A 46-year-old male patient, smoker (more than 20 cigarettes per day), presented with numerous problems related to the bad condition of his oral cavity, in particular, pain and masticatory limitation, difficulty to pronounce certain words or letters, and inadequacy of the aesthetic appearance. The patient was in good health general state. Considering the clinical exam (), radiographic exams (Figures , , , and ), and examination of models (), specialists in periodontics, implantology, prosthetics, and orthodontics made a diagnosis suggesting that the multidisciplinary approach was the best therapeutic choice to adopt for this complex case. A simulation of the final rehabilitation through a diagnostic wax was realized (Figures , , and ) and analysed with the patient, aiming at highlighting what the advantages and disadvantages of the prostheses would be. Treatment objectives included the reestablishment of periodontal health through the elimination of etiological factors and the creation of a stable occlusal scheme for function; the programme included the development of fixed aesthetics rehabilitation on natural teeth and dental implants aimed at improving the aesthetic and functional aspect of the patient. Throughout the periodontal therapy, the patient was maintained periodontally stable and at each control he was motivated to oral hygiene, according to the guidelines set out recently in the seventh European Workshop on Periodontology [].
One month after nonsurgical periodontal therapy had been completed (), implant surgery was carried out. Implants insertion was completed in one surgical time under local anesthesia. Paracrestal full-thickness flaps were elevated; consequently the osteotomy was realized following the surgical stent (). Three implants (Astra Tech OsseoSpeed TX Dentsply) were inserted in a prosthetic guided position [] in site 1.4 with implant 3.5 mm in diameter and 13 mm in length, in site 1.5 with implant 3.5 mm in diameter and 11 mm in length, and in site 1.6 with implant 4.0 mm in diameter and 9 mm in length, respecting the interimplant distance of 2-3 millimeters () according to Tarnow et al. and Elian et al. [, ], throughout the implant length to influence in a positive way osseointegration (). All implants achieved good primary stability with an insertion torque at least of 35 Ncm. During the healing phase, natural teeth were prepared and abutments were then covered with a provisional prosthesis to condition soft tissues, whereas 2.7 and 3.7 were extracted, regarded as hopeless. After four months necessary to osteointegration and conditioning soft tissue () the impression was taken for the definitive rehabilitation. Periodontal probing was within normal limits, and no inflammation was recorded neither around the teeth nor around implants (Figures , , and ). Thus, a final impression was taken using a single-phase technique with double components polyether and individual tray. Lithium disilicate crowns were realized with the cross-mounting technique (Figures , , and ): the occlusal scheme was designed with anterior guidance allowing complete disclusion in both the lateral and protrusive excursions. The final restoration included a tooth-borne fixed partial denture from teeth 1.3 to 2.5 and from teeth 4.4 to 3.4 and one implant-supported fixed partial denture from implant 1.6 to 1.4. The photographs were taken using Nikon D90 and a 105 mm lens (AF Micro Nikkor 105 mm 1 : 2.8 D, Nikon) with a ring flash (EM-140 DG, SIGMA-Nikon).
At the end of the treatment, a maxillary retained night guard was provided to prevent any possible negative effect of parafunctional habits. According to Brägger et al. [] the risk of incidence of complications increases in prosthetic rehabilitation due to parafunctions. From a functional and esthetic perspective, the objectives were achieved restoring good occlusal stability and a pleasant and harmonious smile line (Figures , , and ). Periodic nonsurgical periodontal therapy and accuracy of prosthetic structures helped maintain the amount of bone fairly stable over time. The radiographic check at one year () demonstrated no bone loss around implants and teeth compared to the starting condition (). The multidisciplinary approach [] together with the control of local risk factors such as plaque and smoke [] has allowed obtaining an aesthetic and functional integration of the final rehabilitation on natural teeth and implants.


A 41-year-old Caucasian woman underwent a primary double lung transplantation for cystic fibrosis in 2006. Her medical history was otherwise unremarkable and the patient had no known history of pulmonary tuberculosis or tuberculosis contact. On December 2015, she underwent retransplantation for chronic lung allograft dysfunction. During the month preceding retransplantation, 4 sputum specimens remained negative for acid-fast bacilli and specific M. tuberculosis culture and real-time polymerase chain reaction (PCR) testing. On postoperative day 42, deterioration of her respiratory status prompted a chest-computerized tomography (CT) scan revealing sub-centimeter bilateral nodules primarily located in the apical posterior lobes and a bilateral pleural effusion (Fig. ). The same day, a bronchoalveolar lavage (BAL) yielded a positive real-time PCR for rifampicin-susceptible M. tuberculosis, confirmed by culture on postoperative day 62. Tuberculin skin test (TST) or interferon-γ release assay (IGRA) test were not performed. All the BALs performed on postoperative period yielded no other pathogen except for the one performed on day 60 that cultured Pseudomonas aeruginosa; the adjunctive antibiotic therapy was imipenem-cilastatin, 3 g/d. Histological examination of a lung biopsy performed 6 weeks after retransplantation revealed a caseating granuloma and necrosis. Acid-fast bacilli were identified as rifampicin-susceptible M. tuberculosis by real-time PCR. On postoperative day 65, the patient's status worsened with severe hypoxemia, shock unresponsive to high dose cathecolamines, and multiorgan failure. The patient died on postoperative day 70, despite treatment combining isoniazid, rifampicin, ethambutol, and pyrazinamide. Retrospective real-time PCR testing of the explanted lung and BALs performed on postoperative days 1, 7, and 21 remained negative.
The organ donor died of posttraumatic intracerebral hemorrhage. He was a 47-year-old man with no history of lung disease or risk factors for tuberculosis other than chronic alcohol use and smoking. TST results were not available. During hospitalization, a lung CT-scan showed no signs of active or previous tuberculosis and no TST or IGRA test results were available. Routine cultures of per-transplantation right lung biopsy yielded Candida albicans. Retrospective M. tuberculosis real-time PCR yielded negative results on the left and right donor-lung biopsies. Both kidneys from the same donor were transplanted into 2 other recipients. Six months after transplantation, neither of the kidney recipients had developed any signs or symptoms suggestive of active tuberculosis.


A 55-year-old woman presented with bilateral anterior knee pain nine months after a simultaneous bilateral TKA, using posterior stabilized Scorpio NRG™ prosthesis (Stryker, Kalamazoo, MI) without patellar resurfacing. The pain started following forceful bending of both knees after a fall at home on a slippery floor. Right knee passive range of motion (ROM) was 20-105 degrees and left knee passive ROM was 15-100 degrees. Plain radiographs of both knees revealed bilateral dislocation of both patellas (Figure ).
The patient underwent simultaneous bilateral extensor mechanism repair. Postoperative x-ray was satisfactory (Figure ). Following surgery, the patient was placed in a knee immobilizer for six weeks with restricted ROM and non-weight-bearing. After six weeks, she was allowed weight-bearing as tolerated in a knee brace, eventually progressing to unrestricted ROM. The brace was discontinued at 12 weeks. At 18 months follow-up, both the knees remained stable with no other complaints. The active ROM was 0-115 degrees in right and 0-110 degrees in left knee at the last follow-up.


A 57-year-old woman presented with the acute onset of bilateral knee pain following a fall from standing height. She had simultaneous bilateral TKAs seven months previously using posterior stabilized Triathalon™ prostheses (Stryker, Kalamazoo, MI) with patellar resurfacing. Medical comorbidities included morbid obesity (BMI: 58.9 kg/m2), hypertension, and Type II diabetes mellitus. Passive ROM was 15-100 degrees in both knees, and radiographs revealed bilateral patellar dislocations with component dissociation (Figure ).
The patient underwent simultaneous bilateral patelloplasties with the removal of the patellar components and extensor mechanism repair. Postoperatively, the patient was placed in a knee immobilizer for six weeks with limited ROM and weight-bearing. After six weeks, she was allowed weight-bearing as tolerated in a knee brace, eventually progressing to unrestricted ROM. The brace was discontinued at 12 weeks. At her 14-month follow-up, she remained pain-free with active ROM of 10-100 degrees in both knees.


A 55-year-old man accidentally inhaled a chlorine cloud when cleaning the swimming
pool at his home, evolving to a clinical picture of mild dyspnea, cough with mucoid
sputum, and epigastric pain. He sought emergency care (after 30 minutes), where he
was initially evaluated for respiratory symptoms and received venous hydration,
bronchodilators, and oxygen therapy. However, he presented progressive clinical
worsening over a 3-hour period, with increased expectoration, arterial oxygen
saturation (SpO2) (from 95% to 60%), and cyanosis and was referred to the
reference emergency room, where he was seen in the emergency department. At that
time, he already had signs of acute respiratory failure, associated with intense
burning chest pain and cough with blood-tinged sputum. There was no history of
smoking, respiratory diseases, and other comorbidities.
At admission, the patient was afebrile, tachycardic (heart rate 110bpm), and
tachypneic (respiratory rate 34bpm), with a blood pressure of 134/82mmHg and an
SpO2 of 86% during oxygen macronebulization at 10L/minute. Chest
expandability was decreased due to pain, and respiratory auscultation detected the
presence of generalized decreased vesicular murmur and crackling rales mainly on the
lung bases. No other changes were detected on physical examination. Noninvasive
ventilation with 60% FiO2, 7cmH2O support pressure (SP), and
10cmH2O positive end expiratory pressure (PEEP) was started.
Arterial blood gas analysis revealed a pH of 7.41, a partial carbon dioxide pressure
(PaCO2) of 39.1mmHg, a partial oxygen pressure (PaO2) of
59.5mmHg, an oxygen saturation (SO2) of 87.4%, a bicarbonate level of
29mEq/L and a base excess of +0.7mmol/L. The patient had leukocytosis (leukocyte
count of 27,840 thousand/mm3 with 94% segmented). Electrolytes,
coagulation tests, and liver and canalicular enzymes were normal. Chest X-ray
revealed bilateral alveolar infiltrate in the lower third (). Chest tomography showed consolidation in the
posterior region of the lower lobes and discrete in the upper lobes, associated with
areas of diffuse ground-glass opacity in the upper lobes, in addition to an increase
in the diameter of the pulmonary arterial trunk (3.8cm), indicating hypertension of
the same ().
In the intensive care unit, antibiotic therapy with cefepime (2g every 8 hours),
intravenous corticosteroid (methylprednisolone 125mg every 6 hours), and
nebulization with a beta-agonist and an anticholinergic were started, with
progressive clinical improvement and noninvasive mechanical ventilation (NIV)
maintained intermittently for 4 days. A Dixtal® 3010 mechanical
ventilator with a full face mask interface was used in SP mode, using SP for a
target tidal volume of approximately 6 to 8mL/kg predicted weight and a PEEP ranging
from 5 to 10cmH2O, in addition to an FiO2 required to maintain
an oxygen saturation above 88%. On the first day, the patient remained on a zero
diet and remained on NIV for 24 hours; the PaO2/FiO2 ratio was
99. On the second day, pauses were taken for oral feeding; the
PaO2/FiO2 ratio was 150. On the third day, most NIV shifts
were maintained but with larger pauses; the PaO2/FiO2 ratio
was 230. On the fourth day, NIV was performed intermittently; the
PaO2/FiO2 ratio was 350. On the fifth day, the patient was
kept on oxygen macronebulization. On the sixth day and following until hospital
discharge, which occurred on the seventh day, the patient was spontaneously
ventilated with room air. He remained hemodynamically stable throughout his hospital
stay, without organ dysfunctions. He was discharged on the seventh day of
hospitalization and was given an oral corticosteroid and a bronchodilator. In his
outpatient follow-up, he underwent a chest X-ray, showing dense striae in the right
upper lobe (), with no other
alterations. Spirometry was also performed but did not show alterations.


