Fecal microbiota transplantation in the treatment of systemic lupus erythematosus: What we learnt from the explorative clinical trial.

Systemic lupus erythematosus (SLE) is an autoimmune disease with the characterized presence of autoantibodies and resulting in multiple organ damage, which is incurable and can be lethal. The current treatments are limited and less progress has been made in drug discovery for the last few decades. Researches imply that gut dysbiosis exists in both patients and murine models with SLE, taking part in the pathogenesis of SLE through multiple mechanisms such as microbiota translocation and molecular mimicry. Intestinal interventions on the gut microbiome by fecal transplantations to reconstitute the gut-immunity homeostasis serve as a novel therapeutic option for SLE patients. Fecal microbiota transplantation (FMT), which is usually used in intestinal diseases, has been firstly demonstrated to be safe and efficient in recovering gut microbiota structure of SLE patients and reducing lupus activity in our recent clinical trial, which is the first trial testing FMT therapy in SLE treatment. In this paper, we reviewed the results of the single-arm clinical trial and made recommendations on FMT practice in SLE treatment including therapeutic indications, screening items and dosage regimen, trying to provide references for future study and clinical practice. We also came up with the unanswered questions that need to be solved by the ongoing randomized controlled trial as well as the future expectations for the intestinal intervention strategies of SLE patients.

Physicochemical fingerprinting of thermal waters of Beira Interior region of Portugal.

Mineral natural waters and spas have been used for therapeutic purposes for centuries, with Portugal being a very rich country in thermal waters and spas that are mainly distributed by northern and central regions where Beira Interior region is located. The use of thermal waters for therapeutic purposes has always been aroused a continuous interest, being dependent on physicochemical fingerprinting of this type of waters the indication for a treatment in a specific pathological condition. In the present work, besides a literature review about the physicochemical composition of the thermal waters of the Beira Interior region and its therapeutic indications, it was carried out an exhaustive multivariate analysis-principal component analysis and cluster analysis-to assess the correlation between different physicochemical parameters and the therapeutic indications claims described for these spas and thermal waters. These statistical methods used for data analysis enables classification of thermal waters compositions into different groups, regarding to the different variable selected, making possible an interpretation of variables affecting water compositions. Actually, Monfortinho and Longroiva are clearly quite different of the others, and Cró and Fonte Santa de Almeida appear together in all analysis, suggesting a strong resemblance between these waters. Thereafter, the results obtained allow us to demonstrate the role of major components of the studied thermal waters on a particular therapeutic purpose/indication and hence based on compositional and physicochemical properties partially explain their therapeutic qualities and beneficial effects on human health. This classification agreed with the results obtained for the therapeutic indications approved by the Portuguese National Health Authority and proved to be a valuable tool for the regional typology of mineral medicinal waters, constituting an important guide of the therapeutic armamentarium for well and specific-oriented pathological disturbs.

Successful application of eculizumab in typical haemolytic uraemic syndrome.

A woman in her 40s with no medical history presented on hospital day #0 with 3 days of epigastric pain, nausea, vomiting and bloody diarrhoea. Initial blood work demonstrated acute kidney injury with metabolic acidosis with an elevated anion gap, thrombocytopenia, an elevated lactate dehydrogenase, and an undetectable haptoglobin. She was quickly diagnosed with haemolytic uraemic syndrome from Shiga toxin-producing O157:H7 Escherichia coli Her microangiopathic haemolytic anaemia and renal failure progressively worsened and only improved after the initiation of eculizumab, a monoclonal antibody directed against complement component C5. We report a case of Shiga toxin-producing E. coli-haemolytic uraemia syndrome with a complement-mediated component.

Afatinib treatment of severe respiratory failure due to malignant lymphangitis in a dialysis patient with squamous cell carcinoma of the lung.

Patients on dialysis have limited treatment options for advanced lung cancer because some chemotherapeutic agents are unavailable due to renal dysfunction. A man in his 70s on peritoneal dialysis presented with persistent fever refractory to antibiotics for 2 weeks. Subsequent whole-body CT showed a 5 cm diameter mass in the right lower lobe of the lung with right-sided pleural effusion and osteolytic metastasis of the right iliac bone. The patient was diagnosed with squamous cell carcinoma (cT3N2M1b, stage IVB) harbouring the p.Gly719Ala point mutation on exon 18 of the epidermal growth factor receptor. The patient developed severe respiratory failure due to malignant lymphangitis after a bronchoscopy. He received 30 mg/day of afatinib, resulting in tumour shrinkage and recovery from respiratory failure. We advocate for aggressive screening of driver oncogenes in patients with lung cancer on dialysis, including those with squamous cell lung cancer.

