A 62-year-old female with bilateral symptomatic varus knee osteoarthritis (). A preoperative radiograph shows a left lower limb mDFA of 0° and mPTA of 7° varus, resulting in an aHKA of 7° varus. Following the algorithm (), we should correct the mPTA from 7° to 5° (Principle 2). Her neutral mDFA, would lead to an aHKA of 5°, which is >3° (Principle 1). Further tibial varus reduction (down to 3°) would impact the knee's flexion gaps balance. Instead, following the algorithm, we suggest adding 2° of valgus to the distal femoral cut. No femoral rotation modification is needed, and femoral anatomy modifications are minimized (Principle 4). The overall angle correction was 4° (2 on de femoral side and 2 on the tibial side). We resurfaced the lateral compartment (lateral pivot point, Principle #5) and reduced medial compartment resection thicknesses (~2 mm thinner cuts on both the femur and tibia). To achieve medio-lateral ligament balance, we had to perform a deep MCL release alone. The postoperative radiograph confirms the achievement of our goals with a mDFA of 2° valgus and a mPTA of 5° varus ().
A 79-year-old female with a painful osteoarthritic right knee with a valgus deformity (). The patient has an aHKA of 5° valgus, resulting from a mDFA of 6° valgus and mPTA of 1° varus. Following rKA algorithm (), the mDFA of 6° valgus must be brought to 5° (Principle 2). To obtain an aHKA is <3° (Principle 1) and minimize femoral anatomy modification (Principle 4), further correction is required on the tibial side. A slight tibial varisation from 1° to 2° would lead to an acceptable aHKA of 3° valgus. We resurfaced the intact medial compartment (medial pivot point, Principle #5) and reduced lateral compartment resection thicknesses. Overall anatomy modification for this patient was 2° (1° on both the femur and tibia), and no ligamentous release was required to obtain satisfactory joint laxities. Postoperative radiograph confirms that we achieved our implant alignment goals using computer navigation ().
Further clinical examples are available in Video 4. . Surgeons should also understand how to manage specific/challenging cases (, ).


A 70-year-old female, who previously worked as a Japanese teacher at a junior high school, complained that her lower left molars were moving lingually and that her oral cavity was becoming narrow. According to her assertions, her “wrong occlusion” had been causing oral dryness and burning sensation in addition to pain in her neck and legs. She recounted that these discomforts started at X−1 years; however, her dental and medical histories were longer and more complex. At X−10 years, orthodontic treatment was initiated, which was followed by her complaints of nonspecific sensations in other parts of the body such as numbness in her hand and back pain. The orthodontic treatment was successfully completed; however, her complaints worsened following the placement of a bridge on her upper right molar at X – 5 years. Therefore, despite no evident dental problem, the bridge was removed and replaced by individual temporary crowns owing to her persistent demands (). She claimed that the orthodontic treatment affected her cranial nerves and caused these oral and body dysfunctions. She fervently demanded orthodontic retreatment; she was subsequently referred to our department from orthodontists at X years.
Her complaints seemed to have appeared following orthodontic treatment; however, a further medical interview revealed that there already had been signs of psychiatric impairment before the orthodontic treatment. She had been doctor shopping for over 35 years, which included dentists, psychiatrists, neurologists, orthopedists, dermatologists, ophthalmologists, etc., to resolve her many uncomfortable symptoms, for example, dizziness; palpitation; bloodshot eyes; pain in the eyes, nose, and throat; insomnia; vulvodynia; and so on. She had been taking ethyl loflazepate and etizolam irregularly; however, the details of her past psychotic history and treatment were unclear because she had kept wandering many psychiatrists and never managed accurately. At X−5 years, she was referred to another psychiatrist at our hospital from neurologists and was diagnosed as bipolar disorder with somatoform disorders or pain disorders. Regardless of the recommendation from the psychiatrist at our hospital, she had never undergone the continuous psychiatric treatment and kept doctor shopping.
At her first visit to our clinic in X years, although subjective oral dryness and burning sensation in her oral cavity were also complained, these oral symptoms were merely associated with her chief complain of “wrong occlusion.” Therefore, we diagnosed her symptoms as PBS and explained the typical symptoms of PBS and persuaded that orthodontic retreatment would never cure her symptoms but could probably worsen them. However, she refused our persuasions with her strong conviction that faulty occlusion was the sole reason for all her problems and demanded retreatment or referral to other dentists.


A 48-year-old female, a labor and social security attorney, complained that her occlusion was stressfully too high and sought for the alignment of her teeth since she continuously experienced suicidal thoughts owing to the uncomfortable occlusion. At Y−5 years, she suddenly started to feel anxious regarding the protrusion of her frontal teeth and decided to undergo orthodontic treatment. However, orthodontic treatment exacerbated her symptoms. She complained of shifting of her mandibular teeth on the left side and found it hard to locate the correct bite position. Despite repeated occlusal adjustments, the occlusion never matched the one that she desired. She recounted that it was hard to continue with her job. Almost all her lower teeth were fabricated abnormally high when she was referred to our clinic at Y years (). The previous orthodontist informed us that her demands were aggressive and threatening such that they had to comply with the occlusal adjustments.
Considering her psychiatric history, at Y−15 years, she was found to be depressed and she showed manic episodes and was diagnosed with bipolar disorder at Y−11 years. She presented strong suicidal thoughts for which hospitalization had been suggested, but she always denied it citing the reason that she needed to care for her pet. The insight in bipolar disorders was lacking. She had been prescribed lamotrigine 300 mg, quetiapine 50 mg, clonazepam 0.5 mg, lorazepam 0.5 mg, and olanzapine 2.5 mg (use as needed) per day at her first visit to our clinic.
We have diagnosed her as PBS at Y years. The antidepressants might be effective in several patients with PBS (, ); however, antidepressants have a risk to make mood disorder worse. On consultation with her psychiatrist, aripiprazole 1.0 mg was added. The treatment was initiated by both psychiatrists and dentists in a cooperative manner. No unanticipated events were observed. She has been advised to refrain from further occlusal changes, and she has accordingly avoided occlusal alterations. Six months later, her demands for dental treatment have declined gradually by continuing medication and collaboration between dentists and psychiatrists.


A 38-year-old female, a clothing sales assistant, presented with chief complaints of improper malaligned occlusion, unstable mandibular position, and neck pain. At Z−13 years, these symptoms occurred without any trigger. At Z−12 years, she underwent orthodontic treatment for her uncomfortable symptoms; however, her condition did not improve. At Z years, she was referred to our clinic following consultation with many dentists, including specialists in orthodontics, prosthodontics, and operative dentistry (). She complained one-sidedly and seemed to struggle to listen to our explanation.
Based on the note of her psychiatrist, at Z−21 years, she was diagnosed with neurosis following a complaint of rumbling stomach. She gradually presented social maladaptation at Z−13 years and was subsequently diagnosed with schizophrenia at Z−11 years. At Z−7 years, she was hospitalized for 6 months, and electroconvulsive treatment was performed. Subsequently, although anosodiaphoria was observed, neither loss of the personality level nor thought disorder was observed, and she was able to continue working. She was taking olanzapine 1.5 mg, lorazepam 0.5 mg, and Kampo medicine at Z years.
At Z + 1 year and 4 months, She revisited our clinic and more persistently demanded the addition of composite resin on her molars. The composite resin built up on the lower molars on both sides was already high enough to induce an open bite (). She had continued to receive occlusal adjustments every 1–2 weeks and attributed occlusion adjustment as the solution to her symptoms. She spoke continuously and never listened to our explanation of her diagnosis of PBS. The previous dentists conveyed that she returned soon after the dental treatment and always made constant phone calls. We insisted that she never undergo any further dental treatment and consulted with her psychiatrist regarding the proposal of additional treatment with aripiprazole. At Z + 2 years, she agreed to the prescription of aripiprazole. After the consultation with her psychiatrist, lorazepam was replaced with aripiprazole 1.0 mg, and olanzapine 2.25 mg and Kampo medicine were continued. Besides keeping patients distracted and apart from refraining from occlusal adjustment, psychopharmacotherapy without any adverse events and supportive collaboration have changed her behavior. She was able to wait for appointments and gradually calmed down; also, she made fewer demands for occlusal adjustment. Six months later, she had been prescribed aripiprazole 3.5 mg and olanzapine 2.25 mg and positively stated that her way of thinking had become clear and found it easier to concentrate on her work despite her prevailing uncomfortable occlusal perception.


An 81-year-old male presented to our hospital with complaints of dry cough and progressive shortness of breath for the last 3 months. He also had low grade fever for the last 15 days. There was no history of orthopnea, weight loss, pain abdomen or pedal edema. Significant past history included hypertension for the last 10 years and coronary artery disease and percutaneous angioplasty performed 5 years back. He was on aspirin, beta blockers and ramipril. On examination, there were stony dullness with decreased breath sounds in left infra scapular and axillary region. Chest roentgenogram suggestive of left side pleural effusion and aspiration showed pus in pleural cavity. Laboratory evaluation of collection was exudative in nature and was negative for Mycobacterium tuberculosis on ZN staining (20% H2SO4) and gene-Xpert. BacT/Alert liquid culture for Mycobacterium tuberculosis was also negative. Patient was treated with empirical antibiotics (amoxicillin-clavulanate 1.2 g intravenous 3 times a day) with mild symptomatic improvement and was discharged subsequently. However, he was re-admitted after 20 days with complaints of swelling on back (left posterior chest wall). The development of swelling was within the last 20 days and it did not bother the patient until recently when it became painful.
At presentation, his vitals were stable except tachypnea (respiratory rate of 24/min). He was afebrile and maintaining oxygen saturation of 93% on ambient air. Physical examination revealed pallor and a soft, fluctuant, non-tender swelling of size 12 cm X 8 cm on the left lower posterior chest wall. On auscultation, air entry was reduced on the left infra scapular and infra-axillary region with decreased vocal fremitus. Rest systemic examination was unremarkable. Blood investigations showed anemia (hemoglobin 8.9 g/dl), raised erythrocyte sedimentation rate (58 mm), elevated highly sensitive C-reactive protein (91.5 mg/dl, normal < 1 mg/dl), and mildly raised procalcitonin (0.80 ng/ml, normal < .02 ng/ml). Chest roentgenogram again suggestive of left-sided pleural effusion. His aerobic and anaerobic blood cultures were sterile. On further investigation, Computed tomography of the chest (Fig. a, b, c, d) revealed left-sided moderate pleural effusion with a posterior chest wall collection of size 12.8 × 8.2 × 3.2 cm below the latissimus dorsi with the evidence of fifth rib osteomyelitis. Since the disease was progressive despite taking antibiotics, we kept the differentials of tuberculosis and malignancy however we did not have any evidence of malignancy on radioimaging. In addition, gene Xpert was also negative which ruled out tuberculosis.
Ultrasound guided aspiration of the posterior chest wall collection was performed. Gram staining and modified Ziehl-Neelsen (ZN) staining (1% H2SO4, Modified Kinyoun method) of the aspirated pus revealed plenty of pus cells and numerous gram positive, acid fast thin slender, beaded, branching bacilli, suggestive of Nocardia Spp (Fig. ). Routine aerobic culture on 5% sheep blood agar and Mac Conkey’s agar showed the growth of small whitish to brown, dry, stony hard colonies after 5–6 days of incubation at 37 °C. The isolate was identified as Nocardia Spp based on colony morphology and characteristic staining (Fig. ).
The patient was managed with therapeutic aspiration of chest wall collection and chest tube was inserted for empyema. Three-drug regimen consisting of oral trimethoprim-sulphamethoxazole (600 + 3000 mg/day in two divided doses), intravenous amikacin (900 mg once daily) and intravenous ceftriaxone (1 g twice a day) was started. MALDI-TOF confirmed the species as Nocardia farcinica. The isolate was susceptible to most antibiotics (ceftriaxone, imipenem, amikacin, cotrimoxazole, minocycline and linezolid) except ampicillin. On day 14 of hospitalization, patient showed significant improvement and shifted to oral trimethoprim-sulphamethoxazole which was scheduled to continue for the next 6 months.


