A 53-year-old female presented to the emergency department complaining of abdominal pain that started one day prior. Her past medical history was significant for hypertension and type 2 diabetes. Located in the hypogastric region, the pain woke her from sleeping at night, was constant in character, and described as six out of 10 in severity. The pain was radiating to her right lower quadrant and she did not report any alleviating or aggravating factors. Her medications included enalapril and liraglutide. Surgical history was significant for cholecystectomy and hysterectomy, both of which were over eight years ago. She denied having any family history of malignancy, bleeding issues, or thrombotic events.
Her vital signs and laboratory studies, including hematologic and metabolic panels were within normal limits with the exception of an elevated ESR of 41 mm/hr. An abdominal ultrasound showed no significant findings. A subsequent CT scan showed findings suggestive of acute colitis involving the descending and sigmoid colon. The patient was treated for colitis with antibiotics.
Two days later, amidst no clinical improvement in the patient, the CT report was modified. The modified report was read as showing intrahepatic biliary ductal dilatation, concerning possible cholangitis or other biliary pathology. An MRCP was performed, which showed portal vein thrombosis. The MRCP (magnetic resonance cholangiopancreatography) also revealed biliary dilatation with a shouldering appearance in the ampulla region, raising concern for a possible infiltrative neoplasm. At this point, coagulation studies showed elevated levels of fibrinogen (436 mg/dL) and D-dimer (0.84 ugFEU/mL). Following this result, a hypercoagulable workup was initiated and treatment was started with heparin. An endoscopic ultrasound was unremarkable, revealing a borderline enlarged ampulla without masses. A biopsy of the region was taken which did not contain any abnormal tissue (Figures , ).
The hypercoagulable workup was unremarkable. All the following laboratory results were in normal limits: antithrombin III activity, cardiolipin antibodies, factor V Leiden, protein c, protein s, phospholipid antibodies (beta-2 glycoprotein, phosphatidyl serine). She was not found to have a prothrombin gene or JAK2 (V617F) mutation. After performing an extensive hypercoagulable workup, no specific etiology for her PVT was found and she was diagnosed with idiopathic portal vein thrombosis. She was discharged shortly after in a stable condition.


A 31-year-old male patient was referred to the ophthalmology clinic due to visual impairment. He was diagnosed with DM at the age of four and has been on insulin therapy since then. He has been suffering from visual impairment from the age of 6. He subsequently developed DI and hearing loss at the age of 21. At the time of study, his serum HbA1C level was 7.7%. The ophthalmic evaluation showed the best-corrected visual acuity of light perception bilaterally with no nystagmus. Cataract was observed in both eyes and the intraocular pressure was 18 mmHg bilaterally. Funduscopy revealed proliferative diabetic retinopathy (PDR) in the right eye and moderate nonproliferative diabetic retinopathy (NPDR) in the left eye with no evidence of macular edema. OA with severe optic nerve head pallor was obvious in both eyes [Figure 3a]. The history and ocular examinations approved the progressive OA in the context of WFS. Abdominopelvic sonography revealed mild hydronephrosis in the right kidney with normal kidney size, normal parenchymal thickness, and echo pattern. Also, mild bladder wall thickness with trabeculation was detected. These are consistent with neurogenic bladder. Auditory tests with pure tone audiometry showed sensorineural hearing loss. Brain and lumbar spine MRIs were normal.


A 24-year-old female patient was diagnosed with DM at the age of three who has been treated with insulin NPH and regular. The presence of OA in both eyes was diagnosed at the age of 12. She developed urinary tract disorders and bladder dysfunction at the age of 12 for which she took nitrofurantoin twice daily for prophylaxis. The diagnosis of DI was confirmed with clinical signs and symptoms, laboratory tests and water deprivation test abdominopelvic sonography revealed severe hydroureteronephrosis with cortical loss in both kidneys in addition to irregularity and increment in bladder wall thickness that is consistent with neurogenic bladder [Figure 4]. Her visual acuity was finger counting at 1–2 m. Intraocular pressure was 19 mmHg in both eyes. Fundus examination revealed bilateral severe OA and nerve fiber loss [Figure 3b]. The audiometry showed sensorineural hearing loss in both ears which were moderate at 3000 Hz and severe at 6000 Hz test tone [Figure 5a]. Tympanometry presented type A in right and type A in left ear which suggested the reduced tympanic membrane mobility in the left ear [Figure 5b]. Brain and lumbar spine MRI revealed normal findings.


A 23-year-old man was diagnosed with insulin-dependent DM at the age of four which has been treated with insulin NPH and regular since the diagnosis and subsequently was diagnosed with DI. He subsequently developed visual impairment and OA at the age of 11. His serum HbA1c level was 9.4% which represented uncontrolled DM. His best-corrected visual acuity was finger counting at 20 cm in the right eye and hand motion in the left eye. He underwent phacoemulsification and intraocular lens implantation in both eyes. Intraocular pressure was 18 mmHg bilaterally. On funduscopic examination, there was severe OA [Figure 6]. His abdominopelvic sonography reported normal kidney sizes with normal parenchymal thickness and echo patterns. Neither hydronephrosis nor stone or occupying lesion was detected. Additionally, bladder wall thickness and shape was normal without any evidence of trabeculation or neurogenic bladder. He occasionally reported urological symptoms which was proved by the normal results of his abdominopelvic sonography. He had no complaint of auditory loss and his auditory tests were normal.


A 70-year-old right-handed Caucasian male was brought by his family for an evaluation of progressive memory loss and change in his behavior over the last month. He had not had any prior neurologic or psychiatric illnesses. He became socially withdrawn, and subsequently became unable to independently perform activities of daily living. His speech output lessened to the point that he would speak only in single words. Up to the time of presentation, there had been no motor or movement concerns, hallucinations, incontinence, or fevers.
His history was notable for well-controlled hypertension and hyperlipidemia. He had been diagnosed with rheumatoid arthritis 20 years prior and was treated with long-term oral methotrexate (15 mg per week) and occasional use of diclofenac. He was a former smoker (stopped smoking for 30 years) and a social drinker without history of illicit drug use. His family medical history was noncontributory.
Physical examination
His affect was flat, and he had impaired attention and concentration. He was unable to follow simple commands. There were no detectable abnormalities on ocular or cranial nerve examinations. Strength was intact throughout, but tone was increased in both lower extremities. Coordination examination was notable for bilateral upper extremity action tremor, and ataxia of gait. Hyperreflexia was noted in both biceps and knee reflexes. Palmomental reflex was present and symmetric. The examination was notably absent of clonus, myoclonus, or excessive movements. His presentation was reminiscent of a partially akinetic-mute state.
Investigations
Test results are presented below (Tables , ). Cerebrospinal fluid (CSF) analysis showed elevated protein content with normal white blood cell counts. Special CSF testing showed elevated levels of 14-3-3 protein. Real-time quaking-induced conversion (RT-QuIC) was negative. Autoimmune and paraneoplastic studies were negative. Electroencephalography performed over several days on multiple occasions showed diffuse background theta slowing without epileptiform discharges or electrographic seizures. Magnetic resonance imaging (MRI) brain with and without contrast showed extensive patchy subcortical white matter lesions on T2 and fluid-attenuated inversion recovery (FLAIR) sequences (Fig. ). MRI also showed mild diffuse volume loss without parenchymal or meningeal enhancement. CT angiography of the head and neck was unremarkable. CT of the chest, abdomen, and pelvis showed mild mesenteric and hilar lymphadenopathy. Subsequent mesenteric lymph node biopsy was unremarkable.
The patient’s cognitive impairment and akinetic mutism continued to deteriorate concurrent with development of urinary incontinence. A 3-day course of high-dose intravenous methylprednisolone (1000 mg each day) was empirically given without any clinical improvement. A selective serotonin reuptake inhibitor was tried without success. Two cycles of electroconvulsive therapy (ECT) were not effective. Unfortunately, the patient died a month after presentation from complications of aspiration pneumonia.
This clinical presentation is ambiguous. Progressive cognitive impairment was notably involved with memory, behavior, and mood disturbances along with late-onset urinary incontinence. Upper motor neuron signs and spasticity were detected in the lower extremities with mild ataxia. We will discuss the differential diagnoses of this ambiguous presentation.
Exploring the uncertainty
Progressive multifocal leukoencephalopathy (PML) is a multifocal, white matter disease that occurs in immunosuppressed patients (Table ). It is manifested by altered mental status, cortical symptoms (aphasia, motor weakness), and gait ataxia []. On neuroimaging, PML can appear as symmetrical or asymmetrical, single or multifocal white matter lesions. Sometimes it can also involve gray cortical matter []. The diagnosis is made by demonstrating a positive PCR of John Cunningham (JC) virus DNA with or without brain biopsy. JC virus DNA in CSF has a sensitivity of 92% []. PML with negative CSF JC virus PCR can also be seen in patients with human immunodeficiency virus (HIV) []. The PML diagnosis is possible in this case as the clinical presentation and MRI findings are suggestive. However, it remains uncertain as CSF was negative for JC virus in two separate samples.
Creutzfeldt–Jakob disease (CJD) is a prion disease that is characterized by subacute progressive dementia associated behavioral and motor impairments []. Cognitive decline involves areas of high cortical function such as aphasia, apraxia, and frontal lobe function. Behavioral changes include apathy, emotional lability, and anxiety. All these features were found in our patient. Also, myoclonus can be seen in CJD. Spasticity and extensor plantar responses are found in CJD, which were detected in our patient. Akinetic mutism is also one of the features of late-stage CJD. MRI findings commonly seen are diffusion-weighted imaging (DWI) and FLAIR hyperintensity signals in putamen and caudate nucleus. Sometimes white matter changes can be detected []. The findings of our case were inconsistent with the commonly seen MRI findings in CJD as MRI showed extensive white matter changes only. Moreover, the progression of MRI findings of cases of CJD was not seen with the repeat MRI in our case. Electroencephalography (EEE) in this case did not show the characteristic periodic spike wave complexes that can be seen in 65% of cases with CJD []. Real-time quaking-induced conversion (RT-QuIC) sensitivity ranges from 92% to 95% in cases of CJD []. The negative RT-QuIC makes the diagnosis of CJD unlikely. On the other hand, the specificity of 14-3-3 is around 80%, that is, there are high rates of false positives []. CSF 14-3-3 can be positive in other cases such as paraneoplastic encephalopathies and metabolic encephalopathy. In conclusion, the clinical features were suggestive of CJD, although neuroimaging and CSF testing made the diagnosis unlikely.
Adult-onset leukoencephalopathies are a heterogeneous group of white matter diseases that affect myelination and are manifested by dementia and psychiatric and movement symptoms. Usually they present early in life, but adult-onset leukodystrophies can be seen [–]. Features of leukodystrophies with similar clinical presentation are summarized in Table 3. None of the adult-onset leukoencephalopathies fully explains the clinical picture of this patient. In addition, enzyme levels were not affected.
Autoimmune and paraneoplastic encephalitis have a wide clinical presentation ranging from limbic encephalitis to neuropsychiatric symptoms []. FLAIR lesions can affect both white and gray matter, unlike the MRI findings in this case. Antibody panel that screens for autoimmune and paraneoplastic encephalitis was negative. A whole-body scan was unremarkable except for mild hilar and mesenteric lymphadenopathy, which had not shown any neoplastic features on histological assessment. Lastly, the lack of clinical response to a trial dose of intravenous steroids makes this diagnosis unlikely.
Primary central nervous system (CNS) lymphoma is a rare neoplastic disorder that presents with change in behavior, mood abnormality (depression), and sometimes focal neurological deficits and seizures []. Primary CNS lymphoma appears as either hypointense or isointense on T2 MRI sequence and contrast homogeneously []. This is different from what was seen in this patient. CSF analysis with two cytology screenings was negative for lymphoma cells. All these findings make this diagnosis unlikely.
Finally, methotrexate (MTX)-induced neurotoxicity has been described in multiple cases. It can be divided into acute, subacute, and chronic []. Aseptic meningitis can be seen in the acute setting after receiving MTX. It presents with features of meningitis, including fever, vomiting, and headache, and is generally transient after stopping MTX []. Leukoencephalopathy can be detected after long-term use of MRX and is usually mild and symptomatic and can disappear after therapy cessation. On the contrary, disseminated necrotizing leukoencephalopathy (DNL) is a rare, fatal form of methotrexate-induced neurotoxicity []. DNL usually occurs with intrathecal and intravenous MTX. However, DNL was also reported in patients on low-dose oral MTX []. It can happen months after the initiation of treatment. Clinically, DNL presents with changes in personality, progressive dementia, and sometimes seizures and motor symptoms. It can lead to death in a few months. Brain MRI usually shows extensive subcortical white matter lesions (patchy or confluent) that appear on T2 and FLAIR signals. Sometimes, these lesions can give some contrast enhancement. White matter changes can affect all brain regions, especially the posterior region (occipito-parieto-temporal), and can thus be mistaken for posterior reversible leukoencephalopathy (as initially in this patient), which can also be seen in patients on methotrexate. Finally, DNL is progressive and does not respond to cessation of treatment. The features of DNL do resemble the clinical presentation of this case; however, it is difficult to confirm the diagnosis in the absence of a brain biopsy.


