Reply to Dr. Schneeweiss

Case reports in medicine are fundamentally individual patient stories generally describing unique or unexpected findings in terms of disease or treatment. Anecdotally based, they are considered to be less rigorous an evidentiary base than other types of research. As described by Jenicek (1), although case reports rank low on the scale of types of evidence to be relied on, they are highly important in their frequent role as the “first line of evidence”. Historically, case reports were published without consent of the patient. However, standards have been evolving in law and ethics such that consent should now be viewed as mandatory. The remainder of the present commentary provides justification for this assertion. The interests at stake include, on the one hand, confidentiality and autonomy and, on the other hand, the need for scientific advancement, described by Levine and Stagno (2) as “pedagogical freedom”. Since at least Hippocrates’ era, patients have been seen to be entitled to respect for the confidentiality of their personal health information (3). The elemental value of confidentiality is rooted in the need for absolute trust by patients that revelations of personal matters to health care providers will not be indiscriminately broadcasted. Furthermore, the right of the individual to choose among treatment options has been enshrined in the concept of ‘informed consent.’ Its roots may be found in the right to respect for autonomy, and the right to determine the course of treatment may be extended to the right to determine what may be done with personal information that is garnered along the way. There is also, however, great interest in scientific advancement, which has led to some reluctance to seek patient consent to publication of case reports for fear that a negative decision would result in a lack of opportunity to publicize new information that has been gained by a particular case. Psychiatrists, in particular, have voiced concern that patients may not consent due to the nature of their illness – Munchausen’s syndrome being emblematic of this concern (2,4). Thus, there are legitimate interests on both sides of this issue. However, arguably, confidentiality and autonomy are taking precedence in ethics and in law. Confidentiality is protected through federal and provincial legislation regarding information generally and health information specifically (57-7). Such legislation would require, at the least, that case reports not contain any identifiable information about a patient without the patient’s consent. Likewise, a number of medical journals have enshrined the protection of confidentiality into their guidelines for publication. The International Committee of Medical Journal Editors (8) requires informed consent for publication if identifiable information is to be used, but does not refer specifically to case reports. This is similar to the approach of the Paediatrics & Child Health journal (9). Following legal advice, the British Journal of Psychiatry (10) has adopted a guideline saying that consent must be obtained if an individual patient is described; if consent cannot be obtained, “the report can be published only if all details that would enable any reader (including the individual or anyone else) to identify the person are omitted”. It is important to note that, particularly for case reports in our digital age, the bar may actually be quite high under these laws and guidelines. Case reports often deal with a rare disease or constellation of characteristics and, therefore, a person may be identifiable even if no direct identifiers are mentioned. Furthermore, the prospect of identifiability has increased due to broader access to the case reports themselves, both by professionals and by the public more generally, through medical journals that previously had a circumscribed distribution range, but are now available online. This, combined with the fact that patients are being urged to access health information both online and through libraries, increases the likelihood that case reports will be viewed and individuals may be identified. Confidentiality is the obligation of third parties to guard the secrecy of personal information; informational privacy refers to the person or group’s entitlement to make decisions regarding uses of the information. Even if there is no reasonable prospect that the individual patient would be identified, autonomy and privacy interests are at stake. As stated above, autonomy is the underpinning for the doctrine of informed consent. The Supreme Court of Canada signalled a dramatic shift in the ‘doctor knows best’ phenomenon when it ruled that patients are entitled to make their own decisions (11). Privacy, with its concomitant right to make decisions regarding the use of one’s information, engages the autonomy interest even if identifiability is not of concern (12). There is a consensus in Canadian law that personal health information is “fundamentally one’s own” (13), and that individuals should, in most circumstances, be the ones deciding how the information should be used. It might be argued, therefore, that case reports, even without any identifiable information, cannot be published without consent (but it must be noted that this has not been addressed by any Canadian court). Indeed, this is the position taken by the Journal of Medical Case Reports (14), which has adopted a blanket requirement of informed consent before publication. In the case of immature minors and those unable to provide consent, consent is required from the parents or guardians. No case report is to be published in the absence of consent. It is notable that this Journal, which exclusively deals with case reports, has taken this strong stance in favour of informed consent. This takes us to the bottom line. Consent is certainly required under a confidentiality analysis for the publication of case reports that contain any identifiable information. Consent is arguably required under an autonomy analysis for all case reports.