The patient was a previously healthy, white, 24-year-old female, born and resident in Feira de Santana, BA, Brazil, with a history of abdominal distension, prostration, and an episode of hematemesis 3 months before presentation. She had no history of traumas, prior thromboses, pregnancy, abdominal pains, jaundice, hematoma, or acholic stools. She denied having any degree of Asian heredity. Clinical examination confirmed abdominal distension, with collateral abdominal veins, hepatomegaly, and ascites. Laboratory test results for hepatic enzymes, coagulation, and bilirubin were within normal limits and serum albumin was low. Ultrasonographic examination showed ascites and normal hepatopetal portal blood flow. Computed tomography (CT) with contrast showed hepatomegaly with heterogenous highlighting (known as “nutmeg” liver), hypertrophic caudate lobe, and right and left hepatic veins with contrast retention. Visibility of the middle HV was poor, suggesting thrombosis (). The patient was diagnosed with BCS, probably due to obstruction of the suprahepatic outflow and was referred to the interventional radiology service for venography and treatment, after upper digestive endoscopy with endoscopic sclerotherapy of esophageal varices.
Venography was conducted under local anesthesia and analgesia with conscious sedation, using a transjugular approach, but it was difficult to catheterize the suprahepatic vein. Intravascular ultrasound (IUS) was then employed to achieve better visualization of the HV outflow into the IVC. This confirmed > 80% stenosis of the outflow of the right and left HVs and phlebography demonstrated venous stasis in both these veins, in addition to critical stenosis of the outflow. The middle HV could not be seen. A 0.035 x 260 mm hydrophilic guidewire (Terumo Medical, Somerset, NJ, United States) was then used to cross the critical suprahepatic stenosis, via the right jugular vein. Flow was reestablished by angioplasty of the stenosis using high pressure balloons, initially an 8 mm balloon and then a 12 mm balloon, (). The patient recovered satisfactorily during the postoperative period, with considerable reductions in waist circumference and collateral abdominal vessels, and was discharged from hospital 15 days after the procedure, on rivaroxaban, which it was intended she would take for 6 months.
Postoperative follow-ups at 1, 3, and 12 months were favorable, without signs of portal hypertension syndrome (PHS) in clinical examinations, laboratory tests, or imaging exams. Tests for thrombophilia were run after withdrawal of anticoagulation, with normal results. After 2 years’ follow-up, the patient presented once more, at an ambulatory consultation, 14 weeks pregnant, with no clinical or laboratory signs of decompensation. She was put on anticoagulation with fractionated heparin by the gastroenterology/hematology service. The gestation went to full term, with delivery at 38 weeks and the patient continued to progress well in the postnatal period, still on anticoagulation. After puerperium, CT demonstrated a reduction in the outlet diameter (7 mm) compared to the previous scan (12 mm) and ascites was detected by CT, despite no clinical evidence (). In conjunction with the gastroenterology/hematology service, the decision was taken to perform angioplasty of the suprahepatic vein once more.
The procedure was performed via the same approach, using the same anesthetic procedures described above, and phlebography showed around 50% stenosis of the outlet. Consecutive angioplasties were performed with 10 and 14 mm high pressure venous balloons. The result was satisfactory on venography and the patient was discharged from hospital the day after the procedure (). Control CT 1 month after the procedure demonstrated an improved outlet diameter (12 mm) and absence of ascites. She is currently in follow-up, at 1 postoperative year. Total abdominal ultrasound (US) and duplex ultrasound of the suprahepatic veins are conducted every 6 months and she is asymptomatic and has normal laboratory test results. The patient gave her consent to description and publication of the case.


A 40-years-old man was admitted to our institution with a 10-years history of chest pain and palpitation without significant weight loss. No headaches, fever, or cough was dictated with a body temperature of 36.3°C and blood pressure of 132/92 mmHg at resting conditions. Physical examination revealed that the pulse was 78 bpm. No additional heart sound or significant heart murmur was heard over the chest wall. There were no other notable clinical findings and family history of cardiovascular disease following medical history and physical examination. Also, laboratory tests were unremarkable.
Electrocardiography revealed sinus bradycardia without nodal block. No significant abnormalities were found following chest X-ray examination. Transthoracic echocardiography demonstrated normal ventricular function with a left ventricular ejection fraction of 69%; however, a saccular mass of 32 × 66 mm in size was discovered within the pericardial cavity, which extended toward the left atrioventricular groove. The saccular mass margins were well-defined and close to the left atrium and ventricle. The abnormal structure was heterogeneous with fractional acoustic enhancement and had gelatinous materials (, arrow). Cardiac computed tomography (CT) showed a 54 × 50 mm mass that appeared like densely soft tissue with an oval shape margin. Simultaneously, a contrast-enhanced cardiac CT scan detected a fountain sign from the left atrium's posterior wall to the abnormal mass (, arrow). Cardiac MRI (, arrow) was also performed, which further confirmed the left ventricular posterior wall involvement as detected by the contrast-enhanced CT scan; nonetheless, no other metastatic mass was detected. Interestingly, the pre-operative coronary angiogram was normal.
The operative team evaluated the patient before the surgical excision of the tumor; afterward, a standard median sternotomy incision is performed. Following exploratory pericardiotomy, a botryoidal saccular mass was discovered below the left atrial appendage and above the left pulmonary vein with the size of about 10 × 8 × 6 cm. Due to the saccular mass size and its botryoidal texture, the patient's aorta was cannulated. Separate cannulas were placed in the superior vena cava and inferior vena cava. After full heparinization, cardiopulmonary bypass (CPB) was applied. The saccular tumor was filled with dark red liquid and a fibrous membranous network structure. Furthermore, the abnormal structure was found closely connected to the left atrium and left ventricle.
Notably, complete resection of the saccular structure could not be achieved following intraoperative findings; hence, partial resection of the mass was performed. The patient tolerated the procedure, and the heart was beating in sinus rhythm. After adequate hemostasis and closing the wound in layers, the patient was carefully transferred to the intensive care unit (ICU) in a stable condition. Pathological results of the surgically resected specimen confirmed the diagnosis of lymphangiohemangioma with the proliferation of fibrous tissue, hyalinosis, and lymphocyte infiltration. The results also indicated that the cells were positive for Ki-67, Vim, SMA, MC and partially positive for CR, CK5/6, CD34, CD31, D2-40, and WT-1, but negative for CK, EMA, MOC31, and Des (). The patient recovered without complications and was discharged on the 7th post-operative day with a recommendation for follow-up. Cardiac CT 2- and 4-years post-surgery showed no evidence of remnant lymphangioma progression (, arrow).


A 75-year-old male patient came to the emergency department with diffuse abdominal tenderness 7 days after palliative ERCP stent placement for malignant biliary obstruction and cholangitis; the metal stent could not be placed because of the distal CBD stenosis and unsuccessful SEMS placement, so plastic stent placement had been done (Figs , ). There were no immediate complications within 24 h after the procedure and discharged well after 3 days. The patient came to the emergency department with clinical signs and symptoms of diffuse peritonitis, and the abdominal X-ray found no free intraperitoneal air. Upon exploratory laparotomy, a perforation site was found at the third part of the duodenum, measuring 5 mm in diameter with plastic stent exposing out from the perforation site (as shown in Fig. ). The distal tip of the plastic stent migrated to the third part of the duodenum and perforated at this site. We performed primary suture of the duodenum, cholecysto-enteric bypass, pyloric exclusion, gastro-jejunostomy bypass, and braun anastomosis. Jejunostomy feeding has been placed at the end of the procedures. There were no postoperative cardiopulmonary complication and the patient could tolerate well for oral intake and discharged from hospital at 10th postoperative day. This case study has already been approved by Health Research Ethic Committee of Moewardi General Hospital, Indonesia. Ethical clearance number: 345/III/HREC/2021.


A 52-year-old man with a live-donor liver transplant 11 years prior for Budd-Chiari syndrome presented with several weeks of headache and diplopia. Immunosuppression consisted of tacrolimus (Table ). Neurologic exam identified right abducens and right facial nerve palsies.
Magnetic resonance imaging (MRI) of the brain and spinal cord revealed T2 hyperintensity involving portions of the cervical cord, brainstem, and left centrum-semiovale with leptomeningeal and right facial nerve enhancement (Fig. ).
A thorough investigation for infectious, inflammatory, and neoplastic etiologies was performed (Table ). EBV polymerase chain reaction (PCR) of the cerebral spinal fluid (CSF) was positive. EBV serology was positive for viral capsid antigen (VCA) IgG and early antigen (EA) IgG, but VCA IgM and Epstein-Barr nuclear antigen (EBNA) were negative, indicative of either late primary infection or prior infection.
Pathology from stereotactic biopsy of a left temporal lobe lesion showed perivascular polymorphic inflammatory infiltrate, including B- and T-cells. Immunohistochemical stains revealed CD20 positive B-cells, CD3 positive T cells, CD68 positive microglial nodules, plasma cells, and scattered EBV-encoded small RNAs (EBER) positive cells (Fig. ). Latent membrane protein 1 (LMP1) was negative. These results were initially interpreted as Primary CNS Post-transplant Lymphoproliferative Disorder (PCNS-PTLD). Tacrolimus was withheld, and the patient was treated with rituximab, prednisone, and methotrexate. A subsequent opinion of the pathology changed the diagnosis in favor of EBV encephalitis, prompting initiation of ganciclovir and withholding chemotherapy. The neurologic exam and repeat imaging improved over the course of this hospitalization; tacrolimus was resumed. He was readmitted a month later with new left hemisensory loss. Brain MRI demonstrated new expansile T2 hyperintense lesions (Fig. ). Tacrolimus was again discontinued, and valganciclovir was initiated.
After 2 weeks, he developed leukopenia (white blood cell count of 1.71 K/μL (reference 4.00–11.00 K/μL)) with severe neutropenia (absolute neutrophilic count 0.13 K/μL (reference 1.50–7.70 K/μL)) attributed to antiviral therapy. MRI brain again revealed progressive lesion enlargement. Given the longitudinal clinical, radiographic, and pathologic course, the diagnosis was revised to PCNS-PTLD. All immunosuppression and antiviral therapy were held. SubsequentMRI after one month showed regression of the lesions. At follow-up 6 months later, he remained clinically stable without relapse.