A four-month-old infant boy was presented to the pediatric emergency department of Afzalipour Hospital in Kerman, Iran, with a two-day history of fever, tachypnea, and several times vomiting. The infant was the first child and had consanguineous parents. The infant had respiratory distress, drowsiness, and severe dehydration at the time of admission. Upon admission, the infant's anthropometric measures were weight 5.5 kg, height 63 cm and the vital signs were temperature 39°C, respiratory rate 52 per minute, heart rate 180 per minute, blood pressure of 75/50 mm Hg, and oxygen saturation of 95% in room air.
The laboratory findings (as shown in Table ) revealed hyperglycemia and ketoacidosis. Chest computed tomography (CT) scan reported unifocal ground-glass opacity in the apical segment of the right upper lobe (RUL) (Figure ). Nasopharyngeal swab for reverse transcription-polymerase chain reaction (rRT-PCR) test was positive for SARS-COV-2. The results of blood and urine cultures were negative. Parents did not report contact with any suspected febrile patient.
Treatment with isotonic fluids and intravenous insulin was initiated for him and he was transferred to the pediatric intensive care unit (PICU). Regular monitoring of vital signs, electrolytes, and blood glucose was performed. Apart from supportive therapy, no other treatment was initiated for COVID-19. Gradually, his level of consciousness and general condition improved. The DKA was resolved after two days of treatment. Therefore, breastfeeding and subcutaneous Neutral Protamine Hagedorn (NPH) insulin were initiated for the patient.
The starting dose of NPH insulin for the patient was 1.5 units at night. Blood glucose was measured regularly to adjust the insulin dose. The patient's insulin dose was gradually increased to one unit in the morning and one and a half units at night. After three days of admission, his fever subsided and after seven days of admission, he was discharged.
Results of genetic analysis of Neonatal Diabetes Mellitus (NDM) Exome Panel are shown in Table . A homozygous missense variant was detected in the EIF2AK3 gene. Mutations in Eukaryotic Translation Initiation Factor 2-ALPHA Kinase 3 (EIF2AK3) on chromosome 2p11.2 can cause Wolcott-Rallison syndrome (OMIM 226980; autosomal recessive). The patient's parents were informed about the results of the genetic test. Eventually, they were referred to genetic counseling.


A 13-year-old spayed female domestic shorthair cat was presented to the Veterinary Teaching Hospital of the University of Padua with a recent history of weight loss, progressive dyspnoea, respiratory crises and multiple episodes of regurgitation in the previous week. According to the owners, the cat also experienced difficulty in eating and drinking.
On physical examination, the patient had decreased muscular masses with a reduced body condition score (BCS 4/9), mucus membranes appeared slightly pale with capillary refill time of 2 s. The patient exhibited marked tachypnoea (65 breaths/min), with inspiratory dyspnoea and bilateral reinforced respiratory sound with stridors and wheezes on thoracic auscultation, and slight bradycardia (140 bpm).
Diagnostic workup included haematology, biochemistry and urinalysis, which were within normal limits, and serum protein electrophoresis that revealed a slight decrease in the albumin fraction and an increase in the α2- and β1-globulin fractions.
Head, neck and thoracic x-rays performed under sedation revealed a soft tissue 2.6 × 2.2 cm mass that displaced the larynx dorsally. Moreover, a mild pulmonary interstitial pattern was observed bilaterally.
The laryngeal mass was inspected under sedation by oral cavity examination and sampled for cytology through a trans-oral fine needle aspiration. Cytology revealed a highly pleomorphic cell population. Cells were polygonal or elongated in shape, organized in small groups or individually, with abundant, lightly basophilic cytoplasm that often showed one large, intensely eosinophilic, perinuclear body. Nuclei were round to irregular in shape with granular chromatin and prominent nucleoli. Anisocytosis and anisokaryosis were marked. Additionally, macrokaryosis and multinucleated cells as well as cellular cannibalism were frequently observed (Fig. ). Based on the cytological findings, diagnosis of a malignant, poorly differentiated neoplasm was made. Based on cytomorphology, the differential diagnoses included a poorly differentiated carcinoma and a poorly differentiated soft tissue sarcoma.
Following the cytology results, a contrast-enhanced CT scan of the head, thorax and abdomen was performed for staging purposes and for surgical planning. CT findings showed an ill-defined, moderately contrast enhancing (pre-contrast HU: 36, post-contrast HU: 96) mass surrounding and largely invading the larynx. Both retropharyngeal lymph nodes appeared markedly enlarged and necrotic (Fig. ). No further tomographic changes in distant organs were detected.
The extension of the tumour and its location were not amenable to conservative surgery with complete surgical margins. Due to poor prognosis owners declined further investigations and opted for symptomatic treatment with meloxicam 0.6 mg/kg daily.
After a partial remission of clinical signs over a period of 10 days, the patient showed progressive deterioration of clinical conditions and severe respiratory sings and was euthanized 1 month after first clinical presentation. Euthanasia was performed under general anaesthesia using a combination of a curariform-like agent, a narcotic, and a local anaesthetic.
On post-mortem examination, two distinct, bilateral laryngeal masses were found. Both tumour masses arose from the mucosa of the cuneiform process of the arytenoid cartilage, and protruded in the laryngeal inlet dramatically reducing the lumen. The larger mass measured 2.8 × 2 cm and extended caudally involving the vocal cords, whilst the smaller was located more cranially involving the aryepiglottic fold. Both masses were well demarcated, exophytic, with firm texture, smooth, with white-tan colour on cut surface (Fig. ). Mild hyperaemia of the surrounding structures was observed and no other alterations were found on necropsy.
Both laryngeal masses were sampled, formalin fixed, routinely processed and haematoxylin and eosin stained for histological examination.
All sections were characterised by an infiltrative neoplastic population that expanded the laryngeal submucosa and extended deeper involving the arytenoid cartilage. Neoplastic cells were observed in poorly demarcated, partially encapsulated nodules, in which they were arranged in nests and cords supported by a moderate to abundant fibrovascular stroma. Cells were moderately preserved, oval to elongated in shape, with mostly distinct borders and a variable amount of pale eosinophilic cytoplasm, with scattered basophilic granules and an occasional large (up to 20 μm), brightly eosinophilic, glassy round to oval body, mainly located in the perinuclear area. Nuclei were round to oval, occasionally indented, with coarsely stippled chromatin and one prominent nucleolus. Histological criteria of malignancy, including anisocytosis, anisokaryosis, and macrokaryosis, were marked. Multinucleated cells (up to 6 nuclei per cell), and cellular cannibalism were frequently observed, while mitotic figures were 4 per 10 high power fields (HPFs; diameter of the field of view = 0.55 mm; HPF = 237 mm2; 40× magnification, Nikon Eclipse Ci-L, Nikon Instruments, Japan). Lymphocytic infiltration of the tumour mass and peripheral aggregates of lymphocytes with rare histiocytes were also present (Fig. ).
Based on histology, a diagnosis of undifferentiated malignant laryngeal tumour was made and any possible cellular origin of the tumour between epithelial, mesenchymal, or neuroendocrine was included. In order to further investigate the tumour phenotype, an immunohistochemistry (IHC) panel including pancytokeratin (PanCK), cytokeratin 5/6 (CK 5/6), and cytokeratin 8/18 (CK 8/18) as epithelial markers, p63 and calponin as myoepithelial markers, vimentin as mesenchymal marker, neurofilaments and chromogranin as neuroendocrine markers was performed, while CD3 and CD20 were included to better characterise the lymphocytic infiltrate. All antibodies included in the IHC panel were previously tested in cats (Table ).
Virtually all neoplastic cells showed a strong and diffuse membranous and cytoplasmic immunolabelling for PanCK. In addition, the same cells also showed a diffuse cytoplasmic positivity that ranged from mild to intense for CK 5/6, while mild cytoplasmic positivity for CK 8/18 was observed in scattered neoplastic cells. Occasionally, tumour cells showed a nuclear immunolabelling for p63. Interestingly, aggregates of p63-positive cells were observed specifically adjacent to, and palisading on connective stromal septa. Calponin immunoreactivity was only observed in stromal cells and on vessel walls. Vimentin expression was limited to tumour stromal cells, infiltrating inflammatory cells (lymphocytes and histiocytes) and blood vessels. Immunolabelling for neurofilaments was only observed in the peripheral nerves within tumour nodules, whilst chromogranin was negative. Lymphocytic aggregates at the periphery of the tumour had an equal distribution of CD3+ and CD20+ cells, whilst tumour infiltrating lymphocytes were mainly CD3+ (Fig. ).
In the light of the IHC results, the tumour was deemed an undifferentiated laryngeal carcinoma.
In order to better clarify the content of the large cytoplasmic vacuoles that were consistently observed in both cytological and histological samples, a periodic acid-Schiff reaction (PAS) was performed. However, both on cytological and histological samples, cytoplasmic vacuoles were PAS-negative.
Neoplastic tissue was then excised from paraffin and processed for transmission electron microscopy (TEM) examination. Ultrastructural results confirmed the presence of pleomorphic neoplastic cells with cytoplasmic vacuolations. Moreover, the presence of cytoplasmic, non-membrane bound, electron-dense deposits was also observed (Fig. ). TEM results therefore confirmed the diagnosis of undifferentiated laryngeal carcinoma, with the presence of cytoplasmic accumulations of electron-dense material that was compatible with the eosinophilic bodies observed both on cytology and histopathology.


