A 51-year-old Caucasian male, was diagnosed by his General Practitioner with subclinical hypothyroidism in 2010 based on an elevated thyroid stimulating hormone level [10.7 mU/L, normal reference (NR) 0.40-3.50], normal FT4 and FT3 levels, and elevated thyroid peroxidase antibodies (604 IU/mL, NR 0-35).
His other medical conditions included hypertension, thalassemia minor, impaired glucose tolerance and cholecystitis. The patient was started on thyroxine 50 mcg daily (0.52 mcg/kg/day), and his TSH decreased to 4.09 mU/L after 6 months and then normalized to 2.99 mU/L. After an intervening normal TSH level, indicating adequate thyroxine replacement, the patient reported weight loss and restlessness in July 2016. His biochemistry was in keeping with hyperthyroidism with suppressed TSH (<0.005 mU/L) and elevated FT4 (18.8 pmol/L, NR 9-19) and FT3 (30.5 pmol/L, NR 2.6-6 ). His thyroxine dose was reduced before being totally discontinued by his General Practitioner. Thyroid function tests at this time showed TSH <0.005 mU/L (0.40-3.50), FT4 30.5 pmol/L (NR 9-19) and FT3 19.2 pmol/L (NR 2.6-6).
After 6 months there was little change in his thyroid function tests and he was commenced on propranolol 20 mg daily and referred to a local endocrinologist. On examination, he had a diffuse, mobile goiter, blood pressure of 135/80 mm Hg and a heart rate of 75 bpm with a weight of 95 kg with a BMI of 29.3. He appeared clinically euthyroid with no signs of dermopathy, acropachy, proximal myopathy or ophthalmopathy. A thyroid ultrasound revealed heterogenous echogenicity and increased vascularity (). A pertechnetate uptake scan showed elevated thyroid uptake, consistent with Graves’ disease (). TSH receptor antibody (TRAb) titer was elevated at 15.3 IU/L (NR <2 ). Anti TPO at this time was 407.
He was given advice on precautions regarding agranulocytosis and commenced on carbimazole 15 mg daily. After 6 weeks of treatment with carbimazole, his thyroid function tests continued to show suppressed TSH of <0.005 mU/L with raised FT4 and FT3 of 26.4 pmol/L and 12.2 pmol/L, respectively. His total daily dose of carbimazole was then increased to 25 mg. However, he was subsequently admitted to the local hospital with agranulocytosis and fever of unknown origin twenty six days after the dose of carbimazole was increased. Blood tests on admission showed white cell count (WCC) of 1.2 x109/L and neutrophils of 0 x 109/L. carbimazole was stopped and he was initially treated with filgrastim 300 mcg daily injections, intravenous cefepime 2 g QID for five days and a once-only dose of gentamicin 400 mg. Due to ongoing fever he was also commenced on vancomycin 1.5 g BID for three days concurrently. At this same time his dose of propranolol was increased to 20 mg BID. Subsequently, his neutrophil count improved on day 5. Finally, he was administered Lugol’s iodine BID for 10 days and then underwent total thyroidectomy. Histological diagnosis was Graves’ disease (). Further analysis revealed chronic lymphocytic thyroiditis and oncocytic metaplasia (). He is currently on thyroxine 150 mcg daily.


A 50-year-old female with refractory high-grade neuroendocrine carcinoma of the retroperitoneum currently cycle 2, day 8 of an ICI combination Phase I clinical trial, presented to the emergency center through ground ambulance with new-onset grand mal seizure with generalized tonic-clonic activity, severe headache, nausea, and vomiting. Of note, the patient's family reported a 2-week history of poor oral intake of food and water by the patient. The patient received Versed in route to the hospital. On arrival, the patient did not have any seizure activity and was arousable but confused. Physical examination in the emergency center revealed: heart rate of 139/min, blood pressure of 132/95 mmHg, respiration rate of 18/min, temperature of 36.7°C, and oxygen saturation of 100%. Blood work demonstrated glucose of 106, CO2 of 21, chloride of 98, potassium of 3.6, sodium of 134, creatinine of 4.95, magnesium of 2.3, ammonia of 29, lactic acid of 0.6, antineutrophil antibody vasculitis panel negative, and ANA titer <1:40. Magnetic resonance imaging (MRI) of the brain without contrast showed scattered, symmetrical T2 fluid-attenuated inversion recovery hyperintensity within bilateral posterior cerebral hemispheres without associated infarct or hemorrhage. In the emergency center, the patient was treated with Ativan and Keppra intravenously (IV), a consult was placed for neurology. Subsequently, the patient was placed on Vimpat 100 mg twice/day orally. She did not have any additional seizure episodes and did not require any immunosuppressants. While hospitalized, the patient became hypertensive, with systolic blood pressures ranging between 140 and 170 mmHg. The patient was initially started on Hydralazine 50 mg three times a day and Labetalol 20 mg every 8 h as needed, which was later changed to Nifedipine 20 mg daily with adequate control of blood pressure. A nephrologist was consulted to manage the acute kidney injury (AKI). Renal ultrasound showed increased renal echotexture. Lactic acidosis, starvation ketosis, and infection were ruled out as a cause of the AKI. The patient was treated with gentle IV hydration. She made a full recovery and was discharged from the hospital. Subsequently, she was seen in the clinic with a follow-up MRI of the brain, which showed complete resolution of the T2 abnormality. Nonetheless, the patient was removed from the Phase I clinical trial secondary to PRES. Informed consent was obtained from the patient.


A 3-year-old boy was admitted to the city children’s hospital with complaints of fever up to 40.5°C, single vomiting and limping on the right leg. The first symptoms were reported 7 days before the admission. They included temperature rise of up to 38.5°C and a single macular spot on the right shin. Four days later the boy started limping on his right leg. There was an increase in his body temperature up to 40°C every day.
He was born after a first full-term pregnancy, complicated by dysfunction of the placenta and polyhydramnios via spontaneous vaginal delivery, weight 2900 g. The delay in psychomotor development occurred: he started balancing his head at 6 months, sitting at 10 months, walking at 20 months.
Taking into account high temperature and vomiting, acute meningitis was suspected at the time of his hospital admission. Laboratory testing revealed anemia – hemoglobin (Hb) 10.2 g/dl, leukocytosis 25,600/µl, an erythrocyte sedimentation rate (ESR) of 28 mm/h, C-reactive protein (CRP) 26.8 mg/dl, anti-streptolysin O (ASO) level of 200 IU (reference value < 150 IU) (). Ferritin level was normal 289.7 ng/ml. Spinal puncture with cerebrospinal fluid analysis allowed to rule out meningitis. Upon the results of lab tests, antibiotic therapy was prescribed.
A day later a few other symptoms appeared. The boy got erythematous macular rash on the back, chest and around the right elbow and there was the swelling of the right ankle. Acute rheumatic fever (ARF) was also considered, taking into account fever, transient arthritis and the results of laboratory tests.
However, the patient’s age, lack of data for previous streptococcal infection and ineffectiveness of antibacterial therapy rejected this diagnosis. Immunoglobulin M to the measles and rubella were also negative. Therefore, the rash was considered as a medication allergic reaction and intravenous prednisolone was prescribed for 5 days, then the patient took oral prednisolone in the dose 1 mg/kg/day, and the intensity of rash decreased.
Despite the treatment the patient continued to be febrile once a day, but not every day, and a transient abdominal pain occurred; therefore, leukemia was decided to be excluded. After nine days of the glucocorticoid treatment, prednisolone was rapidly interrupted for one day and bone marrow puncture was performed. Bone marrow test was normal.
On the second day after prednisolone interruption, generalized tonic-clonic seizures with a loss of consciousness and coma over the next 3 days developed. Laboratory testing detected leukocytosis 14,600/µl, anemia (Hb) – 9.1 g/dl, increased levels of lactate dehydrogenase (LDG) – 646.0 U/l, alanine aminotransferase (ALT) – 68 U/l (reference < 37 U/l), aspartate aminotransferase (AST) – 58 U/l (reference < 40 U/l), and ferritin (1389 ng/ml), fibrinogen level was 3.13 g/l (reference 2–4 g/l). Bilirubin and electrolytes were normal. Acute encephalitis was also suspected. Herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Lyme borreliosis were ruled out.
A cranial computerized tomography (CT) scan revealed cerebral edema, purulent otitis media, and cortical atrophy. Lincomycin (due to purulent otitis media), intravenous methylprednisolone (10 mg/kg/day for 5 days), and intravenous immunoglobulins 1 g/kg were prescribed. On the background of the pulse therapy the temperature normalized, the rash disappeared.
The patient was referred to the neurological department of the regional hospital due to seizures and suspected encephalitis. He was presented with enlarged cervical lymph nodes, transient elbow swelling, hepatosplenomegaly, tachycardia and severe sluggishness. Thickened layers of the pericardium was detected on the thoracic CT. Neurological symptoms as movement limitation at the left forearm and hand, speech problems were observed, and they were slowly resolved.
Oral methylprednisolone in the dose of 1 mg/kg was continued. The attempts to reduce the corticosteroid doses were accompanied by the appearance of fever, macular rash on the trunk and extremities and joint pain. Rheumatoid factor (RF) and antinuclear antibodies (ANA) were negative (). Antinuclear antibodies-screen for the most often systemic inflammatory connective tissue diseases and human leukocyte antigen (HLA) B27 were negative.
Taking into account quotidian fever, transient erythematous rash, lymphadenopathy, arthritis and arthralgia, hepatosplenomegaly, serositis sJIA was diagnosed (). Oral methylprednisolone in the dose of 1 mg/kg/day was prescribed. Neurological symptoms were suggested as encephalopathy on the background of autoimmune disease, but encephalitis was not completely excluded.
Further examination revealed a significant increase of ALT 1842 U/l, and AST 1310 U/l and decrease of fibrinogen level to 2.2 g/l. The bilirubin level was within normal range.
Enzyme-linked immunosorbent assay and polymerase chain reaction excluded viral etiology of hepatitis. Increased levels of thallium and arsenic were found in blood and hair samples, which suggested poisoning. However, we couldn’t detect the causes of the poisoning, and these microelements were normal in all family members.
On the background of glucocorticoid therapy during the next 6 months patient’s general condition improved, all symptoms of JIA disappeared and methylprednisolone was discontinued. However, generalized tonic-clonic seizures recurred 3–4 times a month. Symptomatic epilepsy was diagnosed and valproic acid was prescribed.
After eight months of remission, the boy’s condition again worsened. He was admitted to the regional children’s hospital with complaints of fever up to 38°C, joint pain, abdominal pain and sluggishness. The boy was sick for the last one day. Further unstable macular rash on the trunk and extremities, limping on the left leg, transient arthritis of both knees and right ankle developed.
Laboratory testing estimated slight leukocytosis 9,700/µl, ESR of 10 mm/h, CRP 21.56 mg/dl, significantly increased ferritin level 1645 ng/ml. Increased value of ALT 167 U/l and AST 104 U/l was detected.
Ultrasound examination of both knees confirmed bilateral synovitis. Thallium and arsenic levels in blood and hair samples were normal. Oral methylprednisolone was prescribed in the dose of 1 mg/kg/day for 2 months with the further gradual dose reduction. The symptoms of JIA did not recur for the next 2 years after this therapy.
The patient demonstrates a decrease in cognitive functions, hyperactivity, and euphoria. He continues valproic acid intake due to his epilepsy. Taking into account unusual course of sJIA on the background of neurological changes, we suggested a genetic pathology. Whole exome sequencing found the mutation in ATP6V0A1 gene that can be contributed to his neurological condition and need to be experimentally validated.