A 63-year-old man with a deceased-donor liver transplant 16 years prior for alpha-1-antitrypsin deficiency presented to the emergency department after a fall.
Immunosuppression consisted of mycophenolate mofetil and sirolimus (Table ). Physical examination identified right hemisensory loss. Brain MRI revealed an acute left insular infarct (Fig. ). Over the initial three days of his hospitalization, he developed bilateral abducens, left facial, and right oculomotor cranial nerve palsies. Repeat MRI with contrast demonstrated new cortical infarcts and enhancement of the left facial, left trigeminal, and right oculomotor nerves (Fig. ). Investigations (Table ) were notable for a positive CSF EBV PCR with 383,000 copies/mL.
Mycophenolate mofetil was discontinued, sirolimus was continued, and ganciclovir was initiated. The patient became progressively obtunded over several days. MRI one week later indicated disease progression with new infarcts (Fig. ). The patient was transitioned to hospice and died.


A 75-year-old woman with a deceased-donor liver transplant 6 years prior for primary biliary cirrhosis presented with four months of progressive weakness and gait instability.
Immunosuppression consisted of tacrolimus and mycophenolate mofetil (Table ). On examination, she had paraparesis, diminished proprioception, brisk reflexes in all limbs, and bilateral Babinski sign.
Spinal MRI demonstrated a longitudinal extensive T2 hyperintensity of the dorsal columns (C1–C7) with enhancement (Fig. ). Investigations (Table ) were remarkable for a positive CSF EBV PCR. EBV serology detected elevated VCA IgG, EBNA IgG, and EA IgG with borderline VCA IgM., indicating a chronic infection or viral reactivation.
She was treated with methylprednisolone. Mycophenolate mofetil was discontinued with continuation of tacrolimus. At five-month follow-up, she had mild residual paraparesis but was able to ambulate with support. Repeat MRI revealed resolution of the lesion.


73-year-old male patient from California, USA, admitted to our hospital in Houston, Texas, USA, for right lung mass evaluation and mild intermittent headache. Two months ago, patient was treated for pneumonia with a short course of oral levofloxacin. Then, the symptoms recur in one week after finishing the antibiotic course. His past medical and past surgical history are unremarkable. Two months ago, he received a 5-day course of oral levofloxacin and currently he denied taking any medications. Chest X-ray and CT chest were performed by his primary care doctor and revealed right middle lobe mass. Six months ago, patient was in Alaska and Argentina for hunting ducks and fishing. Patient smokes 30 pack-year. He denied drug abuse, sick contact, pets, or tick bites.
On physical examination, his blood pressure was 130/70 mmHg, his temperature was 99.2 F, his pulse was 80 beats per minute, and his respiratory rate was 16 breath per minute. Respiratory examination revealed decreased breath sounds on the right middle lobe. Rest of cardiovascular, neurological, abdominal, and skin examinations were unremarkable. At this point, neoplastic disease was on top of our differential diagnosis list followed by other diseases such as infections or autoimmune disorders.
Initial complete blood count and complete metabolic panel were normal. Serum interferon gamma release assay (IGRA), serum Beta-d-Glucan, serum aspergillus galactomannan antigen, serum coccidioides antibodies, and urine histoplasma antigen were negative. CT chest revealed 3.6 cm right middle lobe mass (Figure ). Patient underwent excisional lung biopsy which showed branching gram-positive rods consistent Nocardia species (Figure ). We started intravenous imipenem and oral Trimethoprim/Sulfamethoxazole. CT head with contrast was unremarkable. For intermittent headache, MRI brain was performed and showed 0.8 cm ring-enhancing lesion in left frontal cortex (Figure ) and 0.6 cm ring-enhancing lesion in left temporal lobe (Figure ). In the sixth day of hospitalization, patient started to complain of posterior right knee pain and lump. MRI of right knee revealed 2.5 X 2.4 cm ill-defined mass involving the distal gastrocnemius muscle (Figure ). Right posterior knee mass fine needle aspiration was performed and resulted as fibroadipose tissue with granulation tissue, plasma cells, macrophages, and neutrophils. Culture of the aspirated fluid showed no growth. HIV test was negative, and CD4 count was normal.
Later, the culture of the lung mass grew Nocardia paucivorans by using 16S ribosomal sequencing and the susceptibility is reported in (Table ). Patient was discharged on IV imipenem and TMP/SMX until resolution of the headache (8 weeks). Then, the treatment course was continued for at least one year with oral TMP/SMX alone with close monitoring to the major side effects such as agranulocytosis, thrombocytopeneia, electrolytes abnormalities, and renal impairment. Patient is following up with an infectious disease specialist at his home town. Patient reported complete resolution of his symptoms at the 8th week of treatment no side effects were reported.


A Caucasian 59-year-old woman, current smoker (10 pack-years), presented with symptomatic dry eye and mouth and inflammatory arthralgia. The patient had no known personal or family history of rheumatic disease. Physical examination at rheumatology consultation revealed bilateral conjunctival congestion and symmetrical polyarthritis affecting proximal interphalangeal and metacarpophalangeal joints. Although sicca symptoms are commonly present in smokers [], this patient also had polyarthritis on physical examination, and for this reason, the investigation for SS was performed. Serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), C3 and C4, IgA, IgM, and proteinogram were normal. IgG1, IgG3, and IG4 were normal; IgG2 was equal to 787 (normal range, 171 to 632 mg/dL). Rheumatoid factor (RF), antinuclear antibodies, and anti-SSA/B antibodies were negative. Hands conventional radiography revealed no erosions. Additional investigation for SS showed decreased parotid gland function on salivary glands scintigraphy, and ophthalmologic examination with Schirmer's test and tear break-up time confirmed severe dry eye. Lower labial mucosa biopsy revealed focal chronic sialadenitis characterized by intense lymphocytic inflammatory infiltrate (1 focus/4 mm2 of glandular tissue). These findings (Schirmer's test and focal labial mucosa biopsy) were consistent with the classification of primary SS according to the American College of Rheumatology/European League Against Rheumatism criteria (2016). The patient did not tolerate hydroxychloroquine and was treated with prednisolone 5 mg/daily and pilocarpine 5 mg four times a day. The patient was evaluated every 6 months, and her symptoms partially improved under these medications.
About two years after the diagnosis of primary SS, the patient started complaining of epigastric pain, nausea, and severe low back pain. She also had asthenia and weight loss (15 kg in 5 months). After a long-haul flight, she developed lower limb deep vein thrombosis and was hypocoagulated with dabigatran. Ten days later, the patient was admitted in the emergency department with an ischemic stroke in multiple vascular territories (). Physical examination revealed a left lower facial paresis and dysarthria. From the stroke study, electrocardiogram revealed sinus rhythm, cervical and transcranial Doppler ultrasound, a total occlusion of the right middle cerebral artery, and transthoracic echocardiography, a redundant oval foramen membrane with a positive right-left shunt. Additional investigation showed normocytic anemia (Hb 10.4 g/dL), leukocytosis (18.000/μL) with neutrophilia (90.3%/13.500/μL), thrombocytosis (510.000/μL), and elevated CRP (73 mg/L) and ESR (62 mm in the first hour). Over time, a progressive elevation of liver cholestasis enzymes occurred: gamma-glutamyl transferase 534 (normal range, 7 to 32 U/L) and alkaline phosphatase 357 (normal range, 30 to 120 U/L), with no cytolysis. Pancreatic enzymes, renal function, proteinogram, and urinalyses were normal. Viral serologies were negative. Abdominal ultrasound and upper and lower gastrointestinal endoscopies revealed no pathological findings. Subsequent cervical, chest, abdomen, and pelvic computed tomography scan (TC CCAP) showed non-specific scattered pulmonary micronodules in lung lower lobes, liver parenchyma with several nodules, and retroperitoneal ganglion cluster in the hepatic hilum.
According to these findings, the diagnostic hypotheses postulated were neoplastic metastasis of a solid tumor or lymphoproliferative disease. In this regard, mammography, peripheral blood immunophenotyping, and bone marrow biopsy were performed which showed no evidence of a neoplastic disorder. Liver biopsy was subsequently performed, and pathologic analysis revealed an adenocarcinoma.
In accordance with the European Society for Medical Oncology and considering the diagnosis of an occult primary neoplasm with unfavorable histological subtype, the patient started an empirical chemotherapy protocol with carboplatin and paclitaxel. After the first cycle, treatment was suspended because the patient experienced a deterioration of her general clinical condition with progressive worsening of cytocholestasis parameters. The patient performed a new TC CCAP that revealed moderate ectasia of biliary tract and pancreatic duct, demonstrating one mass adjacent to the pancreatic head, which may indicate the epicenter of the neoplastic process. About one month after the first chemotherapy cycle, the patient died with a diagnosis of probable metastatic pancreatic adenocarcinoma.