A 61-year-old female with history of pulmonary embolism (PE), not on anti-coagulation, presented to the emergency department (ED) with pressure-like chest pain and associated dyspnea starting approximately eight hours prior to presentation. Her electrocardiogram on arrival had one-millimeter ST elevations in anterior and inferior leads, and the triage physician activated the cardiac alert system ().
On arrival to the resuscitation room in the ED, she was afebrile, had a normal oxygen saturation on room air, a blood pressure of 151/85 millimeters of mercury and a heart rate of 142 beats per minute. The patient reported ongoing chest pain. She was given 325 milligrams of aspirin, and the interventional cardiologist was consulted. The patient was awake and alert and was answering questions appropriately. She reported that her prior PE had been provoked in the setting of childbirth over 20 years earlier but remained anticoagulated until four years prior to her current presentation when she discontinued, after a discussion of risks and benefits with her primary care physician. She had no other significant medical history and was not taking any medications regularly. Review of systems was notable only for a recent diagnosis of shingles, currently on antiviral medications.
Point-of-care ultrasound was performed, which demonstrated markedly reduced ejection fraction with apical hypokinesis, no pericardial effusion, no evidence of right ventricular strain, no aortic flap or dilation, and no evidence of deep vein thrombosis in bilateral lower extremities (). Due to the apical predominant dysfunction, the patient was asked about recent psychosocial life-stressors, which she denied (). She had a single view chest radiograph which showed no mediastinal widening, evidence of pulmonary edema, or pneumonia. Initial laboratory data were unremarkable with the exception of a potassium of 3.4 millimoles (mmol) per liter (L) (reference range: 3.5–5.1 mmol/L), a brain natriuretic peptide level of 227 picograms per milliliter (pg/mL) (0–100 pg/mL), and a troponin of 6.0 nanograms (ng)/mL (<=0.04 ng/mL). Given ongoing chest pain and electrocardiographic findings, the decision was then made in conjunction with the interventional cardiology team to take the patient to the cardiac catheterization lab to rule out an ischemic etiology, although stress-induced cardiomyopathy was a leading diagnosis on the differential.
Coronary angiography showed no evidence of coronary artery disease. The patient was subsequently transferred to the cardiac intensive care unit (CICU) for ongoing management of acute cardiomyopathy. At time of admission to the CICU, the patient’s dyspnea had worsened, and she had a three to four liter oxygen requirement. While in the catheterization lab, thyroid studies resulted with an undetectable thyroid stimulating hormone and a free thyroxine (T4) level of 5.75 ng/dL (0.89 – 1.76 ng/dL). Endocrinology was consulted to assist in management of a presumed thyroid storm. Further history revealed no prior history of known thyroid disease, but mild symptoms of thyrotoxicosis including weight loss (22 pounds in the prior month) and new intermittent tremor over the preceding several months.
Due to concerns that thyroid storm was contributing to heart failure symptoms, the inpatient team started propylthiouracil at 400 milligrams (mg) every six hours, potassium iodide oral solution (SSKI) five drops every six hours, hydrocortisone 100 mg intravenously every eight hours, and an esmolol infusion (to allow careful titration given reduced ejection fraction). Heart rate, palpitations, and dyspnea improved with treatment of thyroid storm. During hospitalization, thyroid stimulating hormone receptor antibody, thyroglobulin antibody, and thyroid peroxidase antibody levels were found to be elevated, consistent with Graves’ disease.


Our patient was a 20-year-old female who presented to the emergency department (ED) with two hours of diffuse abdominal pain. She had similar episodes of abdominal pain in the past that occurred once or twice a year after food intake, which were relieved with pain medication. On current presentation, her pain was far worse than usual.
Initial vitals were unremarkable, without tachycardia and without fever. Upon examination, the patient’s abdomen was soft but diffusely tender from the epigastrium to the hypogastrium. She exhibited no guarding or rebound tenderness. Her laboratory studies included an unremarkable chemistry panel, a slight leukocytosis of 11.3 thousand cells per microliter (K/μL) (reference range: 3.9 – 11 K/μL), and a normal serum lactate of 0.76 millimoles per liter (mmol/L) (normal < 2 mmol/L). An upright chest radiograph did not demonstrate pneumoperitoneum. Intravenous morphine and famotidine were administered with minimal relief of symptoms. Computed tomography of the abdomen and pelvis (CT A/P) with oral and intravenous contrast demonstrated a distended stomach, a duodenum that did not definitively cross midline, mildly dilated small bowel loops that were mostly in the right lower quadrant and, most distinctively, an SMV that twisted in a 360° counterclockwise fashion to the left of the SMA. A presumed diagnosis of malrotation and midgut volvulus was made and prompt surgical consultation was obtained.
The patient was taken emergently to the operating room for an exploratory laparotomy. The bowel was found to be in its proper anatomic position with normal peritoneal attachments and without the presence of any Ladd’s bands. (These fibrous bands of peritoneal tissue are embryologic remnants and the ultimate cause of malrotation.) On postoperative day one the patient underwent an upper endoscopy, revealing erosions and erythema in the stomach and superficial duodenal ulcers. Her postoperative recovery was unremarkable, and she was discharged home uneventfully with the diagnosis of gastritis and peptic ulcer disease.


A 34-year-old gentleman was presented with acute loss of vision in both eyes and headache for one week. It was later followed by a few episodes of epistaxis. The patient had no nasal symptoms like anosmia, nasal congestion, or obstruction. There were also no ocular symptoms like proptosis, periorbital swelling, or diplopia. He did not have any fever, nausea, vomiting, or loss of weight and appetite. He was a non-smoker and had no family history of malignancy. He worked as navy personnel and denied any exposure to coal, coal, chromium, and nickel.
On examination, the patient’s visual acuity in the right eye was 2/60 and 3/60 in the left eye. Optic nerve functions such as light brightness, red saturation, and color vision tests were reduced in both eyes. There were no limitations of extraocular muscle movement with no diplopia and proptosis. Fundoscopy showed a bilateral swollen disc with a normal macula reflex. As the patient had concomitant epistaxis, a rhinologist was consulted. The nasal-endoscopy assessment showed a polypoidal fleshy mass occupying both nasal cavities, obstructing the osteomeatal complex. Other cranial nerves and central nervous system examinations were normal. Systemic examination was unremarkable.
Contrast-enhanced computed tomography (CECT) of the brain and PNS revealed a large lobular extra-axial lesion measuring 4.2 x 4.7 x 3.4 cm in the ethmoidal sinus with surrounding bony erosion. The mass extended to the extraconal compartments of both orbits with compression of both optic nerves and medial recti muscles, nasal cavity, sphenoid sinuses, and anterior base of the skull (Figure ). Biopsy of the mass revealed SNUC with bone and perineural invasion. Immunohistochemistry showed tumor cells were positive for CKAB1/AE3, cytokeratin 7 (CK7), epithelial membrane antigen (EMA), vimentin, CD99, BCL-2, p53, synaptophysin, and Ki67 (Figure ).
The patient underwent successful combined endoscopic and transcranial excision of the tumor. Debulking of the tumor was performed via bicoronal craniectomy with the base of skull reconstruction. Post-operative right eye vision improved to 6/9 but his left eye worsened to no light perception. Funduscopy showed resolving optic disc swelling in both eyes. He was planning for four cycles of chemotherapy. Intravenous cisplatin 75 mg/m2 and 5-fluorouracil 750 mg/m2 on day 1 to day 5 of adjuvant were given for a total of three cycles. Just before his third cycle of chemotherapy, he complained of worsening right eye vision. CECT of the brain and orbit showed a significantly increasing size of the paranasal mass measuring 6.2 x 5.1 x 7.1 cm. The mass was invading the intraconal spaces bilaterally with compression to both optic nerves (Figure ). Subsequently, he underwent intensity-modulated radiation therapy (IMRT) of the fasciocervical region with a dose of 70 Gy for 35 cycles for seven weeks and weekly intravenous cisplatin 40 mg/m2. During his recent follow-up, his visual acuity remained non-perceptive of light in both eyes with left eye proptosis. Fundoscopy showed bilateral optic atrophy. There was no other neurological problem.


This is a case of a 49-year-old female patient, known to have juvenile rheumatoid arthritis currently managed with methotrexate and adalimumab. The patient had undergone a bilateral total knee replacement ten years prior to presentation.
She initially presented after sustaining a low-energy fall from standing height. Plain radiographs were done and showed a supracondylar displaced periprosthetic fracture of the left distal femur ().
The fracture was comminuted with segmental bone defect in the distal femoral region. The patient underwent surgical open reduction and internal fixation (ORIF) with bone graft and lateral plate-and-screw ().
The surgery was performed with neither intraoperative nor direct postoperative complications, and the patient was discharged one week postoperatively. The patient was followed with a series of radiographs to assess for satisfactory healing, alignment, and stable construct fixation. One month postoperatively, a follow-up radiograph showed fracture reduction with start of callus formation ().
Two months postoperatively, follow-up radiographs () showed nonunion with severe comminution in the distal femoral region characterized by significantly low bone stock, which was also seen in the radiographs that followed in seven and nine months postoperatively ().
A computed tomography scan with 3D reconstruction was done one year after the surgery showing failure of hardware, nonunion, and malalignment ().
Consequently, an elective surgical repair was scheduled. The primary lateral plate was removed, and an intramedullary fibular allograft was introduced through the intercondylar region into the medullary cavity supplemented with lateral plate fixation (lateral curved LCP 8 hole condylar plate (Synthes, Beirut, Lebanon)) and medial minimally invasive (MIS) plate (medial curved LCP 18 hole condylar plate (Synthes, Beirut Lebanon)) fixation. Demineralized bone matrix (DBM) and bone morphogenic protein-2 (BMP-2) were also inserted.
Follow-up radiographs () done one month postoperatively showed stable fixation and alignment with beginning of healing and callus formation.
In addition, further follow-up imaging done at three, five, and seven months postoperatively () showed improvement in healing.
The patient progressively improved to a painless, full range of motion mobilization of the knee. She suffered no postoperative complications of graft rejection, infection, or mechanical instability on weightbearing.
Ten months after the surgery, the patient was admitted for bilateral plate removal with bone graft placed in screw holes. Cultures obtained two months later revealed negative tissue and serum results, and plain radiographs () showed complete healing of the fracture with a satisfactory alignment.