A 6-year-old girl was admitted to the regional children’s hospital because of having a fever for 2 weeks. A fever was accompanied by erythematous macular rash, cervical, thoracic spine pain, left wrist and right ankle swelling.
From the history it is known that arthralgia and spine pain developed a few months before the hospital admission. Two weeks before the admission a fever appeared and spine pain became more severe, the erythematous rash occurred on the peaks of fever and disappeared within a few hours when the fever decreased. The patient was treated in the infectious disease department by antibiotics without effect.
Physical examination revealed cervical lymphadenopathy, an enlarged liver (+2 cm), tachycardia, swollen and painful left and right knees, left wrist and right ankle. Laboratory testing revealed leukocytosis 15,300–63,600/µl, an ESR of 20–25 mm/h, CRP (98.1–139.8 mg/dl). Rheumatoid factor and ANA were negative. Serum level of creatine kinase (CK) was normal, LDG (369.0–479.4 U/l) ().
Ultrasound examination revealed the signs of left hip, left and wright knee bursitis and synovitis, left wrist synovitis. Chest X-ray was normal. Antinuclear antibodies-screen for the most often systemic inflammatory connective tissue diseases and HLA-B27 were negative. Taking into account fever that the patient was having for more than 2 weeks, arthritis, typical rash, cervical lymphadenopathy, hepatomegaly, sJIA was diagnosed. Methylprednisolone was administered intravenous for 5 days, than – oral in the dose of 1.0 mg/kg/day. This dose didn’t control a fever; therefore, it was increased to 1.5 mg/kg/day.
The patient’s condition became better, body temperature was normal for 4 days, the rash was not observed. On the 17th day of corticosteroid treatment the child became ill with measles and the fever occurred again. The patient was treated in the infectious disease department for 7 days. The dose of methylprednisolone was reduced. The patient continued to have fever; therefore, she was referred to rheumatology department.
Laboratory examination revealed leukocytosis 26,240/µl, an ESR of 64 mm/h, CRP 277.25 mg/dl, thrombocytosis 492,100/µl. The onco-hematological diseases were ruled out as the bone marrow and abdominal CT was normal. The patient condition deteriorated: a fever increased to > 39°C, severe arthralgias, myalgias and dyspnea developed.
Leukocytosis and thrombocytosis increased up to 51,000/µl and 674,100/µl respectively, an ESR was 30 mm/h, CRP – 26,5 mg/dl. Ferritin level increased () and procalcitonin test was normal.
The signs of pericarditis were revealed by echocardiography, pleuritis – on the chest X-ray. Pulse intravenous methylprednisolone therapy was administered for 3 days, then oral methylprednisolone 2 mg/kg/day and subcutaneous methotrexate 15 mg/m2 were added.
The patient’s condition gradually became better. But the attempts to reduce the dose of methylprednisolone to maintenance (6–8 mg/day) provoked an exacerbation. Currently the patient has started intravenous tocilizumab intake (8 mg/kg/2 weeks) and methylprednisolone is being gradually discontinued.


A 12-year-old girl was admitted to the infectious disease department of our hospital because of a fever of unknown origin, headache, and migratory arthralgia in elbow and knee joints, morning stiffness about 15 minutes. The symptoms developed 6 days before the admission with febrile fever and headache, in 5 days arthralgia joined.
Physical examination revealed slightly painful left elbow and both knee joints without swelling. Lung and heart sounds were normal. Mild hepatosplenomegaly was found. Taking into account neutrophilic leukocytosis 14,600/µl, 80% (11,168/µl) of neutrophils, antibiotic treatment was prescribed. Despite this treatment, the fever continued with the temperature rise up to 39°C.
The results of laboratory testing showed an increase of leukocytosis 30,620/µl, lymphopenia 0,594/µl, ESR of 58 mm/h, anemia – Hb 11.0 g/dl, increased levels of CRP, ferritin, LDG (), ASO 1258 IU/ml (reference < 150 IU/ml).
Procalcytonin serum concentration was normal. Herpes simplex virus, CMV, EBV, toxoplasma, mycoplasma, chlamydia, ureaplasma, hepatitis B and C viruses infectious were ruled out. Antinuclear antibodies and ANA-screen for the most often systemic inflammatory connective tissue diseases were negative. Rheumatoid factor was doubtful (14.2 IU/ml – reference up to 14.0 IU/ml), but anticyclic citrullinated peptide (ACPA ) was normal. Rheumatoid factor after 3 months was also normalized. Blood calprotectin level was 24 µg/ml ().
Taking into account fever, arthralgia, hepatosplenomegalia and the results of laboratory tests oncohematological diseases were considered to be excluded. The bone marrow was normal, chest and abdominal CT confirmed hepatosplenomegaly and revealed pericarditis and lymphadenopathy. Ultrasound examination revealed the signs of left elbow synovitis and left knee bursitis and synovitis.
Taking into consideration fever that the patient was having for 2 weeks, arthritis, hepatosplenomegaly and serositis, systemic JIA was diagnosed. Oral methylprednisolone 1 mg/kg/day and subcutaneous methotrexate 15 mg/m2/week were prescribed. The patient responded to the treatment. In six weeks the full dose of the methylprednisolone was reduced, and in 9 months it was completely discontinued. Currently the patient is in remission and continues taking methotrexate.


A 16-month-old girl was referred from the infectious disease department on the 15th day from the disease onset because of fever and ineffective antibacterial therapy. Child’s mother complained of body temperature that was increasing to more than 39°C once or twice a day (in the morning and in the evening) and was returning back to normal between fever peaks that were accompanied by an erythematous macular rash. The rash appeared on the trunk, extremities and buttocks and it increased at the peak of temperature. Physical examination revealed a few hyperpigmented lesions (“coffe-with-milk spots”) on the child’s skin, a typical macular rash, joint hypermobility, slightly enlarged liver and cervical lymph nodes. There were no signs of arthritis.
The laboratory values were significant for leukocytes, ESR, platelets, CRP and LDG (). Anemia was revealed Hb 9.7 g/dl, and procalcitonin test was normal. Antinuclear antibodies and RF were negative. Antinuclear antibodies-screen for the most often systemic inflammatory connective tissue diseases was also negative. Blood calprotectin level was 92.6 µg/ml. The abdominal ultrasound examination revealed hepatosplenomegaly.
Oral methylprednisolone 1 mg/kg/day was prescribed according to the circadian rhythm, but fever continued to rise once a day at night; therefore, the dose was increased to 1.5 mg/kg/day and it was given in 4 divided doses throughout the whole day. This allowed to achieve the remission.
During the 10 months of follow-up, there was only one flare on the background of a viral infection (4 months after the therapy started, in a dose of methyl-prednisolone 4 mg/day), which was accompanied by fever, rash and arthralgia and required to increase the glucocorticoid doses to 1 mg/kg/day for one week and then again gradually reduce to 4 mg/day. Currently this dose is enough to control fever and inflammation.


A 33-year-old male was admitted with ongoing fever and progressive fatigue. His medical history revealed a congenital corrected transposition of the great arteries, congenital atrioventricular block, tricuspid valve replacement (Medtronic Mosaic®) at the age of 19, and progressive heart failure for which heart transplantation was considered. In the years before admission, echocardiography revealed progressive deterioration of left ventricular function as well as severe degeneration of the tricuspid (system AV−) valve bioprothesis, resulting in severe regurgitation and moderate stenosis.
At first, blood cultures revealed Streptococcus mutans, but no endocardial vegetations valve were observed on transoesophageal echocardiography. Because infectious endocarditis was still clinically suspected, treatment was started with IV Ceftriaxone for 6 weeks. Short after admission he also tested positive for active Q fever infection based on phase I and phase II IgG titres of 1:32 768, as well as positive C. burnetii polymerase chain reaction (PCR) on plasma. Initial Q fever treatment consisted of doxycycline in combination with hydroxychloroquine. The latter drug was not well tolerated because of nausea and antibiotic treatment was changed to a combination of doxycycline and rifampicin. Subsequently, the use of rifampicin led to acute liver failure. Therefore, again another antibiotic regimen had to be selected, resulting in the combination of doxycycline and moxifloxacin orally.
After successful antibiotic treatment, resulting in negative blood cultures for S. mutans, both serology and PCR on plasma confirmed an active invasive infection with C. burnetii. A positron emission tomography-computed tomography (PET-CT) demonstrated increased fluorodeoxyglucose uptake around the tricuspid valve prosthesis suggestive of active endocarditis, possibly due to persisting Q fever (). Due to the critical fact that the infection was limited strictly to the heart and no other spots for infection were revealed, it was decided to place the patient on the waiting list for heart transplantation, while antibiotic treatment with doxycycline and moxifloxacin was continued. Despite repeatingly positive C. burnetii EDTA plasma PCRs and phase I IgG antibody titres, a successful heart transplantation was performed, 2 years after initiation of antimicrobial Q fever treatment. Examination of the explanted heart did not reveal endocardial vegetations but confirmed the C. burnetii endocarditis of the tricuspid valve prosthesis (). Fortunately, C. burnetii PCRs on plasma samples taken in the weeks post-transplantation were all negative, supporting the hypothesis that the Q fever infection was confined to the explanted heart. However, to minimize the risk of relapse, it was decided to continue antimicrobial Q fever treatment during the 1st year post-transplantation, consisting of doxycycline in addition to the immunosuppressive medication. All consecutive PCRs performed on plasma and donor heart tissue after transplantation remained negative and serology titres declined gradually (Timeline). One year after transplantation doxycycline was stopped, after which C. burnetii phase I IgG titres remained low and plasma PCRs remained negative.
The patient is now 5 years after transplantation and still in an excellent clinical condition.


