The case is an 82-year-old female who was originally investigated via gastroenterology for unintentional weight loss and raised inflammatory markers, with normal CT scan of thorax, abdomen and pelvis. She was subsequently diagnosed with giant cell arteritis (biopsy positive) after she presented to the eye clinic with right arteritic ischaemic optic neuropathy and jaw claudication. She received 3 pulses of intravenous methylprednisolone only to be re-admitted 2 weeks later with what was thought to be a flare of her disease. This resulted in her receiving a further 3 pulses of the same corticosteroid.
She was reviewed in the neuro-ophthalmology clinic 3 weeks later appearing unwell despite normal vital signs and unremarkable physical examination. Her CRP had increased and dilated ocular fundus exam revealed bilateral subretinal lesions, which were choroidal abscesses (Figure 1 , Figure 2 ).
She was admitted from clinic and underwent an extensive array of investigations. Three positive blood cultures confirmed that she was suffering from Nocardia cyriacigeorgica and imaging revealed dissemination to multiple organs. Chest x-ray now showed segmental consolidation, MRI brain showed multiple punctate lesions consistent with disseminated CNS nocardiosis; high resolution CT chest now showed scattered lung nodules, MRI spine showed appearances suggestive of a right-sided psoas abscess secondary to discitis of L4/5, and normal transoesophageal echocardiography (Figure 3 , Figure 4 ).
Despite receiving a course of intravenous antibiotics, there was no improvement in her general condition, and after discussion with family, treatment was subsequently withdrawn. The patient was transferred to the local hospice for palliative care where she died.


A 42-year-old African American male with a past medical history of gout, hypertension, and recurrent genital herpes presented to our Emergency Department complaining of right upper quadrant and epigastric abdominal pain with nausea and non-bilious, non-bloody vomiting of one-day duration. Epigastric pain occurred after eating a meal consisting of lobster and steak. It was described as a cramping, intermittent, non-radiating pain with moderate severity and no aggravating or alleviating factors. He denied any fever, chills, diarrhea, hematochezia, yellowing of skin, genital lesions, or burning micturition. He had no recent travel or sick contacts. He was started on allopurinol (100 mg, once a day) 10 days before presentation for longstanding gout and was taking valacyclovir (500 mg, once a day) for recurrent genital herpes. Detailed medication history also revealed the use of herbal medication (black seed bitters) around three months prior to presentation. He reported occasional marijuana use but denied tobacco consumption, excessive alcohol consumption, acetaminophen use, or any other recreational drug use. He denied any family history of hepatobiliary disease. He had a surgical history of anterior cervical discectomy and fusion (ACDF) for a cervical herniation secondary to car accident two years prior to presentation.
Vital signs on presentation showed blood pressure of 126/68 mm Hg, pulse of 73 beats per minute, temperature of 99.1°C, and respiratory rate of 15 breaths per minute with oxygen saturation of 100% on room air. Physical examination revealed age-appropriate skin changes and no acute distress. He had a horizontal occipital scar from a remote injury in his childhood and lateral neck scar from ACDF. He had scattered hyperkeratotic papular rash on the arms, torso, and legs (Figure ), and herpetic lesions on the glans penis. Cardiopulmonary examination revealed findings within normal limits. Abdominal examination showed tender epigastrium with rest of the abdomen soft, non-tender, with no masses or organomegaly. Neurological examination was grossly within normal limits.
Initial investigations were remarkable for cholestatic liver injury with serum alkaline phosphatase (ALP) at 659 IU/L (normal: 52-128 IU/L), aspartate transaminase (AST) at 103 IU/L (normal: 9-48 IU/L), alanine transaminase (ALT) at 152 IU/L (normal: 5-40 IU/L), gamma glutamyl transferase (GGT) at 802 IU/L (normal: 8-54 IU/L), albumin at 3.3 g/dL (normal: 3.4-4.8 g/dL), total bilirubin at 0.5 mg/dL (normal: 0.2-1.1 mg/dL), and direct bilirubin at 0.3 mg/dL (normal: 0.0-0.3 mg/dL). Ultrasound of the abdomen demonstrated increased liver echogenicity without hepatomegaly, normal gallbladder, non-dilated common bile duct, normal pancreas, and patent portal hepatic flow.
The patient was admitted to the hospital for further investigation of hepatic injury. At the time, differential diagnosis included possible drug-induced liver injury (DILI) secondary to allopurinol, autoimmune hepatitis, or biliary disease. Allopurinol was discontinued due to concern for DILI and drug reaction with eosinophilia and systemic symptoms syndrome (DRESS). Viral hepatitis serology demonstrated hepatitis A total antibody positive, hepatitis C antibody negative, hepatitis B surface antibody positive, and herpes simplex virus (HSV) IgM polymerase chain reaction (PCR) negative. Autoimmune liver profile demonstrated normal immunoglobulin G levels and absence of anti-nuclear, liver kidney microsomal, smooth muscle, and anti-mitochondrial antibodies. Acetaminophen levels were <14.9 ug/mL, below normal range for toxicity.
On further questioning, the patient revealed that one week before presentation, he was diagnosed with syphilis by his primary care physician. His syphilis diagnosis was preceded by a two-month history of polyarthralgia, diffuse pruritus, intermittent right upper quadrant abdominal pain, sore throat, fatigue, “cognac” colored urine, and weight loss. The patient had received one dose of penicillin G benzathine (2.4 million units intramuscularly). His diagnosis was serologically confirmed with reactivity on nontreponemal (RPR titer 1:64) and treponemal testing (IgM fluorescent T pallidum antibody absorbance [FTA-Abs]). The patient had blood tests done at his primary care provider's office and he was noted to have abnormal liver function tests prior to the admission (ALP of 722 IU/L, AST of 82 IU/L, ALT of 157 IU/L, albumin of 2.7 g/dL) which predated the recent start of allopurinol, and had normal liver function tests with albumin of 4.2 g/dL, AST of 18 IU/L, ALT of 32 IU/L, and ALP of 55 IU/L one year prior. Based on this information, DILI secondary to allopurinol was excluded, and syphilitic hepatitis became our primary working diagnosis.
The patient’s liver function tests were monitored daily, and a steady downward trend was noted towards resolution. He was discharged after a six-day hospital course with last in-hospital ALP of 461 IU/L, AST of 43 IU/L, and ALT of 79 IU/L (Table ). The patient was instructed to complete syphilis treatment by his primary care physician where he was scheduled to receive his remaining two doses within two weeks. He was advised to follow up in our gastroenterology and hepatology clinic to repeat liver function tests and monitor for resolution of presumed syphilitic hepatitis.


A 19-year-old girl affected by XP had come to our attention for a suspected advanced cSCC.
She was born in Sicily and, initially, she was followed by the dermatological centers in that region. No other family member was affected by the same pathological condition and her parents were not consanguineous. In her medical history, ophthalmic and neurological affections were not reported. Regarding skin involvement, from 5 to 13 years of age, she underwent repeated surgical excisions for a total of 24 neoformations which, on histological examination, were found to be basal cell carcinomas (BCCs) and cSCCs. The last resection was at the age of 14 due to a cSCC of the right lower eyelid. At 18 years, she received vismodegib treatment for an advanced BCC developing alopecia as an adverse event.
We firstly visited the patient in December 2018. On skin examination, a large hard swelling of the right superior eyelid extending to the nasal pyramid has been observed. An incisional biopsy was performed, resulting in a moderately-differentiated SCC. A CT scan was carried out to exclude secondary localizations. The MRI of the facial massif showed an infiltrating lesion of 62 × 47 mm. It extended from the right upper eyelid region affecting the orbital cavity’s medial wall and dislocating the eyeball from which it appeared inseparable. It jutted medially into the nasal cavities infiltrating the nasal septum and, below that, it crossed the floor of the orbit projecting into the ipsilateral maxillary sinus.
The interdisciplinary consultation did not indicate surgical treatment, therefore the anti PD-1 cemiplimab was requested in the nominate use programme and it was decided to add radiotherapy. Pending authorization of the drug, the patient was qualified for proton beam radiotherapy (PBR), which was performed with a total dose of 59.4 Gy in 33 fractions from January to March 2019. The treatment was well tolerated and, in consideration of the remarkable clinical and radiological response, a close clinical and radiological follow-up was established. Subsequent MRI showed stable disease with only a few spots of enhancement in the radio-treated area. ().
Meanwhile, several skin lesions were surgically removed in the following months, specifically seven BCCs and one cSCC of the face and upper limbs.
In June 2020, the follow-up MRI showed a laterocervical lymph node progression with a pathological submandibular lesion of 2 × 2 cm. For this reason, the treatment with cemiplimab 350 mg was initiated with administration every 3 weeks. After the first 2 infusions episodes of diarrhoea CTCAE Grade 1 were reported for which it was not necessary to stop the therapy. After 7 infusions the pathology was clinically and radiologically stable and the treatment was well tolerated without any of the other known adverse events. In addition, the patient did not have to undergo any further surgical excision as some of the lesions, especially on the face and neck, with clinical and dermoscopic parameters of actinic keratoses and BCCs had regressed. ().


