperplastic vessels with hypertrophic endothelium in the dermis; and endothelial cells protruded into the lumen and assumed a spiked appearance (). The vessels were surrounded by a density of lymphocytes and a small number of eosinophils (). The patient was diagnosed with ALHE. Owing to the presence of numerous lesions, staged surgical excision of the lesions was recommended. The patient has already undergone the first stage of excision and will receive the second stage of excision after 3 months. She is now being followed-up.
This report was approved by the Ethics Committee of Huangshi Central Hospital, Edong Health Care Group (V1.0.2021.03.15). Specific information on the patients was completely de-identified in the manuscript. Written informed consent was obtained from the patients for the publication of this report. The reporting of these two case reports follows the CARE guidelines.


Parents of a 6 year old girl reported to the department complaining of mild pain and swelling of gums in the right maxillary molar region. The lesion was small to begin with and had slowly progressed to the present size in the past 18 months. History revealed that the patient had visited a local dentist 1 year back and a biopsy was performed which was reported as ameloblastic fibroma; however, previous radiographs could not be accessed. Extraoral examination showed slight facial asymmetry on the right side of the face []. A solitary gingival swelling was evident in the right maxillary posterior region extending from the primary first molar tooth to the maxillary tuberosity area intraorally. Buccal and lingual cortical expansion was evident. The maxillary primary second molar and the permanent first molar were missing although a cusp-like structure was evident clinically through the enlarged gingival tissue []. On palpation, the lesion was firm to hard, reducible, and mild tenderness was elicited.
Orthopantomograph and lateral skull radiograph showed a mixed radiolucent lesion with multiple radiopaque foci in the right maxillary posterior region. The right premolars, first molar, and primary second molar were displaced superiorly [Figure and ]. Computed tomography showed a well-delineated, expansile, hypodense mass with sclerotic border containing multiple radiodense foci resembling a “cluster of pebbles” in posterior maxilla. Posteroinferior border of the lesion revealed bone resorption [Figure -]. The left-sided deviated nasal septum and left maxillary sinusitis were noted. Mucosal thickening of left maxillary sinus with reduced volume of right maxillary sinus was also evident.
The lesion was diagnosed as AFO based on the history and previous biopsy report. Surgical enucleation was done under general anesthesia. The tissue was sent for histopathologic examination. The deciduous second molar was removed, while the permanent teeth were retained to promote normal eruption and recurrence is not found on follow-up.
Gross tissue specimen was white to cream in color, largest bit measured 1 cm × 1.7 cm × 1.6 cm in dimension, hard in consistency, and showed a nodular surface []. The tissue sections revealed odontogenic epithelium with mineralized tissue [] and primitive ectomesenchyme that resembled the dental papilla focally []. Multiple irregular conglomerate masses of dentin-like tissue, occasionally enamel matrix, enamel spaces or clefts representing decalcified enamel, cementoid globules, and pulp tissue were evident [Figure and ]. Based on clinical, radiographic, and histopathologic features, the case was diagnosed as AFO or CO.


A 46-year-old female patient presented with complaint of pain and mobility in left upper teeth of 3 months' duration associated with mild left facial swelling. She had multiple dental consultations with different dentists for the same in the past and had undergone extraction of one or more regional teeth in each appointment owing to mobility. The procedure had aggravated the pain and swelling leading to difficulty in mouth opening. Consequently, she developed partial nasal blockage and nasal discharge on the left side along with burning and epiphora of the left eye.
Medical history revealed her to be a diabetic with poor glycemic control and also a hypertensive for past 4 years for which she was on oral medications.
Clinically, an indistinct, insignificant swelling over the left middle third of the face with mild obliteration of nasolabial fold was noted []. Intraorally, a mild diffuse tender palatal swelling extending from lateral incisor to the first molar region and mild buccal vestibular obliteration without any secondary changes was appreciated. Teeth 11, 12, 23, 24 elicited Grade I mobility; 21, 22 and 25 were clinically missing (extracted) and 26, 27 were endodontically treated with metal crowns []. Deep periodontal pockets (~7–9 mm) were noted with tooth 23, 24 ( Fédération Dentaire Internationale [FDI] numbering system).