Case report - Introduction Sarcoidosis is a systemic granulomatous disease without a known aetiology. Patients can be asymptomatic and do not require treatment. However, for the severe cases of sarcoidosis, anti-tumour necrosis factor-α (TNF-α) agents have been used in addition to corticosteroids and disease modifying anti-rheumatic drugs (DMARDs). Paradoxically, anti-TNF-α treatment has also been shown to induce sarcoidosis in patients with autoimmune diseases, though what is known about the pathogenesis of this phenomenon is limited. We present a case of renal sarcoidosis occurring following Certolizumab Pegol (CZP) treatment in a patient with psoriatic arthritis. Case report - Case description A 55-year-old Caucasian man presented to the emergency department in Jan 2020 with a seizure and was found to have a stage 3 acute kidney injury. He was diagnosed with psoriatic arthritis (PsA) at age 47 and plaque psoriasis at 20. He has no other past medical history. For PsA, he was initially treated with Methotrexate, but this was stopped due to nausea. After failing on sulfasalazine, he was started on Humira (Adalimumab) and low dose Methotrexate, 10mg weekly. Due to lack of efficacy, he switched to Benepali (Etanercept) monotherapy. One year later, he was switched to Cimzia (Certolizumab Pegol) due to worsening disease activity. He was on the treatment for 7 months before presenting with seizures and renal failure. His seizure was caused by uraemia and hypertension secondary to renal failure. He has severe renal dysfunction (eGFR of 8ml/min/1.73m2), but low-level proteinuria (uPCR of 47mg/mmol). A renal biopsy was performed which showed features of non-necrotising interstitial nephritis, with well-formed granulomas & multiple giant cells, consistent with renal sarcoidosis. Infections were excluded including TB. He was started on high dose prednisolone 80mg daily, a modest improvement in creatinine was observed from 636µmol/L (eGFR 8ml/min/1.73m2) on admission to 526µmol/L (eGFR 10ml/min/1.73m2) on discharge a week later. He did not require renal replacement therapy during admission. The dose of prednisolone was tapered over time, he is now on 10mg per day and his creatinine in April 2020 was 344 µmol/L, (eGFR 16 ml/min/1.73m2). Currently, his psoriatic arthritis is under control, and his latest creatinine in July was 293 µmol/L (eGFR 20ml/min/1.73m2), his prednisolone was reduced further to 5mg daily. In this case report, we reviewed the evidence on anti-TNF-α induced sarcoidosis and options for future biologic agent therapy if there were to be deterioration of psoriatic arthritis or flare of psoriasis. Case report - Discussion Certolizumab-induced sarcoidosis is still a rare, but emerging phenomenon, with an unclear pathogenesis. Of the 87 published case reports of anti-TNF-α agent-induced sarcoidosis, 85 were in patients receiving Etanercept, Adalimumab, and infliximab. In terms of Certolizumab-induced sarcoidosis, a PubMed search using the terms “sarcoidosis, and Certolizumab”, found only two previously reported cases. In the first case, a 45-year-old Caucasian woman with HLA-B27-positive non-radiographic axial spondyloarthritis developed severe renal insufficiency and mediastinal lymphadenopathy following 6 months of Certolizumab therapy. Renal biopsy showed granulomatous interstitial nephritis consistent with renal sarcoidosis, and bronchial biopsies showed non-caseating granulomas. The patient was treated with prednisolone 60mg daily, which was weaned over 6 months along with the initiation of Methotrexate and Secukinumab. This combination led to a minor improvement in her axial symptoms and stabilisation of her renal disease. In the second case, a 69-year-old woman with rheumatoid arthritis developed fatigue, appetite loss and low-grade fever after 6 years of Certolizumab Pegol therapy. She was found to have granulomatous uveitis, bilateral hilar and mediastinal lymphadenopathy, a subcutaneous nodule on her right knee, and micronodules in the upper lobes of both lungs. A video-assisted thoracoscopic biopsy showed noncaseous epithelioid cell granulomas consistent with sarcoidosis. Furthermore, a biopsy of the nodule on her knee showed noncaseous epithelioid cell granulomas. She received 20mg of prednisolone daily to advantageous effect, which was then tapered to 10mg daily without recurrence of sarcoidosis. She was then started on abatacept treatment while further tapering her prednisolone. Case report - Key learning points In these two cases plus this current case, discontinuation of anti-TNF-α agents with systemic corticosteroid treatment resulted in the regression of sarcoidosis. One proposed mechanism of Certolizumab-induced sarcoidosis involves neutralising antibodies, though data on the impact and frequency of anti-drug antibodies in Certolizumab therapy is still unclear. Even the frequency of anti-drug antibodies in Certolizumab therapy is still unclear, with reported percentages ranging from 3.3% to 25.3%. Anti-drug antibodies with Adalimumab is thought to be more common with reported frequency as high as 38.0%, with 21 case reports published about Adalimumab-induced sarcoidosis. There are also case reports on Secukinumab (anti-IL17) associated with onset of sarcoidosis, this is one of the treatment options for psoriatic arthritis and psoriasis as per NICE guidance (TA445). Tofacitinib has been approved by NICE recently (TA543) for PsA, so far, there are no case reports associated with the onset of sarcoidosis, rather, it has been used to treat sarcoidosis successfully. Therefore, Tofacitinib seems to be a potential treatment option for this patient. Key learning points therefore include: Certolizumab-induced sarcoidosis is a rare but increasingly recognised phenomenon.The role of anti-drug antibodies in the pathogenesis of anti-TNF-α agent-induced sarcoidosis remains unclear.Systemic corticosteroid treatment seems to be an effective treatment for anti-TNF-α agent-induced sarcoidosis.Tofacitinib has not been reported to cause drug-induced sarcoidosis and is a viable alternative treatment option.