A 59-year-old woman who lives in a rural area of Republic of Korea presented to the emergency center of a tertiary hospital with a fever that started 3 days prior. She had no known underlying diseases. On admission, she had blood pressure of 90/40 mmHg, pulse rate of 68 beats per minute (bpm), respiratory rate of 20 breaths per min, and a body temperature of 38.3 °C. She had no memory of any insect bites, but reported that she had rabbits, dogs, and chickens living on her property. Neither eschar nor skin rash were observed on physical examination.
After a series of tests, laboratory tests revealed bicytopenia with a white blood cell count of 1200/mm3 (neutrophil count 280/μL), hemoglobin level of 13.9 g/dL, and a platelet count of 113,000/mm3. The serum levels of C-reactive protein, ferritin, aspartate aminotransferase (AST), alanine transaminase (ALT), and lactate dehydrogenase (LDH) were 0.05 mg/dL, 3970.62 ng/mL, 67 U/L, 28 U/L, and 781 U/L, respectively. Serum cardiac enzymes including troponin I and creatine kinase-muscle/brain (CK-MB) isoenzyme were all within normal range. The clinical course of the patient’s laboratory findings is demonstrated in Fig. . A baseline electrocardiography (ECG) displayed a normal sinus rhythm and there was no definite cardiomegaly nor pulmonary congestion in the chest X-ray (Fig. , panel A).
Based on the clinical manifestations, history of raising livestock in rural area, and laboratory finding, tick borne disorder such as SFTS was suspected. In addition, hematologic disorder cannot be ruled out. To determine a microbiological cause of fever, blood cultures were ordered. Reverse-transcription polymerase chain reaction (RT-PCR) was executed to screen for the SFTSV medium (M) segment in blood, indirect immunofluorescence was performed to screen for scrub typhus and Hantaan virus, and passive hemagglutination testing was performed to screen for Leptospira. A bone marrow sample was also taken to evaluate the grade of bicytopenia. The sample revealed decreased trilineage cells with hypocellular marrow, which suggested marrow failure due to systemic infection.
On hospital day (HD) 3, the patient complained of chest discomfort. Subsequently, her blood pressure dropped to 55/37 mmHg and she developed bradycardia (43 bpm). The patient’s heart rhythm also switched to an alternating rhythm of sinus bradycardia and junctional bradycardia. A chest X-ray displayed distinct pulmonary edema (Fig. , panel B). At that time, the serum troponin I titer was elevated (1.60 ng/mL).
Laboratory examinations from HD 3 again revealed bicytopenia with a white blood cell count of 2200/mm3 (neutrophil count 230/μL), hemoglobin level of 12.7 g/dL, and platelet count of 84,000/mm3. The serum levels of C-reactive protein, ferritin, and LDH were 0.01 mg/dL, 7921.17 ng/mL, and 1222 U/L, respectively. Bedside echocardiography revealed severe left ventricular (LV) systolic dysfunction (LV ejection fraction 10%) with normal LV chamber size and a mildly edematous LV posterior wall. An additional cardiac echography file shows this in more detail (see Additional file ).
The patient then suddenly developed an atrio-ventricular conduction abnormality simultaneously with LV dysfunction. As such, it was suspected that the patient was experiencing a myocardial infarction of the right or left circumflex coronary artery, or fulminant myocarditis involving the conduction system. A coronary angiography was performed immediately, which revealed good distal flow through both coronary arteries and a lack of significant stenosis. Due to the patient’s severe orthopnea, agitation, and refractory shock, an endomyocardial biopsy (EMB) could not be performed.
Despite intravenous administration of norepinephrine and dopamine, the patient’s blood pressure did not recover. Therefore, VA ECMO was applied to the patient via the femoral vein and artery. The patient’s blood pressure dropped to nearly 0 mmHg and she developed a near total akinesia of the heart (Additional file ) in the time it took to initiate ECMO, but cardiopulmonary resuscitation was not performed.
On the same day 3, the patient’s blood test result came back positive for SFTSV. Consequently, immune suppressive therapy (IST) with prednisolone (1 mg/kg/day) and 3 days of intravenous immunoglobulin (20 g/day) was initiated. In addition, the patient’s plasma was tested for a panel of 12 different cytokines. Among the panel, the concentrations of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were 3.52 pg/mL, 2.56 pg/mL, and 20.89 pg/mL, respectively. These levels were much higher than the mean values of ten Korean healthy adults, measured in our lab for research purposes, which were 1.55 pg/mL, 1.40 pg/mL, and 3.25 pg/mL, respectively. Levels of platelet derived growth factor (PDGF)-BB were also lower (347.94 pg/mL) compared to healthy adults (2347.76 pg/mL).
On HD 4, the patient still had bicytopenia with a white blood cell count of 2700/mm3 (neutrophil count 1760/μL), hemoglobin level of 11.0 g/dL, and a platelet count of 75,000/mm3. The serum levels of C-reactive protein, AST, ALT, and LDH were 0.01 mg/dL, 300 U/L, 68 U/L, and 1709 U/L, respectively. The patient’s troponin level was 101.56 ng/ml and the level of mass CK-MB was 115.4 ng/mL.
On HD 7, the patient’s heart started to beat again (Additional file ). Further, on HD 12, she was successfully weaned from VA ECMO. By HD 21, cardiac function completely recovered (Additional file ) and the patient was discharged without significant complications.


A 56-year-old male patient was admitted to our hospital on July 20, 2020. He had been diagnosed as LA myxoma in another hospital by echocardiography on July 17, 2020. He had a history of chest tightness and asthma for 6 months and progressive aggravation for 1 month, which disrupted the sleep. He had no headache, fever, palpitation, edema of lower limbs, and relevant family history. On physical examination, increased breath sounds were noted. Auscultation revealed a grade 3/ 6 tricuspid systolic murmur.
On July 21, 2020, high-resolution computed tomography (HRCT) revealed that the cardiac enlargement and showed a lesion with low density in the left side of the heart. (Fig. ). Transthoracic echocardiography (TTE) showed a medium echoic mass measuring 88 mm × 51mm × 43 mm in the left atrium. The mass was attached by a pedicle to the atrial septum and protruded into the left ventricle through the mitral orifice in diastole and returned to the atrium in systole, leading to obstruction of the mitral orifice during diastole. The cardiac atrium was enlarged, and the left ventricular ejection fraction (LVEF) was 65%. (Fig. ). A medium echoic mass measuring 14 mm × 14 mm attached to the LV papillary muscle was also demonstrated by TTE. The mass moved back and forth in the left ventricle. (Fig. ). This was suggestive of LV myxoma with LA myxoma. Additionally, severe tricuspid regurgitation was also found.
On July 22, 2020, surgery was performed on the patient which included tumor resection and tricuspid valvuloplasty. During the surgery, pericardium and right atrium were incised longitudinally. Next, part of the atrial septum was opened below the foramen ovale, and the atrial septum was pulled upward for exploration showing two tumors in the left heart, one of which was attached to the atrial septum, and the other was attached to the lateral wall of left ventricle. The two tumors looked crispy, gelatinous with complete capsule. The tumors and the tissues around their pedicles were resected completely. The tumor attached to the atrial septum measured approximately 80 mm × 53 mm × 43 mm, and the other attached to the lateral wall of left ventricle was about 14 mm × 14 mm × 12 mm. The tricuspid valve was then explored, and severe tricuspid regurgitation was found. Ten sutures were placed the valve ring, tricuspid annuloplasty ring was implanted, and no obvious regurgitation was found at this time. After the surgery, the patient was transferred to intensive care unit for close observation.
On a subsequent histopathological examination, photomicrograph showed irregular shaped cells loosely dispersed within a mucoid ground substance (Fig. ). The postoperative diagnosis was LV myxoma with LA myxoma.
Tracheal intubation and ventilator-assisted breathing were given after the surgery. Ambroxol was used to prevent pulmonary complications, such as atelectasis; omeprazole was used to prevent stress ulcer, and reduced glutathione was used to protect liver function. Antibiotics were also administered. On postoperative day 2, extubation was performed when the patient was fully awake. On postoperative day 3, antibiotics were stopped, and cardiotonics and diuretics were given.
On postoperative day 6, TTE showed mild atrial enlargement, with a left ventricular ejection fraction (LVEF) of 59% and a mild regurgitation in mitral valve, which meant the patient's cardiac condition was well. (Fig. ). The patient was told to rest adequately, avoid strenuous exercise and follow-up every six months. Digital Radiography (DR) revealed mild cardiac enlargement (Fig. ).
On postoperative day 8, the patient 's incision healed well and there was no abnormality on physical examination. The patient was discharged on postoperative day 8, and no medication was required post-discharge. A one-year follow-up revealed no recurrence of the lesion, and we are still closely following the patient. The study protocol was approved by the ethics committee and institutional review board of the First Affiliated Hospital of Wannan Medical College [(2019) Ethics research No. 87]. Written informed consent was obtained from the patient for publication of the case details and accompanying images.


A 66-year-old woman with a history of hypertension and RA was referred to the emergency room for fever for 1 week, and for watery diarrhea and abdominal discomfort for 1 month. She had been diagnosed with RA 2 years prior, after assessment for pain and swelling on her left wrist and morning stiffness that continued all day. At the time of RA diagnosis, her rheumatoid factor (RF) titer was 21 IU/mL (normal range, ≤ 14 IU/mL), anti-cyclic citrullinated peptide titer was 0.4 U/mL (normal range, ≤ 5 U/mL), C-reactive protein (CRP) level was 0.85 mg/dL (normal range, ≤ 0.5 mg/dL), and erythrocyte sedimentation rate (ESR) was 56 mm/h (normal range, ≤ 25 mm/h). Methotrexate and hydroxychloroquine with low-dose prednisone were started after intra-articular injection of triamcinolone into her left wrist. Her disease activity score 28 (DAS28) improved to 2.5 from 4.6, and she tolerated the RA well with the medication for 6 months.
However, she suffered recurrent diarrhea with intermittent abdominal pain for 4 months and was admitted to the emergency room with a week-long fever and prolonged diarrhea with abdominal discomfort for the past month. Her temperature was 38.9°C and blood pressure was 110/83 mmHg. Physical examination revealed no direct or indirect tenderness on her abdomen, and joint tenderness and swelling were not observed. Laboratory results were: white blood cell count, 6,700 cells/μL; ESR, 64 mm/h; CRP, 10.55 mg/dL; RF, 255.4 U/mL; creatinine, 0.66 mg/dL; and albumin, 2.9 g/dL. There was no proteinuria or hematuria in urinalysis. The results of stool culture, parasite test, and clostridium difficile toxin A were negative. Abdominal computed tomography showed segmental wall thickening in the ascending to descending colon and distal jejunum (Fig. A). Endoscopy revealed chronic colitis with mucosal atrophy and erosion (Fig. B). Histopathology of her colon tissue confirmed chronic colitis with distorted crypt architecture, heavy infiltration of lymphoplasma cells, and amyloid deposition in the stroma and vessels, shown as a pink amorphous material positive for Congo red staining (Fig. ).
After 2 weeks of prophylactic therapy for latent tuberculosis, she started 8 mg/kg intravenous tocilizumab and the prolonged diarrhea subsided, with decreased frequency within 1 week. Additionally, her inflammatory markers decreased (ESR 18 mm/h, CRP 0.98 mg/dL) after 1 month. Monthly tocilizumab therapy remains efficacious 2 years later.


A 62-year-old woman was diagnosed with a 4-mm polypoid lesion in the gallbladder during a medical examination in 2014. The patient was followed-up by ultrasonography (US) once a year and was referred to our department because of an increase in size of 4 mm in 6 years. Her medical history included a duodenal ulcer and primary biliary cirrhosis. Blood examinations showed that carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) levels were within normal limits. Abdominal ultrasonography showed a polyp measuring 8 mm with a stalk, in the body of the gallbladder, and computed tomography revealed that there was no significant lymph node enlargement around the hepatoduodenal ligament (A, B). Magnetic resonance cholangiopancreatography (MRCP) revealed a type Ip polypoid lesion in the gallbladder body (A, B). Endoscopic ultrasound (EUS) demonstrated that this lesion represented a parenchyma-like internal echogenic pattern (). Based on these findings, the patient was diagnosed with gallbladder adenoma, and laparoscopic cholecystectomy (LC) was performed. The intraoperative time was 101 min, and blood loss was 5 mL. Intraperitoneal bile leakage was not observed. The excised tissue was a yellowish, pedunculated (type Ip) tumor () measuring 10 mm. On histopathological examination, the tumor showed papillary growth of atypical tall columnar epithelial cells. On immunohistological analysis, the tumor was positive for human gastric mucin (HGM) and negative for Alcian blue, CD10, villin, and CDX2. The mitotic index was <1%, MIB-1 positive (3%), localized p53 positive, mucin expression MUC5AC positive, MUC1 weakly positive, and MUC2 negative. The final diagnosis was gallbladder carcinoma in situ with intracholecystic papillary-tubular neoplasm, gastric pyloric, and simple mucinous type with high-grade dysplasia (A, B). The patient is currently undergoing outpatient follow-up without any postoperative recurrence for one year.