Case of metastatic clear cell odontogenic carcinoma with response to chemoimmunotherapy.

Our patient initially presented with 6 months of left jaw pain and gingival bleeding, leading to the discovery of a radiolucent left maxillary mass on dental evaluation. A biopsy confirmed clear cell odontogenic carcinoma, and the patient was treated with definitive surgery and radiation for localised disease. Unfortunately, the patient was found to have pulmonary metastases 3 months after initial management and was subsequently treated with a combination of cytotoxic chemotherapy and immunotherapy with a partial response. To our knowledge, this is the first case demonstrating the successful use of chemoimmunotherapy in metastatic clear cell odontogenic carcinoma.

Management of iatrogenic acute limb ischaemia in the neonate.

Iatrogenic acute limb ischaemia (ALI) in neonates is a rare but severe event with potentially deleterious outcomes. In the neonatal intensive care unit, this risk is increased due to the high rate of catheterisation procedures. ALI management includes pharmacological and non-pharmacological interventions, but no commonly accepted clinical guidelines are available. In the present case, a peripheral catheter was erroneously placed in the left brachial artery of a term infant, causing blockage and ischaemia in the limb. The catheter was immediately removed, the affected limb was elevated and warm compresses were applied to the contralateral limb. The patient was treated with fresh frozen plasma, heparin, iloprost and topical nitroglycerin. Three nerve block procedures were also performed. At 6-8 days of age, significant improvement was observed. The patient was discharged at 17 days of age with near-complete resolution, whereas complete resolution was observed at postdischarge follow-up.

Trend analysis of proton pump inhibitor consumption and expenditure: The real-world evidence.

INTRODUCTION: Proton pump inhibitors (PPIs) constitute a widely utilized pharmaceutical class, frequently associated with notable instances of therapeutic inappropriateness. Such patterns of misuse not only contribute to elevated healthcare expenditure, but may also exacerbate clinical conditions in certain patients. METHODS: A comprehensive analysis was conducted between 2019 and 2023 to assess all prescriptions dispensed using the Anatomical, Therapeutic and Chemical (ATC) classification system, which allowed trends among primary PPIs to be visualized. This was achieved by calculating the defined daily dose (DDD) and then defining the total expenditure incurred on these drugs. RESULTS: With regard to the prescription of PPIs, an upward trend in consumption was observed with a decreasing expenditure, due to the phenomena of drug generics and increased competition between pharmaceutical companies, ranging from €9,512,481.22 in the first six months of 2019 to €8,509,820.80 in the first six months of 2023. From 2019 to 2023, consumption increased by approximately 3 million DDDs for a total ranging from 18,483,167.59 DDDs to 21,480,871.00 DDDs. Pantoprazole and esomeprazole, the most expensive drugs compared to omeprazole, rabeprazole and lansoprazole, accounted for 61.4% of therapies in the first six months of 2023, up from 2019, where these two drugs were prescribed 54.9%. CONCLUSION: Within this analysis, we provide an illustrative representation of the prescribing trends for PPIs within a European context. Omeprazole, rabeprazole and lansoprazole appear to be the cheapest drugs compared to pantoprazole and esomeprazole. However, the results show that the most widely used PPIs, despite their therapeutic equivalence, are precisely the high-cost ones, thus generating higher expenditure for central governments.

Metastatic HER2-amplified non-small-cell lung cancer treated with trastuzumab deruxtecan.

Human epidermal growth factor receptor 2 (HER2) alterations can occur as gene mutations, gene amplification or protein overexpression. DESTINY-Lung01 and DESTINY-Lung02 demonstrated the efficacy of trastuzumab deruxtecan in the subsequent line setting in patients with unresectable or metastatic HER2-mutated non-small-cell lung cancer (NSCLC). Trastuzumab deruxtecan has not been studied in select patients with HER2-amplified NSCLC. Here, we present the first reported case of metastatic HER2-amplified NSCLC treated with trastuzumab deruxtecan with a durable response to therapy.

Rare presentation of thrombosis with bleeding in Behcet's disease.

Behcet's disease (BD) is a rare autoimmune and autoinflammatory disease characterised by recurrent oral and genital aphthous ulcers as well as gastrointestinal, ocular, neurological, articular and vascular inflammation. Patients are at risk for both thrombotic events and bleeding, so providers are often challenged in deciding whether to start patients on anticoagulation. We report a rare, complex case of a patient with BD who presented with massive gastrointestinal bleeding. This case report highlights the management of recurrent thrombosis due to protein C and S deficiency in a patient with BD who also presents with acute gastrointestinal bleeding.