Hematological investigations disclosed a decreased hemoglobin level of 8.4gm%. Her fasting and postprandial blood sugar levels were 308 mg/dl and 389 mg/dl, respectively.
A panoramic image which was acquired by the previous dentist was available and showed advanced supporting bone loss around teeth 21, 23, and 24. Keen observation of the same revealed permeative type of osteolysis in the maxillary left anterior alveolar bone with breach in the floor of the left maxillary sinus suggesting its involvement [].
Computed tomography (CT) images depicted an irregular bone destruction of moth-eaten pattern extensively involving left alveolus, left maxilla, left zygoma, and zygomatic arch crossing the midline over the hard palate. Breach in the floor of the left nasal cavity was noted. Maxillary antrum on the left showed soft-tissue shadow completely obliterating the sinus with destruction of the medial wall and orbital floor with patchy hyperdensity in the floor. Left buccal soft tissue appeared enlarged as compared to the contralateral side [].
Histopathologic evaluation of the lesion revealed the areas of necrosis with thick-walled broad nonseptate fungal hyphae of mucor. Dense acute and chronic inflammatory cells and few epithelioid cell granulomas along with multinucleated giant cells were also noted []. Potassium hydroxide (KOH) staining confirmed the presence of hyphae. The Periodic– acid–Schiff staining confirmed the presence of right-angled hyphae [].
The patient was hospitalized immediately and was switched on to insulin from oral hypoglycemics. Liposomal Amphotericin B in a dosage of 5 mg/Kg was administered intravenously for a week. De-lining of the left maxillary sinus was carried out as the patient did not consent for excision of bone involved, regardless of the consequences explained. Further, the patient got discharged against medical advice when she was detailed regarding wide spread involvement and questionable prognosis.


A 30-year-old woman with a 17-year history of bipolar affective disorder was transferred to acute care psychiatry service with acute exacerbation of symptoms of manic episode. She had no previous medical or substance abuse history. Before hospitalization, zuclopenthixol acuphase 50 mg IM, haloperidole 10 mg IM, biperiden five mg IM., chlorpromazine 100 mg IM. were applied as needed because of affective elevation at another hospital. At admission, the patient received treatment with clozapine 800 mg/day, amisulpirid 800 mg/day, and chlorpromazine 200 mg/day. She was treated with haloperidol 20 mg/day IM, and biperiden 10 mg/day IM. The dose of clozapine, chlorpromazine, and valproat were diminished gradually and amisulpride was stopped.
On the seventh day of hospitalization, the patient developed rigidity, tremor and incontinence without fever. Haloperidol was stopped for probability of NMS, and ECT was initiated on the eighth day of hospitalization. On day 11 and 12 of hospitalization, haloperidol IM was used for acute agitation. Rigidity, confusion, diaphoresis, tremor, tachycardia, and incontinence occurred at the following day. The patient’s temperature was 36.3 C°, heart rate was 110 per minute, respiratory rate was 15 to-20 per minute, blood pressure fluctuated between 90/70 and 110/70 mm/hg, and oxygen saturation was 97%. Laboratory findings revealed increased levels of CPK (> 2000 IU/L; normal range= 20-200), aspartate aminotransferase (AST) (188 U/L; normal range= 5-45), alanine transaminase (ALT) (66 U/L, normal range= 5-40), lactate dehydrogenase (LDH) (581 IU/L; normal range = 60-200), C-reactive protein (CRP) (1.84 mg/dL; normal range= 0-0.5), and erythrocyte sedimentation rate (ESR) (44 mm/hour; normal range= 0-20). Leukocyte count (6.35 103/µL; normal range= 4.1-11.2) was in normal range. Neuroimaging, EEG (electroencephalogram), and chest x-ray imaging showed no abnormalities. Urinalysis and thyroid hormones were in normal range. There was no focus for infection (pulmonary, urinary etc).