SummaryBackgroundDyspnea is common in patients with advanced cancer. Diagnostic procedures in patients with dyspnea are mandatory but often time-consuming and hamper rapid treatment of the underlying refractory symptoms. Opioids are the first-line drugs for the treatment of refractory dyspnea in palliative care patients with advanced lung cancer.MethodsTo evaluate the knowledge levels of medical doctors with different educational levels on the diagnosis of and treatment options for dyspnea in patients with advanced lung cancer in a palliative care setting, a case report and survey were distributed to physicians at the University Hospital Krems, describing acute dyspnea in a 64-year-old stage IV lung cancer patient. A total of 18 diagnostic and 22 therapeutic options were included in the survey. The physicians were asked to suggest and rank in order of preference their diagnosis and treatment options. Statistical analyses of the data were performed, including comparison of the responses of the senior doctors and the physicians in training.ResultsA total of 106 surveys were completed. The respondents were 82 senior physicians and 24 physicians in training (response rates of 86% and 80%, respectively). Regarding diagnostic investigations, inspection and reading the patient’s chart were the most important diagnostic tools chosen by the respondents. The choices of performing blood gas analysis (p = 0.01) and measurement of oxygen saturation (p = 0.048) revealed a significant difference between the groups, both investigations performed more frequently by the physicians in training. As for non-pharmacological treatment options, providing psychological support was one of the most relevant options selected. A significant difference was seen in choosing the option of improving a patient’s position in relation to level of training (65.9% senior physicians vs. 30.4% physicians in training, p = 0.04). Regarding pharmacological treatment options, oxygen application was the most chosen approach. The second most frequent drug chosen was a ß-2 agonist. Only 9.8% of the senior physicians and 8.7% of the physicians in training suggested oral opioids as a treatment option, whereas intravenous opioids were suggested by 43.9% of the senior physicians and 21.7% of the physicians in training (p = 0.089). For subcutaneous application of opioids, the percentage of usage was significantly higher for the physicians in training than for the senior physicians (78.3% vs. 48.8%, p = 0.017, respectively).ConclusionThe gold standard treatment for treating refractory dyspnea in patients with advanced lung cancer is opioids. Nevertheless, this pharmacological treatment option was not ranked as the most important. Discussing hypothetical cases of patients with advanced lung cancer and refractory dyspnea with experienced doctors as well as doctors at the beginning of their training may help improve symptom control for these patients.