A 42-year-old Korean man visited a cardiology clinic for management of hypertension. He had been prescribed antihypertensive and lipid-lowering agents for years and had been followed up irregularly. The medications include losartan 50 mg, fenofibrate 160 mg and a combination capsule of simvastatin 20 mg and ezetimibe 10 mg. On routine checkup, his blood test results were as follows: fasting plasma glucose (FPG), 555 mg/dL; serum creatinine, 2.29 mg/dL; serum sodium, 140 mmol/L; serum triglycerides, 792 mg/dL; glycosylated hemoglobin (HbA1c), 14.9%. Review of his medical history revealed that he had high FPG levels 1 year prior to the consult during a routine checkup. Treatment had been recommended, but he did not undergo further workup. Our patient was immediately started on oral hypoglycemic agents and was referred to the department of ophthalmology for evaluation of diabetic retinopathy.
On ophthalmic examination, his uncorrected visual acuity (UCVA) was 20/200 and best corrected visual acuity (BCVA) was 20/20 in both eyes. He had mild myopia, with -3.25 diopters (D) of spherical equivalent in both eyes, which was the same as his own glasses. The lenses were clear in both eyes and the remainder of the ophthalmic examination findings were normal.
Three days after the first visit, our patient presented with a sudden decrease in visual acuity and glare in both eyes that had begun 2 days prior to consult. Metformin hydrochloride (Glycomin tablet) 500 mg twice a day was prescribed. However, his blood glucose level was not optimally controlled, so he was prescribed insulin with titration. On the day he was treated with insulin and his blood glucose level began to be controlled, he felt an abrupt decrease in his visual acuity. His BCVA was 20/40 in the right eye and 20/50 in the left eye. A dilated slit-lamp examination showed fine feathery snowflake opacities in the posterior subcapsular region of bilateral lenses (Fig. ). Dilated fundus examination revealed some exudates and cotton wool patches from the macula to the mid-periphery region. Repeated blood test results on the same day showed a rapid decrease in FPG, which decreased to 214 mg/dL. His serum sodium level was 139 mmol/L and serum creatinine and triglyceride levels were reduced to 1.91 mg/dL and 424 mg/dL, respectively.
Ten days after the first visit, he complained that he could not see well with his own glasses. His visual acuity with his own glasses was 20/40 in the right eye and 20/50 in the left eye. His BCVAs were 20/25 in both eyes. Manifest refraction showed mild hyperopia, with +1.0 D of spherical equivalent in both eyes. A slit-lamp examination revealed essentially clear lenses except for scattered fine opacities in the posterior subcapsular region.
Four weeks after the first visit, his BCVA was 20/20 in both eyes. Manifest refraction was -1.25 spherical diopter (Dsph) -0.75 cylindrical diopter (Dcyl) × 30 in the right eye and -1.25 Dsph -0.75Dcyl × 110 in the left eye. On slit-lamp examination, the subcapsular opacity of the lenses had regressed, showing nearly clear lenses (Fig. ). A fundus examination showed decreased exudates and cotton wool patches.
The antihypertensive and lipid-lowering medications that our patient had taken for several years were not changed during these clinical courses (Table ).


A 22-year-old male was referred to our department for further investigation of a mediastinal mass discovered incidentally during routine chest X-ray (Fig. ). The patient has denied symptoms including dyspnea, chest pain, cough, fever, dysphagia, hemoptysis, weight loss, and weakness. Interestingly, his past medical history was remarkable for orchitis 2 years before surgery, which was treated with antibiotics. Due to an inconclusive sonogram finding related to inhomogeneous parenchym, the patient underwent a bilateral testicular biopsy, which however did not show any signs of a germ cell tumor and was negative for the presence of a premalignant lesion such as testicular intraepithelial neoplasia (TIN). The patient had no history of sexual transmitted diseases, no history of maldescended testis, and had a 5-pack-year smoking history, currently smoking one pack per day. Finally, the patient had no history of a diagnosed Klinefelter syndrome (47XXY) or myasthenia Gravis.
Clinical examination was unremarkable and did not reveal a palpable mass on the chest wall, neither has demonstrated any signs of a vena cava occlusion syndrome, while it also did not show depletion of the muscle strength regarding all muscle groups.
Blood tests excluded relevant hematological disorders or signs of anemia, whereas chemistry tests revealed an elevated LDH one and a half time more than the reference rate. Alpha-fetoprotein (AFP) and human chorionic gonadotropin (hHG) values were not elevated. Contrast-enhanced chest computed tomography revealed a lobulated and well-marginated cystic lesion in the anterior mediastinum (Fig. ). The differential diagnosis was mostly related to a multilocular thymic cyst. Speculation regarding a lymphoma, a seminoma, or a soft tissue tumor presence was highly unlikely due to their often “solid” appearance on CT. Therefore, the patient underwent a median sternotomy with an en bloc surgical excision of the tumor.
Surprisingly, the histopathological examination revealed a primary thymic seminoma with a predominate cystic appearance (Fig. ). Macroscopically there appeared a solid nodule of the thymus weighting 148 g, measuring 10 × 6 × 3 cm and showing a cream-colored to pale-yellow and lobular cut surface. The tumor appeared to be well circumscribed and did not grossly involve any adjacent structures. A complete excision was performed (R0-Status) and histology showed sheets of neoplastic polygonal cells interspersed with lymphocytes consistent with pure seminoma. Histology of the neoplastic cells in more details demonstrated that the nodule of the thymus showed a diffuse arrangement of pale cells that were interrupted by fibrovascular septa containing lymphocytes and a granulomatous reaction with small clusters of epithelioid cells and giant cells of the Langhans. The tumor cells had a pale to clear cytoplasm with distinct membranes. The cytoplasmic clarity was attributable to abundant glycogen particles that were demonstrable with the periodic acid-Schiff stain. The nuclei of the tumor cells were polygonal with finely granular chromatin and flattened edges. One or more large centrally located nucleoli were present. Immunohistochemistry of the neoplastic cells showed a cytoplasmic membrane positive stain for c-kit, D2-40, and PLAP, a nuclear positive stain for oct3/4 and SALL4, and a negative stain for SOX2, Pan-CK, and CD30.
The patient received adjuvant cisplatin-based chemotherapy and 38 months after surgery he is alive and remains disease-free.


A 29-year-old male was diagnosed with relapsing-remitting MS (RRMS) in 1999. He was treated with interferon beta until 2010. He started NTZ due to two relapses in previous year (no gadolinium [Gd] enhanced lesions in MRI). In February 2012 NTZ was discontinued due to the presence of 2 risk factors for PML (26 NTZ infusions and anti-JCV+). At this time, he had mild left hemiparesis and needed a cane for ambulation (Expanded Disability Status Scale [EDSS]: 6) but he was fully independent. In June 2012 FTY was started after a washout period of 3 months without adverse effects. One day later the patient was admitted to the emergency room due to drowsiness, disorientation, inattention, bradypsychia, and behavioral changes. 15 days' prior the patient had had a worsening in his left hemiparesis. On admission, neurological examination revealed a moderate encephalopathy with disorientation, severe inattention and bradyspsychia; Language was less fluent without dysphasia, he comprehended simple commands but not complex ones. He presented a worsening of his left hemiparesis with strength of 4/5 in left upper limb and 3/5 in left lower limb with generalized hyperreflexia and severe dysmetria, the patient was unable to stand up with aid (EDSS: 7). The MRI showed confluent bilateral white matter T2 hyperintensities with enhancement of multiple lesions (Figure a,b), also a Vth and VIIth nerve enhancement bilaterally. This enhancement was prolonged further. Spinal fluid examination was normal with absence of JCV by PCR. High-dose methylprednisolone (MTP) for 5 days was started with progressive improvement. Fingolimod was restarted without new relapses but with a marked deterioration in comparison to his prior situation (EDSS:7).


A 28-year-old female was diagnosed with RRMS in 2006. She was treated with interferon, Glatiramer Acetate and since September 2009 (a severe motor relapse the previous year) with NTZ. She presented no evidence of clinical and radiological activity in 2 years. In September 2012 NTZ was stopped due to a positive serology for VJC (EDSS: 1). Within the first month after the discontinuation the patient showed progressive worsening with paresthesia, instability, dizziness, and occasional diplopia. She was treated with several IV steroid pulses (MTP 13gr in total); in January 2013 FTY was started without response (EDSS: 6.5). An MRI revealed multiple T2 hyperintensities, of which at least 11 showed enhancement after Gd administration (Figure c,d). Due to the progressive worsening despite the treatment, the patient was admitted for plasma exchange (PLEX) with progressive clinical and radiological improvement. She was discharged and FTY was continued with a partial recovery (EDSS: 2.5).


A 38-year-old female diagnosed with RRMS in 1999. She was treated with Interferon B 1b with unsatisfactory control (two relapses in 2007), so in January 2008 the patient switched to NTZ. In September 2011, she presented an optic neuritis and was treated with high doses of MTP. In 2012 due to a high risk for PML a change to FTY was proposed. She received the last dose of NTZ in June 2012 (EDSS: 2.0). After a 3-month washout period she started FTY with no secondary effect. In the last week of December 2012, she presented two partial seizures separated by 6 days and she was treated with levetiracetam. In the MRI of January 2013 multiple new lesions were observed in T2, 15 of them presented enhancement post Gd administration (Figure e,f). There were no signs of PML on MRI. Two weeks later she presented a marked worsening with severe paraparesis with moderate dysmetria in upper limbs. She needed a wheel chair for ambulation (EDSS: 7). The patient started treatment with two 5 day cycles of iv steroid pulses; NTZ was restarted 2 months later with progressive improvement (EDSS: 3.5) and no new relapses.


A 32-year-old female was diagnosed of MS in 2007 after myelitis. She started treatment with AG but she was switched to NTZ in July 2008 due to persistence of clinical activity (severe relapse with myelitis) and disability progression. In November 2011 NTZ was stopped because of the presence of two risk factors for PML (>2 years and JCV+) she was included in a clinical trial. During the first 4 months, she received placebo, starting FTY in March 2012, no bridging therapy was initiated (EDSS: 3.5). In March, she complained of cognitive worsening and weakness in lower limbs, she was unable to read, presented a severe inattention and behavioral changes (EDSS: 5); a neuropsychological study was conducted, with normal processing speed, verbal fluency and abstract reasoning. A moderate impairment of visuospatial processing information and visual-constructional execution with dysgraphia was present. Also, Difficulty encoding and retrieval in verbal memory with conservation of such processes in visual memory implying bilateral hemispheric lesion. A MRI was performed showing multiple T2 lesions; 45 lesions presented post contrast-enhancement (Figure g,h), JCV in CSF was negative. The treatment with IV MTP was started with progressive improvement. Five months later the patient was able to walk without aid although behavioral alteration and cognitive decline have not been recovered, EDSS: 4.