Complete resolution of primary myelofibrosis in an infant with steroids and hydroxyurea.

Paediatric primary myelofibrosis (PMF) is exceedingly rare and distinct compared with adult PMF. It is characterised by peripheral blood cytopenias, leucoerythroblastosis, reticulin fibrosis, extramedullary haematopoiesis and hepatosplenomegaly. In the absence of laid down diagnostic criteria, the diagnosis is largely of exclusion. Though early haematological stem cell transplant (HSCT) remains the treatment of choice, spontaneous remission or remission with steroids and/or cytoreductive agents is described in around 20% of cases of paediatric PMF. Moreover, HSCT in paediatric PMF is associated with high mortality (30%-45%). Therefore, it may be prudent to consider a trial of steroids and/or cytoreductive agents in all transfusion-dependent paediatric PMF while considering HSCT and ongoing bone marrow donor search. We describe one such infant with PMF who had complete remission of clinical and haematological parameters with a combination therapy of steroids and hydroxyurea.

Recalcitrant digital calcinosis cutis successfully treated with intralesional sodium thiosulfate under digital nerve blockade.

Dystrophic calcinosis cutis can be associated with severe pain, decreased mobility, increased risk of infection and significantly decreased quality of life. We report a case of recalcitrant calcinosis cutis on the background of eosinophilic fasciitis, which achieved rapid reduction in calcium deposits following a novel injecting protocol of intralesional sodium thiosulfate.

Role of ado-trastuzumab emtansine (T-DM1) in HER2 positive salivary gland tumour with brain metastasis.

Malignant neoplasms of salivary gland neoplasms are rare and often involve the parotid gland. The primary treatment of these malignancies is surgery with or without adjuvant therapy. Chemotherapy or systemic therapy is indicated in recurrent or metastatic disease where surgery or radiotherapy is not possible. Salivary gland carcinomas, which are human epidermal growth factor receptor 2 (HER2) positive, show an aggressive behaviour with a poor prognosis. Targeting the HER2 pathway with drugs designed to block this pathway is an interesting novel therapy to treat salivary gland carcinomas. We report a case of a patient with HER 2-overexpressing parotid gland adenocarcinoma with brain metastasis, who was managed with ado-trastuzumab emtansine (T-DM1): a monoclonal antibody-cytotoxic drug conjugate that combines trastuzumab with the microtubule inhibitor, emtansine. The patient showed excellent response to the therapy. This case highlights the role of systemic chemotherapy with T-DM1 in HER2 positive salivary gland tumours that could be considered a part of the treatment regimen.

Anti-NMDA receptor encephalitis with initial negative markers: diagnostic and therapeutic challenges of a refractory case with 9-month-long follow-up.

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a progressively debilitating, frequently fatal disease caused by autoantibodies against the NMDA receptor. Risk of delayed treatment is high due to variable presentations, lack of awareness and potential false negative diagnostic studies. In this case report, a woman in her 20s presented with psychiatric manifestations and rapidly declined. Dyskinetic movements and dysautonomia were observed. Initial cerebrospinal fluid and serum anti-NMDA receptor antibodies were negative. MRI was inconclusive. Electroencephalography demonstrated extreme delta brush. Pelvic CT revealed an adnexal teratoma. She remained refractory to treatment until day 126 when, after two cycles of cyclophosphamide, she started to improve. She participated in rehabilitation with eventual discharge home on day 269. Recognising the variable presentations of anti-NMDA receptor encephalitis is important in avoiding misdiagnosis and delayed treatment. If clinical suspicion remains high despite negative results, repeat testing should be pursued. Clinical response should guide treatment decisions in refractory cases.

Refractory paraneoplastic hypercalcaemia responding to cinacalcet.

A woman in her late 70s presented with an increased frequency of micturition, suprapubic pain and weight loss. She was found to be having advanced cancer of the urinary bladder, coupled with bilateral hydronephrosis.Whilst undergoing surgical intervention for the latter, she was incidentally found to be having hypercalcaemia. This was found to be paraneoplastic in nature, possibly due to elevated parathyroid hormone related peptide with no evidence of bone metastasis. The histology of the resected tumour revealed squamous and sarcomatoid differentiation. Her hypercalcaemia initially responded to intravenous fluids, and later on zolendronate,but the problem recurred again, with the response to a repeat dose of zolendronate and even denosumab being unsatisfactory. As a last resort cinacalcet was started, and although there was a good response to it, our patient sadly died a few weeks later.We believe our case to be the first case of hypercalcaemia associated with isolated bladder cancer which showed a successful response to cinacalcet.