On day 19, a confusional state developed and by day 20 of the hospitalization, bromocriptin 5mg/day was initiated with the diagnosis of NMS according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders). On the 29th day of admission, all symptoms of NMS disappeared. Antipsychotic treatment was initiated with clozapine 12.5 mg/day because of agitation. The patient developed rigidity as cogwheel sign, dystonia, altered mental status, and autonomic dysregulation after 6 days of clozapine initiation and was admitted to the intensive care unit on the 37th day of admission. After 6 days of hospitalization in intensive care unit, she was transferred back to psychiatry service. On the 43th day of hospitalization, the patient’s bromocriptine was elevated to 10 mg/day to address rigidity and dystonia. At the 57th day, no symptom of NMS were observed (nearest NLR value mesasured on the 62nd day). The patient's informed consent was provided for the publication of this case presentation.


A 19-year-old female patient presented with OCD. This patient has also been diagnosed with depression, Pierre Robin sequence, and mild mental retardation. First, the patient received rTMS for her depressive and anxiety symptoms. Prior to the TMS therapy, the treating psychiatrist followed a pre-rTMS treatment evaluation of the patient, indicating no seizure risk factors. Written informed consent for the rTMS treatment was obtained from the patient. She underwent rTMS treatment targeting the bilateral DLPFC, with the TMS coil being placed over the left and right DLPFC for iTBS and cTBS protocols, respectively. These theta burst protocols were applied using a figure-8 coil and consisted of the following parameters: iTBS: 5 Hz, 20 trains with 8-s intertrain interval, 10 pulses per train, 200 pulses per session, and total duration 3:08 min; cTBS: 20 trains with 0.2-s intertrain interval, 10 pulses per train, 200 pulses per session, and total duration 40 s. The stimulation intensity was set at 120% of the resting motor threshold. The patient received a total of 30 rTMS sessions. In addition to the rTMS treatment, she was taking at intervals some of the following medications: escitalopram, risperidone, lorazepam, promethazine, and olanzapine. After the completion of the treatment period, the mother of the patient reported the following changes: better attitude toward her family members, more kindness, gentle reactions, rule-following, improvement in self-care, restoration of empathy, and better appetite. The patient continued with approximately 20 maintenance rTMS sessions once a week or once a month depending on her availability.
For a period of 18 months, the patient was free of medications, but then she started having more severe OCD symptoms. Following this, the patient underwent rTMS treatment for OCD using the FDA-approved protocol for OCD [] with a double-cone coil (Cool D-B80 coil). The rTMS protocol was administered at 20 Hz and contained 50 trains (40 pulses per train) and 20-s intertrain interval. A total of 2,000 pulses were given per session for 17:58 min. The double-cone coil was placed over the bilateral DMPFC situated 4 cm in front of the leg motor threshold spot, and the stimulation intensity was set at 100% of the leg motor threshold. The patient was on treatment with clonazepam (0.5 mg/day), quetiapine (600 mg/day), and sertraline (100 mg/day) during the new rTMS treatment for OCD. No adverse events were reported during the first 6 sessions.
During the 7th session, the patient experienced a seizure lasting approximately 2–3 min which was accompanied by a fast and tonic fall, facial grimacing, lateral eye deviation, tongue-biting, body shaking, and generalized tonic-clonic movements. The TMS technician stopped the treatment immediately and informed the treating psychiatrist. Until the seizure ended, the TMS technician and the psychiatrist were on the patient's side and put the patient in a lateral decubitus position. Subsequently, the psychiatrist performed a normal neurological examination and checked the patient's breathing and heart rate. An increased heart rate (120 beats per min) was presented immediately after the seizure ended. Her respiration and heart (90 beats per min) rate returned to normal levels after approximately 10 min, and no other adverse events like sweating or vomiting were presented. Her postictal symptoms were confusion and headache. The patient was able to respond to verbal instructions and was discharged home. No risk factors for TMS-provoked seizures were observed on that day [, ].