A 59-year-old female patient had an abrupt presentation of diarrhea (>1 month with 5–9 watery stools daily), abdominal discomfort, weight loss, and several large spontaneous ulcerations on the abdomen, limited within scar tissue from a remote bowel perforation surgery (Figure ). The combination of diarrhea and ulcerations was concerning for inflammatory bowel disease, pyoderma gangrenosum, or malignancy. Laboratory investigations demonstrated anemia and electrolyte derangements to include hyponatremia, hypocalcemia, hypokalemia, and hypomagnesemia. Chronic diarrhea work-up was negative, but lactoferrin and calprotectin were elevated (Table ). A punch biopsy at the edge of an ulcer showed extensive dermal fibrosis with chronic inflammation, numerous eosinophils, and granulation tissue (Figure ). PAS and Lu-5 cytokeratin stains were performed and were unremarkable. The lack of acute or granulomatous inflammation made infection less likely. Otherwise, the classical features of pyoderma gangrenosum, infection, and malignancy were not appreciated. Endoscopy was notable for duodenal villous atrophy, edematous mucosa with scattered area of loss of vascular pattern and ulceration in the proximal colon but histology demonstrated benign colonic mucosa (Figure ). After months of otherwise unremarkable exhaustive evaluation, there was no clear underlying cause. Of note, the patient had been treated with losartan for more than 10 years for hypertension and given the reports of ARB-induced sprue-like enteropathy, losartan was discontinued in October 2019. On follow-up one month after medication was discontinued, patient noted improvement of the diarrhea and the wounds started healing. Patient followed up with wound care, and over the next several months, the wounds completely resolved as well as her gastrointestinal symptoms. (Figure ). One year follow-up noted complete resolution of the patient's lesions with no recurrence (Figure ).


The patient was a 77-year-old, hypertensive, white, Brazilian male with no other comorbidities or risk factors for coronary disease or peripheral arteriopathy. Routine abdominal ultrasonography was performed for evaluation of hepatic steatosis, identifying a mass in the hepatic region, probably of a vascular origin. Abdominal angiotomography was ordered, showing two areas of aneurysmal dilatation of the hepatic artery. The larger dilation was more proximal to the celiac trunk, with a length of around 7.2 cm along its longest longitudinal axis, a maximum caliber of 5.2 cm, and a maximum true lumen caliber of 3.0 cm. The second dilatation was closer to the hepatic hilum, with a length of around 2.0 cm, maximum caliber of 2.0 cm, and a small mural thrombus ().
The management approach chosen comprised digital subtraction arteriography with simultaneous endovascular aneurysm repair using three Lifestream® (Clearstream Technologies Ltd., Ireland) vascular covered stents, sizes 7x58 mm, 8x58 mm, and 8x37 mm, implanted sequentially, partially overlapping, with the aid of an HFAN 7F, valved introducer sheath and 0.35” Roadruner® (Cook Medical Group, Indiana, United States) hydrophilic guidewire followed by an Amplatz StiffTM (Boston Scientific Corporation, Massachusetts, United States) hydrophilic guidewire up to the distal segment of the hepatic artery, to guide the stents as they were advanced (). The procedure was performed successfully, achieving exclusion of the aneurysm (, , ). The patient remained asymptomatic, with adequate flow through the stents shown on two follow-up ultrasound examinations, at 6 months and 1 year, and free from leaks into the aneurysm, which was still thrombosed 2 years after treatment.


A 13-year-old male patient presented to the emergency department (ED) with a prolapsed rectal mass. The patient noticed the mass while attempting a bowel movement, during which he noticed blood on the toilet paper, prompting him and his father to examine the area which contained a round, pink mass protruding from the rectum. A gross image of the mass is shown in Figure .
This patient’s history, aside from some constipation as an infant, contained no prior history of rectal prolapse, colorectal polyps, hematochezia, or melena. The patient also denied any abdominal pain, diarrhea, constipation, nausea, or vomiting. Further, the patient’s father was diagnosed with Crohn’s disease in his early 20s. Laboratory studies at three months of age showed reduced hemoglobin A1, indicating a possibility of β-thalassemia trait at the time, which was never confirmed at a later age. On presentation, this patient had a complete blood count (CBC) that showed a mild microcytic anemia. Given that the mass was noted to have a stalk, a rectal polyp was the leading diagnosis prior to any intervention; other diagnoses on the differential included hemorrhoid, rectal prolapse, and inflammatory bowel disease.
Given the patient’s age, noncontributory history, and subtle presentation, determining the appropriate management for this patient presented a challenge in the initial hours of presentation to the ED. However, the polyp was successfully reduced back into the rectum in the ED prior to further intervention. The size of the polyp was likely to pose endoscopic ligation challenges to a gastroenterologist, which subsequently would have warranted recommending surgical resection by a general surgeon.
Colonoscopy was performed shortly after the mass had been reduced, following bowel prep. Pertinent negatives during the procedure included normal sphincter tone and no palpable rectal lesions. The location of the polyp was found to be in the sigmoid colon, solitary and semi-pedunculated in nature, and measuring 3.3 x 3.0 x 2.8 cm3. Endoscopic ligation using a hot snare was performed to remove the polyp. Figures , depict the appearance of the polyp in the colon.
Finally, both the gross and histological features of the polyp confirmed the diagnosis as a juvenile retention polyp. Grossly, this polyp was round and pedunculated but lacked the characteristic long pedicles seen in adenomatous polyps. Histologic evaluation of the polyp displayed cystically dilated glands, with relatively equal amounts of glandular and stromal proliferation; this appearance contrasts with adenomatous polyps, which display predominantly glandular proliferation. Lastly, the lack of cellular atypia gave strong evidence that this polyp was indeed benign.


We present a case of a 78-year-old gentleman with multiple comorbidities, including type II diabetes mellitus, chronic kidney disease (CKD), hypertension, hyperlipidemia, coronary artery disease (CAD), chronic back pain status post microdiscectomy, status post placement of dorsal column stimulator and gout presented with intractable right-sided lower back pain.
He described severe, worsening right-sided lower back pain, 10/10 in intensity radiating to the right lower extremity, exacerbated by movement associated with numbness, tingling, and difficulty in ambulation. He denied weakness, fever, chills, urinary or fecal incontinence, and saddle anesthesia. The patient had a gout flare-up in his right foot four weeks ago, for which he usually used to take steroids but could not take them due to uncontrolled diabetes. He went to the emergency department one week before the presentation, where he was diagnosed with chronic back pain and was discharged on a course of steroids.
On presentation, the musculoskeletal examination was limited due to pain. He had exquisite tenderness of the right lower back. The neurological examination was unremarkable, with normal power in limbs and no focal deficit. All other joints examination was within normal limits. Gait was normal as well. Laboratory studies showed normal complete blood count, basic metabolic panel was significant, with a creatinine of 1.8 mg/dL and a glomerular filtration rate of 37 mL/min/1.73 m2. C-reactive protein was 3.4 mg/L and uric acid was 11.8 mg/dL.
The pelvis's plain radiograph showed degenerative disc disease of the lumbar spine but no abnormality in the right hip. Computed tomographic (CT) scan without contrast showed moderate disc bulges at multiple levels, including L2-S1 with lateral recess stenosis and moderate-to-severe facet stenosis (Figure ). Magnetic resonance imaging (MRI) spine showed similar results as that of CT scan but with new interval development of fluid within the disc space with endplate edema and reactive changes at level L5-S1 with right paraspinous inflammation without abscess (Figure ). In addition, there was diffuse disc bulging, with persistent moderate left and severe right foraminal stenosis with endplate osteophyte formation. The findings were consistent with discitis without epidural or paraspinous abscess.
In suspicion of infectious L5-S1 discitis, the patient was started on IV vancomycin; infectious workup was done, including urine and blood cultures, which were negative. A fluoroscopy-guided lumbar disc biopsy of the L5-S1 disc space and aspiration on microscopic examination showed deposits of uric acid crystals (gout), accompanied by a mixed inflammatory infiltrate that included neutrophils and histiocytes (Figure ). Gram stain and cultures of the aspirate were negative.
As per biopsy results, a diagnosis of gouty spondylodiscitis was made, and he was started on IV dexamethasone 4 mg every 12 hours. The neurosurgery team consultation was sought for any possible need of surgical decompression; however, the need was obviated since the patient recovered with medical management itself. However, antibiotics were continued in anticipation of infection following gout-related necroinflammation. Upon discharge, the patient was started on an adjusted renal dose of colchicine and tapering of steroids. On follow-up appointment, he was started on allopurinol after resolution of an acute gout flare, and repeat uric acid was 5.1 mg/dL a few months later, and his back pain resolved.


A term girl, small for gestational age, the first baby of the first degree consanguineous couple, was born to a 29-year-old mother by spontaneous vaginal delivery. The pregnancy was insignificant, and there was no history of radiation exposure or drug intake in any trimester; no family history of congenital heart disease or any chromosomal disorders.
A prenatal ultrasound scan at 30 weeks of gestation revealed a hypoplastic left ventricle defect, with no extracardiac malformations. Fetal echocardiography reported hypoplastic left heart, atrial septal defect, and patent ductus arteriosus. Amniocentesis was done at 32 weeks of gestational age, and chromosomal microarray analysis (CMA) revealed partial monosomy and partial trisomy.
An approximately 63 megabases large pathogenic one copy loss (heterozygous deletion) encompassing the entire small arm of the chromosome X (Xp) and extending to the long arm of chromosome X (Xq), X p22.33q11.2 arr[GRCh37] Xp22.33q11.2(168546_63625851)x1) containing 447genes was detected. Furthermore, an approximately 50 megabases large pathogenic one copy gain (duplication) of the chromosomal region 14q11.2q24.2 arr[GRCh37] 14q11.2q24.2(20511672_70922704)x3) containing 437 genes was determined. These findings are suggestive of a chromosome translocation involving the chromosomes X and 14.
The infant cried immediately after birth and required only the initial steps of resuscitation. The Apgar scores were eight and nine at one and 10 minutes, respectively. Birthweight was 2270 grams (below fifth percentile), the length was 48 cm (25th centile), and head circumference was 32 cm (below fifth percentile).
Clinical examination showed a neonate with no apparent dysmorphic features with mild tachypnea (respiratory rate: 65 breaths per minute) and tachycardia (heart rate: 170 beats per minute). The patient's arterial blood gases report was pH-7.30, PaCO2 47 mmHg, base deficit -2 (BE-2); blood pressure was 62/40 mmHg, and oxygen saturation was 90% at room air. She had vesicular breath sounds with few fine basal crepitations. The first and second heart sounds were normal intensity, but with a systolic murmur grade three of six with maximal intensity at the left lower sternal edge.
The postnatal echocardiography report confirmed the diagnosis of HLHS with the hypoplastic left ventricle, mitral atresia, aortic atresia, and moderate tricuspid regurgitation (Figures , ).
The neonate was started on prostaglandin infusion treatment. Physical examination of other systems on admission was normal with stable hemodynamic values. Laboratory blood tests showed normal ranges of white blood cells, hemoglobin, and platelet counts. Abdomen ultrasonography and magnetic resonance imaging of the brain were unremarkable. A patient was diagnosed to have HLHS with partial monosomy X (Turner syndrome) and partial trisomy 14 (14q11.2 microduplication syndrome). We explained to parents the expected poor outcome of the management option of such cardiac defects; as a result, parents accepted the option of comfort care. The patient passed away on the seventh day of life.