A 50-year-old man was admitted to our hospital after resuscitation using an automated external defibrillator following cardiac arrest due to VF. He suddenly collapsed at 11 a.m. while shopping. The emergency medical service team arrived and applied an automated external defibrillator. The documented rhythm was VF that was successfully terminated via a defibrillator shock. There was no family history of syncope or sudden cardiac death. Physical examination on initial presentation revealed normal heart sounds without any murmurs on cardiac auscultation, no rales on respiratory auscultation and no pitting oedema. He was standard height and weight. Thoracic echocardiography indicated good ventricular function without valvular disease. Coronary angiography did not identify any significant stenosis. Based on these results, the patient was diagnosed with idiopathic VF. The patient did not require pacing. Moreover, considering future risk of lead-related complications such as venous obstruction and infection, we believed that S-ICD was more suitable than TV-ICD. A decision was made with him, and S-ICD implantation (EMBLEM, Boston Scientific, Marlborough, MA, USA) was performed for secondary prevention of sudden cardiac death.
The surface electrocardiography screening test for all vectors [primary (proximal electrode ring to can), secondary (distal electrode ring to can), and alternate (distal to proximal electrode)] was positive. Implantation was performed under general anaesthesia using the three-incision technique. The ICD coil was inserted into the standard left parasternal position, and the pulse generator was placed between the anterior surface of the serratus anterior muscle and the posterior surface of the latissimus dorsi muscle by detaching the fibrous tissue in the left mid-axillary line (). Immediately after S-ICD implantation, there was no sensing failure or noise in any vector. The device automatically selected the primary vector, and one shock zone at 170 b.p.m. and back-up pacing after shock were programmed. After the 2nd DFT, we set the shock zone and conditional zone at 220 and 200 b.p.m., respectively.
To perform DFT, VF was induced using a 50-Hz burst via the programmer. Although VF was induced, shock was not appropriately delivered owing to sustained noise (repeated noise markers) with visualization of fine noise on the electrogram superimposed over the fast ventricular events; therefore, external rescue shock was needed at 150 J, and VF was terminated 32 s after induction. Despite sinus rhythm restoration, noise markers persisted in the primary vector (). Therefore, we changed the sensing vector from primary to secondary and performed DFT. Subcutaneous implantable cardioverter–defibrillator could deliver an appropriate shock 17 s after induction and successfully terminated VF at 65 J without noise markers in the secondary vector. During the 2nd DFT, back-up pacing was delivered once after the shock; the sensing vector then automatically switched from the secondary to the alternate vector. However, noise markers were found in the alternate vector despite sinus rhythm restoration (). We changed the vector from alternate to secondary manually and observed that there were no noise markers in the secondary vector. Finally, we deduced that this phenomenon occurred only in specific contexts, such as intraoperative DFT using a 50-Hz burst, and that there were no clinical problems. A treadmill exercise test was performed; however, there was no noise on the electrogram in all the vectors.
Neither appropriate nor inappropriate shocks were delivered during outpatient care after S-ICD implantation.


A 56-year-old male patient (weight 100 kg, height 192 cm) was scheduled for open surgery of supraumbilical and inguinal hernia repair from the right side. Bilateral ESP block was performed before the induction to general anesthesia, at Th10 level with 20 mL 0.25% bupivacaine from both sides. Anesthesia was induced with midazolam 0.04 mg/kg, lidocaine 1 mg/kg, fentanyl 2 μg/kg, propofol 2 mg/kg, and rocuronium bromide 0.6 mg/kg and were same in all patients. It was maintained with sevoflurane (MAC 0.7–1) and additional bolus doses of fentanyl. The total amount of fentanyl was 350 μg. Visual analog scale (VAS) score 2 h after surgery was 2 at rest and 3 on coughing. After surgery, at 6, 12, and 24 h, the pain was 3 at rest and 4 on coughing, thus, 1 g paracetamol was given. 19 h after surgery pain was 10/10 and 100 mg tramadol was given. After 36 and 48 h, the pain was 3 at rest and on coughing, and after 72 h was 2 at rest and on coughing.


A 48-year-old male patient (weight 84 kg, height 186 cm) was scheduled for an ileostomy reversal surgery. ESP block was performed from the left side at the Th8 level with 20 mL 0.25% bupivacaine. The total amount of given fentanyl was 400 μg. After the operation, the patient complained of having pain 5/10 and 1 g metamizole was given. 2 h after operation, the pain was 6 at rest and on coughing, thus, 1 g paracetamol was given. After 6 h, the pain was 3/10 at rest and on coughing, but after 12 h he received 100 mg tramadol (the pain was 6 at rest and 8 on coughing). After 24 h, the pain was 5/10 at rest and 6/10 on coughing, thus, 1 g paracetamol was given, and after 36 h, the pain was 2/10 at rest and on coughing. Pain scores 4/10 at rest and 5/10 on coughing were reported after 48 and 72 h, respectively and 1 g paracetamol was given.


A 67-year-old male patient (weight 70 kg, height 165 cm) was scheduled for open diaphragmatic hernia repair. A bilateral ESP block was performed at the Th8 level. The total amount of fentanyl was 450 μg. 2 h after surgery, patient-reported pain 5/10 at rest and 6/10 on coughing, thus, 1 g paracetamol was given. Pain scores 6, 24, 48, and 72 h after the surgery were the same, 4/10 at rest and on coughing, thus, 1 g paracetamol was given. 12 and 36 h after surgery, patient-reported pain 5/10 at rest and 6/10 on coughing and, thus, 1 g paracetamol was given.


A 65-year-old male (weight 110 kg, height 186 cm) and 54-year-old female (weight 68 kg, height 165 cm) patients were scheduled for laparoscopic cholecystectomy. The total amount of fentanyl given in the male patient was 350 μg and 150 μg in the female patient. 2 h after surgery, the male patient-reported pain 5/10 at rest and 6/10 on coughing, and thus, 1 g paracetamol was given. After 4, 8, and 12 h, the pain was 4/10 at rest and on coughing and 1 g metamizole and 1 g paracetamol were given alternately. 24 h after surgery, the pain was 2/10 at rest and 3/10 on coughing and no analgesic was given. In the female patient, after 1 h of the surgery pain was 5/10 at rest and 6/10 on coughing, and thus, 1 g paracetamol was given. After 4, 8, and 12 h, the pain was 2/10 at rest and 5/10 on coughing and was treated alternately with paracetamol and metamizole. 24 h after surgery pain was 4/10 at rest and 5/10 on coughing, therefore, 1 g paracetamol was given.


A 31-year-old male patient (weight 90 kg, height 187 cm) was scheduled for emergency surgery of acute diverticulitis with abscess. Bilateral ESP block was performed at the Th10 level with 30 mL 0.25% bupivacaine on each side before surgery. The total amount of fentanyl given during surgery was 250 μg. In the postoperative period, at 2, 6, 12, 24, 36, 48, and 72 h, the patient didn't report having pain, pain scores were 0/10 at rest and on coughing, and thus, no analgesic was given.


An 80-year-old male patient, living in a rural area, ex-smoker and social drinker, HIV negative, was referred to the stomatology clinic complaining of lesions on the upper lip, soft and hard palate that had been presented for 9 months, producing severe pain in the affected regions.
The patient underwent two biopsies in other clinical settings with inconclusive results. On physical examination, the right side of the upper lip presented an erythematous swelling associated with a granulomatous ulceration of labial mucosa that extended to the hard palate and seemed to infiltrate to the nasal region [Figure –]. No skin involvement was observed. Cervical lymphadenopathy with inflammatory features as swelling, pain and firm consistency was noticed during palpation.
The clinical hypothesis of tuberculosis, histoplasmosis and SCC were investigated, and an incisional biopsy was performed under local anesthesia. The patient's medical history recorded no relevant data.
The microscopical study evidenced areas of intense diffuse inflammatory infiltrate, with organized areas in the form of granulomas. In addition, the presence of multinucleated giant cells was observed, and a descriptive diagnosis of nonspecific chronic inflammatory process was provided [Figure and ]. Regarding the clinical and histopathological information, the hypothesis of mucocutaneous leishmaniasis was raised, and IDRM test was requested, which confirmed the suspicion. The patient was referred to an infectious diseases specialist to start treatment with Glucantime® (N-methylglucamine antimoniate). The dosage used was 20 mg Sb5 (pentavalent antimonial) +/kg/day intravenously for 30 days. Complete remission of the lesions was observed post treatment and after a follow-up of 12 months the patient remained with no signs of the disease and just a minor cicatricial sequelae.


A 62-year-old male patient, rural worker, smoker, and chronic alcohol user, HIV negative, was referred to the stomatology clinic with upper lip and upper alveolar ridge lesions present for 2 months. During anamnesis, sudden weight loss was reported. Medical history recorded no other important data. Extraoral physical examination showed a cutaneous lesion in the left thigh region [] and along with ulcerated lesions of the nasal mucosa. Cervical lymphadenopathy was undetected on palpation.
Physical intraoral examination revealed ulcerated and irregular lesions in the mucosa of upper alveolar ridge and palate [Figure and ]. An incisional biopsy was performed under local anesthesia considering a differential diagnosis with paracoccidioidomycosis, tuberculosis and leukemia.
Serologies for histoplasmosis and toxoplasmosis were subsequently requested, both resulting in non-reactive antibodies. Therefore, mucocutaneous leishmaniasis was suspected. Histopathologic data showed a non-specific chronic inflammatory process. Immunohistochemistry procedures revealed cells positive for CD68 and Leishmania antigen [Figure and ]. In addition, the positivity of the IDRM test proved the hypothesis. Treatment, therapeutic response and follow-up of this patient were similar to those cited for the previous patient.


A 55-year-old male reported with a chief complaint of a swelling of the lower lip which had been present for the past 4 months []. History revealed that he was apparently symptomless until 4 months ago when he developed this swelling gradually and was treated by a general physician with antibiotics for the same. The swelling did not regress which made the patient seek our consultation, and he currently only complained of the lip swelling. Upon eliciting medical history, we were informed that he was treated for pulmonary TB 4 years ago when he completed his antitubercular treatment (ATT) Directly observed treatment, short course (DOTS) and was certified free of disease. He had a history of smoking 2–5 bidis (country-made cigarettes) in a day for the past 40 years. He also occasionally chewed areca nut and tobacco.
On clinical examination, the lower lip was diffusely swollen measuring roughly 4 cm × 3 cm, but was not involving tissues beyond the normal lip boundaries. No obvious surface changes were observed. On palpation, the consistency was soft with no paresthesia or pain and no discharge of pus or blood. Keeping in mind the age of the patient and the presentation of the lip swelling, an allergy as in the case of a contact allergy or angioneurotic edema was thought of but later ruled out based on the duration and history of the patient where no inciting contact agent could be isolated. With the same history of no associated trauma or inciting event, the diagnosis of a possible foreign-body reaction was ruled out.[]
A blood vessel anomaly was considered. Arteriovenous malformation is a disease with a broad age range. The start of the disease is insidious with the possibility of surface changes in the skin and mucosa. The lesions are usually soft and compressible. The common sites involved are the lip and cheek (80%).[]
Cheilitis granulomatosa could present as an isolated lip swelling. It does not have a definite age, sex and gender predilection. When associated with facial palsy and tongue fissuring, a diagnosis of Melkersson–Rosenthal syndrome may be thought of, but both these signs were not present in our case.[]
Orofacial granulomatosis are a group of diseases based on exclusion and was retained as an important differential diagnosis in the present case. It includes diseases such as Crohn's disease, sarcoidosis and TB. Crohn's disease patients could sometimes develop a diffuse swelling of the lips and face. The patients are usually aged above 40–50 years. Coexisting cobblestone appearance of the mucosa with persistent deep linear ulcerations may be seen sometimes.[] However, the patient did not complain of any associated gastrointestinal symptoms which are invariably associated with Crohn's disease, in which a lip swelling could be the only presentation.
Sarcoidosis could also present as an enlarged lip, but the lack of associated systemic symptoms helped us rule out this entity. TB is very common in South-East Asian countries and should rank high on the list of differentials. The typical presentation is usually an undermined ulcer on the tip of the tongue and less commonly on the lip. In our case, the sole presentation was the lip swelling, but keeping in mind the previous history of treated TB, we retained it as an important differential.[]
Deep fungal infections could also affect the lip but the swelling and associated symptoms are invariably progressive which was in contrast to our case where it was static once it reached the present size 1 year ago.
A tumor of the salivary gland could have been a possibility but the diffuse nature of the swelling ruled it out as minor salivary gland tumors are rather well circumscribed.[]
Idiopathic macrochelia was also thought of in case all advised investigations turned out negative.
After obtaining necessary informed consent, a complete hemogram was performed but no significant deviation from the normal ranges was observed. Due to the financial constraints of the patient, an ultrasonography of the lip was performed which revealed a diffuse area of soft-tissue thickening measuring 40 mm × 18 mm approximately. On color Doppler, the lesion showed both arterial and venous waveforms, with PSV ranging from 15 cm to 25 cm/s which was suggestive of a vascular lesion []. Based on these findings, an aspiration was performed to confirm the vascular nature of the lesion but was found to be negative. This was in contradiction to the ultrasonography findings. We went ahead and performed an incisional biopsy in a hospital setup in anticipation of an inadvertent bleed, with tissue taken from the intraoral labial aspect of the swelling. The biopsy specimen was fixed in 10% formalin to be processed for H and E staining. The stained section showed dense inflammatory infiltrate chiefly composed of lymphocytes in the connective tissue. A few foci of central eosinophilic areas resembling caseation necrosis were seen, surrounded by clusters of epithelioid cells and histiocytes attempting to form giant cells. Many endothelial-lined blood vessels were also seen in the connective tissue. Based on clinicopathological correlation, a diagnosis of a tuberculous granulomatous lesion was arrived at [Figures –].
Keeping in mind our final diagnosis of tuberculous lip swelling and as per the regional guidelines for the management of a patient with TB, he was referred to the Regional TB Treatment Centre where the following investigations were performed: chest radiograph and CB-NAAT sputum examination for acid-fast bacilli (AFB) with TB-polymerase chain reaction being reserved as a second line of investigation if and when required. The chest radiograph revealed involvement with consolidation of the upper lobes []. Sputum examination was positive for AFB in the CB-NAAT. The findings did not necessitate further investigations, and he was started with Category II ATT []. Two-month post-ATT showed a significant resolution of the swelling []. Keeping in mind all the features and results of investigations, we concluded that this case was a reactivated case of pulmonary TB with coexisting oral findings.