An MRI measurement was performed 18 months prior to the seizure episode and 2 weeks after the seizure episode (shown in Fig. ). No visual differences were presented between them. Specifically, both of these MRIs showed several focal lesions of a few millimeters in diameter in the periventricular and subcortical white matter of the frontal and parietal lobes and in the corpus callosum. The patient continued the rTMS treatments 8 days after the seizure induction. The intensity of the treatment was reduced to 70% of the leg motor threshold. No adverse events were presented during the first 5 days with the new reduced intensity. The patient continued with the rTMS treatment to treat the severe OCD and behavioral symptoms which affected her functionality and her interactions with family and others to a great extent. These severe symptoms put herself at risk (such as cutting her hair by herself) in an OCD manner for no reason, with temper tantrums. The outweighed risk from rTMS was lower and was managed by a further reduction of the intensity of the treatment.
Following the first seizure, the patient was diagnosed with unspecified encephalopathy by a neurologist. Regarding her medication, she reduced the clonazepam dose and started taking sodium valproate. A new seizure episode occurred 10 days after her last TMS session with this new reduced intensity and the abovementioned changes in her medication. This second seizure episode happened at her school area. The situation of the patient resolved without medication or hospitalization. The characteristics of the second seizure as well as its duration were the same as the first one. However, the second seizure episode seemed to be unrelated to the rTMS therapy because it occurred 10 days after her last rTMS session and after a change of her medication.


A 72-year-old male patient presented as an outpatient for a routine checkup and was admitted due to acute kidney failure. He had been diagnosed with ulcerate nodular melanoma 10 months earlier. His further medical history included atrial fibrillation and prostatic hyperplasia. At the time of admission, his medication consisted of methylprednisolone (16 mg daily), bisoprolol, and pantoprazole. In June 2020, he had received double immunotherapy with nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg). Fourteen days later, the patient was admitted with high fever (39°C) that was accompanied by mild prerenal AKI or hemoconcentration (fractional sodium excretion <0.1%, otherwise normal urinalysis, and SCr max 1.4 mg/dL). Renal function recovered within 4 days (SCr 1.1 mg/dL) upon volume expansion (Fig. ) before steroid exposure. Three days later, the patient developed grade 3 autoimmune colitis. In accordance with the recommendations of the “American Society of Clinical Oncology (ASCO),” steroid therapy was initiated at 1 mg/kg/day methylprednisolone for the colitis, which was tapered over 5 weeks []. After clinical stabilization, the therapy was resumed with a single dose of 480 mg nivolumab. The asymptomatic patient presented for a routine follow-up after 2 weeks. As SCr had drastically increased from 1.01 mg/dL to 4.93 mg/dL, he was immediately admitted to the hospital. Mildly elevated urinary protein excretion (protein to creatinine ratio 0.22 mg/mg) as well as mild hematuria was observed. The urinary sediment revealed sparse leukocyturia without cylinders or signs of acute tubular necrosis, while fractional excretion of sodium now indicated renal AKI (4.4%). In face of the rapid and unexplained AKI, a percutaneous renal biopsy was performed that revealed a severe, acute, and partly granulomatous tubule-interstitial nephritis with signs of a parenchyma destruction, while there were no signs of glomerular damage (shown in Fig. ). A CD3-positive T-cell infiltrate was found interstitially. CD4-positive cells predominated over CD8-positive cells, being accompanied by sparse B lymphocytes (shown in Fig. ). We escalated steroid therapy to 250 mg methylprednisolone intravenously over 2 days. However, kidney function continued to decline, with an SCr of 5.7 mg/dL. A significant improvement in kidney function was only achieved after further escalation to 500 mg intravenous methylprednisolone for 1 day. The steroid therapy was switched to oral prednisone, and treatment with nivolumab/ipilimumab was discontinued. In a follow-up visit 5 weeks after discharge, a gradual decline of the SCr to 2.23 mg/dL was recorded. Over the course of 3 months under steroids, a continuous decline of SCr levels to 1.74 mg/dL was noted. After 5 weeks during steroid tapering to 40 mg/day, an acute elevation of alanine transaminase (AST) to 474 U/L was observed, suggesting grade 3 autoimmune hepatitis. AST rapidly fell to 83 U/L upon transient steroid escalation to 80 mg. Steroid tapering was resumed and the regime switched to hydrocortisone for this purpose. However, a dose of 30 mg hydrocortisone was maintained. Seven months after the renal biopsy, the patient was readmitted due to progressive disease with disseminated metastatic spread, and therapy was limited to palliative care. In contrast, a decrease of SCr to 1.38 mg/dL indicated further recovery of renal function.