The patient is a 66-year-old man with a history of celiac sprue who presented to the gastroenterology clinic to evaluate a new abdominal wall nodule. The patient was otherwise asymptomatic. Abdominal and pelvic computed tomography showed an ill-defined, round density mass measuring approximately 2.5 cm in greatest diameter, just to the right of midline, with surrounding fat stranding (Figure ). This was monitored clinically.
Surveillance imaging performed 6 months later showed that the mass had doubled in size (Figure ). The mass was adjacent to the transverse colon with noted mesenteric inflammation; however, there was no obvious mucosal invasion. On physical examination, he had an 8 × 10-cm mobile, nontender right upper quadrant abdominal wall mass. Ultrasound-guided fine-needle aspiration (FNA) showed acute and chronic inflammation with no evidence of malignancy.
Owing to the lesion's proximity to the colon and concern for underlying malignancy or inflammatory bowel disease, the patient underwent a diagnostic colonoscopy. This showed scarred, erythematous, and nodular mucosa in the transverse colon (Figure ). An India ink tattoo was placed proximally and distally for possible surgical resection. Biopsies of this area revealed ulceration with histiocytic and neutrophilic infiltrates, no malignancy, and negative acid-fast bacillus and Gram stains. The patient had no systemic symptoms or change in bowel habits at this time.
Given the nondiagnostic results of these studies, the patient went for surgical resection of the right upper abdominal wall mass en bloc with right hemicolectomy to resect the affected mid and proximal transverse colon. Surgical pathology of the abdominal wall mass revealed actinomycosis with abscess formation but was negative for dysplasia or malignancy. The colon pathology was negative except for mild histiocytic and neutrophilic infiltration. The patient completed a 6-week course of IV penicillin. On the 1-year follow-up, the patient was doing well, with no evidence of recurrence and healthy ileocolonic anastomosis on follow-up diagnostic colonoscopy.


A 57-year-old Caucasian female with a history of hypertension and cholecystectomy, and a recent diagnosis of optic neuritis in the left eye with impaired vision, who was treated with intravenous steroids (methylprednisolone 1 gram daily for five days) and discharged on a tapering dose of steroids (initial dose: 60 mg prednisone daily), presented to the emergency room less than 24 hours after the discharge for evaluation of abdominal pain with vomiting.
After discharge, the patient experienced pain in the left side of her abdomen and had an episode of non-bloody vomiting. She had no reported diarrhea, black stools, or blood in the stools. The patient took Aleve (ibuprofen) for pain, which did not relieve the pain completely. She denied alcohol consumption. The patient had no fever, chills, cold, cough, shortness of breath, body aches, urinary complaints, loss of sensation of smell, and/or new changes in vision.
Her prescription medications included metoprolol succinate, spironolactone, albuterol inhaler, multivitamins, and the newly started prednisone 60 mg daily with a tapering regimen. On physical examination, she was noted to have mild tenderness in the left hypochondrium and left lumbar regions with no guarding or rigidity. Murphy's sign was negative. No organomegaly was appreciated. The patient had blurred vision in the left eye attributed to her recent optic neuritis with no new changes in her vision, compared to the previous exam done before discharge. The initial lipase level was 1212 U/L (normal range: 11-82 U/L), which eventually became normalized by the time of discharge 55 U/L (normal range: 11-82 U/L). The laboratory values of the patient at the time of admission are presented in Table .
Computed tomography (CT) of abdomen and pelvis without contrast (Figure ) showed infiltrative/inflammatory change of fat around the pancreas, second and third portion of the duodenum, and to a lesser degree in the left perinephric space. Findings were consistent with pancreatitis, duodenitis, and duodenal ulcer disease with no evidence of perforation or left pyelonephritis. No fluid collections were observed.
An ultrasound of the abdomen showed hepatic steatosis with hepatomegaly and post-cholecystectomy changes with no common bile duct stone. A slightly prominent pancreas was also noted, likely related to acute pancreatitis. A gastroenterologist was consulted for further evaluation and an esophagogastroduodenoscopy (EGD) was performed due to the abnormal CT abdomen and pelvis findings. EGD findings included a 1-cm hiatal hernia with a normal duodenum. Los Angeles (LA) Grade B esophagitis and erythematous gastric mucosa were also noted.
COVID-19 polymerase chain reaction (PCR) pre-procedure testing was negative. Cancer antigen 19 (CA 19-9) was 78.0 U/mL (normal ≤ 35 U/mL). Magnetic resonance imaging (MRI) of the abdomen with and without contrast was performed due to elevated CA 19-9. It showed mild heterogeneous hepatic steatosis and mild hepatomegaly. Ill-defined margins of the pancreas with tiny scattered cystic changes were noted, related to pancreatitis.
With no other identifiable cause of acute pancreatitis, it was concluded that the acute pancreatitis was most likely due to steroid use. Steroids were stopped after consulting the neurologist who prescribed the steroids and supportive care. The patient was treated with intravenous (IV) fluids and analgesics. She improved clinically during the hospital stay and was able to tolerate a soft diet by the time of discharge with no abdominal pain, nausea, or vomiting. The neurologist recommended no further continuation of oral steroids. At the time of release, the patient had no additional worsening of visual symptoms. The patient was advised to avoid steroid use and recommended to follow up with a gastroenterologist as an outpatient with a repeat CA 19-9.


We present a case of a five-year-old female who was diagnosed with Ebstein anomaly and right aortic arch prenatally at 20 weeks of gestation by fetal echocardiography. The pregnancy was conceived via in vitro fertilization by 37 years old nullipara woman. Up to 35 weeks of gestation, the mother of the patient used nadroparin and acetylsalicylic acid as a treatment for a thrombophilia with protein S deficiency. There was no other remarkable family history and all previous standard pregnancy follow ups were unremarkable.
As pregnancy was conceived via in vitro fertilization and thus regarded high risk, the woman was referred to our medical center (Children’s Clinical University Hospital in Riga, Latvia) for fetal echocardiography at 20 weeks of gestation, resulting in the diagnosis of Ebstein anomaly and right-sided aortic arch. The tricuspid valve was noted to be dysplastic and apically displaced with mild regurgitation. The size of the right ventricle was decreased, and aortic arch was coursing to the right of trachea (). Further follow-up visits were done once a month up to the delivery, with no remarkable changes in the condition.
The patient was born at 40 weeks of gestation in spontaneous vaginal delivery weighing 3450 g, having a length of 55 cm and an Apgar score of 9/9. At day 4, patient was transferred to our medical center for further evaluation. Physical exam revealed acrocyanosis and systolic murmur, findings of other organ systems were without any significant deviations from the norm.
Chest x-ray, electrocardiogram, Holter monitoring, transthoracic echocardiography, abdominal ultrasonography, neurosonography, karyotyping, and genetic testing for 22q11.2 deletion syndrome were done. Transthoracic echocardiography confirmed the prenatal diagnosis of Ebstein anomaly and right-sided aortic arch. The electrocardiogram showed a partial right bundle branch block. Other examinations and tests done were unremarkable. At day 11, patient was discharged home in an overall compensated state without any recommendations for pharmacotherapy.
During the first six months of life, monthly follow up visits were done. The patient’s parents had no complaints and imaging studies did not show a significant progression of the condition. Further regular follow up visits with a pediatric cardiologist were done 1–2 times a year. The cardiac function in the first two years of life remained stable. Persistent oval foramen was observed, but it closed spontaneously at the age of three. Starting from the third year of life, progression of the condition was observed. At the age of four, due to progressive dilation of the right atrium and increasing regurgitation of the tricuspid valve, a magnetic resonance imaging was done to better assess the heart’s anatomy and aid in the consideration of the surgical treatment options. The magnetic resonance imaging showed that aortic arch and descending aorta in the mediastinum were located on the right side of the trachea in accordance with the previous diagnosis (see ). It also showed the tricuspid valve placed 23 mm apically from the mitral valve, moderate tricuspid regurgitation, and decreased ejection fracture of the right ventricle.
Although karyotyping and genetic testing for 22q11.2 deletion syndrome (DiGeorge syndrome) were done right after birth and were normal, overtime, some physical, motor, and mental development delays were observed and thus additional evaluation by medical genetic was done. It revealed some external ear anomalies, significant growth retardation (both weight and height below 3rd percentile), which together with congenital heart defects warranted more detailed genetic testing. The genetic test results revealed mutation in the chromodomain helicase DNA binding protein 7 (CHD7) gene, which, together with clinical features, allowed to establish a diagnosis of Charge syndrome.