A 50-year old Caucasian male residing in an urban area with right laterality was admitted to our Neurology Department with the complaint of weakness of the right limbs and impairment of the speaking ability. The symptoms had an acute onset, 5 days prior to presentation to our department. Family history revealed that the patient’s father had type II diabetes mellitus and suffered a cerebral ischemic stroke at 52. The patient had been a smoker (3 packs per day for 30 years) but was abstinent for the last 8 years. He also had class III obesity (body mass index of 42 kg/m22).
Nine days prior to developing neurological symptoms, the patient presented to the Emergency Department nearest to home with dry cough, myalgia, pronounced fatigue, shivers, and fever (up to 39°C). A real-time polymerase chain reaction (RT-PCR) test was performed from a nasal swab sample in order to test for COVID-19, and the test came back positive. The patient was admitted to the Infectious Diseases Unit. A computed tomography (CT) scan of the chest was performed. It revealed bilateral, relatively symmetrical areas with ground-glass attenuation. Notable laboratory findings showed a biological inflammatory syndrome consisting of elevated C-reactive protein (CRP) levels – 8.3 mg/l, upper limit (UL) <5 mg/l), elevated fibrinogen (470 mg/dl, UL<400mg/dl), total leukocytes within the normal range but with lymphopenia – 5.5%, reference range (RR) = 20–40%) and neutrophilia (90.3%, RR=50–70%). During this time, D-dimer levels and platelet count were within the normal range. According to the World Health Organization (WHO) criteria for the severity of COVID-19 infection [], the patient had a moderate form of infection. The treatment regimen consisted of Lopinavir/Ritonavir, Hydroxychloroquine 800mg/day, Enoxaparin 6000 IU/day, and Paracetamol (up to 2g per day). O2 saturation levels remained >96%. During the following week, the symptoms subsided, as well as the biological inflammatory syndrome. After 6 days, another RT-PCR test was performed. It came back negative, and the patient was discharged on the seventh day.
Two days after discharge, the patient woke up with weakness in the right limbs and troubled speaking, associated with generalized headache, nausea, and vomiting. He was transported to the regional Emergency Department. The on-call neurologist examined the patient. On neurological examination, hemiparesis (with a score of 4/5 on the Medical Research Council’s scale (MRC scale), central face palsy, diminished deep tendon reflexes, and extensor plantar reflex regarding the right side were objectified, along with motor dysphasia.
A CT scan of the head without contrast medium was performed (about 6 hours after the patient noted the symptoms), but it did not show any abnormalities in the brain parenchyma. The bloodwork revealed mild leukocytosis (12.000/mm3, RR= 4.000–10.000/mm3) with neutrophilia (8.700/mm3, RR = 2.000–8000/mm3), elevated D-dimers (897.56 ng/ml, RR< 500 ng/ml). An acute cerebrovascular event was suspected, and the patient was started on dual antiplatelet therapy (Aspirin 75 mg per day + Clopidogrel 75 mg per day) and statin (Atorvastatin 40 mg per day). The blood pressure and heart rate were within the normal range. The electrocardiogram (ECG) was also normal. Thrombolysis was not indicated given the uncertainty regarding the moment of onset of the symptoms. A head CT without contrast medium was repeated (about 13 hours after the first one), along with a CT scan of the chest (, ).
The CT scan showed multiple hyperdense lesions, two of them located in the left frontal lobe (, ), the right parietal lobe (), and the left parietal lobe () that the radiologist interpreted as minimal subarachnoid hemorrhage. A small hypodense lesion with a narrow hyperdense rim was seen in the left temporoparietal region that was suggestive of an acute ischemic stroke with minimal hemorrhagic transformation (). The second chest CT was similar to the previous one, with bilateral relatively symmetrical areas with ground-glass attenuation ().
Given the hemorrhagic nature of the lesions seen on the head CT (), antiplatelet therapy was temporarily ceased. The patient received prophylactic Low-molecular-weight heparin (LMWH) – Enoxaparin 6000 IU/day and Paracetamol (up to 2g per day). An RT-PCR test was performed on the second day of admission with an equivocal result and another on the fourth day with a negative result. Nausea and vomiting did not persist after the first day. The intermittent frontal headache persisted during the time of admission, as well as the motor deficit and dysphasia, with a slight improvement. The patient was afterward transferred to our department, 5-days after the onset of the neurological symptoms.
On admission to our neurology hospital, the general and neurological examination and also hematological and biochemical parameters did not reveal any additional information compared to the prior examinations. Intermittent frontal headaches were persistent. The blood pressure (BP), heart rate, and O2 saturation levels were within the normal range. The patient was not dyspneic and had only mild coughing.
A head CT with angiography was performed 6 days after the onset of neurological symptoms. A slight improvement over the previous examination was seen regarding the subarachnoid and intraparenchymal hemorrhages ( and ). A filling defect was observed in the C1 segment of the left internal carotid artery on angiography () that was interpreted as partial thrombosis of the artery. Partial occlusion of the P1 segment of the right posterior cerebral artery, as well as narrowing of the P1 and P2 segments of the left posterior cerebral artery, were observed (). Tubular stenosis in the V4 segment of the left vertebral artery was also noted ().
A pulmonologist was consulted, and Dexamethasone 8 mg/day i.v. for 5 days with subsequent dose tapering was recommended, alongside prophylactic LMWH. Multiple ECG examinations were performed during the patient’s stay in the hospital, but none showed abnormalities.
A head magnetic resonance imaging (MRI) with contrast medium was performed 8 days after the onset of neurological symptoms to evaluate better the heterogeneous lesions in the brain parenchyma as well as the arterial and venous circulation. The cortico-subcortical temporoparietal lesion in the left hemisphere was compatible with a subacute ischemic stroke associated with minimal hemorrhagic transformation in the superficial territory of the left middle cerebral artery (). A similar, smaller lesion without any sign of hemorrhagic conversion was also observed in the left parietal lobe, posteriorly to the first one (). Minimal subarachnoid hemorrhage was described adjacent to the left frontal lobe (). The magnetic resonance angiography (MRA) revealed the same arterial lesions that were previously described on the computed tomography angiography (CTA): a small filling defect regarding the C1 segment of the left internal carotid artery as well as the stenoses of the left vertebral artery and the P1 segments of both posterior cerebral arteries. The MR-venogram did not show any abnormalities.
Given the heterogeneous nature of lesions present in our case and the plethora of atypical neurological complications in COVID-19 described in current literature (see the Discussion section), a lumbar puncture was performed to evaluate the possibility of encephalitis and cerebral vasculitis. Macroscopically, the cerebrospinal fluid (CSF) was clear. The biochemical and cytological examination was normal. Due to technical limitations, RT-PCR was not performed, so the presence of the SARS-Cov-2 genome in the CSF was not evaluated. The IgG index and the IgG ratio were normal as well. The serum biomarkers for autoimmune vasculitis were not present. CSF and serum analysis for various infectious pathogens that could cause encephalitis was performed, and we did not find any causative agents in our patient (, ). Thus, a diagnosis of encephalitis or cerebral vasculitis was considered to be unlikely.
The clinical evolution was favorable during his 7-day stay in our hospital. The headaches disappeared after a few days. The motor deficit and dysphasia showed improvement as well. No abnormal laboratory results were present at the moment of discharge. The patient was referred to a cardiologist, a kinesiotherapist, and a logopedist after discharge, and the treatment plan consisted of Enoxaparin 6000 UI/day for a month and Aspirin 75 mg/day. A neurological re-examination (clinical and imaging) was scheduled one month later.


A 28-year-old male was referred from a primary-level hospital to the University Teaching Hospital (a tertiary-level hospital located in the city of Lusaka, Zambia) for adult onset of malnutrition. The patient had a history of generalized body swelling for 6 months. He also had loss of appetite and watery diarrhea (five times a day) for a duration of 5 months. The patient also gave a history of developing blisters in the lower limbs, upper limbs, and abdomen which later ruptured and peeled off resulting in hyperpigmentation of the affected areas. The lesions started on the lower limbs and then moved upwards to involve the trunk and upper limbs. He also gave a history of hair loss and discoloration. He denied other symptoms such as cough, fever, paroxysmal nocturnal dyspnea, or joint pains. Despite treatment at the local clinic, the condition continued to deteriorate, and therefore, he was referred to our tertiary institution for further management. The patient was a type 1 diabetic and was on insulin for 3 years prior to admission. He was said to be in good health before this illness. He gave a history of smoking and was a heavy alcohol drinker until he became unwell a few months before admission.
On admission to the University Teaching Hospital, the patient underwent a full clinical assessment including laboratory investigations. On examination, the patient was lethargic and was unable to sit without support. His blood pressure was 93/60 mmHg, body temperature was 35.7°C, radial pulse rate was 89 beats per minute, respiratory rate was 24 breaths per minute, and peripheral oxygen saturation was 100%. He had conjunctival and palmar pallor with no signs of jaundice. He was noted to have generalized body swelling mostly involving the periorbital area, hands, and abdomen (ascites). His tongue was glossy and beefy red, and he had gingivitis and angular cheilitis. On local examination of the skin, he was noted to have hyperpigmented patches and erosions with some intact bullae on both the upper and lower limbs and the abdomen. The patient was also noted to have sparse hair with brownish discoloration (). On examination of the genitalia, he was noted to have extensive skin erosions and scrotal swelling. Examination of the respiratory and cardiovascular systems was significant for a resting tachycardia and bibasal posterior crepitations. He had mild pedal edema on the lower limbs, feet, and hands. In addition, he had an infected ulcer on the left antecubital fossa.
A number of laboratory investigations were conducted which included a complete blood count which showed severe anemia, liver function test which revealed a hypoalbuminemia, and kidney function tests which were normal (). A pus swab for microscopy and culture collected from the infected ulcer located on the left antecubital fossa showed the presence of Staphylococcus aureus and Acinetobacter species. Blood culture initially showed Staphylococcus aureus, and a repeat blood culture performed two weeks later showed the presence of yeast cells and Gram-negative bacilli. Other organisms identified on the same culture were Candida and Klebsiella pneumoniae species. A skin biopsy of an intact lesion was performed, and it showed features consistent with AE including spongiosis with epidermal pallor, parakeratosis, and keratinocyte necrolysis (). Upper gastrointestinal endoscopy was performed and showed villous blunting, and biopsies of the duodenum and ilium were also performed and showed blunting of the villi ().
A diagnosis of acquired AE with sepsis was made based on the clinical findings. The differential diagnosis was pemphigus foliaceous. The patient was initiated on oral zinc sulphate at 50 mg three times a day with hematinics (folic acid and ferrous sulphate) and antibiotics. A few days after initiation of zinc, the patient showed remarkable improvement in the skin lesions including a reduction in the edema, resolution of diarrhea, and improvement in appetite (). Measurement of plasma zinc levels was performed several days after the patient had been commenced on zinc sulphate and showed high zinc levels. On admission, he also received a blood transfusion for the anemia.
Despite improvement in the skin lesions and diarrhea, the patient's general condition continued to deteriorate. His sugar levels were fluctuating with episodes of hyper- and hypoglycemia, and he continued to have signs and symptoms of sepsis. The patient eventually died after 25 days of admission.