A 57-year-old man with a medical history significant only for hypercholesterolemia presented to a cardiology clinic with 6 months of progressive exercise intolerance manifest as a gradual increase in his 1-mile running time and a decline from running 30 miles to less than 3 miles each week. Days later, outpatient coronary angiography showed non-obstructive coronary atherosclerosis and ventriculogram left ventricular ejection fraction (LVEF) was 45%. The patient was started on carvedilol and aspirin.
One week later, he awoke with acute left-sided chest pain. Emergent electrocardiography demonstrated sinus tachycardia and ST-segment elevations and repolarization abnormalities (). Repeat coronary angiography revealed no change, but LVEF by ventriculography had declined to 20%. Post-procedurally, he developed hypotension requiring initiation of vasopressors and hemodynamically unstable wide-complex tachycardia requiring defibrillation. He was transferred to our hospital for further management.
On arrival, the patient was comfortable but mean arterial pressure was 55 mmHg off vasopressors. Jugular venous pressure was elevated, breath sounds were decreased in the bilateral lung bases, and heart sounds were distant without evidence of a murmur or gallop. His extremities were cool. Arterial blood gas showed a pH of 7.4, PaCO2 of 29 mmHg, PaO2 of 63 mmHg on ambient air, bicarbonate of 20 mEq/L, lactate of 4.0 mmol/L, troponin I of 2.0 ng/mL, B-type natriuretic peptide of 2600 pg/mL, and a creatinine of 1.4 mg/dL increased from a baseline of 1.0 mg/dL. A Swan-Ganz catheter was placed revealing a right atrial pressure of 20 mmHg and pulmonary capillary wedge pressure of 22 mmHg. Pulmonary artery oxygen saturation was 40% and calculated cardiac output using the estimated Fick formula was 2.4 L/min, with cardiac index of 1.1 L/min/m2. Given the acuity of presentation and the rapidity of clinical decline, urgent laboratory testing and imaging studies were performed.
Transthoracic echocardiography showed biventricular dysfunction and dilation with global hypokinesis, without asymmetric myocardial thickening or structural valvular disease. There was biatrial dilation. Thyroid panel, cortisol, hemoglobin A1c, iron studies including ferritin, and autoimmune antibody levels were normal, while human immunodeficiency virus, Borrelia burgdorferi, respiratory viral panel, and blood culture testing were negative. Urinary toxicology was negative. C-reactive protein was elevated at 13.9 mg/dL. Cardiac myocardial resonance imaging (cMRI) demonstrated patchy gadolinium delayed enhancement within the right and left ventricular myocardia and pericardial thickening with enhancement, consistent with myocarditis or infiltrative disease though without T2-weighted evidence of edema (). Endomyocardial biopsy was not pursued due to the patient’s hemodynamic and electrical instability.