A 19-year-old male patient was admitted because of shortness of breath and fatigue. He had no past medical history. Electrocardiogram showed sinus rhythm with a heart rate of 98 bpm. On auscultation, grade 5/6 systolic murmur was heard. Transthoracic echocardiography (TTE) revealed that the ejection fraction (EF) was 60%, 76/42 mm Hg gradient on bicuspid AV with AV area of 0.8 cm2. Other valves were normal in structure, and mild MR was seen. The patient underwent AVR, but no intraoperative transesophageal echocardiography (TEE) was performed after implantation of the prosthetic valve. During intensive care unit follow-up, new-onset severe MR was detected by TTE. TEE was performed to determine the etiology of MR. Two-dimensional (2D) images showed a 4-mm defect on the base of the anterior mitral leaflet (AML), which caused severe MR, together with mild central MR (, , Videos , ). Three-dimensional (3D) TEE, showing MV from the enface view, revealed two different defects on the A2 scallop of the AML, with sizes of 6×3 and 7×4 mm (, ), and 3D color Doppler drop-out artifacts were ruled out, and true defects were confirmed (, ). The patient had no history of IE or fever, and all infective markers were within normal limits. Considering that MR developed just after surgery with multiple defects in the AML, iatrogenic perforation of the AML was concluded. Because the patient was asymptomatic with normal EF and ventricular size, conservative follow-up with medical therapy was recommended. However, dyspnea and heart failure symptoms developed after 3 years of follow-up. The patient was referred for MV surgery. Two defects in the AML were seen intraoperatively, as well as in the 3D images. MV replacement was performed because the repair was not successful. Postoperative TTE revealed normal-functioning mechanical prosthetic AV and MV with normal EF. The patient was discharged uneventfully.


A 2-year-old girl was admitted on account of fever and fast breathing with cough of 2 months' duration. She had progressive weight loss of 1 month. The patient had incomplete vaccination although immunization card was not available. She was the only child of the mother, but the father had two other children for his first wife who is separated. There was no known contact with adult who had cough or weight loss, although her mother routinely takes her to a commercial market where she trades. None of the parents nor patient have been treated for TB in the past. The child and her parents live in a room apartment with a single window; there is no demonstrable evidence of overcrowding. At admission, she was febrile and dyspneic with Grade 2 digital clubbing and had evidence of chronic illness []; other findings were tachycardia and crepitation with tender hepatosplenomegaly. There was no Bacillus Calmette–Guerin scar. Investigation showed anemia, leukocytosis, and elevated erythrocyte sedimentation rate (ESR) of 97 mm/hr Westergren [], but rapid test for human immunodeficiency virus test was nonreactive for the child and her mother. Her oxygen saturation ranged from 91% to 97%, while her chest X-ray showed nodular opacities on lung zones []. GeneXpert was done using the sample obtained from gastric washout, which confirmed RIF-resistant TB. She was transfused following a packed cell volume (PVC) of 19% and had broad-spectrum antibiotics and antifailure drugs. Her posttransfusion PCV was 35%. Parents were adequately counseled on the line of treatment and the need for their screening for TB but they declined. The patient was subsequently referred to a specialized center for the management of DR TB; the parents were later contacted but failed to go to the treatment center.


A previously healthy female (28 years old, right-handed) was admitted to our hospital with intractable nausea.
Medical treatment for nausea failed.
This patient had no history of past illness.
This patient had no other previous medical history.
No neurological deficit or papilledema was observed in her neurological examination.
Laboratory tests were in the normal range.
In her brain magnetic resonance imaging scan, a large fluid collection could be found at the posterior cranial fossa with a size of 6 cm × 7 cm (Figure -).


An 18-year-old boy presented with a history of fatigue, vomiting, abdominal pain, and distension. Computed tomography (CT) revealed a huge mass (13.7×10.7 cm) occupying the left liver and two masses (8.7×7.3 cm, 3.9×2.9 cm) in the pelvic cavity. Multiple lymph nodes were enlarged in right anterior and posterior cardiophrenic angles (). An initial laboratory investigation showed normal bilirubin, slightly elevated aminotransferase levels (aspartate aminotransferase [AST], 85 U/L; alanine aminotransferase [ALT], 154 U/L) and α-fetoprotein (27.2 ng/mL). He was previously healthy with no signs of chronic liver disease and had negative results on serologic testing for hepatitis B (hepatitis B virus surface antigen, hepatitis B virus surface antibody) and hepatitis C (anti–hepatitis C virus). He underwent fine needle biopsy and was diagnosed with FLHCC (). Considering the extent of the tumor, the patient was not considered a candidate for surgical resection. Systemic chemotherapy was initiated with cisplatin (80 mg/m2 on day 1), doxorubicin (30 mg/m2 on days 1 and 2), 5-fluorouracil (5-FU; 400 mg/m2 on days 1–4), and interferon-α (5×108 U/m2 on days 1–4). At midnight on day 3 of chemotherapy, the patient became agitated and was walking and running around the ward, not responding to verbal stimuli. Laboratory testing revealed a serum ammonia level of 393 μg/dL, AST/ALT level of 201/126 U/L, and total bilirubin level of 0.3 mg/dL. Head CT did not reveal any significant findings. He was diagnosed as HAE, and chemotherapy (4th dose of 5-FU and interferon-α) was stopped. Treatment with rifaximin and lactulose was initiated. However, his serum ammonia level rapidly increased to 500 μg/dL, and his mental status deteriorated to the semicoma state.
The patient was transferred to the intensive care unit (ICU) and was on mechanical ventilator support under sedation using midazolam, remifentanil, and vecuronium. The metabolic and genetics department was consulted, and treatment for hyperammonemia was started as follows: (1) continuous venovenous hemofiltration, (2) intravenous infusion of sodium benzoate at a loading dose of 8.8 g (170 mg/kg), followed by continuous infusion (8.8 g/day) and sodium phenylbutyrate (5 g four times a day, via Levin tube), (3) 20% dextrose for caloric intake (6 mg/kg/min), and (4) administration of lactulose and rifaximin via Levin tube. His ammonia level decreased to 164 μg/dL but rebounded to 442 μg/dL on the third day of ICU care. Sodium benzoate (8.8 g) was loaded again, and his ammonia level decreased to 135 μg/dL. On the sixth day of the above-mentioned treatment, continuous venovenous hemofiltration was discontinued. On the eighth day, the patient was extubated, and sodium benzoate/sodium phenylbutyrate administration was changed to an intermittent schedule, with sodium benzoate 1.8 g administered as intravenously every 8 hours, sodium phenylbutyrate 3 g four times a day, and arginine 2.5 g twice a day. He was started on a low-protein diet (1 g/kg/day) through a Levin tube. Two days later (10th day of ICU care), he became disoriented and could not properly respond to verbal stimuli, with an ammonia level of 173 μg/dL. The low-protein diet was discontinued, and a continuous infusion of sodium benzoate (5.5 g/day, after a loading dose of 5.5 g) was started again, as well as citrulline (5 g three times a day). There were no focal neurologic signs, and brain magnetic resonance imaging (MRI) did not reveal any abnormality. As the serum ammonia level started decreasing (59 μg/dL), his conscious level improved. On the 12th day, he started Levin tube feeding and oral medications (sodium phenylbutyrate 6 g/day, L-carnitine 2,550 mg/day); citrulline was discontinued. On the 14th day of ICU care, sodium benzoate infusion was changed to an intermittent schedule (1.8 g every 8 hours). He resumed the low-protein diet (0.5 g/kg/day), and his ammonia level was maintained in the range of 90–100 μg/dL. He was transferred to a general ward on the 16th day of ICU care, and sodium benzoate was changed to an oral form (3 g three times a day). With sodium benzoate, sodium phenylbutyrate (3 g three times a day), arginine (2.5 g twice a day), and L-carnitine (660 mg once daily), his ammonia level further decreased to 50–60 μg/dL (). On the ninth day at the general ward, laboratory analyses were performed to identify the underlying mechanism of his HAE. The patient’s serum amino acid analysis revealed the following findings: decreased citrulline and ornithine, normal alanine and glutamine. His urine orotic acid level was elevated, and serum acylcarnitine was slightly elevated. These results suggested impaired activity of ornithine transcarbamylase (OTC). However, polymerase chain reaction (PCR) and direct sequencing of the OTC gene did not reveal any pathogenic variant, deletion, or duplication.
On the 20th day at the general ward, the patient underwent a second course of chemotherapy involving cisplatin+doxorubicin+5-fluorouracil+interferon-α. One month later, he underwent extended left hemihepatectomy en bloc with the caudate lobe, excision of pelvic mass, and peritoneal seeding. Extensive lymph node dissection was also performed at the hepatoduodenal, cardiophrenic, para-aortic, and pelvic lymph nodes. Immunohistochemical staining confirmed a profile consistent with that of FLHCC, that is, positive for cytokeratin 7, glypican 3, and CD68. We did not test for the DNAJB1-PRKACA fusion. Next-generation sequencing (NGS) was performed to identify actionable therapeutic targets but only revealed APC mutation (c.4666delA, p.T1556fs), with an allele frequency of 15.53%. His postoperative period was uneventful and the ammonia level further decreased (30–40 μg/dL). One month after the surgery, treatment for hyperammonemia was discontinued. He received two additional courses of chemotherapy involving cisplatin+doxorubicin+5-FU+interferon-α. However, CT and MRI obtained 3 months after the surgery revealed enlarged left external iliac lymph nodes and multiple enhancing nodules at the perihepatic, perigastric, mesentery, omentum, and pelvic cavity. The chemotherapy regimen was changed to vincristine (1.5 mg/m2 on days 1, 8)+irinotecan (50 mg/m2 on days 1–5) and then to gemcitabine (1,000 mg/m2 on day 1)+cisplatin (20 mg/m2 on days 1–5). CT performed after three courses of gemcitabine+cisplatin showed a decrease in the size of the peritoneal nodules and iliac lymph node. Furthermore, the patient experienced severe, recurrent abdominal pain with vomiting, and CT images suggested obstructive ileus. Exploratory laparotomy was performed, and multiple adhesive bands were dissected off the small intestine and excised. Additionally, two metastatic nodules were resected. At the time of this report writing, the patient had just completed the sixth course of gemcitabine-cisplatin, and his disease was stable. He is on normal regular diet and his ammonia level remains normal (30–40 μg/dL).