The Value of Case Reports for Graduate Medical Education.

IN THE EYE OF THE STORM: HYPERVIRULENT KLEBSIELLA PNEUMONIAE

Abtract Aim: Dental implants constitute functional and aesthetic solutions for edentulous patients. Despite their high success rates, complications may occur. Implant fracture is a severe complication since it usually results in loss of the implant. This comprehensive review study aims to present the causes and treatment options for implant fractures. Methods: A literature review was carried out utilizing electronic databases and international scientific journals. Of the articles included, most were reviews of the literature, some reviews of the literature combined with case reports, cohort studies, and case reports. A meta-analysis was also included in the sample. Results: Many factors have been implicated to cause dental implant fractures, including faulty design or production, ill-fitting restorations, loading protocols, bruxism or heavy occlusal forces, design of the restoration, implant location and diameter, metal fatigue, and bone loss around the implant. In the literature, three different treatment options are mentioned: complete extraction of the fractured implant, removal of the coronal portion of the fractured implant, and either placement of a new prosthetic post or leaving the remaining apical part dormant in the bone. Conclusions: As implant treatment becomes popular, dentists are more likely to encounter and treat implant fractures. This is a frustrating complication for the patient and the dentist because it usually leads to the loss of the implant and the restoration. Therefore, it is suggested that clinicians study the possible causes of implant fractures and plan the treatment properly to prevent fractures and apply the best individualized treatment option should it occur.

Nitrous Oxide Gas May be a Promising Therapy for Acute Priapism in Patients with Sickle Cell Disease: A Case Report

A burn is an injury caused by an external agent that acts on the body covering tissue, which can cause partial or total loss of the affected tissue function.Agents can be thermal, chemical, electrical or radioactive.We report a case of a 49-year-old patient suffering from an electrical burn on the upper limb, who underwent reconstruction with a free flap after initial care for the injury.Free flaps are of great importance in the treatment of injuries with loss of substance in the hands, due to the possible scarcity of tissue that may occur in the region after extensive trauma, making regional flaps impossible.We noticed that the anterolateral thigh free flap fulfilled its role, providing good tissue coverage to the lesion, combined with a small morbidity in the donor area.

To the Editor The development of an acute ischemic stroke (AIS) despite anticoagulant therapy has been called an ‘anticoagulation failure’ (1). In their case report, Tabata et al. (2) reviewed the literature pertaining to the use of intravenous thrombolysis in patients on the new oral anticoagulant (NOAC), dabigatran, presenting with AIS. Their article illustrates the challenges that clinicians face in trying to treat patients in situations where there are no evidence-based recommendations. Given the rapidly growing popularity of the direct oral anticoagulants, stroke neurologists are likely to be confronted with scenarios of this sort more frequently in the near future. All in all, the available case reports about thrombolysis in stroke patients on dabigatran paint a mixed picture, and indicate that there is still a significant risk of bleeding. In a recent review, Epple and Steiner expertly discussed the practical issues inherent to this therapeutic dilemma (1). The authors advised caution and concluded that “it is unlikely that patients on NOAC who experience an AIS would be suitable for thrombolysis, unless they have missed their NOAC dose for the last 24-48 hours”. For this reason, we would like to point to a different treatment option. We and others (3, 4) have shown that neurointerventional recanalization might constitute a promising treatment alternative in centers with high neuroradiological expertise. An endovascular approach using mechanical clot extraction devices does not expose patients to thrombolytic agents. Hence, a lower risk of intracranial hemorrhage is conceivable. All three cases reported so far showed a good clinical outcome. An asymptomatic intimal tear with transient extravasation of contrast medium was deemed likely in the first patient, and represents the only complication reported. As rightly commented by Hankey (5), such a “simple solution” remains unproven in terms of whether it is a safe and effective alternative to thrombolysis. Nevertheless, physicians occasionally face complex clinical situations and patient subgroups for which information derived from controlled clinical trials cannot be applied. We believe that case reports like those by Moey et al. and our group could form the basis of future observational studies. In our opinion, endovascular revascularization might emerge as a valuable treatment option for AIS patients on treatment with dabigatran, and possibly other novel oral anticoagulants.