We report a 13 years old boy, who had a fall at age of five years. Following the fall, he complained of left forearm pain and was brought to hospital. He was treated conservatively with Plaster of Paris. Post-injury over the years the left upper limb deformity was noted to progress gradually. In view of tolerable pain initially and only mild angulation of the elbow, the parents did not seek medical attention for the child. However, over the years, the elbow pain progressively worsened with increasing deformity, affecting his daily activities. He presented to our clinic at age of 13. On examination, there was left cubital valgus deformity of 45 degrees without ulnar nerve neuropathy (). The elbow range of movement was full. On palpation, radial head was felt at the anterior elbow. Radiographic assessment revealed anterior dislocation of radial head, Bado type 1 ().
Surgical option was offered to the patient. We performed left ulna osteotomy and gradual lengthening using 2-pin uniplanar external fixator (Monotube). Only one Schanz pin proximally and one distally were inserted from the osteotomy site. No transfixing shanz-pin or k- wire across radius/ulnar distally. Post-operative recovery was uneventful. Gradual distraction was started at day 7 postoperative. Patient was followed-up at two weekly intervals with radiography of the elbow and forearm. At seventh postoperative week, the, radial head was reduced with approximately 3 cm ulna lengthening. Hence the distraction process was stopped.
At three months post-surgery, the lengthening bone gap consolidated. The external fixator was removed and an above elbow backslab was applied for another month. After removal of the cast, all wounds had healed. Clinically, cubital valgus had reduced to 10 degrees, the ranges of motion were full for both supination/pronation and flexion/extension. Radiographs of left elbow showed reduced radial head and corticotomy site consolidated (). At one year follow-up, radial head remained well reduced and stable in all ranges of elbow motion.


A 48-year-old white woman presented to our hospital with enlargement of all groups of peripheral lymph nodes. Lymph nodes formed conglomerates in her left supraclavicular area (up to 6.0 cm in size) with trachea compression and stridor development, and conglomerates in her left femoral-inguinal area (up to 5.0 cm in size) with development of lymphostasis in her left leg. No systemic signs (fever, night sweats, and weight loss) developed. Her medical history was consistent with a 12-year course of SS. At the age of 36, she presented with recurrent polyarthralgia. Serological testing revealed rheumatoid factor at a 1:512 titer (Waaler-Rose test). Subsequently, she developed recurrent parotitis, dry eyes, dry mouth, and recurrent purpura. A contrast X-ray study of her parotid gland indicated parenchymal parotitis. A labial minor salivary gland biopsy showed marked focal lymphocytic sialadenitis with a focus score of 4 (>50 lymphocytes in the 4 mm2 tissue sample). Schirmer's test was positive (<1 mm in 5 minutes). Her anti-Ro/SS-A antibody level was 130 U/ml (normal range <5.0 U/ml). Based on the clinical, serological, and pathological features of SS and the absence of radiographic changes of rheumatoid arthritis, primary SS was diagnosed. Three years before admission, an increase was noted in her left supraclavicular lymph nodes. However, she refused to undergo an examination.
At the time of admission, a complete blood count showed a reduction of her hemoglobin level to 89 g/l. The remaining hemogram parameters were within normal limits. Blood chemistry revealed an increase of total protein to 120 g/l. Her serum lactate dehydrogenase level was normal, and her blood viscosity was 7.9 mPa second (normal range <5.3 mPa second). Antibodies to human immunodeficiency virus (HIV) were absent.
Blood immunochemistry studies revealed a massive M-gradient formed from IgAκ. Her serum monoclonal IgAκ paraprotein level was 72 g/l. Her polyclonal immunoglobulin G (IgG) and immunoglobulin M (IgM) levels were reduced. A urine electrophoresis detected trace proteinuria with serum Aκ paraproteins and monoclonal free κ-type light chains, indicating Bence-Jones (BJ) proteins.
Chest and abdominal computed tomography revealed multiple enlarged lymph nodes of her upper mediastinum, lung roots, abdominal cavity, and retroperitoneal space (merging into conglomerates of up to 6.5 cm in size), as well as enlargement of her liver and spleen. A skeletal X-ray revealed no bone destruction. Her myelogram revealed 1.6% plasma cells and 7.6% lymphocytes. Bone marrow histology showed no signs of plasma cell or lymphocyte infiltration.
A diagnostic biopsy of her cervical and inguinal lymph nodes was performed. The imprint cytology of lymph nodes showed plasma cells, some with distinct atypia (Fig. ). The same findings were revealed in the histological results of her neck and inguinal lymph nodes. The microarchitecture of the nodes was destroyed. Only small remnants of B cell follicles were found, while the interfollicular areas were expanded and infiltrated by plasmacytically differentiated cells (Fig. ). These cells were positive for CD138 (Fig. ), MuM1, and CD43 and expressed IgAκ (Fig. , ). Several plasma cells were positive for CD79a, and some of the plasma cells co-expressed CD20. The plasmacytic infiltration remained negative for CD56, VS38c, BCL6, BCL2, cyclin-D1, and CD23. Germinal centers (CD10+) were not detectable. The proliferative rate (Ki67) reached almost 10%. Plasma cells were negative for human herpesvirus type 8 (HHV-8) and for Epstein-Barr virus (EBV)-encoded small RNA (in situ hybridization). Among the plasma cells, single macrophages and epithelioid histiocytes were noted, represented by granuloma-like small structures (Fig. ).
Based on the examination data, generalized lymph node plasmacytoma was diagnosed. Our patient received nine cycles of doxorubicin, cyclophosphamide, vincristine, and prednisolone (CHOP) chemotherapy. Restaging showed complete remission. However, immunochemical serum and urine studies revealed a residual M-gradient, which was identified by immunofixation as Aκ, indicating residual disease. Three months after completion of chemotherapy the lymphoma relapsed. A 38.0 °C fever developed with rapid enlargement of all groups of lymph nodes (and the formation of conglomerates of up to 6.0 cm in size) and an increase of IgAκ paraprotein to 37.5 g/l. The paraprotein showed rheumatoid factor activity at a 1:81920 titer. BJκ-type protein and Aκ paraprotein reappeared in her urine. Her femoral lymph node was biopsied, and the histology results were similar to those of the primary biopsy. A histological and cytological examination of bone marrow was unremarkable. She received one course of lomustine, VePesid (etoposide), vinblastine, and dexamethasone (CEVD) chemotherapy, which produced an effect. However, she refused any further treatment.
After 19 months, she again complained of progressive weakness and weight loss. On examination, generalized enlargement of peripheral and visceral (up to 6.0 cm diameter) lymph nodes, her liver, and her spleen were found. Monoclonal IgAκ secretion reached a level of 44.5 g/L, and BJκ-type protein was found in her urine. A myelogram revealed 1.0% plasma cells and 18% lymphocytes. After one course of doxorubicin, cyclophosphamide, vincristine, VePesid (etoposide), and prednisolone (CHOEP) chemotherapy, she refused further treatment. No chemotherapy was provided subsequently.
Over the next 16 years, a gradual reduction of her peripheral and visceral lymph nodes to normal size was noted. The lymph node size reduction correlated with a decrease in paraprotein levels to the current undetectable value (the changes in paraprotein levels are shown in Table ). A normal level of immunoglobulins was restored.
The unusual clinical course of the disease has prompted us to exclude the reactive nature of plasma cell infiltration.
We performed polymerase chain reaction (PCR) of slices from paraffin blocks to analyze the gene rearrangements of heavy chains and kappa light chains of immunoglobulins. However, we failed to show monoclonal rearrangements of these genes. At the Department of Pathology, Hematopathology Section and Lymph Node Registry, Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein (Germany), immunohistochemistry of the lymph nodes was repeated, which confirmed the monotypic positivity of the plasma cells for the kappa light chains of immunoglobulins.


A previously healthy 32-year-old white man presented with gradually increasing agitation and confusion. His friends mentioned that he displayed personality changes recently and was more combative and forgetful. The patient was complaining of severe recurrent headaches that started a few months ago and were not accompanied by nausea or vomiting. He had a history of alcohol, tobacco, cocaine, and methamphetamine use for many years. There was no history of seizures, loss of consciousness, syncope, fever, rash, weakness, or involuntary movements. The patient also denied recent travel, camping, and contact with sick persons. There was no family history of neurologic disorders or CNS tumors. The patient was living alone with multiple cats for a long time (four cats for six years).
The patient was afebrile. Heart rate was 90 beats/min, and blood pressure was 115/75 mm Hg. Neurologic examination revealed no motor or sensory deficits. Cranial nerves examination was normal. Bilateral reflexes and gait were normal. However, slow comprehension, poor attention span, naming difficulties, and impaired short-term memory were noticed. Mini–Mental State Examination showed moderate cognitive impairment. The rest of the physical examination was unremarkable.
Laboratory investigation showed normal results of complete blood cell count and basic renal panel. Vitamin B12, folic acid, free thyroxine, thyroid-stimulating hormone, and C-reactive protein levels and erythrocyte sedimentation rate were also within normal limits. Urine drug screen was positive for cocaine.
Computed tomography (CT) of the head showed multifocal white matter lesions. Magnetic resonance imaging (MRI) of the brain revealed extensive cortical and subcortical concentric ring-enhancing white matter lesions throughout both cerebral hemispheres (Figures -).
The lesions were more prominent in left parietal and frontal lobes. The initial differential diagnosis was brain abscesses vs demyelinating disease. MRI of the spine showed no abnormalities. Cerebrospinal fluid (CSF) analysis showed elevated protein levels but no cells. Myelin basic protein and oligoclonal bands in the CSF were negative. Results of visual evoked potential studies were normal bilaterally. No vegetations were noted on the transthoracic echocardiogram. Ophthalmologic examination showed no evidence of chorioretinitis. Blood cultures and HIV test (4th generation enzyme-linked immunosorbent assay [ELISA]) were negative. HIV ribonucleic acid (RNA) was undetectable. CD4 count was 783 cells/mcl, Serum Toxoplasma Immunoglobulin M (IgM) was negative and Toxoplasma Immunoglobulin G (IgG) was positive (>12 IU/ml). Serum immunoglobulin levels were within normal limits. CSF serologic tests for cytomegalovirus, herpes, Toxoplasma, and JC/BK virus were negative. CT scan of the chest/abdomen/pelvis did not identify a primary malignancy. Based on a presumptive diagnosis of a demyelinating disorder (rare multiple sclerosis variant), the patient was given high-dose intravenous corticosteroids for seven days. Follow-up MRI showed increased number and size of brain lesions (Figures -).
A stereotactic brain biopsy was done, and CNS toxoplasmosis was reported after biopsy and polymerase chain reaction analysis (Figures -).
Pyrimethamine 200 mg loading dose, followed by 75 mg daily, sulfadiazine 1.5 g four times daily, and leucovorin 25 mg daily were started and continued for a total of eight weeks. The patient had significant clinical improvement associated with dramatic decrease in number and size of the lesions on follow-up brain imaging within one month (Figures -)
The patient was followed up every three months with serial brain imaging. Dramatic clinical improvement was noticed in memory, concentration, and other neurologic findings, eventually returning to his normal baseline cognitive status.