A 64-year-old man presented with a wide-necked right middle cerebral artery (MCA) aneurysm that was discovered during evaluation for minor head trauma. He was neurologically intact. His right MCA bifurcation aneurysm measured 6 mm. Stent-assisted coiling was planned. The patient was started on dual antiplatelet therapy 5 days before the planned procedure. Two microcatheters were used (SL-10, Stryker, Fremont, CA, USA). The first microcatheter was used to deliver and deploy an Atlas stent (Stryker) across the aneurysm neck, while the second microcatheter was positioned inside the aneurysm sac. First, two coils (6 mm × 20 cm Target, Stryker, and 4 mm × 8 cm MicroPlex, MicroVention-Terumo, Tustin, CA, USA) were deployed smoothly; however, a third coil (4 mm × 8 cm MicroPlex) was deployed after overcoming some resistance. Postcoiling contrast injection showed extravasation from the aneurysm dome. We brought the SL-10 microcatheter back into the M1 segment and deployed a 5 mm × 15 cm MicroPlex coil into that segment, proximal to the aneurysm. The effect of the heparin was reversed with intravenous protamine (30 mg). A subocclusive state was achieved, allowing hemostasis. The coil was retrieved after cessation of contrast extravasation was confirmed with an internal carotid artery (ICA) injection. Final angiographic runs demonstrated good wall apposition of the stent with a coil-packing density of nearly 30%. Postprocedural computed tomography (CT) showed subarachnoid hemorrhage (SAH), but the patient returned to his preoperative neurological status and was discharged on the first postoperative day. The technique is demonstrated in Video 1 and Figure - and illustrated in the schematic diagram, .


A 58-year-old woman presented with Hunt-Hess Grade V and Fisher Grade IV SAH. A CT angiogram showed a 4-mm ruptured right-sided posterior inferior cerebellar artery (PICA) aneurysm. We transferred the patient to the angiography suite for primary coiling. Right vertebral artery injection confirmed a 4-mm PICA aneurysm with a daughter sac arising from the aneurysm neck. A 4 mm × 15 cm HyperSoft three-dimensional (3D) coil (MicroVention-Terumo) was deployed in the aneurysm using a 0.0165” Prowler LP-ES microcatheter (Codman Neuro, Raynham, MA, USA). Postdeployment contrast injection showed herniation of the coil loop from the daughter sac along with some contrast extravasation. At this point, the microcatheter was pulled back into the lumen of the V4 segment of the vertebral artery. Coiling of the V4 segment was performed to produce a subocclusive state. Intravenous protamine (30 mg) was administered immediately to reverse the effect of the heparin administered at the beginning of the procedure. After cessation of extravasation was confirmed with a repeat contrast injection, the temporary coil deployed in the V4 segment was retrieved. At this point, the microcatheter was navigated into the aneurysm sac and coiling was completed by placing two 2 mm × 4 cm HyperSoft 3D coils. Postprocedural head CT showed no significant increase in the amount of SAH. The patient's postprocedural course was complicated by vasospasm and a persistent comatose state. Due to the lack of postprocedural recovery, care was withdrawn at the request of the patient's family 14 days after the initial procedure. The technique is shown in Figure -.


A 60-year-old woman presented with Hunt-Hess Grade III and Fisher Grade III SAH. A CT angiogram demonstrated a 4-mm A1–A2 aneurysm. She was taken for primary coiling. A right carotid injection confirmed a 4 mm × 5 mm multilobulated anterior communicating artery aneurysm. A Prowler 14 microcatheter (Codman Neuro) was advanced into the right A1 segment and into the aneurysm, and one 5 mm × 10 cm Galaxy coil (Codman Neuro) was deployed into the aneurysm. Subsequently, two more coils (4 mm × 6 cm and 3.5 mm × 9 cm Galaxy) were deployed into the aneurysm. Contrast extravasation was noticed after the deployment of the last (third) coil. A 6 mm × 10 cm Galaxy coil was delivered into the right A1 and ICA terminus but not detached to produce a subocclusive state. The coil was recaptured without detachment. A repeat contrast injection showed no extravasation or vessel injury, with excellent flow into the right A1 and M1. Postprocedure head CT showed a slight increase in SAH with minor intraventricular hemorrhage. The patient made an excellent recovery and was neurologically intact at 1-month follow-up. The technique is shown in Figure -.


A 1-year-old male presented at the Orthopaedic Outpatient Clinic of National
Taiwan University Hospital, in June 2009, with a 2-week history of limp, fever
and difficulty in moving the left leg. At the emergency room, a physical
examination showed no gross deformity, swelling, skin lesion, pitting oedema or
local tenderness at the left leg. There were no recent body weight loss,
jaundice, polyuria or palpable lymph nodes noted. Except for leucocytosis, all
laboratory values were within reference range (white blood cell (WBC) count,
14.67 × 103/µl; red blood cell (RBC) count,
4.17 × 106/µl; haemoglobin (Hb), 11.5 g/dl; haematocrit (HCT), 34.2%;
mean corpuscular volume (MCV), 82.0 fl; mean corpuscular haemoglobin (MCH), 27.6
pg; MCH concentration (MCHC), 33.6 g/dl; platelets, 363 × 103/µl;
aspartate aminotransferase, 28 U/l; alkaline phosphatase, 121 U/l; lactate
dehydrogenase (LDH), 220 U/l; and creatinine (CRE), 0.4 mg/dl). Plain
radiography revealed a radiolucent lesion at the left proximal tibial
meta-diaphysis with periosteal reaction (). Osteomyelitis was
suspected and the patient underwent curettage of the lesion and grafting with
tobramycin-impregnated OSTEOSET® T Bone Graft Substitute (Wright Medical
Technology Inc., Arlington, TN, USA; ). The pathology report
revealed diffuse mononuclear cell infiltration with positive immunostaining for
T-cell surface glycoprotein CD1a (CD1a), protein S-100 (S-100), and C-type
lectin domain family 4 member K (CD207) and features of histiocytic origin
(). Immunohistochemical analysis showed that there was no
serine/threonine-protein kinase B-raf (BRAF)-V600E mutation (). Except for the
left tibia, the skeletal survey and bone scan did not show additional skeletal
lesions. Brain magnetic resonance imaging (MRI) was also arranged to assess for
possible multisystem involvement, and this revealed negative findings. The
patient was diagnosed with unifocal osseous LCH.
Two months following curettage, a painless mass was observed at the left
fronto-temporal area. Skull radiographs and MRI images revealed an osteolytic
bone lesion at the left frontal region of the skull, and a mass near the left
temporal facial region with temporalis involvement (). The patient was diagnosed
with multifocal osseous LCH, and started chemotherapy with vincristine and
prednisolone following the Taiwan Paediatric Oncology Group (TPOG) protocol for
treating LCH in low-risk (LR) patients, namely, TPOG-LCH2002-LR (). The lesions
subsided. A follow-up assessment at 9 years showed no recurrence or new lesion
().


A 2-year-old female was brought to the emergency room of National Taiwan
University Hospital, in October 2017, with a history right lower leg painful
contusion after a fall 1 week previously. There was a palpable mass without
cutaneous lesion at the right middle calf. No other mass like lesion, pitting
oedema, recent body weight loss, cough, chest tightness or polyuria was noted.
Standard laboratory test results were within normal limits (WBC,
11.08 × 103/µl; RBC, 5.14 × 106/µl; Hb, 13 g/dl; HCT,
38.6%; MCV, 75.1 fl; MCH, 25.3 pg; MCHC, 33.7 g/dl; platelets,
315 × 103/µl; C-reactive protein, 0.34 mg/dl; LDH, 241 U/l; and
CRE, 0.3 mg/dl). Radiographs revealed an osteolytic lesion at the tibial
diaphysis, with erosion of the medical cortex and laminated periosteal reaction
(). The MRI
showed uneven cortical thickening with amorphous bone marrow hyperaemia and
oedema in the right anterior proximal tibial shaft ().
Osteomyelitis was suspected, and the patient underwent right tibial shaft
debridement. The pathology report revealed scattered dendritic Langerhans cells
() with
positive immunohistochemistry signal for CD1a () and CD207 (), but negative
result for the BRAF-V600E mutation (), indicative of Langerhans cell
histiocytosis. The follow up bone survey showed no other definite bone lesion.
In light of the clinical course in case 1, the patient received prophylactic
chemotherapy following the TPOG-LCH2002-LR protocol (). At the one-year follow-up
assessment, the patient showed no sign of recurrence.


The patient is a 78-year-old Japanese man, with 25 pack-year smoking history, worked as an arc welder for 26 years. He had no history of tuberculosis. Because a transcutaneous pleural biopsy showed fibrous plaques without malignant findings, he was diagnosed with benign asbestos pleural effusion six years prior to admission. Then, he presented with right back pain for two months prior to admission. There was no associated fever, night sweat, or respiratory symptoms. Physical examination showed palpable, immobile masses in the right posterior chest wall. Complete blood examination indicated normocytic anaemia (haemoglobin 8.5 g/dL). The levels of serum lactate dehydrogenase and soluble interleukin (IL)-2 receptor were elevated (453 IU/L and 9740 U/mL, respectively). The levels of tumour markers for lung cancer (carcinoembryonic antigen, cytokeratin 19 fragment, and Pro-gastrin-releasing peptide) were within the normal range. Over an interval of six months, computed tomography (CT) revealed a significant increase in the size of masses between the innermost intercostal muscle and inner intercostal muscle which had invaded into extrapleural fat and parietal pleura (Fig. ). Lymphadenopathy, splenomegaly, and hepatomegaly were not identified. Although pleural fluid analysis and transcutaneous pleural biopsy were performed, a definitive diagnosis was not established. He did not undergo further examination and received palliative care because of his medical complications such as recurrent strokes and diabetes. He expired one month after admission, and a full autopsy was performed. Macroscopic findings at autopsy showed pleural plaques, and the tumour was located outside the parietal pleura. Histopathological staining of the tumour tissue showed the proliferation of medium-sized lymphocytes. These cells were immunohistochemically positive for CD20, CD5, and bcl-2, and negative for cyclin D1 (CCND1), CD10, and CD138. Ki67 was highly expressed in the tumour tissue (80%) (Fig. ). In situ hybridization study demonstrated that the lymphoma was negative for Epstein–Barr (EB) virus infection. Therefore, the findings were mostly consistent with DLBCL. Asbestos bodies were also found in the lungs. He was finally diagnosed with primary DLBCL of the chest wall, complicated with benign asbestos pleural effusion.