On July 2019 a 40-year-old man with personal history of brain arteriovenous malformations (AVM) and thyroidectomy in 2000 for papillary thyroid carcinoma with post-surgical permanent hypoparathyroidism, was hospitalized after repeated episodes of falls due to marked hyposthenia and drowsiness. Additionally, he reported a feeling of early satiety that has arisen two months before, he also reported weight loss in the last three months (from 110 kg to the current 87 kg). Brain computed tomography (CT) and magnetic resonance (MR) imaging were negative. Blood test showed hypercalcemia (15.5 mg/dl, range 8.4–10), elevation of cholestasis markers gamma-glutamyltransferase (874 UI/l, range 8–61), and alkaline phosphatase (526 UI/l, range 40–129). The oral treatment with calcium carbonate and calcium citrate plus calcitriol was withdrawn without a decrease in calcium levels.
During the diagnostic work-up an ultrasound of the upper abdomen was performed and showed numerous hyperechoic solid formations of likely metastatic significance in the liver. Subsequently, total body CT confirmed the presence of multiple liver metastases, affecting 50% of the left hepatic lobe and 30% of the right lobe, and found a voluminous lesion with regular margins, sized 95 × 85 × 75 mm, in the pancreatic tail. Moreover, more metastatic implants, with a maximum size of 24 × 20 mm, were observed in the left subdiaphragmatic area. The patient was then subjected to liver biopsy, the histological examination revealed a liver localization of well differentiated NEN, Ki67 index 5%. Immunohistochemistry was positive for CK 8/18, CD56, synaptophysin, and weakly positive for CDX2 and chromogranin A. Among circulating neuroendocrine markers, calcitonin (958 pg/ml, normal values <10) and chromogranin A (470 ng/ml, normal values <100) levels were found elevated. The patient underwent 68Ga DOTATOC Positron Emission Tomography (PET)-CT which showed uptake of the radiotracer in the pancreatic lesion, and in hepatic and nodal metastases. Subsequently, he started therapy with Lanreotide Autogel 120 mg every 28 days. Given the hypercalcemia, possibly of paraneoplastic origin, Denosumab 120 mg every 28 days was started. To investigate hypercalcemia origin, PTHrP was dosed and was found markedly elevated (451 ng/l, normal values <20). Three months later, CT imaging showed hepatic disease progression. Thereby, peptide receptor radionuclide therapy (PRRT) with 177Lu-LUTATHERA 7400 MBq was prescribed. The patient performed four cycles of therapy from November 2019 to June 2020. The treatment was well tolerated (except for mild leukopenia), and clinical (improved general conditions) and biochemical (stabilization of calcium levels) responses were good. After the first cycle of treatment, PTHrP declined from 451 to 150 ng/l (see ). Moreover, an objective tumor response was observed at CT evaluation after three cycles of treatment: hepatic lesions were reduced at VIII segment (44 × 36 vs 53 × 48 mm), IVa segment (25 × 23 vs 30 × 27 mm), and VI segment (26 × 19 vs 32 × 26 mm) (see ).


A 45-year-old male with history of multinodular goiter and hypertension underwent distal pancreatectomy and splenectomy in 2006 due to the detection of a caudal pancreatic mass 4.5 cm in diameter. Histological examination revealed a G2 pancreatic neuroendocrine tumor (NET) without lymph node metastases, Ki67 was 5% according to the WHO 2010 criteria. Immunohistochemistry showed positivity for synaptophysin, chromogranin, neuron specific enolase (NSE), pan-cytokeratin, and calcitonin. One year later, therapy with somatostatin analogs (SSAs) was started due to onset of multiple liver metastases, and in 2010 Everolimus was introduced due to hepatic progression. Mild serum calcium elevation appeared in 2014, with normal renal function, PTH, and 25-hydroxyvitamin D levels. Neck ultrasound, performed for follow up of a multinodular goiter, revealed a hypoechoic lesion resembling a parathyroid adenoma. Serum calcium levels progressively increased (11.8 mg/dl normal range 8.4–10.2 mg/dl), thus Cinacalcet was introduced at the dosage of 30 mg/daily and increased up to 60 mg/daily. However, it was withdrawn because of its inefficacy. No evidence of disease progression was recorded, but clinical conditions rapidly deteriorated, and hypercalcemia was treated with intravenous saline hydration and loop diuretics to obtain rapid restoration. Subsequently, intravenous bisphosphonate Zoledronate was introduced, 4 mg monthly for 12 months (from October 2018 to October 2019) with normalization of calcium levels. PTH levels remained within normal reference range, while neck ultrasound did not confirm the suspected parathyroid lesion. Clinical and biochemical results strongly support the hypothesis of a hypercalcemia ascribable to a secretion of PTHrP, since all other causes of hypercalcemia were excluded, but unfortunately the assay for PTHrP was not available. In 2018 the dose of Everolimus was lowered from 10 to 5 mg/daily due to hematologic side effects and the total body CT scan showed progressive liver disease, and centimetric bilateral hip and vertebral sclerotic bone metastases, with positive 68Ga DOTATOC PET-CT. The slight bone metastatic involvement without osteolysis could not explain recurring hypercalcemia. Everolimus and Zoledronate were suspended, and the patient began PRRT and Denosumab 120 mg monthly. Disease stability was obtained, but unfortunately osteonecrosis of the jaw occurred and Denosumab was suspended after only two administrations. Calcium levels increased again at 12.1 mg/dl, and intravenous saline hydration and loop diuretics were administered. Prednisone 20 mg daily was needed to normalize calcium levels. Despite disease stability after four cycles of PRRT the patient’s performance status worsened and the patient deceased in 2019.


In July 2007 a 49-year-old woman with a huge pNEN associated with severe hypercalcemia was referred to Niguarda Hospital (Milan, Italy). The medical history of the woman was silent until 4 months earlier, since she had 20 kg weight loss, asthenia, and hyperglycemia. One month before she arrived at our medical facility the patient went to the emergency room of another hospital because of the onset of neurologic symptoms (psychic slowdown, confusional state, sensory dullness). Emergency room blood exams showed severe hypercalcemia (21 mg/dl). The patient was hospitalized in the nephrology unit where she underwent hemodialysis (single treatment), bisphosphonates injections, and continuous infusion of calcitonin to control hypercalcemia. Neoplastic mass embolization through spirals positioning in the splenic artery was performed. Calcium levels normalized in a few days and at the same time a gradual improvement of neurologic symptoms was observed until a complete recovery. Imaging studies showed a 12 cm mass of pancreatic body and tail. A needle biopsy of the mass was diagnostic for a well differentiated NEN. 111In-pentetreotide scan was performed and showed tracer uptake in the abdominal lesion. Patient was discharged and referred to our hospital for further investigations and surgery. When the patient arrived at our facility her calcium levels were between 8.5 and 8.7 mg/dl (normal). Diabetes and anemia requiring blood transfusions were observed. Hormonal examinations showed low-normal PTH levels (12 pg/ml, normal values 10–90), high levels of calcitonin (3,079 pg/ml, normal values 0.10–15.00) and chromogranin A (222 UI/l, normal values <20). Vitamin D metabolites were determined showing low levels of 25-hydroxyvitamin D (8 ng/ml, normal values >20) and high levels of 1,25-dihydroxyvitamin D (85 pg/ml, normal values 16.0–55.0). An abdomen MR confirmed an expansive 12 cm lesion of the body and tail of the pancreas, highly vascularized, with a central necrotic area, with apparent infiltration of the fundus of the stomach and the splenic ileum, and showed thrombus of the splenic vein jutting out within the portal mesenteric confluence. The patient underwent distal pancreatectomy, splenectomy, resection of the gastric fundus, and removal of the neoplastic thrombus. Pathological examination of the pancreatic mass was diagnostic for a well differentiated G1 NET, angioinvasive, massively infiltrating the gastric wall. Immunohistochemical staining for chromogranin A, synaptophysin and somatostatin was observed; MIB1 was <1%. Twenty-four hours after surgery reduction of serum calcium levels was observed, which in the following days dropped to 5.4 mg/dl despite calcium (both intravenous and oral administration) and calcitriol supplementation, post-surgical ionized serum calcium was 1.08 mmol/l (1.18–1.29). A week after surgery, improvement until normalization of serum calcium was gradually observed and calcium and calcitriol supplementations were reduced. The postoperative course was also characterized by pleural effusion treated with drainage placement and antibiotic therapy. Soon after surgery, glycemia, calcitonin, and chromogranin A normalized, whereas PTH levels increased to 180 pg/ml (normal values 10–90), to then return into the normal limits in the following months. Thirteen years after surgery the patient was in good general condition, calcium and PTH levels were in normal range, and there was no evidence of disease recurrence.


In August 2016 a 69-year-old man with personal history of dilatative cardiomyopathy due to ischemic heart disease was hospitalized after the onset of shortness of breath and dyspnea, asthenia, and weight loss (from 98 to 75 kg). Chest radiograph showed a pulmonary nodule of about 40 mm. Total body CT confirmed a pulmonary nodule of 32 × 43 mm located at the apical segment of the lower left lobe, and partly leaning and compressing some bronchial branches, with a small calcification. In addition, a solid liver lesion of 10 mm was detected. Blood tests showed hypercalcemia (14.4 mg/dl, range 8.4–10) and low PTH (4.7 pg/ml, range 15–65). A 68Ga DOTATOC PET-CT was performed showing an uptake of the radiotracer in the left pulmonary lesion. A lung biopsy showed a histological report of a poorly differentiated neuroendocrine carcinoma, Ki67 index 10%. Immunohistochemistry was positive for chromogranin A, CK7, and weakly and focal positive for TTF1. Circulating neuroendocrine markers showed high NSE (107 ng/ml, range 1–16) and chromogranin A (184.9 ng/ml, normal values <100). Liver biopsy showed a hemangioma. Therapy with Zoledronate 4 mg intravenously every 28 days was immediately started, given the hypercalcemia, possibly of paraneoplastic origin. To investigate hypercalcemia origin, PTH-rP was measured and found to be markedly elevated (109 ng/ml, normal values <20). After stabilization of hypercalcemia, a lower left lung lobectomy was performed in line with guideline ().
The histological examination was well differentiated NET positive for chromogranin A and synaptophysin, of the lower lateral lobe, mitosis >2HPF, Ki67 9%. After surgical lung lobectomy, calcium levels were normalized, PTH-rP was significantly reduced from 109 to 5 ng/ml and an improvement of the general conditions was achieved.


A 16-year-old white female with a BMI of 47.7 kg/m2, presented with a seven-day history of fever, vomiting, diarrhea, worsening cough, and shortness of breath (SOB). In the ED, she was alert with no increased work of breathing. She had episodes of pronounced hypoxemia induced by activity with associated oxygen saturations of less than 80%. On physical examination, her lungs were clear to auscultation without any sign of respiratory distress. She complained of mild abdominal tenderness on palpation. She tested positive for COVID-19 by molecular testing of the nasopharyngeal specimen. Chest radiograph (CXR) showed low lung volumes with acute inflammatory infiltrates in the upper lobes accompanied by subsegmental atelectasis (Figure ).
She was started on 3 L/min of supplemental oxygen delivered by nasal cannula which resolved her hypoxemia. The patient developed progressively worsening hypoxemia and respiratory distress requiring escalation of oxygen support to high flow respiratory support by high-velocity nasal insufflation (HVNI) with 100% fraction of inspired oxygen (FiO2). The patient was transferred to the pediatric ICU for further management on day 2 of hospitalization. She was evaluated for COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) and had laboratory evidence of inflammation with the following laboratory abnormalities: hypoalbuminemia, erythrocyte sedimentation rate (ESR) of 41 mm/hr (reference range 0-20 mm/hr), C-reactive protein (CRP) of 6.87 mg/dL (reference range <=0.90 mg/dL), fibrinogen of 445 mg/dL (reference range 200-400 mg/dL), procalcitonin of 0.27 ng/mL (reference range 0-0.10 ng/mL), D-dimer of 1.59 FEU mcg/mL (reference range <=0.49 FEU mcg/mL), ferritin of 889 ng/mL (reference range 4.6-204 ng/mL), lactic acid dehydrogenase (LDH) of 348 Units/L (reference range 25-220 Units/L), total creatine kinase (CK) of 408 Intl Units/L (reference range 29-168 Intl Units/L) and elevated prothrombin and partial thromboplastin times (PT and PTT). Echocardiogram was normal. Blood and urine cultures were negative. Due to continued hypoxemia, respiratory support was escalated to bi-level positive airway pressure. She was then intubated and placed on mechanical ventilation on day four of hospitalization. Serial CXR showed progressive worsening patchy confluent infiltrates throughout the bilateral upper and lower lung zones. She was treated with remdesivir (200 mg intravenously on day 1 followed by 100 mg daily for a total of five days), convalescent COVID-19 antibody serum, dexamethasone, intravenous immunoglobulin, and prophylactic anticoagulation therapy. As her respiratory status gradually improved she was extubated after nine days and was discharged from the hospital eight days post-extubation.