An 81 year-old man presented with subacute disorientation, mild left-side weakness, impaired balance, apraxia and unilateral spatial neglect in May 2015. His past medical history included arterial hypertension and a stable course of PCV, diagnosed at the age of 66, treated with hydroxyurea (HU), low dose acetylsalicylic acid (ASA) and occasional phlebotomy. Upon admission in May 2015 a brain CT scan revealed a hypodense area in the right temporal lobe initially interpreted as a subacute infarction. Mild anemia was found and HU was discontinued. The patient was referred to a rehabilitation clinic, but his condition deteriorated rapidly in the following days. On readmission left-side weakness, marked contralateral limb ataxia, dysdiadochokinesia, bradykinesia, dysarthria, left homonymous hemianopia and left-sided hemianesthesia were evident. Brain MRI performed at this point displayed multifocal and punctate slightly expansive white matter non-contrast enhanced juxta- and subcortical lesions, predominantly in the right hemisphere. These lesions were more confluent around the right trigonum and within the right temporal lobe and brainstem. There was involvement of the right cerebral peduncle, anterior pons on the right side, right middle cerebellar peduncle and the cerebellum around the dentate nucleus. On diffusion-weighted imaging (DWI) lesions were hyperintense but without restricted diffusion as the apparent diffusion coefficients (ADC) were not decreased in the area (Fig. ). EEG-recording revealed non-epileptiform abnormalities such as slow wave activities over right hemisphere and maximum over right temporal region.
A lumbar puncture was performed and yielded normal cell count and protein content in the cerebrospinal fluid (CSF). Enterovirus, herpes simplex 1 and 2, varicella zoster and CMV, were ruled out in the CSF by means of PCR and ELISA analysis. Serology for Lyme’s disease and syphilis in the CSF was also negative. Onconeural antibodies were not detected in blood. A centrifugated CSF sample was analyzed with fluorescence-activated cell sorting (FACS) which identified only few T-cells. Neurofilament light protein (NfL) was markedly elevated (16500 ng/L; reference interval <1850). Analysis for JC-virus yielded 7 400 copies/mL and tests for BK-virus, HIV, and HTLV-1 tests were negative. A second MRI of the brain three weeks after admission displayed an increased number of widespread supra- and infratentorial lesions (Fig. ). Additional laboratory investigation at this point revealed mild lymphopenia with decreased amounts of all lymphocyte fractions but not NK-cells. A flow-cytometric assay of specific cell-mediated immune response in activated whole blood (FASCIA) analysis revealed poor response to mitogens and specific antigens as shown in table (Table ).
Different therapeutic options for PML were considered [], but due to the rapid clinical deterioration treatment was withheld. The patient developed manifest left-sided hemiplegia, horizontal nystagmus, and verbal unresponsiveness. At this point his condition had worsened and the subject became unable to swallow, he contracted recurrent pneumonias and required a percutaneous endoscopic gastrostomy. During the later course of disease he remained in an unresponsive state until he died of pneumonia. Total disease duration in this case was two months. Post mortem studies of the bone marrow demonstrated a picture consistent with PCV but no signs of leukemic transformation. Histopathological analysis of the brain confirmed progressive multifocal leukoencephalopathy (PML) (Fig. ).


We present a 32-year-old male with a past medical history of hypertension, major depression, and cocaine abuse who presented with involuntary head, jaw, tongue, facial, shoulder, trunk, and leg movements; they were rhythmic and choreiform. Voluntary movements would worsen the choreoathetosis. He did cocaine three days before presentation. He initially complained of fevers, chills, and diaphoresis two days before presentation. He then noticed abnormal movements of his head, which then progressed into uncontrolled movements of his arms, shoulder, trunk, and legs. He denied chest pain, dyspnea, nausea, vomiting, diarrhea, dysuria, or leg swelling. He had been recently put on paroxetine by his primary care physician four weeks ago for major depression. He claimed to have not done any other recreational drugs, which was supported by a urine toxicology screen. He presented with a temperature of 37.1°C, Pulse of 90, RR of 20, BP of 165/101 mmHg, and saturating 95% on room air. A comprehensive metabolic panel and thyroid stimulating hormone were within normal limits. There were no pertinent positives on physical exam other than the uncontrolled movements; he remained alert and oriented at all times. Apart from the choreoathetosis the neurological examination was within normal limits. There was no parkinsonian or dystonic features to suggest an alternate diagnosis. He received diphenhydramine and benztropine from the Emergency Department physicians without relief. Toxicology was consulted and concluded these were indeed choreoathetoid movements secondary to cocaine use. There was no head imaging ordered as the diagnosis was established. He was admitted to Medicine and symptoms resolved with IV Lorazepam and intravenous fluids in 48 hours. During these 48 hours the uncontrolled movements were continuous.


A 40-year old male patient of Moroccan origin was admitted in 2012 for diffuse lymphadenopathy confirmed with ultrasound. Blood tests revealed renal insufficiency (serum creatinine: 1.6 mg/dL, eGFR: 48 ml/min/1.73 m2), low serum C3 and C4 levels and hypergammaglobulinemia (4250 mg/dL with oligoclonal banding). Anti-nuclear antibodies (ANA) were positive at 1/640. Anti-dsDNA were negative. Urine tests showed proteinuria (444 mg/L). A thoraco-abdominal computed tomography and positron-emission tomography/computed tomography (PET/CT) were performed. The images were compatible with a lymphoproliferative disorder. Heterogeneous uptake was also noticed in kidneys. Lymph node biopsy was performed and ruled out a hematologic malignancy. Immunohistochemistry showed more than 10 IgG4+ plasma cells per high powered field (HPF) of biopsy sample with more than 40% of IgG+ plasma cells being IgG4+ (Fig. ). Serum IgG4 level was then measured at 2790 mg/dL (N < 201 mg/dL).
This episode was not the first in patient’s medical history. In 2004, the patient had been admitted for lower-limb edemas and diffuse lymphadenopathy. Renal insufficiency (serum creatinine: 3.51 mg/dL, eGFR: 24 ml/min/1.73 m2), low serum C3 and C4 levels and hypergammaglobulinemia (4590 mg/dL) had already been found. Urine tests showed high proteinuria (13800 mg/l) with hypoalbuminemia characteristic of a nephrotic syndrome. Renal ultrasound showed diffuse kidney enlargement. PET/CT showed the same results as the one performed in 2012. A lymphoproliferative disorder was excluded by whole skeleton X-Ray, bone marrow and lymph node biopsy. A renal biopsy was then performed and showed membranous glomerulonephritis (MGN) with IgG and C3d deposits (Fig. ). Severe tubulo-interstitial nephropathy (TIN) with lymphoplasmocytic infiltrate (CD20+, CD3+, CD5+) was associated. Secondary causes of MGN were rejected by appropriate tests. ANA were negative at the time. The proposed diagnosis was a dysimmune state of unknown origin with secondary MGN and reactive lymphadenopathy. Treatment with glucocorticoids (GC) was started with an excellent clinical and biological response.
In 2005, a cutaneous rash appeared on the left arm and was biopsied, showing IgG and C3d deposits. GC were stopped in 2006 given the recovery of renal function. A few months later, the patient started to complain of pain, redness and swelling in small joints of the feet and hands.
In 2008, the first relapse occurred with the same clinical picture that in 2004 (nephrotic syndrome and lymphadenopathy). Full assessment was repeated yielding similar results except for renal biopsy: MGN with IgG and C3d deposits was found again but chronic interstitial nephropathy replaced the severe TIN. Indeed, a mononuclear infiltrate was present in the interstitium without clear sign of tubular involvement. A severe thrombocytopenia (platelets: 8.103/mm3) developed a few weeks later with anti-dsDNA found on blood sample (1/80). Thrombocytopenia was refractory to perfusion of immunoglobulins, GC and cyclophosphamide (CYP). Plasmapheresis and splenectomy were then performed. CYP was next continued for 6 cycles (500 mg/cycle) with good efficacy. Relapsing thrombocytopenia was successfully treated by additional regiments of immunoglobulins and GC. The last cycle of CYP was completed at the end of 2008. Thereafter, the patient experienced a long period without any problem until the next hospitalization in 2012.
In 2012, a renal biopsy was not performed again despite a new relapse of nephrotic syndrome; indeed, the 2008 biopsy had led to a macroscopic urinary hemorrhage which had required embolization. MGN was assessed again and anti-phospholipase A2 receptor (PLA2R) antibodies were negative. Diagnosis of IgG4-RD was finally made on the basis of the lymph node biopsy, with IgG4-related generalized lymphadenopathy and IgG4-related MGN (associated with IgG4-related TIN in 2004). The patient was given GC again at high dose (methylprednisolone 96 mg daily) for 1 month followed by a progressive decrease of the dose. Rituximab use was discussed in 2013, due to a new relapse in spite of maintenance low dose GC therapy and development of side effects; unfortunately, the patient failed to obtain the reimbursement and the medication could not be given in this context. For now, the patient is well stabilized with low dose GC. Rituximab in compassionate use could be reconsidered in case of a new relapse. Figure shows the evolution of various biological markers and serum creatinine during 2013.


We describe a 29-year-old woman, who was referred to our center for the treatment of gradual exacerbation in dyspnea on exertion and easy fatigability of 6 months' duration. A known case of congenitally corrected transposition of the great vessels (CC-TGV), the patient had undergone single-chamber permanent pacemaker implantation via the right subclavian vein owing to complete heart block 14 years previously. Four years later, there was a rise in the capturing threshold of the right ventricular lead, prompting the treating physicians to implant a new lead ().
On her referral to our center, she underwent echocardiography, which showed moderate to severe systolic dysfunction of the morphological (systemic) right ventricle. Considering the persistence of the symptoms despite medical therapy, decision was made to implant a CRT device in accordance with the new American College of Cardiology/ American Heart Association 2012 guideline, stipulating that patients with severe systemic ventricular systolic dysfunction and ventricular pacing > 40% of the times be upgraded to CRT.
The well-documented challenges of the implantation of a CRT device from the right side (especially in patients with complex congenital heart disease) led to the decision to abandon the old leads and implant a completely new system from the left side.
Under general anesthesia, three separate punctures from the left axillary vein were obtained. An attempt to introduce the right ventricular lead into the right ventricular apex in the anteroposterior (AP) view failed, but advancing the right ventricular lead (Medtronic CapSureFix®) into the right anterior oblique (RAO) 30˚ view proved easy. Pacing the lead confirmed a good ventricular capture (capturing threshold = 0.75 × 0.5 Volt msec). The implantation of the coronary sinus lead was done using a peel-away long sheath while injecting through mandarin in the left anterior oblique (LAO) 30˚ projection. A suitable posterolateral branch was visualized. A 4-French dual cathodic Medtronic lead (Attain Ability®) was employed in order to advance the lead as far as possible, minimize the chance of the phrenic nerve stimulation, and maximize interventricular resynchronization (capturing threshold = 1 × 0.5 Volt msec). The coronary sinus lead having been secured, the right atrial lead (Medtronic CapSureFix®, 52 cm) implantation was done in RAO and LAO projections during pacing to find the best atrial capturing threshold (capturing threshold = 1 × 0.5 Volt msec) (). After the leads were secured to the underlying pectoral tissue, they were connected to the pacemaker generator.
Immediately after CRT device implantation, electrical resynchronization, manifested as a QRS duration of 80 msec, was achieved (). One month later, exercise capacity increased and dyspnea on exertion decreased. Six months later, systemic ventricular ejection fraction rose from 35% to 40% with a decrease in end-systolic and diastolic dimensions.