Immunotherapy in stage IV non-small cell lung cancer in a patient with Grave's disease: safety and biomarkers of response.

Patients with cancer and pre-existing autoimmune diseases have been excluded from immunotherapy clinical trials. So, studying these patients who received immunotherapy is critical to increasing evidence of the treatment's safety and efficacy in this population. Furthermore, a complete and durable response to immunotherapy in metastatic non-small cell lung cancer (NSCLC) is rare. Therefore, it is imperative to study patients with a complete response in order to identify potential predictors of response to immunotherapy. In this case report, we highlight a 62-year-old man with a smoking history and Graves' disease who achieved a complete response with immunotherapy for metastatic NSCLC, with a long-lasting response and no immune-related adverse events. Male gender, high programmed death-ligand 1 expression, current smokers, epidermal growth factor receptor and anaplastic lymphoma kinase wild types could be biomarkers of response to immune checkpoint inhibitors presented at baseline. Caution should be exercised when interpreting this finding because it represents our patient.

Phytotherapy in obstetrics - therapeutic indications, limits, and dangers.

The wide access to varied, attractive, and aggressively promoted information can induce pregnant women to think that any form of complementary therapy can be a saving solution for a medical problem because these therapies are natural, therefore, harmless. Updated information from literature about indications, benefits, limits, and risks of phytotherapy in pregnancy was presented. Valuable therapeutic resources with proven clinical efficacy (evidence-based medicine) were presented for each trimester of pregnancy, during labor, postpartum, but also during breastfeeding. For some phytotherapeutics, there are scientific studies. There is also a detailed presentation about some possibilities for therapeutic errors, which should be avoided during pregnancy. Positive results of phytotherapy deserve to be known and applied by the obstetrician for the certain benefit of future mothers.

Intravitreal ranibizumab for the management of serous maculopathy secondary to optic disc coloboma-associated choroidal neovascularisation.

We report the case of a 19-year-old patient with symptomatic unilateral serous maculopathy associated with an optic nerve coloboma. Fluorescein angiography detected a focal late leak at the temporal edge of the coloboma which was later found to correspond with an area of choroidal neovascularisation on optical coherence tomography angiography. A course of intravitreal ranibizumab achieved good clinical and structural response. This report contributes to the evidence that maculopathies associated with cavitary optic nerve anomalies may in some instances result from choroidal neovascularisation. It also highlights the importance of angiography to identify potential choroidal neovascular membranes, particularly in the absence of haemorrhages and neovascular membranes on fundus examination and conventional optical coherence tomography.

Oral S-ketamine effective after deep brain stimulation in severe treatment-resistant depression and extensive comorbidities.

This case report describes successful maintenance treatment with oral S-ketamine in a patient with severe depression, who previously was resistant to electroconvulsive therapy and deep brain stimulation, and who also had comorbid psychotic and obsessive compulsive symptoms.

Intravenous ketamine for rapid treatment of major depressive disorder in the general medical hospital.

Major depressive disorder (MDD) is common in general medical settings, and can usually be treated with conventional oral antidepressants. For some patients, however, oral treatment is refused or not possible, and the untreated symptoms can have a significant impact on the treatment of the acute medical problem. Use of intravenous ketamine has been widely reported in mental health settings for the treatment of MDD. We describe use of intravenous ketamine in a general medical hospital for the treatment of MDD in an 83-year-old male patient who refused food, fluid and medical investigations following a stroke.

Favourable outcome in a child with acute lymphoblastic leukaemia and pulmonary mucormycosis managed with combination antifungal therapy of liposomal amphotericin B and caspofungin.

Pulmonary mucormycosis (PM) accounts for more than half the cases of mucormycosis in paediatric haematological malignancies, with mortality reaching as high as 90%. Surgical debridement of lesion along with liposomal amphotericin B (L-AMB) constitutes the mainstay of management of mucormycosis and offers best chances of survival. There are no reliable data available in the literature justifying the use of combination antifungal therapy (CAfT). We describe a child with acute lymphoblastic leukaemia (ALL) who developed multiple localised PM during induction chemotherapy. He was managed with CAfT with L-AMB and caspofungin in view of progressive PM on high-dose L-AMB monotherapy. There was complete resolution of PM after 6 months of CAfT at the end of intensive chemotherapy of ALL. There were no significant side effects of CAfT. CAfT may be of value in cases of mucormycosis refractory to high doses of L-AMB, where surgical debridement is not feasible.