A 15-year-old white female with a history of poorly controlled asthma, untreated hypothyroidism, and BMI of 44.16 kg/m2 presented to the hospital with a five-day history of fever, congestion, cough, SOB, and headache. In the ED, she was alert and had mild respiratory distress with oxygen saturation of 86% on room air. On physical examination, she had decreased breath sounds in the bilateral lower lung lobes and crackles over the posterior lung fields. She was noted to have intermittently worsening hypoxemia with desaturations to as low as 80% with ambulation or on lying supine. Positional hypoxemia improved with change in position to lateral or prone. She tested positive for COVID-19 by molecular testing of the nasopharyngeal specimen. CXR showed diffuse bilateral interstitial opacities (Figure ).
She was evaluated for COVID-19 associated MIS-C but did not meet the laboratory criteria. Complete blood count, comprehensive metabolic profile, PT/PTT, fibrinogen, D-dimer, and ferritin levels were all normal. CRP and ESR were elevated to 3.65 mg/dL (reference range <=0.90 mg/dL) and 54 mm/hr (reference range 0-20 mm/hr), respectively. She had an initial elevated level of total CK to 2459 Intl Units/L (reference range 29-168 Intl Units/L). Thyroid-stimulating hormone was elevated to 55.31 mcIU/mL (reference range 0.470-3.410 mcIU/mL) and the free T4 level was less than 0.40 ng/dL (reference range 0.58-1.64 ng/dL). She was started on 2 L/min of supplemental oxygen by nasal cannula with associated oxygen saturation of 92%. Over the next eight hours, she developed worsening hypoxemia with associated dyspnea, most notably during and following ambulation, and was transitioned to high flow respiratory support by HVNI with 50% FiO2. During the next 12 hours, her hypoxemia worsened, and she was transferred to the pediatric ICU and was continued on high flow respiratory support at 25 L/min with 70% FiO2 by HVNI. Her oxygen saturation improved to more than 92% but she continued to have intermittent positional and exertional hypoxemia. She was treated with albuterol, dexamethasone, prophylactic anticoagulation therapy, and thyroxine. On day 5 of hospitalization, she began showing clinical improvement and her oxygen support was weaned over the next 48 hours. She was transitioned to room air and was discharged home after seven days of hospitalization.


A 33-year-old woman at 26 + 5 weeks of gestation was referred to our centre because of the ultrasound examination revealed a bilateral, grade II hydronephrosis and unilateral mild ventriculomegaly, which was estimated at 10.2 mm. Her husband was 37 years old, and the couple was unrelated. The family history was unremarkable, and no teratogenic exposure was noted. At 12 + 4 weeks of gestation, nuchal translucency was 1.4 mm (50th centile), and crown-rump length was 61 mm. Based on these measurements, hormones and maternal age, the risk for trisomy 21 was 1:7,304 and for trisomy 18 as 1:2,258. A CMA in amniotic fluid reported the diagnosis of Koolen-De Vries syndrome.


A 74-year-old male patient visited our hospital in October 2020 with a mass above the stoma that had persisted for 2 months. He had no history of abdominal pain, fever, or cough. In 2016, he underwent an abdominoperineal resection procedure for carcinoma located in the distal one-third of the rectum. He also had a history of open appendectomy. The patient was an active smoker, was on medication for diabetes, had no chronic obstructive pulmonary disease, and was not using any immunosuppressive drugs. He had also received chemotherapy (10 cycles of FOLFOX6) for carcinoma. There was no history of any other comorbidities. Family, psychosocial, and genetic histories were insignificant.
The patient's blood pressure was 140/90 mmHg, heart rate was 82 beats/min, respiratory rate was 20 breaths/min, and body temperature was 36.4°C during the examination. His body mass index was 27.5 kg/m2. Abdominal examination in the erect position revealed a mass with a diameter of ~5 cm protruding above the stoma. He had midline and gridiron incisional scars. There was a parastomal hernia at the outer edge of the rectus abdominis muscle. The hernia was soft and reducible to the abdominal cavity in the supine position.
Computed tomography (CT) examination revealed a parastomal hernia () with a diameter of 3 cm. Laboratory tests revealed a leukocyte count of 5.90 × 109/l, hemoglobin concentration of 65 g/l, neutrophil percentage of 61.8%, and platelet count of 149 × 109/l. Glycosylated hemoglobin A1c (HbA1c) level was 6.5%. The renal function test showed that creatinine was 79.2 μmol/l and urea was 7.21 mmol/l. Electrolytes and coagulation function were normal. There were no abnormalities detected in the electrocardiogram, chest X-ray, and echocardiogram. The diagnosis at admission was post-operative rectal cancer with a parastomal hernia.
Under general anesthesia, endotracheal intubation or a laryngeal mask and pre-operative indwelling urinary catheterization were applied to the patient, who was in a supine position. The surgeons were standing contralateral to the stoma with the monitor over the surgical site. The stoma was sealed with an adhesive incise drape. The surgical field was divided into right and left partitions using the sterilized surgical towel to prevent any potential contamination.
An incision of 1.2 cm through the skin and subcutaneous adipose tissue was made at the right iliac region. The incised subcutaneous tissue was separated using a pair of retractors to expose and dissect aponeurosis of the external oblique muscle. Hemostatic forceps were used to separate the internal oblique and transversus abdominis muscles. The primary extraperitoneal space was created using a finger. To create the preperitoneal space, 2 sets of 5-mm trocars were inserted at the site of surgical incision using the retrograde puncture technique (); the trocars were placed at ~5 cm to each side of the incision, and a 12-mm observation trocar was placed through the incision (). After successfully placing all three trocars, extrapneumoperitoneum was induced (11 mmHg CO2) for endoscope insertion.
The further extraperitoneal space was created under direct endoscopic guidance down to the pubic floor and up to the bladder, where it was easier to create. We then moved to the contralateral side of the abdomen; as the long midline incision in the abdomen made it very difficult to separate the peritoneum, the membrane was cut while avoiding damage to the tissue at the middle of the incision, thus weakening the abdominal wall. When performing cephalad dissection, we targeted the space between the rectus abdominis and posterior sheath. To create the space, we opened the lateral edge of the posterior sheath to penetrate the extraperitoneal space between the lateral and mid-abdomen. The TEP technique was used for this separation. The dissecting plane of the lateral space was the extraperitoneal space between the peritoneum and parietal plane. During separation, the peritoneum was dissected and observed to avoid damage to the bowel around the stoma. Through the space that was created by separation, we enlarged the extraperitoneal space within a 15- to 20-cm radius around the stoma, providing a large field for mesh placement ().
At the end of the procedure, the abdominal wall defect was closed with a 2-0 non-absorbable suture (). The peritoneum defect was secured using a 3-0 absorbable suture with the enterostomy loop positioned outside the peritoneum.
A 15 × 15-cm polypropylene mesh was cut in the middle and placed around the colostomy loop (), then sutured and fixed. After a careful re-examination, the surgical field was clean, and no drainage tube was placed. Then extrapneumoperitoneum was relieved to complete the operation.
The total operation time was 240 min while the peritoneal separation time was 115 min. The patient was discharged 48 h after the operation. At the 3-month follow-up, the patient had a regular oral intake and defecation, no pain around the stoma, no seroma formation, and no infection at the incision site. The follow-up abdominal CT scan showed no recurrence of the hernia ().


A 67-year-old Korean male with no past medical or surgical history presented to his primary care physician with indigestion and epigastric discomfort. His physical examination was unremarkable. Laboratory assessment demonstrated a mild elevation in his hepatic transaminases (serum glutamic oxaloacetic transaminase 43, serum glutamic pyruvic transaminase 75), which prompted a transabdominal ultrasound. A hypoechoic 1.1 cm cystic mass without significant vascularity was identified in the body of the pancreas without ductal dilation (). A subsequent magnetic resonance imaging (MRI) of the abdomen demonstrated a 1.3 cm indeterminate solid mass in the pancreatic body with very subtle T2 hyperintensity and a very subtle hyperintense signal on diffusion weighted images. The lesion was isointense with the background pancreatic parenchyma on postcontrast images and was suspicious for a pNET or PDAC (). Of note, a background of hepatic steatosis was noted. An endoscopic ultrasound with fine needle aspiration (FNA) was performed and demonstrated a hypoechoic 11.3 mm by 8.3 mm oval mass in the pancreatic body with well-defined borders (). Cytology from the FNA demonstrated monomorphic epithelial cells (pankeratin and cytokeratin antibody positive in a number of carcinomas [OSCAR] positivity) of hepatocellular origin (hepatocyte-specific antigen positivity) on immunohistochemistry. The Ki-67 was very low to absent. These findings were consistent with a well-differentiated HCC, concerning for either metastatic or primary HCC of the pancreas. A hepatitis panel and tumor markers such as alpha-fetoprotein (AFP), carcinoembryonic antigen, and cancer antigen 19-9 were all negative.
The case was discussed in a multidisciplinary tumor board and surgical excision was recommended. Diagnostic laparoscopy demonstrated no evidence of masses in the liver and no evidence of peritoneal or omental metastasis. A total of six ports were placed and the robot was docked. An intraoperative ultrasound demonstrated that the mass was distal to the pancreatic neck. A tunnel under the neck of the pancreas at the superior mesenteric vein and portal vein confluence was established. A stapler was used to divide the pancreas immediately medial to the gastroduodenal artery. The splenic artery and vein were dissected circumferentially and divided using a linear stapler. The remaining attachments to the retroperitoneum were divided and the specimen was removed. A drain was left adjacent to the pancreatic staple line. The patient's postoperative course was unremarkable, his drain amylase level was low, and his drain was removed before discharge on postoperative day 4.
The final gross pathology demonstrated a 1.5 cm tan-brown solid soft well-circumscribed lesion. Rare cells contained cytoplasmic pigment suggestive of bile. The final pathology was consistent with a 1.5 cm well-differentiated carcinoma with hepatoid features (). All margins were negative and all 18 lymph nodes evaluated were negative for carcinoma. In addition, two incidental neuroendocrine microadenomas were identified.