A 75-year-old woman was admitted because of wide complex tachycardia with right bundle branch block pattern and right inferior axis. She was treated with adenosine and verapamil with no effect. Sinus rhythm was achieved by DC shock. Transthoracic echocardiography revealed normal systolic function without wall motion abnormalities, moderate concentric hypertrophy, and severe aortic stenosis. Coronary angiography showed nonsignificant stenosis of left anterior descending artery.
The patient underwent electrophysiological study. The procedure was performed under conscious sedation. Standard multielectrode catheters were placed in the His bundle region, coronary sinus, and RV apex through the right and left femoral veins. Ventricular tachycardia (VT) resembling the clinical tachycardia was easily induced by programmed electrical stimulation from the RV apex. The arrhythmia was nonsustained and became sustained after isoproterenol infusion. Spontaneous changes in QRS morphology were observed (). 6 mm cryoablation (Freezor MAX 3, Medtronic, Inc., Minneapolis, MN) catheter was advanced into the left ventricle (LV) via deflectable sheath through a transseptal and transmitral approach. Intravenous heparin was administered to maintain an activated clotting time of 300 s. A 2-dimensional intracardiac echo (ICE) probe was advanced via femoral vein and localized at right ventricular outflow tract to visualize real-time location of cryocatheter during mapping and ablation. Activation mapping by the cryocatheter revealed that the site of origin was at anterior PM of LV as confirmed by ICE (). No Purkinje potentials were recorded at the ablation site during sinus rhythm. Prepotential preceding the surface QRS by 35 milliseconds was recorded at the ablation site during VT (). The VT was mechanically interrupted by the contact of the cryocatheter with the base of anterior PM but nonsustained VT recurred until freezing was started. During and after the first application, VA could not be induced with and without isoproterenol (). Another 2 applications were done at both sides of anterior PM (Figures and ). Finally, 3 applications up to 240 s with freeze-thaw-freeze cycles were done. During 45 minutes after the end applications, no VA could be induced. No mitral regurgitation was seen at the end of the procedure. Three-dimensional mapping system was not used. The patient was free of VA and free of mitral regurgitation during follow-up of 4 months.


A 54-year-old male with end-stage renal disease (ESRD) secondary to chronic, long-standing type II diabetes mellitus presented in January 2011 with decreased urine output and swelling over the whole body for 3 months. He was trained for CAPD in a stable state of health. The patient was compliant with medical care and had been free from peritonitis to date. However, he presented to the nephrology outpatient department in January 2013 with complaints of fever, abdominal pain and cloudy PD effluent. As the abdominal pain worsened, the patient was admitted to the hospital. The patient denied any contact with soil or plant material. His past medical history was uneventful except for diabetes mellitus for the past 11 years. On physical examination, his blood pressure was 140/80 mm Hg−1, temperature 100.8 ° F, pulse 72 min−1 and respiration rate 18 min−1. His head, eyes, ears, nose and throat examination was unremarkable. There was no clubbing, cyanosis, lymphadenopathy or icterus. His lungs were clear and no cardiac murmur was heard. His abdomen was tender in all quadrants with rebound tenderness. Bowel sounds were present and active. Pertinent laboratory values were Hgm (Hemoglobin) 7.2 gm dl−1, white blood cells (WBCs) 24000 mm−3, platelets 2.28×105 µl−1, serum creatinine 9.3 mg dl−1, serum blood urea nitrogen 45 mg dl−1, serum uric acid 4.9 mg dl−1, serum sodium 131 mmol l−1, serum potassium 3.5 mmol l−1, serum albumin 3.3 g dl−1, serum bilirubin (total) 0.45 mg dl−1, serum aspartate transaminase 19 U l−1, serum alanine aminotransferase 13 U L−1, serum alkaline phosphatase 105 U l−1, serum amylase 29 U L−1, serum calcium 8.9 mg dl−1, serum phosphorus 5 mg dl−1 and serum lactate dehydrogenase 514 U l−1. PD fluid was sent for cell count, Gram stain and culture. The WBC count in PD fluid was 6400 mm−3 with 82% neutrophils. Gram staining of the fluid showed plenty of Gram-negative bacilli. A presumptive diagnosis of CAPD peritonitis was made and empiric intraperitoneal cefazolin and tobramycin were started. PD fluid culture yielded catalase-positive, oxidase-positive, non-spore-forming and non-fermenting Gram-negative bacilli. The isolate was positive for urea hydrolysis and nitrate reduction. Negative reactions were found for the production of H2S, indole, lysine decarboxylase and ornithine decarboxylase for the hydrolysis of gelatin. The identity of the isolate was confirmed as R. radiobacter sensitive to trimethoprim/sulfametoxazole, ceftazidime, ceftriaxone, ampicillin-sulbactam, cefoperazone-sulbactam, piperacillin-tazobactam, amikacin, gentamicin, tobramycin, ciprofloxacin, imipinem and meropenem. It was resistant only to aztreonam. Empiric antibiotic therapy was continued and the patient’s abdominal pain subsided and the peritoneal fluid counts decreased to 50 WBCs mm−3 on day 4. However, on the eighth hospital day, the patient again complained of abdominal pain and the PD fluid count increased to 300 WBCs mm−3. The catheter was therefore surgically removed and the tip sent for culture. The tip yielded growth of R. radiobacter.


A 46-year-old man presented in February 2007 with pT2bN1 M0 melanoma of the right lower leg (Figure ) treated with excision, sentinel node sampling, inguinal dissection, and adjuvant interferon. In April 2008, he developed upper thigh in transit metastases. He underwent radiotherapy (40 Gy/10 fractions) producing transient erythema and desquamation. All skin metastases resolved. In December 2008, he developed a chest wall and lung metastases. Tetanus booster was given anticipating chemotherapy. However, no further systemic treatment was given. All metastases resolved and he remains in remission last having been seen in 2016.


A 51-year-old woman presented in December 2007 with pT4N1M0 melanoma of the left thigh (Figure ) treated by excision, sentinel node sampling, and node dissection. In August 2008, she developed in transit metastases in the upper thigh. Computed tomography (CT) showed lung metastases, mediastinal and pelvic adenopathy. She underwent radiotherapy (40 Gy/10) producing erythema and desquamation. All cutaneous disease resolved and repeat imaging showed resolution of pulmonary metastases and shrinkage of adenopathy. In July 2009, she developed brain metastases treated with radiotherapy. No systemic therapy was administered and she remains in remission with the resolution of brain metastases and subcentimetric retroperitoneal nodes on imaging last having been seen in 2016.


A 64-year-old female presented with pT4 N2a M0 melanoma on her right foot (Figure ) in June 2008. She was treated with resection, sentinel node biopsy, node dissection, and induction interferon. In June 2009, she developed right leg in transit metastases and underwent limb perfusion with Melphalan and Actinomycin D. Her disease progressed in skin, and pelvic nodes. In April 2010, she received radiotherapy: right upper thigh (18 Gy/1), right anterior shin and right calf (30 Gy/5). In May 2010, she had four more leg lesions irradiated (20 Gy/1). She additionally commenced herbal/acupuncture therapy. By July 2011, all disease had resolved except an upper thigh tumor which was irradiated (35 Gy/5). No further systemic treatment was administered. She remained in remission when last seen in 2013.


A 74-year-old lady presented with T3N0M0 right knee melanoma (Figure ) treated with resection and sentinel node sampling. In February 2008, she developed skin metastases treated with radiotherapy (20 Gy/1) to right knee and right calf and 32.5 Gy/5 to right ankle. In April 2008, three other right calf nodules were irradiated (20 Gy/1). The irradiated lesions regressed completely. In February 2009, she developed extensive in transit metastases throughout her right leg. She was started on a clinical trial of intralesional Vical in June 2009. Her best clinical response between June 2009 and April 2010 during this therapy was stability with many lesions growing but less than 25% increase. In April 2010, imaging showed lung, liver, and pelvic nodal metastases and Vical was stopped. She received radiotherapy to her right knee (37.5Gy/10). She remains in remission with one palpable leg nodule representing either tumor or fibrosis. She was last seen in 2016.


We report the case of a 53 year-old woman, originally from Haiti, living in France since 1989. She was hospitalized in the infectious diseases department of Bichat Claude Bernard University Hospital in Paris in March 2016 for alteration of general condition, fever and nasal deformity evolving for at least 6 months.
Her medical history is characterized by an HIV infection diagnosed in 2006, which was classified at AIDS stage in 2008 due to cytomegalovirus infection. At the same time, she suffered from pulmonary histoplasmosis that was treated with itraconazole. CD4 cell count nadir amounted to 7/mm3 in 2008. A first line of Highly Active Antiretroviral Therapy (HAART) was started 3 weeks after those diagnoses consisting in Efavirenz (EFV), Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC). After 1,5 months the patient decided to interrupt this treatment, a second line of HAART was initiated 6 months later with nevirapine and TDF/FTC. She only took secondary prophylaxis with itraconazole for 6 months and then stopped being compliant with any treatment and was lost to follow-up over 7 years. No history of recent travel to endemic areas or contact with neither birds nor bats was reported. She never smoked, did not have excessive alcohol consumption and did not inhale any nasal drugs.
At hospital admission, physical examination revealed a nasal tip collapse, a disappearance of the nasal septum and a large perforation of the hard palate, resulting in naso-oral communication. Facial skin, alar and triangular cartilages were undamaged. However, maxillary teeth [, ] were loose, and teeth 11, 21 and 22 fell spontaneously. Mucosa of the nasal cavity was ulcerated with crusts and partially necrotic (Fig. ). The sinus CT-scan and the magnetic resonance imaging performed showed: a complete loss of the nasal septum, a maxillar osteolysis, a communication between oral and nasal cavities and bilateral maxillary sinus opacities (Fig. ). The chest X-ray showed an interstitial pneumonia. She did not manifest dyspnea, cough, cutaneous eruption, neurologic deficit, visceromegaly or lymphadenopathy. HIV viral load was 56,943 copies/ml and CD4 cell count was 9/mm3 (2%). In blood: Treponema Pallidum Hemagglutination Assay and Veneral Disease Research Laboratory, Cryptococcus antigen, Toxoplasma polymerase chain reaction (PCR), Leishmania PCR, galactomannan antigen, blood and mycological (×4) cultures were all negative. β-D-Glucane was positive at 338 pg/ml. Blood Hcc PCR was positive. In bronchoalveolar fluid: cultures, Cryptococcus antigen were negative, Pneumocystis jirovecii PCR level was barely positive (18,000 copies/mL), After 3 months, Mycobacterium tuberculosis sputum cultures were negative.
Surgical biopsies of oral, nasal and maxillary mucosa were performed and analyzed. Microscopic examination revealed fungal yeasts (Fig. ), mycological cultures identified the presence of Hcc then confirmed by PCR.
Those tests enabled a final diagnosis of DH with naso-oral involvement in an AIDS-stage patient.
The patient received 200 mg per day of intravenous Amphotericin B (AmphoB) liposomal for 1 month. In the follow-up, we observed: negativation of blood histoplasmosis PCR in 10 days and clinical stabilization of naso-maxillary osteolysis with normalization of mucosa. Treatment was switched to 400 mg of oral itraconazole per day for a minimum of 1 year, in accordance with international guidelines [].
HAART by ritonavir-boosted darunavir and TDF/FTC was reintroduced after 3 weeks of positive response to DH treatment. After 6 months, HIV viral load was undetectable and CD4 cell count at 40/mm3. At 9 months, biological results were stable and she had gained 17 k. Strategy of directly observed therapy permitted full compliance and the patient didn’t report any side effect with any treatment. Blood levels of itraconazole and HAART were both in the standards.
Ulceration and inflammation of the mucus decreased, enabling a palatal prosthesis to be implemented. A reconstructive surgery will be proposed to the patient upon completion of antifungal therapy and stabilization of HIV infection.