We present the case of a 71-year-old woman with a past medical history significant for systemic lupus erythematosus (SLE), focal segmental glomerulosclerosis, status post renal transplant 15 years prior, and type-2 diabetes mellitus. Her medications included tacrolimus and mycophenolate for pharmacologic immunosuppression following transplantation and sliding scale insulin.
She initially presented to the emergency department for care following four days of progressively worsening cough, shortness of breath with generalized weakness, chest tightness, fever, and chills. She was diagnosed with SARS-COV-2 pneumonia which was managed with a one-week course of 6 mg daily dexamethasone and remdesivir. Her symptoms steadily improved and she was discharged to home care with rivaroxaban prophylaxis following completion of treatment.
She represented to the emergency department the next day with shortness of breath, altered mental status, and chest pain which was exacerbated on inspiration. Her vitals on presentation were notable for a blood pressure of 172/81. Her physical examination was notable for an audible friction rub over her anterior chest wall and chest pain reproducibly improved by leaning forward. An electrocardiogram was obtained (Figure ), which showed ST-segment elevations with PR interval depressions in leads II, III, aVF, and leads V3-V6. Additionally, her troponin was elevated at 283 ng/L which trended downward to 145 ng/L after two hours. Given her history of SLE, inflammatory markers were studied and showed elevations of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) at 1.6 mg/dL and 82 mm/hour, respectively. These findings suggested an infectious etiology, rather than an SLE exacerbation, as the reason for the inflammatory marker increase. Her other laboratory workup on presentation was unremarkable. Her anion gap was normal. A chest X-ray and transesophageal echocardiogram were also conducted due to suspicion for acute pericarditis but showed no signs of pleural effusion or pericardial effusion, respectively.
Given this constellation of findings, she was admitted to the hospital with presumptive pericarditis secondary to SARS-COV-2 infection. Management of pericarditis was achieved with 650 mg aspirin three times daily and 1.2 mg colchicine twice daily. Her cognition and chest pain markedly improved after the initiation of these therapies along with supportive treatment. Colchicine was reduced to 0.6 mg twice daily after one day. She was discharged two days after treatment in stable condition with 0.6 mg colchicine twice daily for three months and 650 mg aspirin three times daily to be tapered over two to four weeks following symptom resolution.


A 17-year-old girl, was admitted to the adult emergency room (ER) with a 4 days history of mild abdominal pain and nausea. She was well known in pediatric endocrinology for diabetes type 1A (positive anti-glutamic acid decarboxylase and anti-insulin antibodies). The past medical history was notable for diabetes type 1A diagnosed in Ecuador at age 4 years. Access to insulin therapy had been limited until the age of 9, resulting in poorly controlled diabetes. Following her migration to Switzerland at age 12, she was noted to have protuberant abdomen, severe hepatomegaly (17.5 cm to the midclavicular line, uniform echogenicity on abdominal ultrasound), growth retardation, Cushingoid features, moon face and proximal muscle wasting leading to the clinical diagnosis of Mauriac syndrome. IGFBP-3 was borderline low 2.5 and 3.5 mg/l (reference values for 12 years 2.9–8.6) possibly related with growth impairment []. Initial optimization of insulin therapy allowed for better diabetes control, normalization of liver size and some catch-up growth; however, her height remained under familial target (Fig. ). Treatment included long-acting insulin at a dose of 0.21 UI/kg/day and short acting insulin at a mean dose of 0.43 UI/kg/day. Unfortunately, non-compliance recurred, and diabetes remained undercontrolled with glycated hemoglobin increasing progressively from 8, 0% to 13, 5% despite close follow-up. Liver size remained normal.
Upon admission to the ER at age 17, she was afebrile with heart rate of 87 beats/min and blood pressure of 122/99 mmHg. Her height was 149.3 cm (< 3rd percentile; WHO growth curves []) and her weight was 59.5 kg (P50-P75) with a body mass index of 26.69 kg/m2. Tanner stage was 5 (post-pubertal). Abdominal examination revealed mild tenderness on palpation but no rebound and no hepatomegaly. Her blood glucose level was 44.1 mmol/l without acidosis (pH – 7.376, pCO 2–39.8 mm of Hg, HCO 3–22.9 meq/l, base excess – 2.4 mmol/l), and urine ketones were 1.5 mmol/l (normal, < 0.3 mmol/l). There was mild hyperosmolar hyponatremia (Na - 130 mmol/l, osm − 316 mmol/kg H2O). Liver transaminases, lactate, blood cell count, kidney function tests were normal. Her HbA1c was 11%. Acute hyperglycemia with no signs of ketoacidosis was recognized as the cause of abdominal pain and nausea. Management included fluid replacement as a rate of 20 ml/kg/h for 2 h which lead to a fall in serum glucose from 41.1 mmol/l to 31 mmol/l. Subsequently, rapid acting subcutaneous insulin therapy at a dose of 0.13 U/kg (8 Unit) was given. When serum glucose reached 11.1 mmol/l, fluid replacement was stopped. A second insulin injection at a dose of 0.07 U/kg (4 Unit) was given 7 h later. During infusion and insulin therapy, lactate levels increased from 1.65 mmol/l prior to insulin administration to 6.02 mmol/l 125 min after the injection of insulin aspart (8 U, Fig. ). Blood pH remained normal at 7.367 (Table ). Following the next 12 h, lactate levels progressively decreased to 2.16 mmol/l (Fig.). Urine ketones were repeated at this time with similar result as the day of admission (1.5 mmol/l). While we did not determine plasma ketones directly, the absence of acidosis and the low urinary ketones at admission and the day after, as well as the absence of clinical signs of DKA indicate that hyperlactatemia did not develop secondary to DKA. Abdominal ultrasonography and magnetic resonance imaging showed a normal liver parenchyma and liver size (15 cm to the midclavicular line).
As genetic variants at the KJCN11 and PHKG2 genes had been previously described in association with Mauriac syndrome [, ], an exome gene panel for glycogen storage diseases including AGL, GYS2, PHKA1, PHKA2, PHKB, PHKG2, PYGL and KCNJ11 was analyzed with next generation sequencing technology. No pathogenic variants were identified.


A 43-year-old man presented with a thyroid nodule detected on screening carotid ultrasonography. He had shown hypertension at 42 years old and he had no contributory family history, including coagulopathies. He was referred to our hospital for diagnosis and treatment of the nodule. Blood tests showed: hemoglobin, 15.1 g/dL; platelets, 27.5 × 104/µL; prothrombin time (PT), 11.0%; and activated partial thromboplastin time (aPTT), 32.0 s. Coagulability was normal. Ultrasonographic findings showed an 11 × 11 × 14-mm, hypoechoic nodule with irregular margins on the left lobe of the thyroid gland. No obvious extrathyroidal extension or lymph node metastasis was identified. Fine needle aspiration biopsy revealed findings suggestive of papillary thyroid carcinoma. Computed tomography showed a nodule in the left lobe of the thyroid gland and no distant metastatic findings in the lung.
The patient underwent left lobectomy and central compartment lymph node dissection under the diagnosis of papillary thyroid carcinoma (cT1bN0M0). The histopathological diagnosis was papillary thyroid carcinoma (pT2N1aM0). Intra-operatively, there was no finding of abnormal hemostasis and intraoperative blood loss was less than 1 ml. Operative time was 54 min. No sign of bleeding was seen on examination at 20-h postoperatively. However, the patient’s neck appeared swollen at 27 h postoperatively. Emergency reoperation was performed to evacuate hematoma. No arteriovenous points of bleeding were evident, but diffuse oozing was identified. Two days after the reoperation, on removal of the drainage tube, fresh red blood was seen dripping from the drain insertion site. We therefore applied pressure around the drain insertion site with gauze for 2 days, and prescribed carbazochrome and tranexamic acid for 3 days. The patient was discharged from hospital on postoperative day (POD) 6 after confirming that neck swelling had resolved. We had recommended continued hospitalization and observation, but the patient strongly desired to be discharged to home. On the fifth day after discharge (POD 11), neck swelling was observed again. Since the swelling was mild, the hematoma was conservatively absorbed. We considered the possibility that repeated postoperative hemorrhages were attributable to abnormalities in blood coagulation factors. Subsequent testing revealed factor VIII antibody activity had decreased to 33.9%, van Willebrand factor (vWF) was within the reference range (Table ), and cross-mixing test showed a downward convex pattern (Fig. ). The patient was also found to have shown difficulty in achieving hemostasis during a previous tooth extraction. He had factor VIII deficiency, normal level of vWF and bleeding episode. Eventually, congenital hemophilia A was diagnosed.


A 54-year-old woman (gravida 0, para 0) was transferred to our department with an extensively distended abdominal wall and leg pain. Regular menstruation started at age 14, and she experienced menopause at age 48. She had no history of regular hospitalizations. Over the past few years, she had noticed a gradual progression of abdominal bloating, but she had not decided to go to the hospital. Finally, when it became difficult for her to walk by herself, she went to a nearby hospital and was transferred to our department.
Her vital signs were stable; however, her abdomen was markedly distended from the cardiac fossa to the lower abdomen, making it difficult for her to stand by herself (). Marked pitting edema was found in both legs.
Contrast-enhanced computed tomography showed that the tumor occupied the whole abdominal cavity (38 cm × 40 cm × 48 cm), and both kidneys were being pressed significantly dorsally (). Most of the tumor was uniform, and its density was like that of subcutaneous fat. There were no hypervascular lesions, and the right ovarian artery and vein flowed into the tumor (). No obvious venous thrombosis was detected; however, pleural effusion was detected in the right thoracic region (). The tumor was too large to obtain useful information from magnetic resonance imaging.
Blood test results showed that the CA125 value was slightly elevated, and there was a marked increase of estradiol and a marked suppression of luteinizing hormone and follicle-stimulating hormone levels (), which indicated a benign ovarian solid fibroma or thecoma with Meigs syndrome.
We planned to surgically remove the right adnexa, but because of concerns about potentially severe complications, we organized a multidisciplinary team of general surgeons, anesthetists, radiation oncologists, and plastic surgeons to plan the treatment course.
We placed two surgical beds side by side for the operation. During the laparotomy, the patient was placed in the left lateral decubitus position to maintain hemodynamic stability and because the tumor was assumed to be of right ovarian origin (). With the help of general surgeons, we confirmed that there were no adhesions between the tumor and the abdominal wall, and the surface of the tumor was smooth (). We confirmed that the right ovarian artery and vein truly flowed into the tumor (). Her uterine and left adnexa were intact. We cut both vessels, the right fallopian tube, and the ovarian intrinsic ligament and successfully removed the right adnexa. The tumor weighed 36 kg. Because the subcutaneous fascia and skin were markedly stretched by the tumor, a plastic surgeon trimmed the excess fascia and skin and reformed the umbilicus. During the operation, the patient's vital signs were fairly stable. The amount of intraoperative blood loss was 420 mL, and the operation time was 4 hours and 17 minutes.
The patient was then extubated and moved to the intensive care unit for recovery. There were no signs of major complications, and she was moved to the general ward on the 1st postoperative day. A chest radiograph on the fourth postoperative day showed a marked decrease in the right pleural effusion (). The postoperative course was generally favorable, and the patient was discharged on the 7th postoperative day.
A pathological examination showed that the tumor was macroscopically nearly white, but there were no obvious necrotic lesions (). Microscopically, the tumor was composed of thin spindle cells in a whorled arrangement, but nuclear atypia and mitosis were not observed, and the fibroma diagnosis was confirmed (Figures and ).
On the 29th postoperative day, the patient visited the outpatient, and the wound was observed to be healing well. A blood test performed 7 months after the surgery confirmed that her hormonal status had returned to the menopausal status (), and she did not show any complaints.