This is a 37-year-old male, known case of diabetes mellitus, Presented to the Emergency Department complaining of Generalized abdominal pain for 2 days duration. Associated with abdominal distension, fever, nausea, vomiting and obstipation. He denied any history of eating from outside, but he gave a history of persimmon intake. Unremarkable past surgical history. His family, drug and psychological history were unremarkable. On examination, He was tachycardic, other vital signs were within normal. Abdominal examination showed abdominal distention and Sluggish bowel sound. Digital rectal examination showed an empty rectum. Laboratory investigations showed leukocytosis 16 thousands per cubic milliliter, other labs were unremarkable. Abdominal X-ray revealed multiple air-fluid levels. Abdominal CT scan with IV contrast revealed dilated small bowel loops reaching up to 3.8 cm with intraluminal mass in the ileum measuring 3.4 × 2.2 × 3.3 cm () and intra-gastric mass measuring 3 × 7 × 3 cm (, ) with bezoars suspicion. After resuscitation, he underwent a trial to remove the intra-gastric bezoar by upper endoscopy, a small part of the bezoar removed. After that, he underwent exploratory laparotomy, gastrostomy to remove intra-gastric bezoar (), and enterotomy to remove the ileal bezoar (, ) by a general surgeon. The histopathological examination of the bezoars revealed vegetable materials with inflammatory cells. Eventually, he was discharged home in a good condition.


A 57-year-old male smoker and alcoholic with comorbidities of diabetes mellitus, systemic hypertension, and chronic kidney disease presented to our hospital with the complaints of dysphagia and pain on the left side of the neck radiating to the ear for the past 3 months. He was hemodynamically stable. Oral cavity examination was unremarkable. Indirect laryngoscopy revealed a growth in the left lateral pharyngeal wall extending to the left tonsil superiorly and to the left pyriform fossa inferiorly. Neck examination revealed no significant lymphadenopathy.
Blood investigations revealed raised renal function tests and low creatinine clearance. Upper gastrointestinal endoscopy revealed a large ulceroproliferative growth in the left lateral pharyngeal wall extending proximally to the left tonsillar fossa and distally up to the upper one-third of lateral wall of the left pyriform fossa. The esophagus showed a small area of unhealthy mucosa at 31 cm. Narrow band imaging showed the unhealthy area as an erosion due to reflux disease. Biopsy from the hypopharyngeal lesion was suggestive of squamous cell carcinoma Grade II–III. Computerized tomography (CT) revealed a 4.5 × 4 × 2 cm lesion in the left pyriform fossa and left lateral pharyngeal wall. Hence, the patient was diagnosed with carcinoma of hypopharynx T3N0M0 Stage III.
The surgical oncologist opined to proceed with organ preservation approach. The medical oncologist opined to get the nephrologist’s opinion for proceeding with chemotherapy. The nephrologist advised to avoid platinum-based drugs in view of chronic kidney disease. After discussion in the multidisciplinary board, the patient was planned for radiotherapy with concurrent nimotuzumab.
The patient received radiotherapy of a total dose of 66 Gy (200 cGy/fraction up to 33 fractions) using conformal technique (Varian Linear Accelerator) along with 5 cycles of weekly nimotuzumab (200 mg) (). During radiotherapy, the patient developed Grade II mucositis, Grade II pharyngitis, and Grade I neutropenia. The patient completed the treatment without much treatment related side effects. Follow-up upper gastrointestinal endoscopy after 6 weeks revealed post-radiotherapy changes with no evidence of disease. The patient is on regular follow-up with a disease-free interval (DFI) of 7 months.


A 33-year-old Rumanian woman was admitted to the Endocrinology Department of Bari University hospital (Italy) for hirsutism. The patient worked as a translator at the police department in her city. The clinical history was unremarkable for endocrinological or gynecological disorders and neoplastic diseases. Twenty days before hospitalization for hirsutism, she had developed mental confusion, restlessness and aggressiveness treated with medical sedatives (Fig. ). At hospital admission, cardiovascular and respiratory examinations were unremarkable. The chest X-ray was inconsistent for lung disease; the electrocardiogram showed a sinus rhythm and the body temperature was 37.5 °C. Laboratory tests 1 day later demonstrated an increased cortisol level (> 2000 μg) with low adrenocorticotropic hormone (ACTH) (5 ng/L), low albumin 1.5 g/dL, neutrophils 93.3%, platelets count 60 (× 10 + ^3/uL), lactate dehydrogenase 892 U/L, p-fibrinogen 900 mg/dL, P-D-Dimers 4.28 mg/L, hemoglobin 9.8 g/dL, glucose 160 mg/dL, urea 39 mg/dL, calcium 7.9 mmol/dL, ferritin 4449 ng/dL, AST 52 U/L, c-reactive protein 470 mg/L, s-haptoglobin 5.6 g/L, normal sodium levels, procalcitonin 2.9 ng/mL, S-NT-proBNP 10,543 pg/mL, phosphate 2.5 mg/dL; creatinuria 24/h 1118 mg/24 h, glycosuria 24/h 792 mg/24 h, microscopic hematuria. Full body computed tomography-scan showed no masses and tumor markers were negative. Urine culture and rectal swab were negative for common microorganisms. No antibiotic therapy was administered. Three days after hospitalization, owing to a rapid rise in fever, mental confusion, severe headache, and respiratory failure, she was transferred to the intensive care unit (Fig. ). The laboratory tests were indicative of cardiac distress (S-NT-proBNP 105,797 pg/mL, S-troponin I 24.100 ng/mL cardiac), the chest X-ray showed pneumonia in the right lower lobe and a small quantity of pericardial fluid, consistent with pericarditis. A diagnosis of community-acquired pneumonia with sepsis was made, and broad-spectrum antibiotic therapy was administered pending new microbiological tests, urgently requested on secretions taken from the endotracheal tube and on serum. Unfortunately, the patient died in the meantime. The clinical diagnosis of septic shock was made, and autopsy was performed. The results of the microbiological test by multiplex Polymerase Chain Reaction (PCR) for the detection of Legionella spp., Chlamidia pneumoniae and Mycoplasma pneumoniae in the tracheal aspirate showed positivity for Legionella pneumophila serotype 1. Positivity for Candida albicans (> 2.000.000) and serum Aspergillus antigen (> 12.70) were also detected. The autopsy revealed multi-organ necrotizing exudative disease involving the lower right lobe (lobar pneumonia) (Fig. a), the heart (pancarditis) (Fig. c) and the brain, mainly involving the white matter (encephalitis) (Fig. e), histologically evident as neutrophilic abscesses (Fig. b-d-f). The macroscopic and microscopic examinations of the pituitary gland were negative for tumors. The adrenal glands were diffusely hemorrhagic and the other organs, including ovaries, showed no significant alteration. Results of analyses of water samples carried out in the patient’s apartment showed that the technical measures limit was not exceeded. The search for Legionella in the culturable investigations was performed according to guidelines of the multicenter study conducted by the Italian Study Group on Hospital Hygiene (GISIO) of the Italian Society of Hygiene, Preventive Medicine, and Public Health (SItI), Italian Association of Aerobiology (AIA), and the Italian Multidisciplinary Society for the Prevention of Infection in Healthcare Organizations (SIMPIOS) [].


A 43-year-old woman visited our department on July 7, 2020, with a chief complaint of numbness, weakness, and coldness of the left upper extremity, with radial pain from the shoulder to the elbow. She had been diagnosed with CSR 2 years ago and was treated with neurotrophic drugs and painkillers, including MeCobalamin tablets (0.5 mg, PO, TID) and loxoprofen sodium tablets (60 mg, PO, TID). However, as the symptoms were not completely relieved after intermittent treatment for 3 months, the patient sought acupuncture. On physical examination, the left brachial plexus traction test was positive, and the results of the thoracic outlet syndrome, cubital tunnel syndrome, and carpal tunnel syndrome tests were all negative, bilateral Hoffman sign was not elicited, upper limb muscle strength and tension were normal, and the patient's numbness and pain were scored as 10 and 6 using Tanaka Jingjui's CSR-20-point score and the visual analog scale (VAS), respectively.[
Acupuncture methods: (1) Acupoint selection: The LU 2 acupoint was selected for the treatment. The patient was instructed to lie down with her hands akimbo and elbows leaning forward slightly to fully separate the thorax and shoulder joint, fully expose the acupoint, and form a triangular depression visible at the lower edge of the clavicle's outer end. The depression on the inner edge of the scapula's coracoid process is the LU 2 acupoint. It is recorded in the A-B Classic of Acupuncture and Moxibustion that improper acupuncture at the LU 2 acupoint will lead to pneumothorax, which is why this is seldom used clinically, except in the treatment of cough. To ensure the patient's physical safety, the operation at the LU 2 acupoint was performed under computed tomography (CT) guidance, as shown in Figure . (2) Acupuncture operation: First, the skin over the LU 2 acupoint was disinfected with disposable 75% alcohol swabs. With the patient lying down as previously mentioned, a sterile needle (Huatuo, Medical Supplies Factory Co., Ltd., Suzhou, China; sterile needle length, 40 mm; diameter, 0.30 mm) was inserted into the acupoint at an approximate depth of 1 cun (1 cun = 25 mm). Then, the inserted needle was gently lifted to the subcutaneous tissue, turned back vertically as above, and finally rotated in a small range of the acupoint. The 2 operations were repeated alternately for 1 min until the patient experienced a special feeling, such as local acid swelling, ant bite pain, and other special feelings. After stimulation, the needle remained in the acupoint for 20 min before being pulled out.
After the LU 2 acupoint operation, the patient was instructed to lie in the right lateral decubitus position and was treated with the neck-seven-acupoint, including Fengfu (GV 16), Fengchi (GB 20), Tianzhu (BL 10), and Wangu (GB 12). Apart from the GV 16 acupoint, the other 6 acupoints were bilaterally symmetric. Similar to the LU 2 acupoint stimulation in which the needling sensation of the neck-seven-acupoint was elicited, these needles were also retained for 20 minutes, with manipulation once every 10 minutes, before removal. The specific depth and direction of the acupoints are shown in Figure .
After all the needles were pulled out at the end of the first treatment session, the patient described alleviation of numbness and a feeling of relaxation of her left arm and shoulder, although coldness was still not completely relieved. The patient was advised to undergo treatment on alternate days and 5 times during the course of treatment. On July 15, 2020, the patient received a fifth acupuncture treatment. Evaluation of treatment results showed that pain and discomfort of the neck and shoulder were relieved, although numbness and coldness of the upper limb skin persisted, but to some extent, symptomatic relief. She was assessed for her CSR-20-points score, which ranged from 10 to 16 after her fifth treatment session. Following this remedy pattern, the patient underwent 5 more treatment sessions; the last treatment session was on July 25, 2020. At the end of the treatment, the patient no longer experienced weakness, coldness, or numbness in the left upper limb. In addition, the stiffness in the neck and shoulders was reduced. On physical examination, the patient's left brachial plexus traction test was negative, reassessment of the CSR-20-point score scale showed a perfect score, and the VAS score was 0. No recurrences occurred during follow-up in the next 2 months. Written informed consent was obtained from the patient for publication of this case report and accompanying images, and all procedures involving the patient were conducted in accordance with the ethical standards of the Ethics Committee of the Second Affiliated Hospital of Shandong University of Chinese Medicine.