Accolade TMZF trunnion corrosion and mechanical failure 9 yr after primary surgery: A case report and treatment options

Prolonged SARS-CoV-2 shedding and mild course of COVID-19 in a patient after recent heart transplantation.

BackgroundAdrenocortical carcinoma (ACC) is a rare malignancy occurring in the adrenal cortex characterized by its low incidence rate, aggressive tumor behavior with high propensity of invasion and distant metastasis, and poor prognosis. When detected, it usually appears as advanced tumor with limited treatment options. Systemic chemotherapy is the only recommended treatment option and EDP-M plus sintilimab has recently emerged as a new treatment option. In the present study, we report a case of ACC treated with EDP-M plus sintilimab.Case DescriptionWe present a 30-year-old female patient with ACC and bilateral lung metastases. PET-CT scan showed multiple metastatic sites in both lungs, among which the largest one was located in the lower lobe of the right lung, with a size of 42 mm × 22 mm. A space-occupying lesion was also found in the right adrenal gland with a size of 92 mm × 51 mm. The patient was treated with EDP plus sintilimab for four cycles in our hospital and mitotane was introduced after the first cycle. Follow-ups after the second and fourth cycles found significantly reduced lung metastases with all imaging examinations indicating PR status. The patient received maintenance therapy thereafter with sintilimab plus mitotane. Until recently, the patient’s lung metastases have basically disappeared and no disease progression has been observed. The progression free survival (PFS) of this patient has been extended to about 7 months.ConclusionsAlthough deemed as the standard chemotherapeutic regimen for advanced ACC, the efficacy of EDP-M is not satisfactory. This case study demonstrates the clinical effectiveness of EDP-M plus sintilimab in the treatment of advanced ACC with good patient tolerance, suggesting that this regimen combination can be a promising treatment option for refractory ACCs.

Vesical Hemangioma in a Patient with Klippel-Trenaunay-Weber Syndrome

Introduction: Anterior crossbite is a major aesthetic and functional concern to parents during the developmental stage of a child. Anterior crossbite is the lingual positioning of the maxillary anteri­or teeth in relationship to the mandibular anterior teeth. There are several methods for solving this problem. In this case report we present the treatment with a removable lingual plane. The aim of the following case report is to present the achieved good results after the early treatment of an anterior crossbite. Materials and Methods: This report describes the treatment of an 8-year-old girl in the Department of Orthodontics, Faculty of Dental medicine, Medical University - Varna. Diagnostic data was gathered from clinical photographs, cast models from intraoral impressions, cephalometric analysis based on lateral cephalograms and panoramic radiographs. Results: We established a crossbite of tooth 21 and laterodeviation. According to lateral cephalomet­ric analysis the patient has a retroclination of the upper central incisor on the left. There was suffi­cient mesiodistal width to achieve labial movement of the maxillary tooth. To align the maxillary an­terior central incisor and correct the crossbite, a removable acrylic appliance with posterior occlusal surfaces was used. A screw incorporated in the appliance was activated by 0.25 mm every 4 days for 12 days. After these 12 days the crossbite was corrected. Conclusion: There are many treatment options available for the correction of crossbites according to the number and site of the teeth/tooth involved, the stage of the dentition and its etiology. Based on the results presented here, a removable appliance with a screw may be considered the first choice of treatment to correct anterior dental crossbite of one incisor. This method is a safe, cost effective, rap­id and easy alternative for the treatment of an anterior crossbite.

Neurofibromatosis is an autosomal dominant genetic disorder characterized by developmental abnormalities of the nervous system, skin, and bones. Clinically, it is relatively rare and is often associated with various benign and malignant tumors. However, reports of its association with malignant melanoma are scarce, and has been reported as a case report in this study. Case reports and treatment options are discussed below. A 71-year-old male presented with long-standing skin nodules and plaques including a growing and itchy black patch on his left heel. Pathological examination revealed neurofibroma in the nodules and malignant melanoma in the heel lesion. The diagnosis was neurofibromatosis type l with acromelanoma. Due to financial constraints, the patient refused surgical excision of the tumor and opted for conservative treatment with interferon injections. The patient is currently under follow-up observation. This rare case underscores the importance of monitoring genetic disorder patients for tumor risk, emphasizing timely intervention.