A 9-month-old boy, who was born from a non-consanguineous marriage, presented to our clinic with complaints of continuous high grade fever for the past 15 days. His body temperature was over 39.5°C in spite of ibuprofen/acetaminophen and anti-infection therapy. The development of his body frame was normal, weighing 10 kg. Clinical examination revealed mild pallor, gray hair and patchy hypopigmentation of the skin (), red rashes on the trunk, submandibular lymphadenopathy and protuberant abdomen with massive hepatosplenomegaly. The boy had no mucocutaneous bleeding and iris pigmentation, and cardiovascular and nervous systems were normal. His history since birth was negative for frequent chest infections, draining bilateral ears and fever. There was no family history of the disease.
Routine blood examination revealed pancytopenia with febrile neutropenia (hemoglobin of 72 g/L, white blood cell count of 9.05×109/L, neutrophil count of 0.9×109/L, and platelet count of 43×109/L). Blood biochemical examination revealed elevated C-reactive protein (69.4 mg/L), high ferritin levels (>2000 ng/mL), low fibrinogen levels (0.66 g/L), hyponatremia (129.5 mmol/L), hypoalbuminemia (20.1 g/L), and hypertriglyceridemia (4.99 mmol/L). Relevant hematological findings were LDH 1062 U/L, ALT 92.8 U/L, AST 339.1 U/L, GGT 350 U/L, and TBA 241.4 μmol/L. Routine urine and cerebrospinal fluid examination were normal. Blood cultures were negative. Epstein-Barr virus (EBV) DNA detection was 1.34×106 IU. Abdominal ultrasound revealed hepatosplenomegaly. Lung CT images revealed double pneumonia with multiple patchy lesions ().
Peripheral blood smear revealed several abnormal giant granules in most leukocytes. Bone marrow aspirate revealed prominent granules within the lymphocytes and myeloid cells (). Furthermore, hemophagocytosis was observed on the bone marrow aspiration smear. Light microscopic images of the boy’s hair revealed abnormal clumping of melanin. Pigment clumps were small and uniformly distributed along the hair shaft ().
HLH-related genes (including AP3B1, FASLG, PRF1, TNFRSF1A, BIRC4, ITK, RAB27A, UNC13D, CASP10, ITPKC, SH2D1A, CD27, LYST, STX11, FAS, MAGT1 and STXBP2) were detected with high-throughput sequencing. It was found that LYST gene mutations at c.11183delA, p.N3728fs and c.9453delA, p.K3151fs were separate from his mother and father. Based on HGMD (Human Gene Mutation Database) analysis, these were novel frameshift mutations, validated by Sanger sequencing ( and ).
The boy was diagnosed with CHS in the accelerated phase due to his typical clinical characteristics, laboratory examinations and the detected LYST gene. According to the 2004 revised guidelines of the Histiocyte Society (), the patient fulfilled the diagnostic criteria for HLH (five out of eight criteria). The HLH-2004 treatment protocol, including cyclosporine A (5 mg·kg-1·day-1), dexamethasone (10 mg·(m2)-1·day-1, half dose every 2 weeks), and etoposide (150 mg/m2, twice a week for the first 2 weeks and once a week during the following 6 weeks), was administrated (). Maximal supportive care was provided, such as antibacterial and antiviral treatment (meropenem and ganciclovir), liver and cardiac protective agent, high doses of intravenous gamma globulin (2 g/kg), multiple transfusions, including platelets and packed red blood cells for anemia and fresh frozen plasma to improve the function of blood coagulation, prophylactic oral cotrimoxazole, and antimycotic voriconazole (). After the initial 8 weeks of therapy, all blood parameters returned to normal, pneumonia was cured (), and the disease was in temporary remission. Continuation therapy of the HLH regimen was then started. To date, the boy is in good condition. Stem cell transplantation has been planned.


The patient was a 38-year-old G2P0020, blood group O Rh positive, genotype AA with a BMI of 19 kg/m2. She presented to our service because of secondary amenorrhea and infertility of 2 years’ duration. She had a history of pulmonary tuberculosis that was treated for 6 months in Cameroon with rifampicin, ethambutol, isonazide and pyrazinamide for 2 months and rifampicin and isonazide plus vitamin B to prevent peripheral neuropathy for a further 4 months. There was no family history of premature ovarian insufficiency or auto-immune disease. Her history was notable for laparoscopic surgery in Paris, France, in 1998, where 2 small fibroids were removed and biopsy done on both ovaries. Histology showed right ovarian dystrophy with no primordial ovarian follicles or corpus luteum scar, and uterine leiomyomata. There was left ovarian atrophy with one primordial follicle and one atretic follicle. The diagnosis of Stein-Leventhal syndrome was incorrectly made. Her hormonal profile done in France, revealed an estradiol of 15ρg/ml, FSH levels of 68.2 IU/ml and 92.03 IU/ml, LH 61.7 IU/ml and 43.91, and inhibin B 15ρg/ml (normal >45ρg/ml). Complementary laboratory test results done in Cameroon revealed Prolactin 91.57 mIU/l, T3 1.53 nmol/l, T4 90.68 nmol/ml, THS (ultra sensitive) 0.65 ng/ml and Testosterone 0.06 ng/ml.
The patient underwent the progesterone challenge test with Synergon® (progesterone, estrone) which was negative. The husband had normal semen parameters. The diagnosis of premature ovarian insufficiency was discussed and the couple was counseled to undergo egg donor In-vitro fertilization.
After obtaining informed consent, we matched the anonymous donor-controlled ovarian stimulation cycle with the recipient’s endometrial preparation. For this purpose, we used the short agonist protocol (triptorelin (Decapeptyl®) 0.1 mg/day plus menotropin (Menogon®) 150 IU/day) starting from the third day of the donor’s cycle untill we obtained three leading follicules of 17–18 mm in diameter. The donor was monitored with standard trans-vaginal sonography and serum estradiol levels.
We prepared the patient’s (recipient YE) endometrium for embryo transfer with estradiol valerate (progynova®) 8 mg/day in three divided doses for 14 days starting from the first day of the donors menses. A trans-vaginal sonogram was performed every 3 days to monitor the endometrial thickness until we obtained an endometrial thickness of about 14 mm. The husband’s sperm was prepared with the density gradient centrifugation as previously described [–]. A total of four fresh donor oocytes were obtained and were inseminated and the patient (recipient) began progesterone (utrogestan® vaginal tablets) 600 mg/day from the day of oocyte insemination. Two fresh 8-cell (grade A) embryos were transferred to the recipient YE (patient) on day 3 of insemination after the standard IVF procedure. The remaining two (grade C) embryos were discarded for lack of facilities for gamete freezing at the time. (However, since 2012 our IVF centre has the facilities to freeze gametes and embryos.)
After embryo transfer, the recipient continued with progesterone suppositories(utrogestan®) and estradiol valerate (progynova®) and underwent her first plasma beta hCG assay 2 weeks after embryo transfer. The test result was positive, with a value of 248 IU/L. She underwent a trans-vaginal ultrasound scan 2 weeks after the positive pregnancy test that revealed an intra-uterine gestational sac of 13 mm diameter (Fig. ). A repeat trans-vaginal ultrasound scan done about 2 weeks from the latter showed a singleton intrauterine pregnancy with a crump-rump length of 17 mm corresponding to 8 weeks 1 day gestation Fig. ).
Her pregnancy follow-up was uneventful until she developed preterm labour at 36 weeks 4 days gestation and fetal distress was diagnosed on cardiotocography. She gave birth by cesarean section to a female baby who weighed 2360 g. At cesarean section, the presentation was breech with two turns of nuchal cord. One and 5-min Apgar scores were 8 and 10, respectively. The baby was sent to the neonatal intensive care unit (NICU) for follow up. Two years later, YE requested for IVF with autologous eggs which, it was explained, was not possible. She is now living with one child.