We report the case of a 70-year-old woman who was brought at the emergency service for evaluation of a sudden epigastric pain and nausea. She denied any history of trauma or heavy lifting. Her past medical history included total hip replacement, caesarean section, and a femoropopliteal artery bypass. She had no previous abdominal surgery history. She smoked for over 55 pack years.
Clinical examination revealed an important unreductible epigastric swelling. Biologically, haemoglobin was normal (Hb 13.3 g/dL), WBC count reached 20800/mm3 with presence of a discrete inflammatory syndrome (CRP 47 mg/L), and hepatic cytolysis ranged twenty times the normal values (GOT 796 U/L, GPT 895 U/L, and LDH 671 U/L).
An abdominal CT scanner showed huge epigastric hernia containing the left liver lobe associated with small amount of ascites within the hernia sac (Figures and ). A supra-umbilical laparotomy was performed for ventral hernia reparation. An important hernia sac was dissected and opened revealing epiploic and liver content. The exploration found a liver segment III that did not recover totally after liberation, and therefore, liver resection was performed (). DynaMesh IPOM® hernia cure was performed in the retromuscular position. Liver anatomopathological analysis has shown subcapsular hemorrhagic suffusions associated with inflammatory remodeling and microabscesses ().
Postoperative course was marked by an important ileus requiring a nasogastric tube for five days.


A 27-year-old, multiparous, female, poor patient with a history of umbilical herniorrhaphy eight years ago, and otherwise healthy, presented to our emergency department with acute onset abdominal pain, nausea, vomiting, constipation, on and off fever, and urinary retention from last three days. The pain was relieving with analgesics but exaggerated with physical activity. She said, she experienced the same episode of pain two years ago but was diagnosed as gastritis on endoscopy, for which she was treated. The sonologist at that time suggested her to seek a surgeon's opinion, but she ignored it. She had no previous records with her at the time of admission. Drug and family history was unremarkable.
The vital signs were BP 110/70 mmHg, RR 22/m, PR 70 b/m, Temp 37.5 °C, and SpO2 97%. On physical examination, the abdomen was mildly distended with a midline surgical scar and hypoactive bowel sounds on auscultation. A mobile palpable mass with a smooth surface in the right lower abdomen extending into the pelvis was observed, which was painful on movement. No signs of peritonitis were observed. Blood investigation results were TLC 11,000/mm3 (normal 4000–11,000), neutrophil 83% (normal 40–75), Hb 12.8 g/dl (normal 11.5–16.5), INR 1.18, blood group A + , anti HCV Ab + , HbsAg, and HIV were negative.
Ultrasound result was not diagnostically significant, so an abdominal CT scan with and without contrast was advised, which showed an empty splenic fossa and mildly enlarged ectopic spleen measuring 15.5 cm in length, present in the right lower abdomen extending into pelvis resting on the bladder fundus. No enhancement of the spleen was noted after iv contrast. The bright capsule of the spleen was observed, indicating collateral flow (rim sign). Regional ileus of the small and large bowel was also seen, as shown in Fig. . A whirl sign indicating torsion of the pedicle of the spleen was observed on the axial section, as shown in Fig. . Other advanced technologies for investigations such as scintigraphy and splenic angiography were not available, and the patient could not afford them as well.
Laparoscopic surgery was not feasible because of lack of technology and expertise, so laparotomy was performed, and mildly enlarged congested and ischemic spleen with 1800 twisted pedicle was found, as shown in Figs. and . After detorsion of the spleen and waiting for some time, no colour change was observed. The spleen was not viable, and a splenectomy was performed, which showed thrombosed splenic vessels, as shown in Fig. .
The patient recovered well without any complication and was discharged on 3rd post-operative day. She was followed up for a month without any complaints.


A 13-year-old male presented to a rural ED with a five-day history of progressively worsening shortness of breath and a three-day history of left-sided chest wall pain and swelling. He had been sick, with, what seemed to be a cold, for the seven days prior. He reported subjective fever, nausea, and multiple episodes of vomiting. His review of systems was also positive for orthopnea, diaphoresis, and adenopathy. In the ED, he was afebrile, ill-appearing, in respiratory distress with dyspnea and accessory muscle use. He had muffled heart sounds with visible left-sided chest wall swelling. He was tachycardic and tachypneic, with stable blood pressure (BP) and oxygen saturation; his vital signs were: BP 123/89 mmHg, pulse: 126 beats/minute, temperature: 97.9°F, respiratory rate: 28 breaths/minute, and pulse oximetry of SpO2: 95%. There was complete opacification of the left hemithorax with a significant shift of the mediastinum, and tracheal deviation, to the right on chest x-ray (Figure ).
The right lung showed lung markings without increased vascular congestion or acute infiltrate. These findings could be indicative of atelectasis, pleural effusion, or a large pulmonary mass. Transfer to a higher-level pediatric hospital with more resources available was arranged as POCUS was done concurrently. His neck did not exhibit any compressive masses or jugular venous distention; however, POCUS of the chest revealed a large pleural effusion and small pericardial effusion, with a possible underlying mass, and hyperdynamic heart with tamponade (Figures , ).
Complete blood count (CBC) revealed leukocytosis (11.7, normal 3.8-10.4 thou/cmm), thrombocytosis (604, normal 177-381 thou/cmm), mild polycythemia (5.47, normal 4.20-5.30 mill/cmm), and elevated RDW (15.6, normal 11.4-13.5%). Differential revealed elevated absolute neutrophils (9.1, normal 1.7-7.0), absolute monocytes (0.9, normal 0.1-0.6), neutrophils (77, normal 38-64), and monocytes (7, normal 3-5), as well as decreased lymphocytes (14, normal 26-43). Lactate dehydrogenase was elevated (290, normal 87-241 U/L).
In preparation for transfer and discussion with the receiving pediatric intensive care unit (PICU) team, it was decided to defer chest tube placement in the ED (unless tension physiology developed) because they were better equipped to manage complications and the possibility of biopsy was being entertained.
The patient was supported with 2 L O2 via nasal cannula and IV fluids and then transferred to the PICU at a tertiary center for further management. Chest tube placement by pediatric surgery at the receiving hospital provided a marked improvement in hemodynamics and respiratory status, with 2500cc of fluid initially evacuated. A repeat chest x-ray suggested a left mediastinal mass (Figure ). This was confirmed with contrast-enhanced CT adhering to as low as reasonably achievable (ALARA) dosing principles at the tertiary hospital (Figure ). T-cell lymphoblastic lymphoma was diagnosed via biopsy taken during chest tube placement, and the patient was started on chemotherapy.


A Five-day-old female infant, born to a 23-year G2P1L1 mother by spontaneous vaginal delivery at 39+2 period of gestation was brought to the emergency department with a complaint of multiple episodes of bilious vomiting along with abdominal distension and unable to pass stool since birth. There was no history of fever, lethargy, inconsolable cry, and irritability. The female had no history of spontaneous abortion and her first child is healthy and normal.
On examination, the child was conscious and ill-looking with a small head but prominent occiput, low set abnormal ears, small jaw, upturned nose, widely spaced eyes, small neck with widely spaced nipples, clenched hands with overlapping fingers, flexed big toe, and prominent heels; features suggestive of Edward's syndrome (). She was afebrile but tachycardic (heart rate: 160/min) and tachypneic (respiratory rate-70/min) and other vitals were stable. The abdomen was distended, tense with dilated veins, everted umbilicus, and absent bowel sound. The orogastric tube was thus placed for decompression.
All the hematological parameters were within normal limits. X-ray abdomen supine view revealed marked dilatation of large bowel with no gas in the rectum (). USG abdomen and pelvis revealed a gaseous abdomen with minimal interloop ascites. There was no passage of stool even after the rectal wash. Considering the possibility of intestinal obstruction, an exploratory laparotomy was done which revealed multiple bands of approximately 3 cm and 10 cm distal to an ileocolic junction along with malrotation of the gut. Bands were released and the malrotation was corrected. Furthermore, Biopsies were taken from splenic flexure and descending colon which showed the absence of ganglion cells suggestive of HD (). With typical clinical features of ES and the absence of ganglionic cells, a diagnosis of Hirschsprung disease with ES was made. The baby underwent colostomy and her first stage of the Soave procedure for the management of HS is planned at 6 months of age. All the procedures were performed by the experienced team of gastrointestinal surgeons of Tribhuvan University Teaching Hospital and were well tolerated by the patient. Parents were counseled regarding the disease diagnosis and expected long-term outcomes, quality of life, and the prospects of poor prognosis even with the multiple surgical interventions. The patient is under regular follow-up.