On 9 April 2020, a 56-year-old obese man (BMI 35) of Black African origin with discoid lupus erythematosus (treated with hydroxychloroquine 200 mg twice a day) presented at the emergency department (ED) of the Centre Hospitalier Universitaire Saint-Pierre (CHUSP) with dyspnea for 2 weeks, dry cough, chest pain, myalgia, headache, ageusia, and diarrhea. One week earlier he had returned from the Democratic Republic of Congo (DRC) where he resided for 2 months. Malaria prophylaxis (atovaquone/proguanil) was taken correctly. Upon admission, a nasopharyngeal swab was taken and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected by real-time reverse transcription polymerase chain reaction (RT-PCR) (RealStar® SARS-CoV-2 RT-PCR Kit 1.0, Altona Diagnostics GmbH, Hamburg, Germany; targeting E-gene and S-gene) with a crossing point (Cp) of 36, but no abnormalities were observed on a chest computed tomography (CT) (Fig. ) and oxygen saturation was 100%. His body temperature was 37.1 ℃ and the following laboratory parameters were within normal limits: C-reactive protein (CRP; 1.0 mg/L), leukocytes (4.3 × 103/μL), lymphocytes (1.8 × 103/μL), neutrophils (1.8 × 103/μL), platelets (214 × 103/μL), and hemoglobin (14.7 g/dL). The patient was placed in home quarantine for 2 weeks.
On 28 April he presented himself to Universitair Ziekenhuis Brussel's (UZB’s) ED with chest pain, abdominal pain, and diarrhea for a week. The imaging was repeated, but again no abnormalities were observed on a chest CT (Fig. ). However, cardiac troponin T was slightly elevated (0.011 μg/L), suggesting the diagnosis of pericarditis. Aspirin (1000 mg four times a day) was prescribed and the patient was discharged.
On 4 June, SARS-CoV-2 RT-PCR (RealStar®) was performed prior to a planned 1-day hospitalization in UZB for gastroscopy because of postprandial bloating. This test was negative. No abnormalities were found by the gastroscopy, and the patient decided to discontinue hydroxychloroquine on his own initiative as gastrointestinal discomfort can be a side effect of the drug.
A serological analysis (LIAISON® SARS-CoV-2 S1/S2 IgG, Diasorin, Saluggia, Italy) performed 127 days after the initial episode (14 August) could not detect anti-SARS-CoV-2 IgG antibodies against spike protein.
On 28 August (141 days after the initial episode), the patient presented at UZB’s ED with dyspnea, productive cough, malaise, fever, dysosmia, and dysgeusia for 3 days. A nasopharyngeal swab was taken showing a strong positive result for SARS-CoV-2 (Cp 14) (RealStar®). Moreover, laboratory analysis showed a mild leukopenia (3.2 × 103/μL) and lymphocytopenia (0.9 × 103/μL), however CRP (1.8 mg/L), neutrophils (1.6 × 103/μL), platelets (168 × 103/μL), and hemoglobin (13.2 × g/dL) were within normal limits. No abnormalities were observed on a bedside chest radiograph (Fig. ). The patient was placed in home quarantine, but presented himself again 4 days later (1 September) because of persistent complaints with decreased oxygen saturation (93.9%). He was hospitalized and oxygen therapy was started (2 L/min). The oxygen could be stopped after 12 hours (oxygen saturation 99%) and he stayed in the hospital for 1 week with symptomatic treatment. An evaluation for humoral immune deficiency was performed, however no general antibody deficiency was observed by measurement of serum immunoglobulin levels (IgG, IgA, IgM). Only 4 days after his hospital discharge, the patient presented at CHUSP’s ED with dyspnea, productive cough, and chest pain. Laboratory results showed an elevation of D-dimer (4183 ng/mL) and CRP 32 mg/L. The following parameters were within normal limits: leukocytes (8.3 × 103/µL), lymphocytes (1.9 × 103/µL), neutrophils (5.4 × 103/µL), platelets (314 × 103/µL), and hemoglobin (13.0 g/dL). A CT pulmonary angiogram was performed showing pulmonary embolism and ground-glass opacities compatible with viral pneumonia (Fig. ). Serological analysis performed 158 days after the first episode (14 September), showed the presence of anti-SARS-CoV-2 IgG antibodies to spike protein (130 AE/mL, Diasorin). Anticoagulation by tinzaparin sodium was initiated (followed by rivaroxaban after 14 days, 15 mg twice a day), as well as empirical antibiotic therapy by ceftriaxone (2 g daily for 7 days). No antiviral therapy or supplemental oxygen was started. On 29 September he was discharged, 173 days after the initial episode.
Genome sequencing was performed on nasopharyngeal swabs from the first and second episode with a MinION (Oxford Nanopore Technologies, Oxford, United Kingdom) using the ARTIC network nCoV-2019 sequencing protocols and analytic pipeline by Josh Quick []. From the sample of the initial episode, taken 2 weeks after the first symptoms, only a fragmented genome (6028 out of 29903 bps) could be determined, most likely due to a low viral load of the nasopharyngeal swab (Cp 36). A full-length sequence of the second episode could be determined, revealing a lineage B.1. SARS-CoV-2 [].
Seven mutations were identified across the genome of the two strains (Table ). Especially the key block mutation at positions 28881 to 28883 (AAC to GGG) in the nucleocapsid phosphoprotein region resulting in an amino acid change (lysine-arginine to arginine-glycine), indicates that the patient suffered from a reinfection []. The coverage for this triplet region was 121-fold for the first episode and 1586-fold for the second episode (with presence of the mutation in 100% of the reads).


Case 1. A 58-year-old woman recently diagnosed with acute myeloid leukemia (AML) started induction therapy with cytarabine and daunorubicin, as well as IFI prophylaxis with posaconazole. The patient had a fever since presentation and at day twenty after beginning of induction she presented severe headache localized to the right frontal and temporal lobes and right orbit, associated with photophobia, diplopia, reduced visual acuity, papilledema, ptosis and third and fourth cranial nerve palsies. CT-scan showed pansinusitis and MRI showed infiltration of the right cavernous sinus and sphenoid sinus and a massive pseudoaneurysm suggesting IFI. Empiric treatment with liposomal amphotericin B was initiated and she underwent a maxillectomy, right ethmoidectomy and bilateral sphenoidotomy. Biopsy of these structures confirmed the presence of Aspergillus hyphae. Despite reduction of symptoms and antifungal therapy there was almost no improvement of lesions and the patient eventually died.


Case 2. A 42-year-old man with previous history of non-specified pulmonary infection, presented productive cough, respiratory distress, fever, night sweats and pleural effusion. CT-scan showed moderate right pleural effusion and a heterogeneous consolidation process with hypodense areas, foci of cavitation, and air bronchogram. Lung biopsy showed pulmonary parenchyma involved by a necrotizing inflammatory process, in the presence of fungal structures (suspected aspergillosis). Patient started voriconazole but PCR for Aspergillus and Mucorales was negative in the biopsy sample. Further molecular studies were performed and a Clasdosporium sphaerospermum was identified. One month later, the patient was diagnosed with a B-cell acute lymphoid leukemia BCR-ABL+, with central nervous system involvement, and chemotherapy was started. During chemotherapy, voriconazole was changed to liposomal amphotericin B due to hepatic toxicity. Later on, it was possible to restart voriconazole. Despite all this, there was only mild improvement of pulmonary lesions in imagiological evaluations.


Case 3. A 66-year-old woman admitted with acute myeloid leukemia started induction therapy with cytarabine and daunorubicin and IFI prophylaxis with posaconazole. One month later she developed febrile neutropenia. CT-scan showed several nodular opacities of ill-defined limits, predominantly in the lower pulmonary lobes, and bilateral ground glass nodules. She started empiric cefepime and voriconazole. Antibacterial regimen was later changed to meropenem and amikacin due to persistent fever. PCR on bronchoalveolar lavage was positive for Pneumocystis jirovecii. Trimethoprim/sulfamethoxazole was initiated, but fever and respiratory symptoms persisted leading to the suspicion of an emergent IFI. Patient started liposomal amphotericin B with improvement of symptoms, defervescence and imagiological regression of the lesions. Nonetheless, no agent was identified.
Conclusions: These clinical cases illustrate how invasive fungal infections are very heterogenous and difficult to approach with unpredictable outcomes in hematological patients. Establishing a definite diagnosis of IFI is particularly challenging in immunocompromised patients, but delayed initiation of appropriate antifungal therapy increases mortality. A strategy of empirical or preemptive introduction of antifungal therapy is very important in this population.


AB is a 3-year-old-boy who came to the health centre because of different burns on his head and upper limbs. As the initial protocol of data collection, information was sent to the group, with photos of the child and the main problems. According to our data analysis, it was included in route 3. Our group concluded by the photos that almost 28% of the body had first- and second-grade burns caused by boiled water (head and left upper limb), which had subsequently scarred over. There was a persistent rigidness in the hand, with closed fist; in the face, his left eyelid could not be closed, and his mouth was not able to open, close, or move. He spoke by a little lateral gap between the lips and could not fed or maintain properly the food in his mouth.
The urgency of the case made the group give indications to the family for scar treatment while recovering more information about the adherence of the scars, functionality of the hand, and pain of the skin. According to the information returned, because of the eyelid damage, there was reduced visibility and an excessive dryness of the eye, which could lead to ulcers. We trained the personnel in Kalana in the Galveston technique, Kinesio Tape, and cohesive bandage through a specific protocol, and she gave the appropriate indications to the family about the use of both cohesive bandage and k-tape (the health centre could buy them to provide it to the family) to treat the adherence of the scars and eyelid, as well as the indications regarding cleaning and hydration of the scar to avoid limitations in joint range and mobility. Once a month, or once every two months, the family returned to the health centre so we could provide new indications about improving the mobility of the hand and the feeding.
After one year of intervention, the child can now feed properly, holding the food within the mouth with a good use of the orofacial musculature without losing it. He can close his eye voluntarily and is able to do grasp and precision grips to participate in his daily living activities with the rest of the family. With this, he can join his family life.


Echocardiography in a fetus at 25 weeks of gestation (WG) from a 19-year-old woman, without history of familial CHD, showed: (i) a typical partial common AVCD with a cleft on the left atrioventricular valve (AVV) without stenosis or leak and a large ostium primum atrial septal defect (ASD); (ii) Ebstein abnormality of the right AVV with a significant leak, causing a dilatation of the right atrium (RA) (; ); (iii) “functional pulmonary atresia” with inconstant anterograde passage and (iv) retrograde flow in a tortuous ductus arteriosus. Other cardiac structures were normal. Cytogenetic analysis via amniocentesis had normal results. At 30 WG, moderate atrialization of the right ventricle and a pulmonary insufficiency were noted ().
After vaginal birth at 37 WG, she was polypneic and cyanosed, with a pulse oxymetry at 70%. There was a cardiomegaly on the chest X-ray. The EKG showed no pre-excitation syndrome and a typical left QRS axis. The postnatal transthoracic echocardiography (TTE) confirmed the diagnosis. The right ventricle was functional with an insufficient antegrade pulmonary flow, so-called “functional pulmonary atresia”. Color Doppler imaging showed severe regurgitation of the right AVV and right to-left shunt through the ostium primum defect, but the left-sided AVV was not restrictive and only leaked minimally. The Great Ormond Street Echo (GOSE) score was 0.7 (grade 2). Nevertheless, the large partial AVSD was an obstacle in calculating the GOSE score accurately. The initial management consisted of alprostadil infusion, nitric oxide (NO) and non-invasive ventilation. A specific delivery device of inhaled NO was used with non-invasive ventilation. This device provided a reliable and precise nitric oxide blend with a constant concentration proportional to the ventilatory flow. Indeed, elevated pulmonary vascular resistance may reduce flow across the pulmonary valve. The administration of inhaled NO may help in this situation. During the first 2 weeks, the saturation improved, and treatments were weaned. She was discharged and had a normal somatic growth without treatment. Close follow-up mainly showed the progressive dilation of the right cardiac structures (RA + atrialized right ventricle), and elective surgery was planned at 20 months of age and 10 kg of weight.
The surgical inspection confirmed the lesions: Ebstein’s disease was atypical and severe and was an intermediate type between B and C []. The following description starts from the anteroseptal commissure and goes clockwise: the anteroseptal commissure was very unusual, as if a first part of the anterior valve was missing. A portion of the septal band, the posterior division of the moderator band, reached the atrioventricular valve ring. Then, a small part of the next anterior valve was normally developed. The opening was like the “tricuspid funnel” type and therefore was quite primitively directed towards the infundibulum (). Moving to the right and downwards, we quickly found a muscularized valve; then, in some places, a portion was indissociable from the right ventricle (which corresponds more or less to the beginning of the posterior valve, which nevertheless existed), but also, in some other places, was delaminated. Thus, it was unquestionable that it was an Ebstein, although rather atypical. For example, the only real “atrialized” part was in fact at the level of the anterior septal commissure.
Partial AVCD was also indisputable with respect to the left side. There was no ventricular septal defect, and the left atrioventricular annulus was complete and glued to the septal crest. There were three components: one anterior, one posterior and one mural valve (). The cleft was not complete; a few mm of tissue united the anterior and posterior components paraseptally. There was a typical ostium primum. Thus, the procedure consisted of a tricuspid “cone” repair with the complete closure of the ostium primum ASD via an autologous pericardial patch and the closure of the left atrioventricular cleft.
Transesophageal echocardiography and TTE showed trivial to mild insufficiency of the left and right AVV, without stenosis, no residual shunt, a moderate dysfunction of the RV free wall and a normal left ventricular function. No rhythm or conduction disorders were noted. The post-operative course was marked by some RV dysfunction (improved with NO and sildenafil). All treatments were rapidly weaned, and a successful extubation was achieved 9 h after her admission to the pediatric cardiac intensive care unit. She was discharged home after 14 days.
One year later, the child is NYHA I, with normal growth. TTE shows a good biventricular function, mild tricuspid insufficiency without stenosis and no stenosis or leak on the left AVV.