A 2-year-old spayed, female, beagle dog was presented to the Virginia Maryland College of Veterinary Medicine (VMCVM) Veterinary Teaching Hospital for progressive paroxysmal episodes of muscular hypertonicity, lordosis, and difficulty ambulating. Approximately three weeks prior to presentation to VMCVM, the patient starting exhibiting intermittent episodes of rigidity in all four limbs, each lasting <10 s, followed by a rapid return to normalcy. The events became longer and more frequent, culminating in multiple daily episodes of stiffness that interfered with ambulation. The patient was admitted to the referring veterinarian’s hospital (Day 0), and treated with intravenous diazepam (0.5 mg/kg/h constant rate infusion [CRI]), phenobarbital (4 mg/kg q 12 h), and methocarbamol (33 mg/kg q 8 h) which had no demonstrable effect on the frequency or severity of the episodes.
The following day (Day 1), an MRI examination of the brain was performed under general anesthesia, which revealed structural changes consistent with Chiari-like malformation (CM) and secondary syringomyelia (Fig. ). Cerebrospinal fluid (CSF) was collected from the cerebellomedullary cistern. The CSF protein concentration was elevated at 100 mg/dl (Table ; reference interval <25 mg/dl) and a marked mononuclear pleocytosis was present with 981 total nucleated cells/μl (reference interval <3 cells/μl; differential 95.6% monocytes, 4.4% lymphocytes). The dog was empirically treated with doxycycline (5 mg/kg PO q 12 h), clindamycin (10 mg/kg PO q 12 h), prednisone (1 mg/kg q 24 h) and cytosine arabinoside (100 mg/m2 IV CRI over 48 h) for infectious and immune mediated encephalitides. No clinical improvement was noted after 96 h of treatment with this regimen, at which time the patient was referred to VMCVM. Urine, CSF, and serum samples were submitted for canine distemper viral and Bartonella species PCR and cryptococcal antigen assays, all of which were negative.
On presentation to the VMCVM (Day 5) the patient’s vital parameters were within normal limits. The dog was obese, with the remainder of the general physical examination being unremarkable. The dog demonstrated rigidity of the axial and proximal appendicular muscles resulting in lordosis (Fig. ) that impaired ambulation. Superimposed upon the stiffness were spontaneous and tactile stimulus-induced generalized muscular spasms that had a stereotyped appearance, characterized by an initial flexion and abduction of the limbs (Fig. ). Joint flexion appeared truncated due to reciprocal contraction of antagonistic muscles. This progressed to a hyperlordotic and opisthotonic posture with generalized hypertonicity (Additional file 1: Video S1) that subsided within 1 min. Episodic spasms were associated with autonomic signs including mydriasis and tachycardia. During episodes, which ranged in duration from 1–10 min, the patient appeared anxious but did not lose consciousness. The patient’s cranial nerves, postural reactions, and segmental spinal reflexes were normal between episodes. Given the results of the neurological examination, prior MRI examination and CSF analyses, differential diagnoses included a paroxysmal dyskinesia associated with generalized dystonia secondary to syringomyelia or encephalomyelitis, or other movement disorder.
Cervical vertebral radiographs were obtained to evaluate for atlanto-occipital and atlantoaxial instability and were unremarkable. Electroencephalography revealed background slowing with significant movement and muscular artifact associated with periods of hypertonicity. An EMG was also performed, and continuous motor unit activity was noted in the cervicothoracic and lumbar axial muscles at rest (Fig. ). Similar discharges were detectable in axial and appendicular musculature during an episode of hypertonicity. The patient was started on gabapentin (5 mg/kg PO q 12 h). The dog demonstrated variably severe but persistent muscular rigidity that was exacerbated by handling throughout the period of hospitalization, but resumed attempts to voluntarily ambulate by the end of Day 5. Baclofen (1 mg/kg PO) and levetiracetam (21 mg/kg PO q 8 h) were added to the treatment regimen.
On Day 6 general anesthesia was induced and the EMG repeated. No abnormal activity was present in axial or appendicular musculature. Cerebrospinal fluid was collected from the cerebellomedullary cistern and was grossly, cytologically, and biochemically unremarkable (WBC 1 cell/uL; RBC 0 cell/uL; protein 24.9 mg/dL); though the IgG index was elevated and anti-GAD antibodies were observed in CSF and serial serum samples obtained from the patient (Table ). Intravenous immunoglobulin (IVIG) was administered as a CRI (1 g/kg IV over 6 h) on Day 6. On Day 7 the patient demonstrated improved ambulation, with persistent gait stiffness. There was an approximate 50% reduction in the total number of lordotic episodes per day. On Day 8 the dog was discharged from the hospital. Medications included prednisone, phenobarbital, levetiracetam, gabapentin, and baclofen.
A recheck was performed on Day 25. According to the owner, the dog had exhibited no lordotic or opisthotonic episodes during the previous 7 days. The patient was normal on general physical exam. Mild muscular hypertonicity and gait stiffness persisted, but no other abnormalities were noted, and no opisthotonic episodes were induced during the examination. An additional IVIG infusion was recommended but declined by the owner. The baclofen, prednisone, phenobarbital, levetiracetam, and gabapentin therapies were continued. The dog was rechecked by the referring veterinarian again on Day 100, at which time mild persistent gait stiffness was the only reported abnormality.
The dog was lost to follow up until 18 months later, at which time it presented to the VMCVM emergency department for joint pain and effusion, secondary to Borrelia burgdorferi polyarthritis. A neurological examination performed at that visit was normal. The owner reported that all previously prescribed therapies had been gradually discontinued, with the patient being off all medications for at least one year. Occasional phantom scratching was noted, but the owner reported that no episodes of lordosis or gait disturbance had been witnessed since before the Day 25 recheck.
Routine and electrophoretic serum and CSF analyses were performed as previously described []. Anti-GAD IgG (isoform 65) antibodies in serum and CSF were quantified using a human commercial ELISA kit (Euroimmun, Luebeck, Germany), performed according to the manufacturer’s instructions. Test samples consisted of 25 μl of undiluted serum or CSF, and all samples were run in triplicate. Negative controls consisted of pooled serum and CSF obtained from healthy normal beagle dogs (n = 6) []. Positive controls consisted of serum samples obtained from a human patient with insulin dependent diabetes mellitus (IDDM) that was known to have GAD65 antibodies based on western blotting and ELISA analyses. On the basis of the lowest reproducible absorbance change relative to reagent blanks, the detection limit of the assay was defined as 5.0 IU/ml. The intra- and inter-assay coefficients of variation reported by the manufacturer of this ELISA are 7.3 and 5.7%, respectively.


A 57-year-old male patient was transferred to the emergency department after a road traffic accident. He had a fall from his bike and his right arm was crashed by the following car. On clinical examination, he had pain and obvious deformity in the shoulder while he was unable to move his arm in any direction, especially in external rotation. He had numbness in the regimental badge region of the axillary nerve and normal radial pulse at the wrist. Radiological examination showed an anterior shoulder dislocation with impaction of the humeral head underneath glenoid and associated fracture of the greater tuberosity (Fig. ). He had no other skeletal or visceral injuries. After conscious sedation, an effort for closed reduction (3 attempts) was performed in the emergency room but was unsuccessful. For reasons unrelated to the patient or the disease a CT-scan of the shoulder was not possible to be performed at that time. The patient was transferred immediately to the operative theatre for closed manipulation under general anaesthesia in order to reduce the dislocation and avoid further neurological compromise; a CT-scan and/or MRI has been scheduled for the next morning. Despite prompt sedation and muscle relaxation the shoulder was still unable to interpose. Open reduction was accomplished thereafter using the deltopectoral approach; the biceps tendon was found entrapped posterolateral between the humeral head and the tuberosity fragment preventing once again reduction of the glenohumeral joint. (Fig. ). Tenotomy and tenodesis of the frayed biceps at the level of pectoralis major was performed using a bone anchor; the transverse ligament at the bicipital groove had been torned. Next, the subscapularis was incised, 1 cm medial to its insertion at the lesser tubercle, and retracted medially after separated from the capsule. The latter was incised and the labrum was clearly visualized and was found to be intact inferomedially. Using longitudinal traction and finger manipulation in an anterior direction the humeral head was finally reduced revealing a large triangular Hill-Sachs lesion at its posterior part. The greater tuberosity was fixed back to its bed using heavy transosseous sutures (Fig. ). The capsule and subscapularis tendon were repaired anatomically with sutures and the shoulder joint was found stable through a full range of motion of internal rotation and external rotation with the arm in adduction and at 90° of abduction. The patient had an uneventful postoperative recovery without neurovascular compromise. Pendulum exercises initiated from the second postoperative day followed by passive assisted forward flexion and limitation of active internal rotation for 4 weeks. At the last follow up, one year postoperatively he had a stable joint, full range of motion and a Constant score of 90 (Fig. ).


A 27-year-old post-partum female presented to the clinic with severe lower back pain radiating to the left lower limb for one month. The visual analog scale (VAS) was used to measure pain intensity and pain affect and the Oswestry Disability Index (ODI) was used to measure the degree of disability due to lower back pain [-]. The patient's initial scores on the VAS and ODI scales were 9 and 46 respectively.
The lower back pain developed suddenly during labor. It was initially masked by labor pain and was unrecognised for a few days post-partum. The pain gradually increased over a few weeks and radiated to the dorsum of her left foot. She was given a trial of conservative management for three weeks following which she failed to show any signs of improvement. She had no history of lifting heavy weights, previous surgery, injuries to the back, fever, weight loss, abnormalities of bowel or bladder movements, weakness or loss of coordination of upper or lower limbs.
On examination, vital parameters were within normal limits. Her gait was slow, limited by lower back pain radiating to the dorsum of her left foot. Inspection of the lower back revealed normal anterior curvature of the lumbosacral spine without overlying skin abnormalities. Her range of motion was limited in a forward flexion. There was moderate tenderness present over the lower back. Straight leg raise (SLR) was 20 on the left side. This test is done with the patient in supine position. The examiner lifts one leg upward keeping the knee fully extended. If the patient experiences sciatic pain during the leg raise, the test is positive and suggests herniated disc as a possible cause of pain. Power in the left extensor hallucis longus (EHL) was 3/5 and the left ankle reflex was absent. All sensations were intact. Peripheral pulses were well felt bilaterally in both lower limbs. A systemic examination did not reveal any significant abnormality.
A magnetic resonance imaging (MRI) scan at this point showed a large herniated disc bulge at the level of L4-L5, causing a large radiculopathy (Figure ).
The patient was then given a trial of conservative management in the form of bed rest, physiotherapy, and analgesics. However, with conservative management, the patient did not show improvement and decided to undergo ozone disc nucleolysis.
The procedure was done under local anaesthesia in the catheterization laboratory on the Siemens rubber tired gantry (RTG) single-plane digital subtraction angiography (DSA) suite. With the patient in prone position, the C-arm was rotated such that the lateral one-third of the disc remained free from the lateral margin of the facet joint. Under local anaesthesia, a 22 gauge 17-cm long needle was introduced percutaneously via paraspinal approach into the disc via the transforaminal route. The intradiscal position of the needle was confirmed in the antero-posterior and lateral view. The ozonator was used to generate ozone on site by partly converting medical grade oxygen. 10 ml of ozone-oxygen mixture (concentration of 30 micrograms per ml) was injected intradiscally and in the periganglionic epidural space. Additionally, a mixture of local anaesthetic agent lidocaine 2%, hydrocortisone 100 mg, triamcenolone 45 mg, and hyaluronidase 1500 IU was also injected in the periganglionic epidural space.
Post-procedure, the patient was advised to remain in supine position for one hour, following which she was gradually mobilised and advised light activity for the following three weeks. She showed significant improvement immediately after the procedure and there was a further improvement in symptoms over the next six weeks.
Post-procedure follow-up at three months revealed a VAS score of two and an ODI score of 10. The axial and sagittal T2-weighted (T2W) images on the MRI scan at three months showed significant resolution of the large postero-central disc protrusion at the level of L4-L5 following ozone disc nucleolysis (Figure ).
Post-procedure follow-up at six months revealed a VAS score of 1 and an ODI score of 4. The patient was counselled to avoid strenuous activity for six months. She was also advised physiotherapy to strengthen core muscles. There were no complications following the treatment.
The MacNab criteria was used to determine the satisfaction and well-being of the patient post procedure []. Her outcome on MacNab was in the excellent category.


A 4-year old girl presented acute tonsillitis and was treated with benzathine penicillin. She also had additive and chronic polyarthritis with edema, tenderness and pain on motion during 2 months. The affected joints were elbows, right wrist, all proximal interphalangeal joints, knees, ankles and first metatarsophalangeal joint.
The patient presented morning stiffness during 30 to 60 minutes associated with limited motion in elbows, right wrist and knees, and was diagnosed as JIA prior to coming to our service.
After 45 days, she also presented painful subcutaneous nodules and erythematous-violaceous lesions in the extensor region of upper and lower limbs ( and ). She was admitted to the teaching hospital due to high fever, malaise, myalgia, anorexia, loss of 1.0kg, severely painful skin lesions and severe functional disability. She was bedridden by chronic polyarthritis with limitation on motion ().
Systolic and diastolic blood pressures were greater than the 95th percentile for height. She received naproxen 20mg/kg/day, paracetamol and tramadol. Laboratory tests showed hemoglobin 10.9g/dL, white blood cell (WBC) count 25,380/mm3 (67% neutrophils, 19% lymphocytes, 13% monocytes and 1% eosinophils), platelets 683,000/mm3, erythrocyte sedimentation rate 53mm/first hour, C-reactive protein 246.4mg/dL (normal range: 0 to 0.3mg/dL), aspartate aminotransferase 15U/L (normal range: 15 to 40U/L), alanine aminotransferase 9U/L (normal range: 10 to 35U/L), urea 24mg/dL (normal range: 15 to 45mg/dL) and creatinine 0.35mg/dL (normal range: 0.6 to 0.9mg/dL). C3 was 174mg/dL (normal range: 90 to 180mg/dL) and C4 was 21.2mg/dL (normal range: 10 to 40mg/dL). Anti-streptolysin O was 1,687UI/mL. Urinalysis was normal and urine protein/creatinine ratio was 0.39g/day.
Immunological tests, such as antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), anti-Sm, anti-RNP, antineutrophil cytoplasmic antibodies (ANCA), anti-topoisomerase, anti-Ro/SSA, anti-La/SSB, and IgG and IgM anticardiolipin antibodies were negative. Serologies for hepatitis (A, B and C) virus, HIV, VDRL, Epstein-Barr virus, cytomegalovirus and toxoplasmosis were also negative. Echocardiogram and Doppler ultrasonography of renal artery were normal. Thoracic and abdominal magnetic resonance angiographies were also normal.
Skin biopsy revealed necrotizing vasculitis in medium- and small-sized vessels compatible with PAN. Therefore, childhood PAN was diagnosed according to the EULAR/PRINTO/PRES criteria. Prednisone 2.0mg/kg/day was administered with complete resolution of skin lesions and arthritis, and also improvement of proteinuria (0.26g/day) after 15 days.