A 2-year-old boy was evaluated for dysmorphic features, history of early-onset recurrent seizures, and brain malformations. He was the first-born from a dichorionic diamniotic twin pregnancy, conceived by intracytoplasmic sperm injection (ICSI) and complicated by intrauterine growth retardation (IUGR) in the third trimester. The baby was delivered at 37 + 1 weeks of gestation by caesarean section. His parents were nonconsanguineous. The twin sister was healthy. Family history revealed a maternal second-degree cousin with epilepsy but was otherwise unremarkable. Birth weight was 1710 g (− 2.8 SD), length 43 cm (− 2.4 SD) and occipitofrontal circumference (OFC) 31.5 cm (− 1.6 SD). Physical examination showed diffuse hypotonia, partially improving during the perinatal period. Dysmorphic features included frontal bossing, highly arched eyebrows, bilateral ptosis combined with blepharophimosis, epicanthus, down-slanting palpebral fissures, micrognathia with tent-shaped mouth and thin upper lip, and low-set posteriorly rotated ears. Brain ultrasonography was normal. At 6 months, global developmental delay was noticed, with persistent head lag and hypotonia with severe thoracolumbar scoliosis (Fig. d). From age 7 months, the boy experienced two isolated tonic-clonic seizures. Interictal EEG revealed high voltage spikes and waves complexes over the mid-temporal regions, with increased activity during sleep. Brain MRI showed lack of periventricular white matter bulk with mild enlargement of lateral ventricles and subarachnoid spaces. Furthermore, anterior pituitary hypoplasia and dysmorphic brainstem with midbrain hypoplasia were identified (Fig. e-h). aCGH revealed a heterozygous 4.8 Mb deletion extending from 15q25.3 to 15q26.1. This rearrangement spanned 83 genes, including 39 OMIM genes (ABHD2, ACAN, AEN, ANPEP, AP3S2, BLM, C15orf38, CHD2, CIB1, CRTC3, DET1, FANCI, FES, FURIN, IDH2, IQGAP1, ISG20, KIF7, MAN2A2, MESP1, MESP2, MFGE8, MRPL46, MRPS11, NGRN, PEX11A, PLIN1, POLG, PRC1, RGMA, RHCG, RLBP1, SEMA4B, SLCO3A1, ST8SIA2, SV2B, TICRR, UNC45A, VPS33B). At age 24 months, during or immediately after eating, the patient suffered from recurrent seizures characterized by staring and upward eye deviation and eyelid myoclonus. The seizures were very short (2–3 s) but occurred in cluster lasting 2–3 min. Ictal EEG revealed a brief discharge of high-voltage spikes and sharp waves mainly evident on mid-temporal areas bilaterally (Fig. d). Therapy with sodium valproate (300 mg daily) and topiramate (75 mg daily) did not allow complete seizures control. Furthermore, topiramate was discontinued due to hyporexia and levetiracetam (700 mg daily) was started, with partial seizures control.


In November 2007, a 66-year-old man underwent excision of cutaneous melanoma on the first toe of his right foot (Breslow thickness >4 mm, ulcerated, Clark level V) with positive inguinal sentinel node and left femoral–iliac lymphadenectomy negative for metastatic lymph nodes (stage IIIA, AJCC 7th edition). Due to the occurrence of metastatic disease on the right maxillary sinus, from October 2008 to January 2009, he received first-line chemotherapy with cisplatin, vinblastine and dacarbazine (CVD regimen) and radiotherapy (total dose administered was 30 Gy in 7 fractions), with a good local control of disease. In May 2009 and August 2012, the patient underwent surgical resection of isolated subcutaneous metastases on the back and axillary region, respectively. From July to September 2014, due to the spread of subcutaneous metastases to the upper and lower limbs, the patient was treated with ipilimumab; he obtained a stable disease as best response. This response was maintained until July 2015 when a subcutaneous, soft tissue, bone and pulmonary progression of disease occurred. In August 2015, due to the presence of BRAF mutation, treatment with the BRAFi dabrafenib (150 mg twice daily) and the MEKi trametinib (2 mg once daily) was started. Treatment was well tolerated except for recurrent episodes of grade 2 hyperpyrexia (with body temperature as high as 40.0°C) not resolved by temporary dabrafenib ± trametinib discontinuation and finally leading to progressive dose reductions (lower dose schedule: dabrafenib 50 mg twice daily and trametinib 1 mg once daily). At the first radiological examination with 18F-FDG-PET, a partial response in the lungs, soft tissues and right maxillary sinus was documented with stable disease in the bone. The response lasted 19 months until March 2017, when the treatment was discontinued due to progression of the right maxillary sinus lesion and of subcutaneous lower limb metastases. From March to July 2017, the patient received six infusions of the anti-PD-1 antibody (pembrolizumab), followed by systemic progression of disease on all metastatic sites and the appearance of a single brain lesion, for which he received stereotactic radiation. Between September and November 2017, the patient was treated with a single agent, dacarbazine, with progression of disease on the right maxillary sinus and with the appearance of a new brain lesion in the temporal lobe. As further new treatment options were not available, and clinical conditions were good (ECOG PS 0–1), in December 2017, the patient resumed treatment with dabrafenib and trametinib and received stereotactic radiation in a single fraction on the new brain lesion. LDH value at the time of the start of treatment was high [>1 to <2 × upper normal limit (UNL)]. Due to previous severe dose-limiting hyperpyrexia in concomitance with the same agents, the dose of dabrafenib was ab initio reduced to 75 mg twice daily while maintaining the full dose of trametinib (2 mg once daily). The first radiological evaluation with computed tomography (CT) scan in May 2018 showed a partial response in the brain, lungs and right maxillary sinus lesions and a stable disease for bone metastases. In September 2020, due to ulceration of the maxillary lesion suggestive of local progression of disease, we decided to treat the patient locally with electrochemotherapy for cytoreductive purposes and local control. After 34 months of rechallenge, at the time of this report, treatment with dabrafenib and trametinib was being continued: at the last radiological evaluation with a CT scan in November 2020, partial response in all disease sites, including the maxillary lesion was maintained. Treatment was tolerated; some episodes of pyrexia were controlled by temporary discontinuation of the BRAFi alone and without a further dose-reduction of both dabrafenib and trametinib as for previous treatment with the same agents.


In November 2008, a 35-year-old man was diagnosed with melanoma on the left cervical region (Breslow thickness 1.2 mm, not ulcerated, negative neck sentinel node; pT2a, positive for the BRAF V600E mutation). The published data on rechallenge of targeted therapy are summarized in . In December 2014, the patient underwent left cervical lymphadenectomy with 1/19 metastatic lymph nodes (stage IIIA, AJCC 7th edition) for cytologically confirmed neck lymph node metastases. From January to September 2016, due to clinical and radiological evidence of new multiple cutaneous metastasis, the patient (at that time ECOG PS 0) was treated with the BRAFi dabrafenib (150 mg twice daily) and MEKi trametinib (2 mg once daily), obtaining stable disease/minor response as best response. The treatment was well tolerated without dose reductions and only grade 1 dermatological toxicity and grade 1 pyrexia treated with temporary dabrafenib interruption as per the toxicity algorithm. Despite clinical control of known cutaneous metastases, in September 2016, multiple secondary brain lesions were detected by CT scan. In the absence of central neurological symptoms, the patient was treated with nivolumab until July 2017 when the MRI and CT scan showed a progression of brain lesions, subcutaneous metastases were controlled. The patient underwent whole-brain radiotherapy (total dose 30 Gy in 10 fractions) and continued nivolumab until January 2018 when the therapy was interrupted due to a further progression of disease in the brain, cutaneous, subcutaneous, soft tissue (on the right pre-hyoid region) and laryngeal as confirmed by 18F-FDG-PET/CT in January 2018. LDH value was >1 to <2 UNL. In our opinion, the fast-aggressive disease was not amenable for crossover to ipilimumab. Hence, in February 2018, clinical condition was good (ECOG PS 1), we decided to offer the patient a rechallenge with full-dose dabrafenib and trametinib. The first radiological control showed stable disease on brain lesions (as documented by MRI at 4 months since the beginning of treatment) and a metabolic complete response on all other sites of disease, as shown by 18F-FDG-PET/CT in June 2018, with clinical improvement of dysphonia. Clinical evaluation showed a partial response of cutaneous metastases. Tolerability to rechallenge was good without the appearance of pyrexia and only grade 1 erythema at the site of a tattoo. In October 2018, further progression of disease in the brain occurred, and a second course of palliative brain radiotherapy (total dose 20 Gy) was administered. In January 2019, the patient died due to the progression of metastatic lesions in the brain.


In January 2011, a 57-year-old man went through radical excision of a lesion in the scalp and left cervical lymphadenectomy for palpable nodes with a final diagnosis of superficial spreading melanoma (Breslow thickness 0.8 mm, not ulcerated, Clark level IV) with 7/38 metastatic lymph nodes, stage pT1 pN3 M0, IIIC as per AJCC 7°edition. In November 2011, a 18F-FDG-PET/CT showed multiple nodal and soft tissue lesions and the BRAF mutation test revealed the presence of BRAF V600 mutation. For this reason, from January 2012 to January 2020, the patient was treated with vemurafenib (960 mg twice daily) in the MO25515 trial with a complete response. In January 2020, the CT scan showed a massive progression of disease with the occurrence of brain, lung, liver and soft tissue metastases and concomitant high LDH values. Therefore, we decided to treat the single temporal metastases with stereotactic radiotherapy, and, in March 2020, the patient started immunotherapy with nivolumab. In May 2020, a progression of disease in the lungs, soft tissue and liver was documented with hepatic failure and obstructive jaundice (bilirubin 8 mg/dl) with dilatation of biliary system. The LDH value was superior to two-times UNL (2028 U/L). After biliary stent placement and subsequent normalization of liver function analyses, taking into account the prior very long-term response (8 years) to BRAFi monotherapy and the poor therapeutic options in this patient with rapid clinical progression disease but still acceptable ECOG PS 1, we decided for a rechallenge with BRAFi and MEKi (dabrafenib and trametinib). The patient received the treatment only for 1 month with good tolerability, which was a short-lived clinical benefit and an initial reduction of LDH values but, unfortunately, the patient died in July 2020 for rapid progression of disease.


In June 2012, a 46-year-old man underwent primary excision of melanoma on the back (Breslow thickness >4 mm, ulcerated) and right axillary lymphadenectomy with 14/14 positive metastatic lymph nodes (stage IIIC, AJCC 7th edition). In January 2013, for cytologically confirmed lymph node relapse of disease, the patient went through a left maxillectomy and right laterocervical lymphadenectomy with 4/34 positive lymph nodes for metastatic disease (BRAF V600E mutation positive). In June 2013, due to local recurrent disease on the left maxillary sinus and the appearance of new lung metastasis, the patient, who was in good clinical condition (ECOG PS 0), was enrolled in the coBRIM clinical trial, receiving the BRAFi vemurafenib (960 mg twice daily) until July 2014; he obtained partial response as best response. From August to November 2014, after the evidence of progression of disease in the lungs, the patient received immunotherapy with four cycles of ipilimumab, obtaining a partial response that lasted until July 2015 when a CT scan showed a further progression of disease in the lungs. For this reason, the patient was enrolled in the CheckMate 067 randomized clinical trial and received nivolumab as single agent with a complete response on lung metastases until December 2016, when the treatment was discontinued due to the appearance of isolated small intestine metastases. Therefore, the patient underwent bowel resection (large and small intestine) with histological confirmation of melanoma metastases. The clinical–radiological follow-up was negative until November 2018, when a new pathological abdominal lymphadenopathy (paraaortic, retroduodenal, external iliac) appeared and retreatment with nivolumab was offered to the patient. Anti-PD-1 antibody was administered until April 2020 when a new isolated rectus abdominis muscle lesion was documented on 18F-FDG-PET/CT. Hence, the rectus abdominis and left oblique muscle lesions were surgically removed with a histological result compatible with melanoma metastasis. In August 2020, due to radiological evidence of abdominal soft tissue and nodal progression of disease and considering the good clinical condition (ECOG PS 1), the patient started targeted therapy rechallenge with dabrafenib and trametinib. LDH values at that time, were within normal limit. At the beginning of therapy, some occasional episodes of nausea and vomiting (G2) treated with metoclopramide were reported, with good symptom control. At the first clinical re-evaluation after 4 weeks of treatment, the patient showed a clinical response with reduction in size of inguinal lymphadenopathy. In December 2020, the first radiological revaluation with CT scan documented stable disease. The treatment is still ongoing and well tolerated.