We present the case of a 29-year-old nulliparous, 39-week pregnant woman who was hospitalized for irregular contractions in early labor, no ruptured membranes, no bleeding and very good fetal movements. The pregnancy follow-up was uneventful, with both first and second-trimester anomaly scans within normal limits. There was no other associated pathological medical history. Clinical examination and vital signs were normal. At the ultrasound examination, the placenta was high posterior, there was normal amniotic volume, cephalic presentation and active fetal movements, and estimated fetal growth of 3500 g with normal umbilical, cerebral and uterine arteries doppler.
During routine cardiotocography, a pathological trace was recorded—tachycardia and late deceleration (). As per guidelines [], immediate action to correct reversible causes and additional methods to evaluate fetal oxygenation were required. Because the patient requested a vaginal delivery and chronic hypoxia needed to be excluded, the artificial rupture of membranes was performed to rule out the presence of meconium and to assess other possible causes of fetal hypoxia. The amniotic fluid had a normal aspect, with no signs of meconium, blood or foul smell. Having excluded infection and chronic hypoxia, and because the trace was reassuring with stable baseline and normal variability, the plan was to reassess progress in 2 h under continuous CTG monitoring, IV hydration and maternal repositioning. Two hours later, another event raised the concern of suspected fetal compromise—a prolonged 4 min late deceleration immediately after a high amplitude fetal movement ()
A decision was made for a category 2 cesarean section. A healthy 3500 g male was delivered in good condition (Apgar score 8). The macroscopic placental examination was normal. During the first routine clinical examination of the neonate, a Wharton’s jelly anomaly was identified at the abdominal umbilical cord insertion. For approximately 1 cm of length, umbilical cord vessels were completely uncovered by Wharton’s jelly. The condition required surgical thread elective ligation of exposed umbilical cord vessels ().


Case 1 was a 40-year-old woman with a history of food intolerance, preliminarily diagnosed as an unspecified allergy, and she was admitted in 2018. Gastrointestinal symptoms, such as cramping, abdominal pain and flatulence, and problems with defecation, manifested for six years, usually up to 30 min after eating. The cytotoxic test (Metabolic code 203) indicated, among others, gluten intolerance and a mandatory recommended elimination of products containing gluten. Due to the fact that celiac disease and gluten allergy were excluded, the introduction of small amounts of gluten products under the control of clinical symptoms was recommended before IgG4 examination. The highest value of IgG4 concentration was obtained for egg white and casein (). A four week diagnostic diet was proposed by excluding flour, dairy, and egg products and then successively introducing these products one by one every two weeks. After introducing eggs, no changes in the patient’s wellbeing were reported, while stomach pain was recorded after drinking milk. Moreover, when gluten products were reintroduced for two days only, digestive problems were noted (). Currently, the patient is on a strict gluten-free diet. Preliminary diagnosis was corrected into malabsorption induced by intolerance. Three heterozygous variants, c.2528G > C (rs558054487), c.8673G > T (rs57672167), and c.9313T > G (rs2065958), were reported in patient one (A–C).


Case 2 was a 44-year-old woman diagnosed with an unspecified allergy due to non-specific symptoms after consuming food, observed for the past five years. The following problems were recorded: hand trembling (after eating almonds), feeling alternating cold and hot, stinging eyes, feeling “lumps in the throat” and on the cheeks, drooling, andscratchy throat (after cookies and biscuits). Two years before the visit, she underwent a cytotoxic test (Metabolic Code 203) and confirmed a higher level of intolerance to most products, mainly wheat, yeast, and dairy products. The patient noticed an improvement after eliminating some of the products but was concerned about a weight loss of 5 kg. The increased results of IgG4 concentration against food allergens were obtained for eggs and peach (), which were eliminated for four weeks, followed by their introduction one after the other. At present, the patient tolerates eggs in small quantities. However, she avoids peaches, especially raw fruits, which may provoke cross reactions with pollen allergens. The patients are sensitive (positive skin prick tests (SPT) for birch, hazel, and alder allergens and a periodic runny nose in spring). She rarely drinks milk, which is also suspected of exacerbating the symptoms. The elimination of bread was also recommended due to the clinical symptoms observed in the patient (). One heterozygous variant c.9536T > G (rs2065957) was detected in patient two (D).


Case 3 was a 23-year-old woman with a suspected food allergy who has been observing gastrointestinal symptoms, including diarrhea and flatulence, and, less frequently, skin symptoms for about 2–3 years. As the symptoms occurred several hours after ingestion, it was not easy to observe what kind of products might have caused them. She connected the symptoms with dairy products and eliminated them for six months, bringing about short-term improvement. Therefore, she rarely eats dairy products. She also attempted to eliminate eggs from her diet, but after reintroducing them, she did not observe any difference in symptoms manifestation, although she did not eat scrambled eggs. She thought that the symptoms could also have been intensified by wheat bread, citrus fruits, or cocoa. An ImuPro test (in IgG class) showed a level of IgG ≥ 20 µg/mL (defined as “high”) for some vegetables, such as broccoli, red cabbage, carrots, celery, and for eggs and yeast, which were eliminated together with eggs. The patient is very fond of egg dishes and, therefore, did not fully comply with these recommendations. Due to abdominal discomfort, she limited the consumption of bread and dairy products. The highest IgG4 titer was obtained for egg white and casein; thus, a 4-week diagnostic elimination diet was introduced, excluding dairy and egg products (). Baked and boiled eggs are well tolerated. However, flatulence still appears after the consumption of dairy products (cottage cheese and yogurt), although cheese was tolerated well (). The introduction of low-lactose products (lactose-free cheese is tolerated), testing for lactose intolerance, and a visit to the gastroenterologist were recommended. In patient three, two heterozygous variants were identified as follows: c.9313T > G (rs2065958) and c.9536T > G (rs2065957) (E,F).


Case 4 was a 49-year-old woman suspected of food allergy who came to CEAC with abdominal ailments, which appeared for the first time in 2012 after eating Russian dumplings and an initial diagnosis of unspecified allergy. The patient reports that abdominal pain frequently appeared after eating fatty foods, dairy products, eggs, and sugar. However, it is difficult to state them accurately because they usually appear 2–3 days after consumption. The abdominal ultrasound examination performed in 2014 revealed no pathological changes, while endoscopy of the upper part of the gastrointestinal tract (in 2015) singled out the presence of a sliding hernia of the esophageal solution. An ImuPro test for food intolerance showed positive results for wheat, rye, barley, oats, gluten, yeast, banana, and pineapple (). Discontinuation was recommended as follows: products containing gluten proteins, avoiding yeast, sugar, alcohol, and consumption of lactose-free products. Serological and pathomorphological diagnostics towards celiac disease were negative. The IgG4 examination indicated the highest value for eggs and peaches (). An observational elimination diet was recommended for dairy products (because of symptoms occurrence), eggs, bread (mild symptoms), and peaches, after which she did not report any severe symptoms after consuming dairy products (). After consuming dumplings and using some cosmetics, abdominal discomfort and skin symptoms (erythema on the forehead) were noted. Comparable to patient three, the same variants (c.9313T > G (rs2065958) and c.9536T > G (rs2065957)) were reported in patient four (G,H).


A 39-year-old young female with no history of heart disease was admitted with palpitation, shortness of breath for 2 years and aggravation for 6 months. On admission, her blood pressure was 110/60 mmHg and her heart rate was 68 beats/min without cardiac murmurs. Her lower limb were not swollen. Electrocardiogram and laboratory examinations were normal range.
Chest radiography revealed that her cardiac shadow was enlarged to the left. Echocardiography showed a mass of the pericardium. Coronary computed tomography angiography (CCTA) demonstrated that the distal segment of the LCX was significantly dilated with contrast agent filling and with huge thrombi (Fig. a) in the pericardium. Volumetic reconstruction showed that distal segment of the LCX were remarkably dilated (Fig. b). The left anterior descending branch and left coronary trunk were normal. The patient underwent the coronary angiography and selective micro catheter angiography of the LCX, which revealed a distal fistula of the LCX communicating with the pericardium (Fig. ). The right coronary artery and the left ventriculography were normal. Therefore, a diagnosis of the LCX fistula complicated with false aneurysm was confirmed.
The patient was admitted to the department of cardiac surgery for the LCX repair, partial resection of pseudo aneurysm wall and for coronary aneurysm thrombectomy after all examinations were complete. During the operation, a mass with a size about 25 × 20 mm was found in the left rear of the left ventricle, which was located under the epicardium. Then cardiopulmonary bypass was established, a massive thrombi inside the pseudoaneurysm were observed after the left rear of the mass was opened (Fig. a). And the total amount of thrombi was about 250 g (Fig. b). After that, the CAF was explored. It was found that the CAF opened on the outer wall of the pseudoaneurysm, with a length of about 3 mm. Finally, the fistula was sutured with 4–0 silk thread and most of the pseudoaneurysm wall was resected. The excised lesions were sent for pathological examination. The pathological diagnosis was pseudoaneurysm and mixed thrombi. Follow-up has been carried out for six years, the patient was in good condition after surgery.