The patient is a 66-year-old female with pain in both knee joints for more than 20 years. She was admitted to hospital with suppurative osteoarthritis and presented with a history of diabetes and hypertension. She developed lesions 5 days after the surgical of left knee replacement. The patient's left lower leg initially presented as purplish erythema and then gradually developed into large area of ecchymosis and bullae, and the small pustules on the surface partly fused into a large ulceration (); along with these dermatology processes were high fever and temporary unconsciousness. Antibiotic treatment was ineffective, and cultures for bacteria and fungi from pustules were negative. Routine blood tests showed that neutrophils, white blood cells, and high-sensitivity C-reactive protein (CRP) were significantly increased (). Histopathologic examination of skin biopsy revealed that a large number of neutrophils infiltrated in the dermis with granulomatous changes in the subcutaneous tissue. Based on the clinical and histological features, the patient was diagnosed with PG and was treated with high-dose intravenous immunoglobulin (IVIG) plus corticosteroid, which induced a great improvement in her lesions (). After treatment, the patient was in remission, and blood neutrophils and CRP gradually decreased.


A Saudi male patient aged 32-year-old right-handed government employee by profession presented with a progressive left thumb swelling that started 6 years ago. There were no other associated symptoms such as pain nor muscular atrophy. He was diagnosed with a multilocular soft-tissue lipoma on the volar aspect of the left thumb based on magnetic resonance imagining (MRI) findings, he is otherwise healthy and medically stable (). He doesn't smoke nor is he a second-hand smoker. There is no history of drug abuse, and travel history is insignificant. The rest of his history was unremarkable. Physical examinations were all within the normal limits.
For more investigations, the patient underwent several imaging workups. An MRI of the left thumb was ordered to confirm the findings, which showed a multilocular soft-tissue lesion along the volar aspect of the left thumb. The lesion extends from the level of the mid-distal phalanx to the first metacarpophalangeal joint. The lesion measures 2.2 × 2.8 × 4.3 cm in anteroposterior, transverse, and cranio-caudal diameters respectively. The lesion is surrounding the anterior, medial, and lateral borders of the flexor pollicis longus tendon with no deep extension to the tendon. After contrast administration, there is no definite enhancement. While the tendon of the flexor pollicis longus demonstrates a nonspecific abnormal signal intensity 1 cm above the base of the proximal phalanx. The remaining part of the tendon demonstrates normal signal intensity and thickness . The patient was admitted to our institute for excision of the left thumb swelling. Under aseptic precautions and tourniquet control, a rectangular radially based incision was made over the left thumb over the thumb and the flap was raised in order to secure the neurovascular bundle. The mass was excised completely from the left thumb with no immediate or late complications ).


A 29-year-old man from a rural area of Mexico suffered many years of physical abuse during his childhood. He had a seizure at age 24. Approximately 4 years later, he developed confusion, weakness, fatigue and diarrhea, so his mother brought him to the United States for medical care. Ten days following the onset of his symptoms and 8 days after his arrival in the United States, he was brought to an urban outpatient clinic in the Southwest United States. In the clinic at 14:00, his temperature was 36.7o C, pulse rate 100 beats/minute, blood pressure 90/50 mm Hg, respiration rate 20 breaths/minute, hematocrit 16.3% (RR: 42-52%), and white blood cell (WBC) count 12,500/mm3 (RR: 4,500-11,000/mm3). An intravenous infusion of normal saline was started and the patient was sent to a large public hospital emergency department.
On arrival in the emergency department at 16:42, the patient’s pulse rate was 84 beats/minute, blood pressure 112/70 mm Hg and respiration rate 16 breaths/minute. He had a grade 2/6 systolic ejection murmur and yellow stool with gross blood in it. He was unable to cooperate for detailed interviewing or physical examination because of “altered mental status”. His hematocrit was 17.3%, hemoglobin 4.8 g/dL (RR: 14-18 g/dL), and WBC count 11,100/mm3. Chest x-ray showed patchy bilateral peripheral nodular infiltrates and pleural effusions.
The following morning, at 07:00, an order was written to transfuse 2 units of red blood cells over 1 hour each as soon as possible. The patient’s hemoglobin was 4.4 g/dL, hematocrit 14.9%, mean corpuscular volume (MCV 52.3 fL (RR: 80-100 fL), WBC count 15,500/mm3, bilirubin 0.3 mg/dL (RR: 0.1-1.2 mg/dL), alkaline phosphatase 150 U/L (RR: 35-110 U/L), alanine aminotransferase (ALT) 8 U/L (RR: 5-40 U/L), aspartate aminotransferase (AST) 12 U/L (RR: 5-40 U/L), lactate dehydrogenase (LDH) 285 U/L (RR: 120-300 U/L), albumin 2.3 g/dL (RR: 3.9-5 g/dL), blood urea nitrogen 11 mg/dL (RR: 10-20 mg/dL), creatinine 0.3 mg/dL (RR: 0.4-1.3 mg/dL), calcium 7.7 mg/dL (RR: 8.6-10.3 mg/dL), and creatine phosphokinase (CPK) 25 U/L (RR: 35-345 U/L). A hematology consultant obtained further blood tests showing hemoglobin 4.6 g/dL, hematocrit 16.5%, MCV 52.9 fL, WBC count 9,400/mm3 (58% segmented neutrophils, 1% bands, 14% lymphocytes, 4% monocytes, 22% eosinophils), folate 4.9 ng/mL (RR: 2.5-20 ng/mL), vitamin B12 419 pg/mL (RR: 250-1000) pg/mL), normal hemoglobin electrophoresis, and normal thyroid functions tests. Peripheral blood smear showed hypochromasia, microcytosis, teardrop cells, target cells, red blood cell fragments, anisocytosis, poikilocytosis and markedly increased platelets. The hematology consultant recommended parenteral iron instead of transfusion. The order for transfusion was rescinded, although the patient had already been premedicated for it. He was transferred from the emergency department to an inpatient unit where he passed two loose yellow foul-smelling stools with no blood in them.
The next morning, hospital day 3, the medicine resident who took over the patient's management noted confusion as a new problem. The medicine resident ordered a computed tomography scan of the head, which showed no abnormalities, and at 16:30, performed lumbar puncture. Opening pressure was 20 cm H2O. The cerebrospinal fluid was clear. Approximately 45 minutes following the lumbar puncture, the patient was found on the floor, unresponsive, with cyanosis, shallow respirations and fecal incontinence. He was given an ampule of 50% dextrose intravenously and supplemental oxygen at 6 L/minute. He became responsive, but remained confused. At 17:45, the patient ceased breathing and the cardiac arrest team was summoned. Despite full cardiopulmonary resuscitative efforts, the patient could not be revived.


The patient, a 13-year-old female, presented with constitutional symptoms and complete blood count (CBC) demonstrated a white blood cell (WBC) of 25.3 × 109/L, hemoglobin of 5.7 g/dL, hematocrit of 16.5%, platelets of 63 × 109/L, and 38% blasts with 58% blasts in the bone marrow (Figure ). Flow cytometric analysis (FCA) revealed a leukemic immunophenotype with expression of myeloid and lymphoid antigens: dim CD45+, CD34+, CD13+, CD33+, partial CD117+, partial CD7+, dim myeloperoxidase+, partial TdT+, partial CD19+, CD20-, CD10-, cytoplasmic CD3-, HLA-DR+, CD123+, CD38+. Additional analysis revealed two distinct blast populations, with one population expressing lymphoid antigens CD22+ and CD79a+ (Figure ). This immunophenotype was consistent with B/myeloid (B/My) MPAL, as per current WHO 2017 guidelines. Chromosome analysis showed normal karyotype and fluorescence in situ hybridization (FISH) was negative for KMT2A, ETV6, RUNX1, CBFB, and BCR/ABL gene rearrangements, and microdeletions on 5q, 7q, and PAX5. Microarray revealed a deletion involving the 5′ portion of the NSD1 gene, suggesting a NUP98-NSD1 rearrangement (Figure ). FISH analysis using the NUP98 probe confirmed the cryptic t(5;11)(q35;p15.5) translocation resulting in the NUP98-NSD1 gene fusion in 90.8% of interphase cells (Figure ). Next generation sequencing (NGS) detected a NRAS p.Gly61Arg alteration.
Given predominant myeloid features, and poor prognosis with a NUP98-NSD1 fusion, AML directed therapy was chosen with the goal of HSCT after remission. The patient's cytogenetic findings, and immunophenotypic responses are summarized in Table . The acute leukemia follow up panel has a level of threshold of detection of 0.1%, is based on a “different from normal” approach, and consists of seven tubes (marker combinations) which include 4-color, 6-color, and 8-color tubes. The following antibodies are included in this panel: CD16, CD57, CD7, CD4, CD3, CD56, CD8, CD2, CD45, CD7, CD13, CD33, CD19, CD5, kappa, lambda, CD10, CD38, CD20, CD45, TdT, MPO, cytoplasmic CD3, CD34, CD22, CD79a, CD36, CD123, CD64, CD14, HLA-DR, CD58. Despite morphologic and immunophenotypic remission after Induction II, an appropriate donor was not immediately available, so FLAG-DaunoXome was used as a bridge to HSCT, which was complicated by sepsis and prolonged intubation. Bone marrow evaluation after this course showed no evidence of leukemic blasts by FCA, but persistent cytogenetic abnormality. Despite further delays from cholecystolithiasis requiring a cholecystectomy, repeat disease evaluation demonstrated no definite blast population by FCA, but 80.6% of cells were positive for the NUP98-NSD1 fusion.
Despite this persistent cytogenetic abnormality, the patient remained in flow cytometric remission, and received a 7/8 HLA mismatched unrelated allogenic HSCT 6 months after diagnosis. Reduced intensity conditioning (RIC) with busulfan, fludarabine, and anti-thymocyte globulin (ATG) was chosen over myeloablative conditioning (MAC) given prior infectious complications. Graft-vs-host-disease (GvHD) prophylaxis included tacrolimus and mycophenolate mofetil (MMF). She developed grade II skin acute GvHD and was treated with systemic and topical steroids. Day +60 bone marrow had 24% blasts by FCA with a similar immunophenotype to diagnosis, except near absence of CD19 expression. FISH revealed the NUP98-NSD1 fusion in ~60% of cells. Bone marrow chimerism analysis showed 59% donor cells.
Recent HSCT and acute GvHD precluded enrollment on clinical trials. Azacitidine and sirolimus were started with a subsequent decline in both the peripheral WBC count and blast count. Bone marrow evaluation after 3.5 months revealed 23% blasts by FCA and NUP98-NSD1 fusion in 87% of cells. Five months into therapy she developed a grade III septic joint, and both immunosuppressive agents were held. The patient experienced further disease progression 6 months from the start of relapse therapy and was transitioned to palliative care and died 2 months later.