A 10-year-old male child with unknown immunization history, living away from his parents, was apparently healthy when he presented to a local primary care practitioner with 2 days of high-grade fever, cough with expectoration, and mild swelling of the neck. After initial management for another 5 days, the patient was taken to a secondary care center in view of worsening cough and neck edema. There, the patient was clinically suspected to have diphtheria and crystalline penicillin was administered, following which diphtheria antitoxin was arranged. However, toxigenic symptoms continued and patient was shifted to a tertiary care center. The child was admitted to the pediatric ICU and was started on 60% oxygen via venturi, IV fluids, inotropic support, and antibiotics.
Examination revealed anemia (Hb = 8.8 g/dL), leukocytosis (26.4 103/μL), and mild edema of lower limbs. Tonsils were congested, partially covered with a grayish-white membrane, and severely tender. Upper motor neuron facial nerve palsy and palatopharyngeal incompetence (9th and 10th cranial nerves) were also noted on examination. Mild hepatomegaly and deranged liver functions was also noted (aspartate aminotransferase = 4266 IU/L; alanine aminotransferase = 4398IU/L). Chest radiograph revealed cardiomegaly with pulmonary plethora. In view of significant nephrotic proteinuria (24 h urine protein = 224 mg/m2/h) and acute kidney injury (serum creatinine = 4.82 mg/dL), renal functions were maintained with diuresis and fluid resuscitation.
On repeat throat swabs at the tertiary center, diphtheria was confirmed by staining and culture []. Antimicrobial susceptibility testing (AST) was not performed due to the poor accuracy of automated methods and demanding AST techniques.[] The strains were tested for rpoB and tox gene on polymerase chain reaction (PCR) and were found positive []. The strains were further sent to a reference laboratory at Christian Medical College, Vellore where it was confirmed. Patient was discharged against medical advice and was found to have expired 2 weeks following discharge.


A 14-month-old female child was brought by her parents with a progressively increasing swelling over the lower back and weakness of both lower limbs since birth. There were no complaints of bowel or bladder incontinence. She weighed 15kg and her head circumference was 47 cm. There was no history of any CSF leak from the swelling and no prior history of hospital admission for meningitis. On examination, the girl was paraplegic (0/5 Medical Research Council [MRC]). The lumbosacral mass with a normal overlying skin was fluctuant and had a positive transillumination test and cough impulse. The swelling, which measured 45 cm × 40 cm × 35 cm, had obliterated the intergluteal cleft. Due to the huge mass, she was unable to sleep supine. Magnetic resonance imaging (MRI) revealed the classical imaging appearance of a TMC []. A dilated central canal (trumpet-like flaring) of the terminal cord had herniated into a giant meningocele through a spina bifida defect at L4-S2 level. Two separate sacs (sac within a sac appearance) could be seen distinctly on the MRI. There was no chiari, syrinx, or hydrocephalus on screening MRI of the brain and whole spine.
Surgery was planned for this patient, keeping in mind that her neurological status was unlikely to improve after surgery but mere cosmetic repair and reduction in the size of the mass will allow for better care. The patient had to be induced and intubated in lateral position. To position the patient prone, about 6000mL of CSF was drained from swelling (the meningocele sac) percutaneously with a wide bore needle with simultaneous fluid replacement to prevent hemodynamic instability. Subsequently, the patient was positioned prone and a vertical incision was made. This opened up the meningocele sac and the inner sac (TMC) was clearly observed []. Myelocystocele was then opened and about 1500mL of clear CSF was drained. Continuation of the myelocystocele into the normal central canal cranially could be easily seen at surgery []. Pial sutures (neurulation) were taken with 8-0 nylon after excising the cyst wall. Primary dural reconstruction followed by multilayered closure of the incision was carried out. She was nursed in lateral position for 48h and received intravenous antibiotics for 24h post-surgery. Patient was discharged on postoperative day 5. On follow-up, sutures were removed on postoperative day 10. At 1 and 6 months follow-up, the patient was doing well, although she was neurologically unchanged.


A 6-year-old girl had best-corrected visual acuity (BCVA) of 6/60 in both eyes (BE) due to GCD1 in May 2013 []. The opacities were noted at 105 μ (right eye/RE) and 110 μ (left eye/LE) from corneal surface [].
Parents (nonconsanguineous marriage) had normal vision with minimal GCD1 changes [] on 2020. Paternal grandfather had dense GCD1 changes (visual decline starting in the fifth decade) in the anterior and mid stroma.
PTK was done under total intravenous anesthesia (TIVA) – midazolam and propofol in BE (May 2013). BE regained BCVA of 6/18 (+2.0).
The dystrophy recurred (BCVA RE-3/60, LE-6/60) requiring repeat PTK in December 2014 (RE) and January 2015 (LE). BCVA improved to 6/18 BE (+4.0) after 1 month. In February 2016, central corneal thickness (CCT in ASOCT) was 545 (RE) and 538 μ (LE) respectively.
Recurrence necessitated third PTK (May 2016). BCVA improved to 6/18 (+6.0D BE) 3-weeks postoperatively.
When GCD1 recurred again [Figs. , , and ] (BCVA 6/60 BE), PTK + PRK with Mitomycin C (MMC) 0.02% for 30 s (to correct + 9D hyperopia, subjective refraction + induced hyperopia) was done (RE: November 2017, LE: January 2018), which improved corneal clarity and flattening [Figs. , , and ].[] After initial PTKs, keratorefractive-surgical corrections were not done due to good BCVA with hyperopic glasses. However, with increase in hyperopic refraction in this possibly amblyogenic age, the case was discussed with peers, and PRK was performed. In September 2017, CCT (on OCT) was RE-478 μ and LE-534 μ.
BCVA was 6/9 (RE + 2.5/+1.50 × 110) in December 2017 and 6/12 (LE + 2.75/+1.0 × 90) in February-2018. In January 2018 (before LE PRK + PTK), CCT (on OCT) was RE-416 μ and LE-530 μ.
On the last visit (June 2020, 2 ½ year after the last surgery), BCVA was RE-6/18 (+2.50/+1.50 × 10) and LE-6/12 (+2.75/+1.00 × 90) with more severe recurrence [Fig. and ].


A 22-year-old-female who underwent an uneventful LASIK surgery presented with chief complaints of difficulty in focusing and glare 18 months post LASIK. Her preoperative refractive error was –5DS/–1.25DCx 170 degrees in the right eye (OD), 6/6; N6 and –5.25DS/–1.00 DC × 10 degrees in the left eye (OS) 6/6; N6. Her pre-operative NPA and NPC with glasses were 7 cm and 6 cm, respectively. Duochrome test was balanced for both eyes. Stereopsis was tested using the Titmus fly test was normal. Pre-operatively her topography showed with the rule astigmatism with no evidence of ectasia. Cycloplegic refraction was performed preoperatively. She underwent uneventful refractive surgery and post-operatively her UCVA was 6/6 with plano in both eyes. Her corneal topography showed no evidence of ectasia. She was an IT professional with 9 hours of screen time per day. On evaluation at 18 months postrefractive surgery her vision was 6/12 in both eyes improving to 6/6 with –1.25 DS OD and –0.75 DS OS. She was advised cycloplegic refraction and BVA. Cycloplegic refraction revealed emmetropia with no significant refractive error. However, orthoptic evaluation showed high positive relative accommodation (PRA) of-3.5D, low negative relative accommodation (NRA) of + 1.5 D and difficulty with plus lenses on accommodative facility. Monocular estimation method (MEM) retinoscopy finding was –0.5D, suggestive of a lead of accommodation. Thus, the above findings suggest that patient had an accommodative excess. The patient was advised to reduce screen-time and follow visual hygiene practices. With vision therapy as outlined in the flowchart [] her symptoms resolved, and unaided vision returned to 6/6 in both eyes in 8 weeks.
Note: Accommodative excess can be an important cause of post-refractive surgerypseudo-regression. Cycloplegic refraction and detailed orthoptic evaluation can help clinch the diagnosis and administer treatment on time.
Vision therapy is preferred over the use of cycloplegics in the treatment of accommodative excess to keep accommodation flexible. However, in resistant cases, cycloplegics must be used initially and gradually tapered off.


27-year-old-male visited the refractive clinic 1 year after uneventful Trans-epithelial PRK (Trans-PRK) with complaints of blurring of vision after prolonged screen use or reading and halos. The patient had difficulty with near activities and complained of discomfort and eyestrain associated with reading. His pre-operative refractive error was –3.00 DS (OD) and –2.75 DS (OS). Pre-operatively, he underwent cycloplegic refraction and orthoptic evaluation (including NPA, NPC and duochrome balance test with glasses) was within normal limits. Stereopsis tested using the Titmus fly test was within normal limits OU. His pre-operative corneal topography showed a thinnest corneal thickness of 486 microns in both eyes (OU) so Trans- PRK was planned. On examination, his UCVA in OD was 6/9P and OS was 6/6P whereas the BCVA OU was 6/6 with +1.0DS OD and +0.75 DC OS. Near vision was 6/6 but the patient complained of intermittent blurring while reading. On orthoptic evaluation patient had a receded NPA (16 cm), reduced amplitude of accommodation for age, low PRA -1.25 D, high NRA of +3D. MEM retinoscopy revealed a lag of accommodation (+2D). Thus, the patient was diagnosed with accommodative insufficiency and underwent vision therapy. After 12 weeks of vision therapy [], his UCVA in both eyes was 6/4.5. There was a significant improvement in symptoms as well as accommodative amplitude.


A 29-year-old-man reported to our clinic with chief complaints of starburst appearance, glare and halos 8 months post successful SMILE surgery. He also complained of intermittent blurring with occasional doubling and difficulty with driving at night. His preoperative BCVA was 6/6 with -4.5DS OU. His corneal topography showed no evidence of ectatic corneal disorders. Pre-operative cycloplegic refraction was performed and orthoptic evaluation (including NPA, NPC and duochrome balance test with glasses) was normal. Stereopsis was tested using the Titmus fly test was normal. Post-operatively, on visual acuity testing with Snellen's chart his UCVA was 6/6. Aberrometry and topography were within normal limits. Cycloplegic refraction and orthoptic evaluation were repeated. Cycloplegic refraction revealed no significant refractive error. On orthoptic evaluation patient had an exophoria for near and intermittent exodeviation for distance. Exodeviation for distance was 20 PD and greater than that for near, by 12 PD. Patient had normal amplitude of accommodation and high AC/A ratio of 8:1. PFV was low for distance and borderline for near. NFV was within normal limits. With office and home-based exercises for Divergence excess as outlined in flowchart [], and exercises to improve binocular fusion and stereopsis, his PFV and control over exodeviation improved, and the visual disturbances gradually resolved.