Case 1: A 36-year-old woman was referred to our hospital with acute abdominal pain. She had undergone urgent laparoscopic cholecystectomy at our hospital 2 years previously for acute cholecystitis. Because of severe inflammation around Calot’s triangle, laparoscopic SC was performed at the previous operation. Her blood biochemical data at presentation to our hospital were as follows: white blood cells, 8430/µL (4000–9000/µL); hemoglobin, 12.7 g/dL (11.0–15.0 g/dL); platelets, 28.6 × 104/µL (15.0 × 104–45.0 × 104/µL); albumin, 4.2 g/dL (3.4–4.8 g/dL); total bilirubin, 0.7 mg/dL (0.2–1.2 mg/dL); AST, 540 U/L (13–33 U/L); ALT, 242 U/L (6–27 U/L); γ-GTP, 341 IU/L (6–46 IU/L); C-reactive protein (CRP), 0.24 mg/dL (0.00–0.30 mg/dL) and prothrombin time international normalized ratio (PT-INR), 0.95 (0.80–1.30). Contrast-enhanced computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed remnant gallbladder calculi, but no choledocholithiasis (Fig. ). Laparoscopic remnant cholecystectomy for the remnant gallbladder calculi was planned. The patient was administered 0.25 mg/kg of indocyanine green (ICG, Daiichi Sankyo Co., Japan, Tokyo) intravenously 16 h before surgery for NIFC. A trocar for the laparoscope was inserted into the umbilicus by the open method, and three trocars were placed in the right upper quadrant. The laparoscopic system was VISERA ELITE II OLYMPUS CLV-S200-IR (OLYMPUS Co., Japan, Tokyo). There was adhesion of the duodenum to the hepatoduodenal ligament (Fig. a). After adhesionectomy of the duodenum (Fig. b), the common bile duct was identified by NIFC (Fig. c). The remnant gallbladder was identified as a defect in the fluorescent image. Since the remnant cystic duct showed inflammatory thickening, it was divided after one ligation and two clips (Fig. d). Since the cystic artery was cauterized by Sonosurg (OLYMPUS Co.) at the first operation, it could not be identified in this operation. Cholangiography was performed through a preoperatively placed ENBD-tube to confirm the presence of calculi, but the tip of the tube migrated to the duodenum. No further intraoperative treatment was performed because the calculi were confirmed in the resected specimen. The surgical duration was 114 min and the estimated intraoperative blood loss was 10 mL. The resected specimen of the remnant gallbladder was 2.0 cm in diameter and the calculi were 5 mm in diameter (Fig. ). The patient’s postoperative course was uneventful, and the patient was discharged on postoperative day 4. The abdominal pain and elevated liver enzymes improved immediately after surgery.


Case 2: A 40-year-old woman was referred to our hospital with epigastralgia caused by calculi in the remnant gallbladder. Ten years ago, she had undergone urgent open SC for severe acute cholecystitis with a midline incision. Her blood biochemical data at presentation to our hospital were as follows: white blood cells, 9600/µL (3500–9100/µL); hemoglobin: 14.7 g/dL (11.3–15.2 g/dL); platelets, 32.2 × 104/µL (13.1 × 104–36.9 × 104/µL); albumin, 4.5 g/dL (3.9–4.9 g/dL); total bilirubin, 0.6 mg/dL (0.1–1.1 mg/dL); AST, 21 U/L (9–37 U/L); ALT, 34 U/L (3–49 U/L); γ-GTP, 53 IU/L (6–71 IU/L); CRP, 0.13 mg/dL (0.00–0.20 mg/dL) and PT-INR, 0.93 (0.89–1.07). Contrast-enhanced CT and MRCP showed the remnant gallbladder and a calculus, but revealed no other findings as the cause of the upper abdominal pain (Fig. ). Laparoscopic remnant cholecystectomy was planned. ICG was administered intravenously, as in Case 1. Trocar placement and the laparoscopic system were the same as for Case 1. There was extensive adherence of the greater omentum from beneath the midline incision to the caudal surface of the liver. After dissecting the adhesions, a duodenum-like structure adherent to the gallbladder bed and the hepatoduodenal ligament was seen (Fig. a). NIFC clearly showed the border of the duodenum-like structure (Fig. b). Accordingly, the border was dissected as the margin of the duodenum and remnant gallbladder. However, dissection at the border caused injury to the bulb of the duodenum (Fig. c). The fluorescent part of the duodenum-like structure was in fact a part of the duodenum, because the fluorescence of the remnant gallbladder penetrated the duodenum. Thus, after adhesionectomy of the duodenum, the remnant gallbladder could be detected at the dorsal side of the duodenum (Fig. d, e). The cystic duct, cystic artery and common bile duct were identified (Fig. f), and the cystic artery and cystic duct were divided. Intraoperatively, the tip of a nasogastric tube was placed beyond the bulb of the duodenum into the descending duodenum for decompression of the suture site, and the duodenal wall was sutured primarily. Surgical duration was 280 min, and intraoperative estimated blood loss was 100 mL. The resected remnant gallbladder was about 3.0 cm in diameter, and the calculus was 6 mm in diameter (Fig. ). The nasogastric tube was removed on the 3rd postoperative day, and the intraoperatively inserted drainage tube was removed on the 5th postoperative day. Oral intake was initiated from the 6th postoperative day. The patient was discharged on the 15th postoperative day with an uneventful course. The patient had no abdominal pain after the operation.


A 15-year-old girl presented with a palpable mass in her right breast, which she has had for 2 months; during this time, she noticed that the lump had not increased in size. She did not have systemic symptoms or a history of weight loss. During the physical examination, two solid and painless masses were appreciated in the upper-outer and the central-low quadrants; the skin overlying the lesions was completely normal and there were no palpable lymph nodes. Blood count, liver and kidney function tests, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), and uric acid blood levels were in the normal range. Ultrasound (US) showed a 6 cm hypervascular mass with indistinct margins in the upper-outer quadrant and other two smaller masses (diameter 1.9 cm and 2.1 cm, respectively), probably connected to the largest one, in the central-low portion; moreover, two enlarged homolateral axillary lymph nodes (maximal diameter 1.7 cm) were identified. On breast magnetic resonance imaging (MRI), a 6.5 cm single and irregular mass with intense contrast enhancement and three suspected axillary nodes (maximal diameter 1.5 cm) were described. US-guided needle biopsy of the right breast lesion was performed; analysis was carried out with a Leica microscope (dm2000 led, Objective: x63), Leica ICC50HD camera and Leica Acquire software for Macbook pro 16’ 2,6 GHz 6-Core Intel Core i7; histologic examination (Figs. and ) showed a diffuse large B-cell lymphoma, not otherwise specified (DLBCL, nos), CD19+, CD20+, of germinal center origin according to immunohistochemical algorithms (CD10+, BCL6+, IRF4/MUM1+, FoxP1+, LMO2+, HGAL+), with high proliferation index (MIB-1 80%). A high expression of c-MYC protein was found (70%); however, fluorescence in situ hybridization (FISH) analysis was negative for MYC translocation (Vysis break apart and IGH/MYC dual fusion translocation probes) as well as for BCL2 and BCL6 translocations (Break apart translocation probes), excluding a high-grade B-cell lymphoma with double hit. Finally, no evidence of Epstein-Barr virus (EBV) was found with in situ hybridization for the Epstein-Barr virus-encoded small RNAs (EBERs). The staging was completed with bone marrow aspirate, lumbar puncture, brain MRI, neck-thorax-abdomen computerized tomography (CT) scan, and whole-body positron emission tomography (PET)-CT scan (Fig. A); a high fluorodeoxyglucose (FDG) uptake with a maximum standardized uptake value (SUVmax) of 11.5 was evidenced in the right breast. No other organ involvement was ascertained. According to St. Jude staging [] and the new revised International Pediatric Non-Hodgkin Lymphoma Staging System (IPNHLSS) [], the stage was IIE (single extranodal tumor with regional node involvement). The girl received intensive combination chemotherapy according to the AIEOP LNH-97 trial (risk group 3) [] plus rituximab (Table ). After the second block of chemotherapy, breast MRI and whole-body PET-CT scan showed a complete radiologic and metabolic response (Fig. B). These examinations were repeated at the end of the treatment, confirming the disappearance of any lesions. The total duration of chemotherapy was approximately 3 months and the girl is alive without any evidence of disease after 20 months from the end of treatment.


A 14- month-old boy was referred to our hospital at the age of three months with the diagnosis of post-COVID-19 bronchiolitis obliterans for further management. The child was born at 39 weeks to a COVID-19 positive mother and consanguineous parents by normal vaginal delivery with a birth weight of 3.7 kg. He neither required any resuscitation at birth nor did he develop any respiratory distress. On day 2 of life, the baby tested positive for COVID-19 and was admitted for nine days. His investigations were found to be within normal ranges. He was kept on nasal cannula support for four days only. Three months after discharge, the child was readmitted due to difficulty breathing, cough, and poor feeding. Lab investigations were normal, with a negative respiratory viral panel. Initial chest X-ray showed bilateral opacities at mid and lower lung zones (Figure ).
He was initially treated as post-COVID-19 bronchiolitis with possible superimposed infection, for which he received a course of antibiotics. Furthermore, as the child’s condition was not improving, further imaging studies were obtained. A CT scan of the chest with contrast showed mosaic attenuation pattern in both lower lungs, bilateral ground-glass opacities with areas of reduced attenuation, areas of oligemia and air-trapping, cylindrical bronchiectasis, mild bronchial wall thickening in areas of ground-glass attenuation, fibrotic changes with distorted lung architecture, and few mediastinal lymph nodes, all of these were features suggestive of bronchiolitis obliterans (Figures -).
The baby was referred to our hospital with an impression of post-infectious bronchiolitis obliterans (PIBO) on oxygen support and fluticasone, azithromycin, and montelukast (FAM) regime.
On admission, further history was taken. Parents mentioned that the child was always having fast breathing with sweating and brief cyanotic episodes after feeding. On physical examination, a hypotonic and poorly nourished child with weight below fifth centile, chest examination showed mild tachypnea with subcostal and intercostal recession, bilateral fine crackles, other systems examinations were unremarkable. Initial investigations like complete blood count (CBC), electrolyte, liver, and kidney function tests as well as inflammatory markers were unremarkable. The child remained oxygen dependent with frequent desaturation below 75% and required admission to the intensive care unit (ICU) due to respiratory distress. At this time, in view of his clinical progression, review of the radiological findings, and lab tests, suspicion of interstitial lung disease was raised. Keeping in mind the differential diagnosis of the interstitial lung disease, we extended our scope of investigations. Flexible bronchoscopy was carried out with normal morphology. Bronchoalveolar lavage (BAL) showed many foamy macrophages with dispersed bronchial epithelial cells and degenerated epithelial cells mixed with inflammatory cells, mainly neutrophils with negative culture. The child was evaluated further with a cardiac echocardiogram, swallow study with the fiberoptic laryngoscope, and ultrasonography of the urinary system (US KUB), all of which were normal except for a right ectopic kidney on the US.
Further genetic evaluation for childhood interstitial lung diseases (chILD) panel was sent, which revealed a homozygous pathogenic variant mutation in the ABCA3 gene. The child was started on oral steroids, but he did not improve. He was admitted multiple times with aspiration pneumonia. He remained on 4L oxygen at home by nasal cannula.
At the age of seven months, as the child had a poor response to steroids, we decided to start a course of hydroxychloroquine 45 mg daily with azithromycin restarted 10 mg/kg/day for three days per week. Later, at the age of 13 months, the child was also started on methylprednisolone pulse therapy as 10 mg/kg/day for three days monthly. Currently, the child is 14 months old, gaining weight and height, on 0.5 L oxygen at home, and can last a couple of hours during the day without oxygen support (Figures -).
The repeated high-resolution CT of the chest (HRCT) revealed diffuse ground-glass opacities, septations, central bronchiectasis, subpleural small cysts, and fibrotic changes, which did not show any progression from previous imaging (Figure ).
We plan to continue on combination therapy with hydroxychloroquine, azithromycin, and methylprednisolone pulse therapy.