An 8-year-old spayed female German Shepherd was referred for investigation and treatment of lower back pain combined with lameness of the right pelvic limb. The joints of both pelvic limbs were normal, and mild lameness of the right pelvic limb together with mild muscle atrophy was detected. The neurological examination was unremarkable, but pain could be found during the palpation of the LS area. The radiographs of the referring veterinarian showed signs of DLSS.
The CT scan showed moderate cranial telescoping of the sacral roof and moderate central disk protrusion, leading to moderate to severe compression of the cauda equina. In addition, there was lateral spondylosis with consequential stenosis of the right LS foramen. The right L7 nerve had lost its fat attenuation and appeared to be thickened (Figure ).
The patient was medically managed with activity restriction, gabapentin (10 mg/kg TID), and carprofen (2 mg/kg BID). Two weeks later, the dog was presented again because her condition had deteriorated, and she exhibited obvious difficulties in getting up and sitting down. A surgical treatment with a L7S1 traction-fusion procedure was discussed. But because such a stabilization does not allow visualization of the pathologies latero-ventral of the LS foramen, and the amount of the enlargement of the foramen by the traction is more unpredictable because of the tissue proliferations, the owner agreed to perform a dorsal L7S1 decompression, followed immediately by a right-sided CCIO.
The dog was premedicated with methadone (0.3 mg/kg subcutaneously) and acepromazine (0.05 mg/kg subcutaneously). After induction with propofol (4 mg/kg intravenously), carprofen (4 mg/kg subcutaneously) was administered, and anesthesia was maintained with isoflurane/O2. Standard equipment was used to monitor the anesthesia, and no antibiotics were given to this patient. During the L7S1 dorsal laminectomy, the cranial sacral lamina was removed to eliminate the dorsal nerve root impingement, and a partial annulectomy reduced the ventral cauda equina compression. After completion of the laminectomy, the patient was placed in left lateral recumbency, and the affected right pelvis was surgically prepared from the L4 to the greater trochanter. The CCIO procedure was performed as described earlier. The LS foramen was enlarged cranially. Fibrotic tissue covered the L7 nerve adhering it to the bone, making dissection with magnification lenses and micro-instruments necessary to mobilize the nerve from the sacral bone proliferations (Figure ). The nerves were covered with autologous fat, and the osteotomy was realigned and stabilized with a dorsally placed 2.4 LCP locking plate, using the thicker dorsal ilium rim for screw anchoring, and a ventrally 1 mm cerclage wire to counteract the forces generated by the medially inserting muscles (Figure ). A more ventrally placed locking plate may make the cerclage unnecessary. Then, the medial gluteal muscle was sutured back with single stitches using 3-0 absorbable monofilament, and a routine wound closure was performed using 3-0 monofilament suture material. The postoperative CT scan showed adequate dorsal decompression and enlargement of the right LS foramen.
Intravenous Ringer lactate fluids at a rate of 4 ml/kg/h were continued after the anesthesia, together with a fentanyl constant rate infusion at a rate of 5 μg/kg/h. Carprofen (2 mg/kg BID) and gabapentin (10 mg/kg TID) were added the following day. The patient recovered quickly and could walk and urinate outside after 12 h. Thirty-six hours after the surgery, no opioids were necessary, the dog walked normally and was discharged with carprofen (2 mg/kg BID) and gabapentin (10 mg TID) for 4 weeks. Controlled rehabilitation using passive range movements, muscle massage, and a water treadmill was done twice a week. Four and eight weeks after the surgery, the dog was examined and showed no signs of pain, and the lameness had resolved. No complications have been noted from the iliac osteotomy. Radiographs of the pelvis at 8 weeks showed healing of the ilial osteotomy. Four months after the procedure, the dog was doing well, and no complications of the osteotomy were recorded by the referring veterinarian, the physiotherapist, or the owner.


A 7-year-old Caucasian male presented to urology services with symptoms of left flank pain and pyrexia, and a 6-month history of intermittent back pain. On examination, he was normotensive with left flank tenderness, and urinalysis was positive with microscopic hematuria, proteinuria, and leucocytosis. Inflammatory markers were elevated with C-reactive protein (CRP) 156 mg/L and hemoglobin (Hb) low at 10 g/dL. A CT abdomen was in keeping with unilateral XGP (). Following 14 days of antimicrobial therapy, he underwent a left open nephrectomy with good clinical response. Histopathology confirmed XGP, with Proteus mirabilis isolated on microbiological culture (). Postoperative contralateral renal ultrasound was normal and renal function preserved, creatinine pre-operatively was 0.57 mg/dL, with creatinine 0.53 mg/dL, and estimated glomerular filtration rate (eGFR), calculated by the modified Schwartz method, of 102 mls/min/1.73 m2 on discharge.
Three months later, the child represented with a 24-hour history of cola-colored urine and reduced urine output. On examination, he was pyrexial and clinically dehydrated. He was normotensive with no abdominal tenderness or edema. Urinalysis was positive for microscopic hematuria and proteinuria with sterile culture. Renal function was impaired with creatinine 1.7 mg/dL and eGFR 32 mL/min/1.73 m2. Hb was 11.5 g/dL, white cell count 1.8 × 109/L with neutropenia of 0.55 × 109/L. C-reactive protein was raised at 150 mg. C3 was mildly raised, but C4 was normal. Cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA), perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). and antinuclear antibodies were negative, and antistreptolysin O titre (ASOT) was positive at 800 units/L. Immunoglobulins were normal, and viral and microbial screening was negative. Renal ultrasound scan was normal, excluding XGP in the contralateral kidney.
A working diagnosis of poststreptococcal glomerulonephritis was made, and intravenous antimicrobials (co-amoxiclav) commenced with careful fluid management. The patient’s clinical condition continued to deteriorate with persistent pyrexia, oliguria, and declining renal function. By day 3 of admission, eGFR had fallen to 21.9 mL/min/1.73 m2. Renal biopsy was deferred at this stage due to the associated risks of a single kidney. A day-7 repeat ultrasound showed a single enlarged hyper-echogenic right kidney consistent with acute glomerulonephritis (GN) or pyelonephritis. IV antimicrobial treatment was broadened with ciprofloxacin and meropenem to cover for organisms associated with XGP; however, repeat blood and urine cultures were sterile. CT of the abdomen excluded recurrent XGP. Inflammatory markers remained elevated with a continual decline in eGFR to 11.1 mL/min/1.73m2 on day 12 of admission. The patient developed clinical manifestations of acute renal failure with hypertension, pulmonary edema, and fluid overload necessitating hemodialysis.
No antihypertensive medication was required. A trial of high-dose methylprednisolone was commenced at 500-mg IV daily for 3 days followed by 60 mg/m2 daily oral prednisolone for presumed rapidly progressive glomerulonephritis. Despite this, creatinine continued to climb to a peak of 6.5 mg/dL (eGFR 8.5 mL/min/1.73 m2) and the decision was made for renal biopsy. Histology revealed strong linear IgG deposition along the GBM with greater than 95% of glomeruli demonstrating crescents and evidence of acute tubular necrosis (). Anti-GBM antibodies confirmed the diagnosis of anti-GBM disease with titers of > 8 AI (normal range 0 – 0.9 AI). The patient’s tissue typing confirmed the presence of the HLA DR15 antigen.
Treatment was commenced with plasmapheresis and oral cyclophosphamide at 3 mg/kg/day for 8 weeks. High-dose steroid therapy and thrice weekly hemodialysis was continued. Nineteen plasma exchanges were performed over 28 days with normalization of anti-GBM antibodies to 0.4 AI. Following cessation of plasma exchange, 4 further hemodialysis sessions were required for fluid and blood pressure control. Renal function gradually improved, with serum creatinine at time of last dialysis (day 78 following admission) 2.76 mg/dL and eGFR 20 mL/min/1.73 m2. Cyclophosphamide was temporarily discontinued due to neutropenia and subsequently reintroduced at alternate-day intervals, with no adverse effect, to a cumulative dose of 168 mg/kg.
The patient is now 12 months post completion of plasma exchange for anti-GBM disease and remains dialysis free. He continues on a weaning dose of alternate day prednisolone. Anti-GBM titers remain normal at 0.2 AI/mL. Renal function is stable with serum creatinine of 2.1 mg/dL, eGFR 26 mL/min/1.73 m2.


In 2011, a 77-year-old Brazilian woman was admitted to our service due to refractory anemia. She was treated with vitamin B12, folic acid, and iron, but she showed no improvement. A bone marrow aspirate (5 January 2011) showed dyserythropoiesis greater than 20%, dysgranulopoiesis greater than 20%, and 4% of blasts; her iron level was normal. A second bone marrow aspirate (8 June 2011) showed hypocellularity with dyserythropoiesis and dysgranulopoiesis (less than 10%), 1% of blasts, and absent iron. A third myelogram (18 August 2013) showed mild dysmyelopoiesis, hypocellularity with 7% dysmegakaryopoiesis, and moderate dysgranulopoiesis (12%); there was also a reduced deposit of iron and 0.5% of blasts (Fig. ). The first bone marrow biopsy (8 June 2011) showed hypocellularity, 20% of dyserythropoiesis, abnormal localization of immature myeloid precursors (ALIPs), and dysplastic megakaryocytes. The second bone marrow biopsy (12 August 2013) showed hypocellular bone marrow with dysmegakaryopoiesis and dyserythropoiesis associated with myelofibrosis degree II. The immunohistochemical studies of p53 expression and anti-CD34+ were negative. Serology for hepatitis B, hepatitis C, human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) were negative. Her thyroid hormones, ferritin, and dehydrogenase lactate levels were normal. A differential diagnosis for aplastic anemia was performed. Cytogenetic analysis showed a normal female karyotype. She was diagnosed as having multiple lineage dysplasia MDS, according to World Health Organization (WHO) 2016 and classified as very low risk based on IPSS-R (score-1). She currently shows no clinical or laboratory manifestations of the disease (Table ).