A 74-year-old man with no previous medical history visited our hospital with complaints of fever and sore throat. A polymerase chain reaction (PCR) test confirmed that he had COVID-19, and he was hospitalized in a negative pressure isolation ward. He had difficulty breathing, which gradually worsened. Ten days after admission, he was intubated and mechanical ventilation began. Diffuse viral pneumonia was identified on chest radiography and computed tomography (Fig. ). After a month of mechanical ventilation, he was weaned off of the ventilator. However, critical illness and prolonged treatment in the ICU resulted in severe muscle wasting and deterioration of physical function.
For a comprehensive rehabilitation treatment, he was referred to the Department of Rehabilitation Medicine. During the initial assessment, he needed moderate support for static sitting balance and scored 0 on the Berg Balance Scale and 8 on the Modified Barthel Index. The strength of both the upper and lower limbs was grade 3 following the Medical Research Council (MRC) grade. He was clinically diagnosed as ICU-acquired weakness because the MRC sum sore consisting of both wrist extension, elbow flexion, shoulder abduction, ankle dorsiflexion, knee extension, and hip flexion was 36 points, which was less than 48 points suggested by the guideline.[ Various types of rehabilitation exercises were carried out in a step-by-step manner according to the patient's function (Fig. ). The bed manual joint range of motion (ROM) exercise (step 1) and position change were performed six times daily for 10 minutes by a healthcare provider authorized to enter the quarantine ward while wearing Level D protective equipment. After two consecutive follow-up PCR tests were negative for COVID-19, the patient was transferred to the general ward. There, rehabilitation therapy was performed by a physical therapist and an occupational therapist. In addition to the ROM exercises previously performed, sitting balance training (step 2), upper and lower extremity strength exercises, and pulmonary rehabilitation were done. The pulmonary rehabilitation included inspiratory muscle strength training using an incentive spirometer, air stacking exercise, and airway secretion removal using a cough induction machine. The exercises were performed daily for 30 minutes on a one-to-one basis by the patient with the therapist in the hospital room. The therapist wore a working gown, disposable cap, latex gloves, and N95 mask as protective equipment, while the patient wore a mask. During the videofluoroscopic swallow study (VFSS) test for evaluation of dysphagia, aspiration was observed with both thick and thin fluids. Feeding through the Levin tube was continued, and the rehabilitative dysphagia treatment including chin tuck against resistance, thermotactile stimulation and electirical stimulation therapy was performed for 30 minutes daily.
Two weeks later, he was able to maintain sitting balance with supervision and static standing balance with moderate support. From this point on, the rehabilitation treatment consisted of standing balance training (step 3) and sit-to-stand training (step 4).
After a total of 4 weeks of treatment, the patient was transfered to the local hospital specialized in rehabilitation and continuously performed in the rehabilitation. In the evaluations just before transfer, the patient's Berg Balance Scale improved to 4 and Modified Barthel Index to 18. The MRC grade of both the upper and lower limbs improved to 3 plus. During the follow-up VFSS test, aspiration was observed only with thin fluid, and only penetration was observed with thick fluid, semisolid, and solid diets. Oral feeding was started with a soft diet and food thickener. During the pulmonary function test (PFT), forced vital capacity (FVC) was 1.19 L (31% of the predicted value), forced expiratory volume in 1 second as 1.14 L (31% of the predicted value), forced expiratory volume in one second 1/FVC was 96% and peak expiratory flow was 4.24 L/sec. The PFT test suggested a moderate restrictive lung defect based on the FVC. The PFT could not be performed at the time of initial evaluation due to the poor general condition of the patient and his inability to abey commands.


A 19-year-old Comorian man was referred to the Thoracic Surgery
Unity at the Joseph Ravoahangy Andrianavalona Hospital after
complaining of chest pain at the MSJ that was exacerbated by slight
movements. The man had fallen from a mango tree and had his neck
flexed a week prior. There was no history of loss of consciousness at
the time of injury. The airway, breathing and circulation were intact.
During physical examination, he was conscious with stable vital signs.
A careful palpation revealed a ‘stair step’-looking deformity located
at the anterior chest wall at the level of the MSJ. The examination
of the cardiovascular system and electrocardiography were normal.
The cardiac contusion markers revealed no pathology. The frontal
chest X-ray (CXR) and cervical spine were normal. Standard CXR
and computed tomography (CT) scans confirmed the diagnosis
of manubriosternal disruption . It was decided to fix the
sternal dislocation under general anaesthesia with single lumen
intubation in a supine position . He made an uneventful
recovery. The recovery process involved the removal of the drainage
tube, enhancing the mobilisation of the patient and discharge after
complete wound healing. To ensure a correct surgical reduction, a
CXR was carried out in two planes immediately post operation. The
patient was discharged home on day 2 post operation and returned
to his work as physiotherapist after 3 weeks. No. complications were
observed at 4 weeks and 6 months of follow-up care .


A 32-year-old Caucasian student male was admitted to our intensive care unit (ICU) for right total hemiplegia and aphasia evolving for 4 hours associated with chest discomfort.
His past medical history revealed no cardiovascular risk factors or symptoms. He was occasional cannabis smoker and reported daily consumption in the last 5 days.
An initial exam showed stable hemodynamic parameters, the patient was conscious and executed orders successfully with his left extremities, but he had an incomprehensive verbal response. An electrocardiogram showed ST-segment elevation in the anterior leads, compatible with an ST-elevation myocardial infarction (STEMI).
Emergent contrast-enhanced computed tomography (CT) scan showed spontaneous hyper-density regarding the left frontal cortex, a sub-cortical left frontal, and multiple supratentorial regions of hypodensity in a vascular distribution occurred in the white matter- grey-matter. (
) In the cervicothoracic section, it showed thrombosed dissection of the left internal carotid artery, extending over 21 mm in height. (
)
The evolution was marked by spontaneous regression within 30 minutes of ST segment elevation and appearance of anterior negative T waves.
Echocardiography showed limited left ventricular anterior and apical wall motion abnormalities with conserved systolic ejection fraction (LVEF: 55%). The laboratory results were normal except for elevated cardiac enzymes.
Early cardiac catheterization showed an acute thrombotic dissection of the proximal left descending artery with TIMI III blood flow. (
) The circumflex artery and the right coronary artery were normal. We decided to respect the lesion, and to put him under double antiplatelet therapy (clopidogrel 75 mg per day, aspirin 160 mg per day), unfractionated heparin, nitrates, and bisoprolol.
A second cerebral CT scan followed 48 hours later and showed favourable evolution of the cerebral lesions, so we decided to continue conservative treatment with close follow up. In-hospital outcome was favourable, with regression of aphasia and hemiplegia starting from the fifth day of the hospitalization. He was discharged after 15 days on clopidogrel 75 mg per day, aspirin 160 mg per day, atorvastatin 40 mg per day, and bisoprolol 2.5 mg per day.
At 3-month clinical control check-up, he retained right lower limb motor sequelae. Cardiac control showed the absence of symptoms, with a good electrocardiographic and echocardiographic evolution (LVEF: 60–65%).


A 52-year-old male, with no comorbidities, presented to the emergency department with a 10-day history of fever and dry cough followed by progressive exertional shortness of breath. The patient is a non-smoker and worked as a driver. Examination showed a febrile, ill-looking patient, in respiratory distress, with a respiratory rate of 36 breaths per minute and requiring 6 L/min of Oxygen via a nasal cannula. Chest auscultation was significant for bilateral crackles, without evidence of raised jugular venous pressure (JVP) or lower limb edema. Other examination findings were within normal parameters. The initial investigation was significant for white blood cell (WBC) - 17 x10^3/uL, C-reactive protein (CRP) - 131 mg/L, ferritin - 836 ug/L, and bilateral pulmonary infiltrates in chest X-ray (CXR). (Figure ). COVID-19 rRt-PCR tested positive; hence was diagnosed with severe COVID‑19 pneumonia and was started on treatment according to the COVID-19 management protocol.
Over the subsequent five days, his oxygen requirements gradually increased, reaching 11 L/min via a non-rebreather mask. A follow-up chest x-ray showed progression of previously seen bilateral infiltrates (Figure ).
He was started on methylprednisolone and non-invasive ventilation. Two weeks into admission, his condition continued to deteriorate and endotracheal intubation with mechanical ventilation was required. Two weeks later, the patient started to have a high-grade fever, with further sepsis workup revealing Pseudomonas aeruginosa and Stenotrophomonas maltophilia in tracheal aspirate culture; hence started on piperacillin-tazobactam and teicoplanin. CT thorax was done and revealed bilateral diffuse ground-glass infiltrates and airspace involving almost all lung segments and minimal left-sided pleural effusion (Figure ).
Over the next few days, the patient was afebrile, however, repeat tracheal aspirate culture was persistently positive for Pseudomonas and Stenotrophomonas maltophilia. Five days later, the patient was extubated but re-intubated again due to respiratory distress and hypoxemia. After multiple failed attempts to wean the patient off mechanical ventilation, the patient was tracheostomized and eventually de-cannulated. The patient was transferred to the medical ward after staying in the critical care unit for a total of 38 days. The patient was on room air when admitted to the medicine ward. However, a few days later, he started to desaturate gradually. Follow-up CXR showed diffuse coarse reticular interstitial changes. COVID-19 rRT-PCR was negative and sepsis workup was unrevealing. A follow-up CT chest showed a slight improvement of the diffuse bilateral ground-glass opacities with re-demonstration of some crazy-paving appearance at both apical segments of the upper lobes, and it also showed progression of the interstitial fibrotic and bronchiectatic changes predominantly in the anterior aspects of both lungs (Figure ).
The patient was referred to a long-term care hospital for oxygen supplementation, chest physiotherapy, and physical therapy for his critical care myopathy.