A 24-year-old female presented with chief complaints of intermittent blurring of vision for distance and near, asthenopia OD 9 months post an uneventful transepithelial PRK. Her pre-operative examination record showed her BCVA was 6/6, N6 OU with -1.25DS/-0.75DC at 80 degrees OD and -1.25DS OS. Her NPA and NPC with glasses were within normal limits and the Duochrome test was balanced. Her stereopsis was tested using the Titmus fly test and was normal. She was advised Trans-PRK in both eyes, since here thinnest corneal thickness (TCT) was 483 μm OD and 498 μm OS respectively on Pentacam pachymetry map []. She underwent uneventful OD Trans-PRK followed by OS Trans-PRK 2 days later on Schwind Amaris 1050 (Peramis; SCHWIND eye-tech-solutions, Kleinostheim, Germany). Her UCVA on postoperative day 1 was 6/6 OU. Her immediate post-operative period was uneventful. She was a teacher and an avid computer user, spending approximately nine hours a day using computers. On examination at 9 months post trans- PRK her BCVA was 6/24 with +3.75DS/-3.00DC at 90-degree N10 OD and 6/6; N6 with plano OS. Slit-lamp biomicroscopic examination revealed the presence of clinical grade 2 haze OD which corresponded to the corneal densitometry map on the Pentacam showing evidence of post-PRK scaring [Fig. -]. The rest of the anterior and posterior segment examination was within normal limits in both eyes. Hence, a diagnosis of late-onset post-PRK haze was made and she was prescribed a tapering dose of eye drop prednisolone along with eye ointment tacrolimus 0.03% at bedtime and tablet vitamin C 500 mg three times a day for 12 weeks. At 12 weeks follow up, the slit lamp examination showed minimal haze OD with corresponding reduction of the same on corneal densitometry map OD [Fig. -]; nevertheless, the complaints of eye strain and blurring of vison persisted OD. Her BCVA OD was 6/6 with +1.25 D/-0.75 DC at 90 degrees; however, the clinical picture did not correlate with the magnitude of the hyperopic shift, so she was advised to undergo a detailed orthoptic evaluation which revealed esophoria for distance on cover test and Maddox rod test. She also had low near point of accommodation, low positive fusional vergence (PFV) at distance and near, low negative fusional vergence (NFV) at distance and near and low binocular accommodative facility (BAF), reduced cycles per minute on monocular accommodative facilities (MAF). Based on these findings a diagnosis of fusional vergence dysfunction was made and she was prescribed +1.25 DS/-0.75DC at 90 OD glasses and was started on orthoptic exercise initially at the clinic which was then subsequently shifted to home-based exercises [] She was re-evaluated 8 weeks post orthoptic exercises, her BCVA improved to 6/6 with +0.25DS OD and her symptoms had significantly resolved.
Vision therapy is the mainstay of treatment in convergence insufficiency. However, correction of refractive error, as with any other NSBVA is important. Low myopia perhaps may be corrected after starting vision therapy. Pencil push-ups are one of the most common exercises prescribed for CI. Convergence insufficiency treatment trail (CITT) evaluated efficacy of office-based vision therapy, office-based placebo therapy, home-based pencil push-up (HBPP) and home-based computer vision therapy + pencil push up. 73% improved in officed based vision therapy group as compared to 43% in HBPP group and 33% in homed based computer vision therapy plus pencil push up group.[] Hence whenever possible office-based vision therapy must be insisted upon as monitoring of techniques performed by the patient with feedback and correction is very important.
Home-based vision therapy can be advised for patients who cannot attend office-based vision therapy: Pencil push-ups, Brock string, lifesaver cards, and eccentric circles are the various options. Office-based vision therapy is outlined in .


The patient was a 39-year-old man. In August, he developed hyperglycemia symptoms, and was diagnosed with diabetes and referred to the Hospital of University of Occupational and Environmental Health, Kitakyushu, Japan, in November. He was diagnosed with acute-onset type 1 diabetes based on positivity for the glutamic acid decarboxylase antibody.
On admission, the patient was lean, weighing 45.8 kg. As shown in Table , his urinary ketone bodies were 3+, anti-glutamic acid decarboxylase antibodies were 300 U/mL and urinary C-peptide immunoreactivity showed low insulin secretion. Although his thyroid function tests were normal, both the anti-thyroglobulin and anti-thyroid peroxidase antibodies were positive, and thyroid echo showed mild thyroid enlargement. The provisional diagnosis was APS-3 associated with chronic thyroiditis and type 1 diabetes. The results of human leukocyte antigen typing were consistent with disease susceptibility to APS-3.
The patient’s diabetes was controlled by multiple insulin therapy with the combination of insulin aspart and degludec. However, the patient developed fever, headache and general fatigue on hospitalization day 4. Furthermore, various mental symptoms started to appear, including hallucinations, delusions and mood depression on day 7. At first, we suspected a mental disorder; however, on day 13, he developed convulsive seizures, suggesting autoimmune encephalopathy. Accordingly, the Department of Neurology was consulted; electroencephalography showed sustained slow waves and burr head, whereas neck magnetic resonance imaging showed no intracranial abnormalities. Additional tests were carried out for immune-related encephalitis; however, results for the anti-voltage-gated potassium channel complex antibody and anti-amino-terminal of the α-enolase antibody were negative. Analysis of the cerebrospinal fluid showed no abnormalities in the cell number, total protein and glucose, but serological tests showed mild positivity for the anti-NMDA-R antibody, with a titer of 1:10 (normal <1:1). Accordingly, the diagnosis was considered anti-NMDA-R encephalitis. Further neck, chest, abdominal and pelvis computed tomography was negative for apparent malignant tumors, and immunological fecal occult blood test was negative twice.
The patient was administered levetiracetam for seizures, and two courses of steroid pulse therapy (methylprednisolone 1,000 mg infusion for 3 days) were administered. His hallucination, delusions and depression gradually improved after these therapies. The Hasegawa-type dementia scale improved from 9 to 18 points at 1 week, and to 28 points at 3 weeks after steroid pulse therapy. He received rehabilitation before discharge 4 weeks later, and returned to work 3 weeks after that. One year after discharge, the patient was continuing to work and had not experienced any recurrent symptoms.


A spayed female 12-year-old domestic shorthair cat was presented to a referral hospital (Western Australian Veterinary Emergency and Specialty) for an 8-month history of intermittently reduced appetite and gradual weight loss. The patient did not have any ocular abnormalities prior to presentation. Abdominal ultrasonography revealed a mid-jejunal mass and mesenteric lymphadenomegaly. The patient subsequently underwent a coeliotomy where a jejunal resection and anastomosis were performed. An oesophagostomy tube (O-tube) was placed on the left side of the patient’s neck for assisted feeding to ensure adequate caloric intake as the patient was hyporexic preoperatively.
During recovery the patient was placed in right lateral recumbency and the left cervical region was prepared for surgery. A 10 F red rubber catheter was measured to the level of the distal third of the oesophagus. Curved Rochester–Carmault forceps were inserted into the oral cavity and directed distally into the oesophagus equidistant between the thoracic inlet and the pharynx, and the tips of the forceps were used to deviate the oesophagus laterally. A sharp incision was made with a size 15 Bard–Parker scalpel blade between the tips of the forceps. The tube was grasped with the forceps and pulled out orally, then redirected aborally into the oesophagus. The tube was sutured in place with a Chinese fingertrap suture using 3/0 polydioxanone. A soft padded bandage was applied around the neck to hold the tube in place.
Two hours after surgery the patient developed miosis and enophthalmos in the left eye (OS) consistent with Horner syndrome. Four days later a full ophthalmic examination confirmed ptosis, miosis, enophthalmos, prolapse of the nictitans membrane, narrowed left naris and decreased nasal airflow on the left side (, also see video in the ). One drop of phenylephrine 1% was applied topically OS for neurolocalisation; pupillary dilation and resolution of ptosis were observed 10 mins after application, identifying the lesion as post-ganglionic. The rest of the ocular examination was unremarkable. Physical examination was unremarkable other than good healing of the abdominal incision and O-tube stoma. Histopathology of the resected jejunal mass identified small cell T-cell lymphoma, so the patient was started on prednisolone (2 mg/kg PO q24h [Pred X-5 Apex]) and chlorambucil (4 mg PO q24h for the first 4 days and then once every 3 weeks [Leukeran; Aspen Pharmacare]). A repeat ocular examination performed 2 weeks later revealed that the signs of Horner syndrome were starting to resolve.
On day 20 after the O-tube placement the patient developed signs clinically resembling Pourfour du Petit syndrome, including mydriasis and a widened palpebral fissure OS (). The ipsilaterally narrowed naris and nasal congestion had resolved at that point. The patient remained clinically well and there were no other ocular abnormalities. Between days 25 and 26 the patient developed mild miosis OS consistent with Horner syndrome again. On day 32, the O-tube was removed as the stoma was inflamed and the patient was eating well on its own. Repeat examination on day 33 revealed complete resolution of mild miosis OS. Repeat examination 15 months later did not show any recurrence of ocular signs.


A 29-year-old pregnant women presented at 26 weeks of gestation with fever and cough for 4 days to the emergency room at our tertiary care maternity hospital. This was her second pregnancy. In her previous pregnancy, 2 years ago, she had a full-term caesarean delivery. During the present pregnancy, she had regular antenatal visits. Her body mass index was 35 kg/m2. Her anomaly scan at 20 weeks and glucose tolerance test at 24 weeks were normal. Her last routine antenatal visit was 2 weeks prior to the emergency admission.
On admission, her X-ray showed patchy infiltrates suggestive of pneumonia, and nasopharyngeal swab confirmed COVID-19. She was initially admitted to the isolation ward and started on prophylactic medication as per National Guidelines for Clinical Management and Treatment of COVID-19 in the United Arab Emirates.
As her condition worsened, she was shifted to the ICU by the third day of admission. The antibiotic was changed to intravenous piperacillin–tazobactam. A therapeutic dose of enoxaparin was given, and she was started on continuous positive airway pressure with noninvasive high settings. As her respiratory distress worsened further, she was intubated and given mechanical ventilation ().
The patient was unable to maintain saturation even on high settings of mechanical ventilation. Her pre-ECMO settings were synchronised intermittent mandatory ventilation with pressure-regulated volume control with fraction of inspired oxygen (FiO2) 100%, respiratory rate 20, positive end-expiratory pressure (PEEP) 15 cm H20, mean airway pressure 22 and tidal volume 500 mL.
A multidisciplinary team consisting of senior intensivists, cardiothoracic surgeons, obstetricians and anaesthetists decided after a detailed discussion with the patient’s family to opt for ECMO insertion. This was a crucial decision of favouring ECMO over urgent delivery of the fetus, in a critically ill pregnant woman with a viable fetus.
Midazolam (5 mg/hour) and fentanyl (300 µg/hour) on continuous flow were administered for analgesia and sedation, and cisatracurium (8 mg/hour) on flow was used for the neuromuscular block. Effective anticoagulation by heparin infusion was achieved. This was confirmed with an activated partial thromboplastin time (APTT) of 53.2 seconds.
Under ultrasound guidance, using the Seldinger technique, 23 French ECMO drainage cannula was inserted in the right femoral vein, and 21 French ECMO return cannula was inserted in the right internal jugular vein. VV-ECMO circuit was initiated with a flow rate of 4.8 L/min, pump speed of 3000 rpm and sweep rate of 4 L/min. The ECMO run was similar to that used in the non-pregnant patients. A senior obstetrician monitored the fetal heart during the process. After inserting the ECMO circuit, the patient was transferred to Dubai Hospital where ECMO facilities are better established for further management.
The patient was monitored in the surgical ICU by a multidisciplinary team of cardiothoracic surgeons, obstetricians, perfusionists, anaesthetists and intensivists. As she was about 27 weeks of gestation, daily fetal cardiotocography was done to monitor her fetus. Her repeat COVID-19 swab after 7 days was negative. The pateint’s condition improved, and she was weaned off ECMO after 5 days. Postdecannulation of ECMO patient maintained haemodynamic stability without inotropic support ().
The patient was monitored in the general antenatal ward for 1 week. She has regular chest physiotherapy sessions in the ward. The fetal growth parameters and Doppler Studies of the umbilical artery were found to be normal and corresponding to the period of gestation.