A 20-year-old mother gravida 1 para 0 (G1P0) with history of congenital lobar emphysema was referred for fetal cardiac evaluation at 22 weeks of gestation because of suspected fetal cardiac anomaly with ventricular septal defect. Parents were first cousins with a family history of congenital bronchiectasis in the mother’s uncle and congenital cardiac abnormality (single ventricle physiology) in a paternal uncle. Fetal scan also revealed possible bronchial compression, single umbilical artery type 2 with persistent vitelline artery, and hypoplastic abdominal aorta. Fetal echocardiogram revealed superior–inferior ventricles with normal atrioventricular and ventriculoarterial relationships, a drop-out in the membranous ventricular septum suggestive of a defect, abnormally short ascending aorta, elongated subclavian artery, and a large AP window (Figs. , , ). Pregnancy was smooth and the patient delivered at term by elective cesarean section (C/S) due to her pulmonary emphysema.
The baby was born with a birth weight of 2750 g, Apgar scores were 1, 6, and 8 at 1, 5, and 10 min, respectively. The baby was intubated right after delivery and was admitted to the neonatal intensive care unit (NICU). Post-natal echocardiogram confirmed the presence of superior–inferior ventricles. There was normal atrioventricular and ventriculo-arterial connections, a small secundum ASD, and a large AP window. There was no ventricular septal defect. Cardiac valves were morphologically and functionally normal except for a bicuspid aortic valve with no significant stenosis or regurgitation. The aortic arch was very difficult to visualize adequately due to its unusual course and tortuosity. The pulmonary artery was significantly dilated, the abdominal aorta showed significant flow reversal secondary to the AP window.
Cardiac computed tomography (CT) showed upstairs–downstairs relationship of the ventricles, a distal non-restrictive AP window (Fig. ). The head and neck vessels had an abnormal branching from a low short “pseudoarch” at the posterior aspect of the AP window. There was an abrupt termination of the abdominal aorta and the branches supplying the abdominal viscera and lower extremities were all gracile. Airway findings included a distal concentric tracheal stenosis with bronchus suis type airway to the right upper lobe. There was discrete narrowing of the distal trachea and near obliteration of the proximal main bronchi. The carina and proximal main bronchi were compressed as they pass between the right pulmonary artery and the distal main pulmonary artery-aortic continuation, with secondary areas of atelectasis. Having this rare and complex cardiac defect, consensus was to do cardiac cath to get more imaging to help understand the anatomy more precisely. Closing the AP window could have been also a reasonable ‘bridge’ management, allowing the patient to grow, which can help explore more extensive treatment options in the future.
Angiography showed dextrocardia, horizontally superimposed ventricles with the RV superior, and the LV posterior leading to the great vessels arising horizontally, low position of the great vessels in the thorax, and a large AP window. Because of the position and orientation of the great vessels, the position, branching, and direction of the pulmonary arteries were also unusual. Similarly, branching of the aorta was uncommon with neck vessels originating low from the descending aorta with a long vertical course in the chest to the arms, neck, and head. The abdominal aorta was interrupted with highly abnormal vascularization to the abdominal organs and legs through small vessels. Post-catheterization, the baby’s clinical status deteriorated with signs of decreased perfusion requiring vasopressor support and fluid resuscitation. A flexible bronchoscopy and bronchogram showed critical stenosis with malacia of left main bronchus with pulsatile compression noted and resultant ball-valve effect on the left lower lobe (Fig. ).
A multidisciplinary team discussion led to a consensus that the airway lesion with extensive vascular airway compression and malacia were likely futile. Palliative care was offered and no intervention was performed. The baby was extubated to noninvasive ventilation and expired shortly afterward.


A 59-years-old woman, a cook, presented to the Outpatient Clinic. The first symptoms, according to her husband, began a year earlier in the form of memory problems, the patient quickly forgot new information, did not attend appointments, and had difficulties with everyday activities such as cooking (she often left the pot on the stove burning the food). The patient had been fired from her job several months earlier because she was unable to fulfil her responsibilities. Other than apathy, no other behavioural disturbances were observed. Her family history showed that her brother, 5 years older, had been diagnosed with Alzheimer’s disease several years earlier. The patient’s mother (who died at the age of 84) had suffered from dementia for 10 years. The results of the neurological examination were normal. The subject scored 23/30 on the Mini Mental State Examination (MMSE) (she was not oriented to the month, date, lost 3 points when counting backwards and 2 when recalling words after distraction), and 10/10 on the Clock Drawing Test (CDT).
On follow-up examination, all laboratory results were normal. A CT scan of the brain (the patient did not consent to the MR scan due to claustrophobia) showed slight subcortical and cortical atrophy in the frontal, temporal, and occipital lobes ().
The neuropsychological profile of cognitive impairment showed episodic memory impairment and executive dysfunction. Molecular genetic analyses of the PSEN1, PSEN2, APP, APOE genes were performed by Sanger sequencing method. The patient had APOE3/3 genotype. A variant c.185G>A in one allele of PSEN2 gene was found. This variant was classified as benign/likely benign in ClinVar NCBI. In the Human Gene Mutation Database (HGMD), the patient with sporadic AD carrying this variant was registered [CM981662]. The pathogenic role of the PSEN2 Arg62His mutation has not been demonstrated in a family with frontotemporal dementia (FTD), where the variant was found in an asymptomatic mother and her symptomatic daughter, and the authors argued that other factors, including APOE genotype, may influence the onset of the disease in carriers of the variant []. The variant has been reported as a common variant in African populations [] and, after in vivo functional analysis, as a rare polymorphism with no effect on neurodegeneration []. On the other hand, this variant has also been shown to affect the stability of the protein, making it more susceptible to degeneration [].
Based on the specific clinical phenotype (predominant executive function impairment, in addition to impairment of episodic memory in cognitive tests and the presence of apathy) and the results of genetic testing, the patient was diagnosed with frontal variant Alzheimer’s disease [].


Fourteen months later, a 55-year-old man, a blue-collar worker, presented to the Outpatient Clinic because of memory impairment. The patient’s wife had noticed the first symptoms 4 years before the visit: memory problems, disorientation in space, and difficulty handling money. The patient was still independent at home for simple activities of daily living but required supervision for more complex tasks because he immediately forgot what he was doing. His wife complained that the patient was very apathetic. She reported no other behavioural disturbances. The patient’s mother, who was 83 years old at the time, had had memory problems for 5 years and required constant care from others.
Neurological examination results were normal. He scored 20/30 on MMSE (he did not orient to time, lost 3 points when counting backwards and 3 points when recalling words after distraction), and 10/10 on the CDT. A head MR scan performed 17 months before presentation showed frontoparietal cortical atrophy, small disseminated vascular lesions up to 6 mm in the frontal and occipital lobes, and an enlarged Virchow-Robin space in the left globus pallidus (5 × 10 mm) ().
At follow-up, all laboratory findings were normal. Neuropsychological evaluation revealed episodic memory impairment and executive dysfunction. Routine molecular genetic analysis of the PSEN1, PSEN2, APP, APOE genes were performed by Sanger sequencing. A variant in one allele of PSEN2 gene c.185 G > A was revealed. The patient had APOE3/3 genotype. Based on the specific clinical phenotype (predominant executive function impairment, in addition to impairment of episodic memory in cognitive tests and the presence of apathy) and the results of genetic testing, the patient was diagnosed with frontal variant Alzheimer’s disease [].
The polymorphism in the PSEN2 gene found in both cases is so rare that we started investigating whether the two patients were related. They turned out to be second line cousins.
At the same time, the outpatient clinic gained access to NGS. Due to the strong suspicion of the genetic basis for dementia in the family and weak data on the pathogenicity of detected variant in PSEN2, the patient’s DNA was sent for further testing. A panel of 118 genes associated with neurogenetic disorders (based on HPO, OMIM, Genereviews, Orphanet) was used, for which a library was prepared using the KAPA Hyper Plus kit (Roche), sequencing was performed on MiSeq platform using the MiSEq reagent Kit v3 (150 cycles) (illumina), and the results were analyzed using BaseSpace Variant Interpreter and Integrative Genomics Viewer (IGV) (average read depth was 119.2×; 96.2% sequences was covered more than 30×).
The work was conducted in accordance with the Helsinki Declaration. All patients gave their written consent for genetic testing. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.


Case 1: A six-year-old girl was referred from a local clinic to the Department of Pediatric Dentistry at our University with a complaint of ectopically erupting permanent maxillary right and left first molars. Her medical and dental histories were normal. Radiographic examination revealed a mesioangulated permanent maxillary first molar with partial root resorption of the primary second molar. A piston-elastic device was attached to both of the maxillary first molars. The patient performed regular check-ups every three to four weeks, and the elastic was replaced. Within three months, the eruption direction of the teeth was confirmed to be improved ().


Case 2: A 12-year-old healthy girl without any history of dental trauma or systemic disease visited the same clinic. As mesially angulated impaction of the lower second molars was found bilaterally, and piston-elastic devices were attached. This patient also had regular check-ups every three to four weeks, and the elastic was replaced. After three months, directions of the lower second molars improved, showing a full eruption reaching occlusal contact ().


Case 3: A 13-year-old healthy girl was receiving orthodontic treatment at our clinic. Mesially angulated ectopic impaction of the right second molar was observed during orthodontic treatment. As the buccal surface area was not enough for bracket attachment, a piston-elastic device was attached to the exposed occlusal surface. After attaching the device, regular check-ups were performed four weeks later, and the elastic was replaced only once. At two months post-attachment, a definite change in the eruption path was observed, and the tooth had successfully erupted, completing the orthodontic treatment ().