Milrinone and furosemide infusions were initiated, nitroprusside was added, and an intra-aortic balloon pump was eventually implanted for persistent cardiogenic shock (). He remained oliguric, and continued to have atrial and ventricular arrhythmias requiring defibrillation despite amiodarone infusion. Though the differential diagnoses of sarcoidosis and giant cell myocarditis were discussed, the patient was not initiated on corticosteroids. Due to continued hemodynamic and electrical instability he was femorally cannulated for veno-arterial extracorporeal membrane oxygenation (ECMO). Upon transplantation, pathological examination of the explanted heart revealed diffuse biventricular fibrosis, non-caseating granulomas, and multi-nucleated giant cells consistent with severe cardiac sarcoidosis ().
The patient was discharged home from the hospital two weeks after transplant and continues to do well. He has completed cardiac rehabilitation and started running again. His immunosuppression regimen consists of prednisone 5 mg daily, tacrolimus 2 mg twice daily, and mycophenolate 1000 mg twice daily. He has not had allograft rejection.


The combined surgical and electrochemotherapy technique proposed was adopted to treat a 72-year-old male patient with an RRC developed in a long-standing ulcerative colitis of the rectum. In 1991, the patient underwent surgery for intra-abdominal total colectomy with terminal ileostomy for acute severe UC. In 2018, he noticed the appearance of right ischial-rectal abscess associated with a perianal fistula with evidence of rectal adenomatous villous lesion with high-grade dysplasia. So, the patient went to surgery with proctectomy in November 2018 for adenocarcinoma G2 infiltrating the muscle tunic (pT2 pN0 M0 sec. ajcc 2017). The surgical resection margins were free from neoplastic localization.
After a multidisciplinary consult, an adjuvant chemotherapy and pelvic radiotherapy treatment was proposed to the patient, but he refused and avoided to undergo oncological follow-up until October 2019 when he noticed the appearance of a hard-wooden swelling in the soft tissue of right perineal region (6–7 cm in diameter). After a CT scan () and MRI that confirmed a local recurrence of cancer, following a multidisciplinary discussion between surgeons, radiation oncologists, radiologists and oncologists, a surgical resection indication was given.
However, the CT investigation documented a close relationship between the neoplastic lesion and the root of penis and urethra, with consequent difficulty in obtaining the certainty of disease-free margins without a major demolition procedure that the patient firmly refused.
To increase the chance of best treatment of the margin and perform a local remediation of the tissue adjacent to the neoplasm, it was decided to associate resective surgical treatment to ECT.
Intraoperative time I: the mass infiltrated the perineal muscles and appeared anteriorly tightly close to the prostate plane and root of penis. Removal of the neoformation was made en-bloc with a portion of skin and perineal muscles.
Intraoperative time II: after intravenous infusion of Bleomycin (28 500 IU), intraoperative electrochemotherapy on the muscular and prostate planes was performed (n. 30 electrical discharges). The electrodes were set with a depth of 1.5 cm in order to treat the tumor bed with attention to the anterior wall where the margins were surely closer ().
An aspiration drain was placed in the residual surgical cavity, and the skin was sutured without the need of cutaneous flap.
Histological examination documented moderately differentiated mucinous adenocarcinoma with component mucosecernent representing about 95% of the neoplasm and intense positivity for CDX2, CK19, CK20, CK7, MUC2, MUC1 and MUC5AC, in agreement with intestinal primitiveness.
The resection margins were microscopically free of disease (variable distance between 0.1 and 0.4 cm from the neoplasm).
The postoperative course was regular and without complications.
Pelvic MRI with contrast was performed during the follow-up at 4 and 7 months after surgery without documenting neoplastic recurrence.
Clinical follow-up was conducted for 9 months, and during this period, the patient presented no clinical signs of neoplastic recurrence or other noteworthy perineal, genitourinary or sexual problems.