A 43-year-old male presented to the emergency department of our hospital with a 5-day history of typical chest tightness radiating to his back. He was previously fit except for a 3-year history of recurrent cough and fever between 37 and 38°C with a significant weight loss of ~7.5 kg. He was diagnosed as asthma and had been received regular Seretide inhaler (salmeterol and fluticasone propionated inhalation) therapy for 1 year.
In the emergency department, his electrocardiogram (ECG) showed acute myocardial infarction (). Physical examination revealed sinus tachycardia of 116 beats per minute. His blood test revealed elevated creatine kinase-MB 38 U/L (normal 0.10–4.94 U/L) and high-sensitivity troponin-T 1.19 ng/ml (normal < 0.014). The total white blood cell count was 18.97 × 109/L with marked eosinophilia 9.42 × 109/L (normal 0.05–0.50 × 109/L). Chest CT indicated multiple lung infiltrates and small patches of ground-glass appearance in both lungs (). Transthoracic echocardiogram (TTE) showed normal systolic and diastolic function (ejection fraction: 63%); however, increased echogenicity of endocardium and slightly reduced wall motion was detected in the basal segment of inferior wall. Thus, coronary artery disease could not be excluded. Considering it had been more than 12 h since the onset, coronary angiography (CAG) was not performed until Day 7, showing normal coronary arteries (). Thus, the diagnosis of MINOCA was confirmed. Cardiac magnetic resonance imaging (CMR) showed normal wall motion with inflammatory edema (), and late gadolinium enhancement (LGE) was found in multiple foci ().
Noticing his blood test of significant eosinophilia, we made further examinations to evaluate the underlying causes of MINOCA. The level of IgE was elevated to 3,739.00 IU/ml (normal 0–120 IU/ml). Anti-neutrophil cytoplasmic antibody was negative, while IgG and IgG4 were markedly elevated (19.10, 6.700 g/L, respectively normal: 10.13–15.13, ≤ 2.00 g/L, respectively) (). Bone marrow aspiration and biopsy were performed, and no parasites or hematological diseases were found. Furthermore, hematologic tumor cloning biomarkers were all negative.
In addition, paranasal sinus computed tomography (CT) revealed whole group sinusitis. Electromyography showed partial peripheral nerve damage in the upper and lower limbs and abnormal F waves. Since he fulfilled all the criteria of the six American College of Rheumatology (ACR) classification criteria for EGPA () and all other possible hypereosinophilic diseases were excluded, the diagnosis of EGPA-associated MINOCA was made.
After being diagnosed as EGPA, the patient started on intravenous methylprednisolone (40 mg/day), and his eosinophil count, CRP, IgG, IgG4, and IgE returned to normal within 1 week (), and the lung infiltrates obviously disappeared (). He was discharged from the hospital without any discomfort, and mycophenolate mofetil dispersible (0.75 mg QD) was added to methylprednisolone as maintenance. After 3 months, echocardiogram performed showed normal wall motion and cardiac function. ECG showed that the R wave amplitudes in lead II and avF increased significantly compared with those at the onset of MINOCA (). CMR showed regression of edema () and significant resolutions of myocardial fibrosis (). Now, the maintenance dose of prednisone for this patient is gradually decreased to 17.5 mg per day, and the patient is still under follow-up.


A 45-year-old man underwent robotic-assisted intersphincteric resection with covering ileostomy for a moderately differentiated adenocarcinoma (ypT3N0M0) low rectal cancer following long-course neoadjuvant chemoradiotherapy. Circumferential margin was 1 mm with evidence of perforation. He completed adjuvant chemoradiotherapy (FOLFOX) and underwent ileostomy reversal 6 months later. Over the next 3 years, he complained of perianal pain and discharge due to anastomotic stricture and chronic fistula with pelvic abscess. Sigmoidoscopy showed no evidence of tumour recurrence. Serial CT abdomen and MRI pelvis showed increasing presacral fluid collection. He underwent laparoscopic ultra-low Hartmann’s operation. Intraoperatively, there was severe pelvic inflammation and pus within presacral space was drained. Pelvic dissection was performed laparoscopically until the anus and dissection was completed transanally within intersphincteric space. After bowel transection, specimen was delivered transanally and hand-sewn closure of anal mucosa was performed. Laparoscopic application of the mesh was performed after copious irrigation of pelvic cavity and placement of transabdominal pelvic drain followed by formation of end colostomy. He stayed for 38 days after surgery due to complication from iatrogenic bladder injury requiring bilateral percutaneous nephrostomy. After follow-up of 17.5 months, there was a history of admission to another hospital for small bowel obstruction due to adhesion that did not require surgical intervention.


A 42-year-old man with perianal abscess and fistula due to low rectal cancer had completed long-course radiotherapy but was unable to complete FOLFIRI regimen due to elevated liver enzymes because of his underlying chronic hepatitis B. He underwent robotic-assisted abdominoperineal resection (APR) 6 weeks later. Mesh placement was performed laparoscopically after placing transabdominal pelvic drain (). He developed perineal wound infection on postoperative day 4 requiring wound dressings and antibiotics. He was discharged 17 days after surgery but was readmitted 28 days after initial operation for presacral abscess requiring percutaneous drainage. Subsequent CT abdomen showed resolution of presacral collection. Histopathological examination showed moderately differentiated adenocarcinoma ypT3N0M0. He completed adjuvant capecitabine and after 12.5 months, there was no evidence of unhealed perineal wound or small bowel descent.


A 72-year-old man underwent open low anterior resection with covering ileostomy for mid rectal cancer at another hospital after completion of long-course neoadjuvant chemoradiotherapy. Ileostomy reversal was performed 3 months after surgery. He developed intestinal obstruction secondary to anastomotic recurrence 6 months later. Sigmoidoscopy and biopsy confirmed the presence of recurrent adenocarcinoma. CT abdomen showed infiltrating soft tissue mass at right pelvic cavity with involvement of presacral area and ileal loop. He was admitted to our centre and underwent laparoscopic small bowel resection. Intraoperatively, small bowel was adherent to pelvic cavity and site of recurrence resulting in proximal small bowel dilatation (). Small bowel adherent to the recurrence site was resected and side-to-side small bowel anastomosis was performed. The anastomotic recurrence was unresectable (). Transabdominal pelvic drain was inserted followed by mesh placement. He was discharged after 8 days and after a follow-up of 12.1 months, did not develop further small bowel obstruction.


A 64-year-old woman with history of total abdominal hysterectomy and bilateral salphingo-oophorectomy was diagnosed with sigmoid colon cancer with vaginal invasion and lung metastases. After 4 cycles of FOLFIRI and cetuximab, she underwent robotic-assisted low anterior resection and partial vaginectomy. She completed 12 cycles of FOLFIRI and cetuximab. Over the years, she developed systemic disease progression requiring several changes of chemotherapy and targeted therapy regimen with resection of lung and liver metastases. Two years after initial diagnosis, she developed peritoneal and pelvic recurrence. She underwent radiotherapy for pelvic recurrence and was started on oral neucloside TAS-102 after her disease progressed further. She developed recurrent mechanical obstruction 1 year after radiotherapy and underwent laparoscopic small bowel resection. Intraoperatively, iatrogenic perforation of the distended small bowel occurred during laparoscopic port access and was repaired with absorbable suture. The tumour had invaded the bladder and an adherent loop of small bowel had caused proximal bowel dilatation. Small bowel transection with side-to-side small bowel anastomosis was performed followed by mesh placement. Two transabdominal drains were inserted within pelvic cavity; 1 below and 1 above the mesh. There was no postoperative complication related to the surgery. She was discharged after 15 days. After a follow-up of 6.6 months, there was no recurrence of small bowel obstruction.


A 58-year-old man with obstructed upper rectal cancer underwent laparoscopic low anterior resection with covering ileostomy at another hospital. Ileostomy reversal was subsequently performed. He only completed seven cycles of FOLFOX due to oxaliplatin-induced persistent peripheral neuropathy. He developed anastomotic stricture due to pelvic recurrence and lung metastases as confirmed by sigmoidoscopy and CT thorax, abdomen and pelvis 9 months after his treatment necessitating transverse loop colostomy. He underwent chemoradiotherapy with capecitabine that was later changed to FOLFIRI and bevacizumab. He subsequently underwent robotic-assisted Hartmann’s procedure due to persistent pelvic pain and abscess. Intraoperatively, there was pelvic abscess due to disrupted neorectum from the pelvic recurrence. The hostile pelvic environment did not allow further dissection and proximal bowel up to the disrupted neorectum was then transected followed by formation of end colostomy. After copious irrigation of the pelvic cavity, mesh was applied using robotic assistance. Transanal drain was inserted into the opened distal neorectum lumen. There was no wound complication, and he was discharged after 31 days as he had to undergo several ganglion nerves blocks for pain management. After a follow-up of 5.2 months, there was no occurrence of small bowel obstruction.


A 54-year-old woman presented with a tumor in her left breast. The patient had no relevant medical or family history. During physical examination, an elastic hard mass measuring ~6 cm in size was palpated in the upper-outer area of the left breast (). An induration of ~4 cm was also found on the right cheek (). Mammary ultrasonography revealed an irregular hypoechoic tumor of measuring 45.0 × 43.0 × 32.0 mm in size in the upper-outer quadrant of the left breast (). Core-needle biopsy performed in the same site revealed a high degree of mixed T and B lymphocytic and plasma cell infiltration, as well as interstitial fibrosis (). Many plasma cells were IgG positive, of which >40% were IgG4 positive (). These biopsy findings led to a diagnosis of IgG4-RM of the left breast. Computed tomography exhibited no significant findings besides the left mammary mass and left axillary swelling (). IgG4-RD was diagnosed based on hematological examination results revealing elevated serum IgG4 levels (332 mg/dl). Based on comprehensive diagnostic criteria for IgG4-RDs, we diagnosed the patient with IgG4-RM. The condition was treated with prednisolone (30 mg/day, 0.6 mg/kg/day) for 4 weeks, which resulted in a decrease in the tumor size. The patient is currently being followed up with maintenance therapy.