A 46-year-old man, with a history of heart valve replacement for rheumatic heart disease and taking warfarin 2.5 mg daily since 2008 was admitted to the emergency department at our hospital with hematemesis and tarry stool without any previous abdominal discomfort. Physical examination showed an anemic appearance with a hemoglobin level of 84.0 g/L without other abnormalities. His vital sign measurements were as follows: body temperature, 36.0°C; blood pressure, 108/44 mmHg; respiratory rate, 18 breaths/minute; and pulse rate, 77 beats/minute. The results of routine blood coagulation tests were as follows: prothrombin time, 21.7 s; international normalized ratio, 1.95; activated partial thromboplastin time, 46.2 s; fibrinogen, 1.47 g/L; and thrombin time, 16.9 s. He underwent upper GI endoscopy and was found to have a bleeding submucosal tumor at the stomach fundus, which is shown in . An exposed pulsatile vessel was seen at the defect. The patient and his family consented for him to undergo endoscopic obturation with tissue adhesive, and it was performed to treat the defect, as shown in . A modified “sandwich” method was used twice for the treatment. The injection was 2.0 mL of 50% glucose, 0.25 mL of undiluted tissue adhesive, and 3.0 mL of 50% glucose. The bleeding was successfully stopped, as shown in . No recurrence of bleeding was observed through a gastric tube and 6 days after endoscopic obturation, the patient underwent laparoscopic partial gastrectomy. The tumor size was 4.0 cm ×3.5 cm × 3.0 cm. Histologic analysis of the specimen showed a gastric stromal tumor, and the tumor cells were positive for CD117, Dog1, and CD34, as shown in . The postoperative course was uneventful, and at the 1-year follow-up, the patient has had no recurrence of GI hemorrhage.


The index patient is a 23-year-old male who presented with complaints of fever, chills, left flank pain of 4 days duration. He did not give a history of dysuria, hematuria, cough, vomiting, loose stools, breathlessness, chest pain, joint pains, oral ulcers, or dryness of eyes. The patient was non-smoker and non-alcoholic. Clinical examination revealed a BP of 160/100 mm Hg and mild left lumbar tenderness. Computed tomography (CT) urography revealed absent contrast in the left urinary system, left renal artery thrombosis, and multiple renal infarcts []. The laboratory workup revealed, Hb-13 gm/dl, total leukocyte count (TLC)-13710/cmm, platelet-4,17000/cmm, creatinine - 1.46 mg/dL, blood urea nitrogen (BUN) -27.37 mg/dL, normal electrolytes and normal prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT). The homocysteine levels were high (170 mmoL/L), serum antinuclear antibody (ANA) was negative. Patient was started on injection heparin (5000 IU bolus, followed by 1000 IU/hr). Diethylene-triamine-pentaacetate (DTPA) (Tc 99m) scan confirmed the absence of tracer uptake in the left kidney. Urine examination showed 2–3 rbc/hpf, no pus cells, and absent protein. Lipid profile showed elevated LDL (190 mg/dL), 2D ECHO was normal, and cardiac monitoring did not reveal arrhythmia. The serum C3 and C4 were normal. Protein C, protein S, anti-thrombin III were within normal range & factor V Leiden mutation, and APLA antibodies were negative. The fundus examination did not reveal retinal infarction. Computed tomography head did not reveal any area of infarction. Left nephrectomy was performed. In view of hyperhomocysteinemia, the patient was started on tab folic acid (10 mg/day). His serum creatinine reduced to 1.1 mg/dL, and he was discharged on warfarin and folic acid.
One week after getting discharged, the patient now developed right-sided flank pain associated with vomiting and decreased urine output, with no c/o fever, or chest pain. On physical examination, he had a BP of 154/100 mm Hg and a mild right lumbar and pelvic tenderness. Non-contrast CT abdomen did not show any significant abnormality. His creatinine increased to 3.2 mg/dL within 24 hrs. The INR was 2.1, and the DTPA scan now showed reduced tracer uptake in the right kidney. The ultrasound renal doppler showed resistive flow in the right renal segmental artery. The patient was restarted on anticoagulation (heparin 1000 IU/hr). His creatinine increased to 9.0 mg/dL, and he became anuric. He was started on hemodialysis and a repeat CT renal angiography [] was suggestive of right renal segmental artery thrombosis with multiple renal infarcts. Urgent renal angiography and intra-arterial thrombolysis were done with alteplase, infused intravenously as an initial dose of 5 mg over 10 min, followed by 1 mg/hr for 36 hrs. He was continued on heparin (500 IU/hr) to avoid clotting in the arterial sheath. Check renal angiography revealed improved blood flow in the thrombosed vessel []. The patient required alternate day hemodialysis. Subsequently, in the next 2 weeks, the patient's urine output started improving gradually. After 3 weeks, the patient had 2.0 L/day of urine output, and his creatinine decreased to 2.8 mg/dL. In his family, his father had undergone coronary reperfusion (Percutaneous transluminal coronary angioplasty (PTCA)) at the age of 45 years. His grandfather and grandmother died due to myocardial infarction and stroke, respectively. On further investigations, the patient's thrombophilic profile revealed plasminogen activator inhibitor factor deficiency, and genetic mutation studies revealed a methylene-tetrahydrofolate reductase (MTHFR) mutation. These two defects predisposed him to a thrombotic state. His paternal aunt and uncle both were also found to have elevated homocysteine levels but no thrombotic event so far. The genetic analysis for hyperhomocysteinemia did not reveal any mutations in other family members. He was discharged on heparin (5000 IU twice per day), folic acid, aspirin, and statin. His serum creatinine came down to 2.4 mg/dL. It was proposed to start novel anticoagulants.


A 36-year-old gravida 5 para 3013 was referred to our fetal treatment centre at 24 weeks of gestation with a fetal diagnosis of congenital high airway obstruction syndrome (CHAOS) without additional anomalies (). Fetal imaging revealed a gap in the trachea, but sufficient tracheal length was present to permit access for tracheostomy. Fetal cytogenetics from an amniotic fluid sample revealed a normal karyotype and microarray. In a multidisciplinary conference involving the family, options were discussed to include termination of pregnancy, delivery with neonatal comfort care and an EXIT-to-airway procedure. The family was well informed that without an established airway at the time of delivery, a neonatal demise would be imminent. Fetoscopic laser decompression of CHAOS, feasible in select cases, was not considered in this scenario secondary to the long gap defect noted on fetal imaging, which would result in a low likelihood of a successful procedure, as well as the associated risks of surrounding tissue injury. Prematurity is also higher following fetoscopic procedures, and an EXIT procedure remains necessary regardless of decompression to develop an adequate airway at delivery. The family elected for a re-evaluation in the third trimester and returned at 31 weeks of gestational age for a repeat ultrasound and fetal MRI. She received weekly ultrasounds at the referring centre to determine fetal viability, monitor amniotic fluid volume and assess for signs of premature labour until she relocated to our centre. Findings on follow-up remained stable when compared with her earlier evaluation, with the exception of asymptomatic polyhydramnios.
After follow-up counselling, the family elected to undergo an EXIT-to-airway procedure scheduled for 37 weeks of gestation. At this point, a call tree was established placing all key specialties on 24-hour availability until the procedure was completed. The gestational age chosen for the procedure was established to allow for further fetal growth and to promote fetal lung maturity.
At 34 weeks 5 days of gestation, she presented to labour and delivery at 03:00 on a Sunday morning with the complaint of gross rupture of membranes. On examination, her cervix was noted to be 4 cm dilated; there was gross pooling of amniotic fluid; and the umbilical cord was prolapsed through the cervix up to the level of the introitus (). The fetus was in the breech presentation. Contractions were occurring regularly at 4 min intervals with persistent variable fetal heart rate decelerations down to 80 beats/min. The call tree was activated. The patient was taken to the operating room and underwent general anaesthesia with endotracheal intubation, while the multidisciplinary team congregated to discuss adjustments to the procedure. The time from patient presentation in labour and delivery triage to induction of general anaesthesia was 59 min, with all essential team members present.
The decision was made to make a maternal midline laparotomy to provide sufficient access to completely exteriorise the late-preterm gravid uterus and to make a fundal hysterotomy to deliver the fetal head and neck first. The placenta was anterior, and the fetus was in the breech presentation in the setting of anhydramnios secondary to rupture of membranes. An attempt at external cephalic version was not deemed safe in the setting of anhydramnios, active labour and existing cord prolapse. For these reasons, the original plan to perform a maternal abdominal transverse skin incision with a low transverse uterine hysterotomy was therefore abandoned. The midline skin incision was made to just below the umbilicus with placement of a large Olexis O retractor (Applied Medical, Rancho Santa Margarita, Californis, USA) allowing the uterus to be exteriorised. The anaesthesiologist provided maximal halogenated agents with a mean alveolar concentration of 3, along with both nitroglycerin and terbutaline. Unfortunately, uterine relaxation was not sufficient to maintain optimal placental perfusion to the fetus. In an effort to expedite the procedure, the surgical team proceeded by placing a haemostatic myometrial box stitch at the fundus placed well away from the placental edge. The uterus was incised within the box stitch with electrocautery, and the amniotic sac was entered. Bainbridge clamps were used to compress the myometrium prior to placing uterine haemostatic staplers. Due to inadequate uterine relaxation, the thickened myometrium prohibited sufficient compression of tissue to allow for stapling. At this point, the uterine entry point was extended with electrocautery, and Allis clamps were used along the length of the hysterotomy to provide haemostasis. The fetal head and neck were then delivered followed immediately by an intramuscular injection of a cocktail containing atropine, rocuronium and fentanyl. A rapid intravenous infusion device was used to infuse warm lactated Ringer’s solution through the hysterotomy to assist in maintaining uterine volume. Fetal monitoring performed throughout the procedure by fetal cardiology demonstrated intermittent bradycardia with rate as low as 88 beats/min and as high as 129 beats/min with depressed biventricular function. At this time, the paediatric surgeon and paediatric otolaryngologist worked in concert and established an airway via an endotracheal tube through a tracheostomy incision. The time from delivery of the head and neck until airway establishment was 3 min. The remainder of the baby was delivered; the umbilical cord was clamped and cut; and the infant was passed off to the neonatology team.
The neonatal response to initial resuscitation was an immediate return to a heart rate in the 150’s bpm with an oxygen saturation of 100%. After stabilisation, bronchoscopy revealed laryngeal atresia below the level of the vocal cords with an intact trachea ().
The parturient was extubated after the placement of bilateral transversus abdominus plane blocks for postoperative pain control. Unfortunately, during the first 24 hours postpartum, the mother developed uterine atony necessitating the use of uterotonics and uterine balloon tamponade. She received a transfusion of 2 units of packed red blood cells. Subsequently, the mother remained inpatient for three postoperative days and was discharged in good condition without further complications from the surgical procedure.