In April 2019, a 47-year-old male visited the outpatient clinic in the Department of Laser Therapy, The Fifth People's Hospital of Hainan Province, Haikou, Hainan Province, China with a 10-year history of gradually-worsening bilateral periorbital wrinkles. The patient had never received periorbital invasive or non-invasive antiaging treatment. Before treatment, static wrinkles with a pronounced appearance were observed on his bilateral periocular area (: A1, B1, C1, D1). He received a viable therapy to manage his periorbital wrinkles as follows: the left orbital area was subjected to 2940 nm Er:YAG lattice laser and then HG (Changchun JA Biotech, Changchun, China) 10 h/day combined with recombinant bovine bFGF gel (Beifuxin gel; Essex Bio-Pharmaceutical, Zhuhai, China) twice daily for 4 days (hereafter, LHG); while 2940 nm Er:YAG lattice laser and bFGF gel twice daily for 4 days (hereafter, LG) were applied to the right orbital area as the control. This therapy was explained to the patient and he provided written informed consent prior to the procedure. The VISIA® facial image analysis system (Canfield Scientific, Parsippany, NJ, USA) was used to monitor the periorbital areas on days 1, 4, 7, and 30 after treatment. The LHG therapy improved postoperative swelling and pigmentation compared with the LG therapy (: A2–A5, B2–B5). Noticeably, the wrinkles on the LHG side on day 30 were obviously improved, while the control side had more wrinkles because of the unsmooth wound surface caused by crusts (: C2, D2). LHG therapy accelerated the wound healing process as it effectively reduced the blood vessels due to the laser treatment (: C3–C5, D3–D5).
The patient agreed to the publication of his case report and written consent was obtained. The publication was approved by the Ethics Committee of the Fifth People's Hospital of Hainan Province. The case report conforms to the CARE guidelines.


An 85-year-old female patient was referred to our department for the evaluation of a mass in the right upper lobe (Figures and [same as ], ) on chest computed tomography (CT) before lumbar spine surgery at the Department of Orthopedics. The patient was a non-smoker with a medical history of dyslipidaemia and hypertension, and a family history of gastric cancer. Histological examination via fibreoptic bronchoscopy revealed an adenocarcinoma, harbouring ROS1 rearrangement, with multiple brain metastases (Figure ). The clinical stage was cT1cN3M1c (BRA), stage IVB. The ROS1 rearrangement was diagnosed by next-generation sequencing (Oncomine Dx Target Test Multi-CDx system, Life Technologies Corporation Japan).
She was initially treated with crizotinib 250 mg twice daily. The primary tumour resulted in a partial response (PR) on day 33 after crizotinib administration, and brain metastases exhibited a complete response without any radiotherapy on day 38. She developed crizotinib-induced nausea and vomiting on day 8 (grade 1 by Common Terminology Criteria for Adverse Events [CTCAE] ver. 5). On day 57, this worsened to CTCAE grade 2. The dose was then reduced to 250 mg daily. DI-ILD due to crizotinib was documented on chest CT on day 115 (Figure ), when the PR of the primary tumour was maintained (Figure ). Thereafter, crizotinib was discontinued, and treatment with prednisolone at 30 mg/day was initiated and tapered to 10 mg/day in 10 days, which was continued to prevent the flare of DI-ILD. DI-ILD responded well to prednisolone, and entrectinib was introduced as the second-line treatment 15 days after crizotinib cessation. She lost weight during crizotinib treatment. Her height, body weight and body surface area (BSA), calculated using the Fujimoto formula at the time of entrectinib initiation, were 148 cm, 56 kg and 1.43 m2, respectively. Infants receive entrectinib at 300 mg/m2. Based on this, the patient received entrectinib at a dose of 400 mg once daily to account for her age, BSA and small physique. Tumour shrinkage with a marginal response was observed on day 28 after entrectinib initiation (Figure ). The patient has continued receiving treatment 6 months after entrectinib initiation without any adverse events.