Biliary Dyskinesia in Stiff Person Syndrome: An Association Between Reduced GABA Production and Gastroenteric Dysmotility.

Stiff person syndrome (SPS) and biliary dyskinesia are two rare but potentially debilitating conditions that can significantly impact quality of life. SPS is a rare neurological disorder characterized by muscle stiffness, rigidity, and muscle spasms that primarily affect the trunk and limbs and is associated with extra-axial manifestations involving the gastrointestinal tract. Biliary dyskinesia is a gastrointestinal disorder characterized by abnormal gallbladder emptying, leading to symptoms of intense abdominal pain, nausea, and vomiting. Despite their distinct clinical presentations, studies have suggested a possible connection between the two disorders. This link may be due to involvement of similar neurotransmitters and autoantibodies in both conditions. In this report, we present a case of biliary dyskinesia in a 58-year-old male with prior history of chronic gastrointestinal symptoms, autoimmune disease, and SPS. Given the rarity of these conditions, there is a need for increased awareness and improved diagnostic modalities to facilitate early detection and management.

Fusobacterium nucleatum Pyogenic Liver Abscess and the Role of Bacterial Virulence and Gut Microbiota Dysbiosis.

In the United States, pyogenic liver abscesses are often due to monomicrobial infection and are rarely documented to be a consequence of Fusobacterium infection, a common cause of Lemierre's syndrome. Recent advances in gut microbial studies have identified Fusobacterium as a commensal gut flora that becomes pathogenic in the setting of dysbiosis resulting from colorectal diseases, such as diverticulitis. While the bacteria's tropism for the liver remains to be elucidated, the virulence pattern of Fusobacterium and the portal venous drainage system have allowed us to understand the bacterium's propensity for causing right hepatic abscesses. In this case report, we detail an immunocompetent man with a history of sigmoid diverticulitis who developed a right hepatic abscess due to Fusobacterium nucleatum, while delineating a review of the literature on the virulent properties of the bacterium and the impact of gut microbiota dysbiosis in its pathogenicity. A descriptive analysis was also performed to identify the characteristics of patients who are at risk in hopes of further improving the clinical diagnostic schema for this condition.

Impact of Antiretroviral Therapy on Kidney Disease in HIV Infected Individuals - A Qualitative Systematic Review.

Kidney disease is the fourth most common cause of non-AIDS-related mortality in people living with HIV. Combination antiretroviral therapy (cART) remains the cornerstone of treatment. However, little is known about the impact of cART on disease outcomes in patients with HIV-associated nephropathy (HIVAN) and HIV-immune complex kidney disease (HIVICK). This systematic review evaluates the impact of cART on progression to end-stage kidney disease (ESKD) and other outcomes in HIV-infected individuals. We conducted a literature search utilizing PubMed, and Cochrane database and 11 articles met inclusion criteria for analysis of which nine HIVAN studies showed decreased progression to ESKD or death for subjects when treated with cART versus those untreated. However, two studies showed no survival advantage with cART. Three HIVICK studies showed improvement in delaying ESKD in subjects on cART compared to untreated subjects. cART appeared to reduce the risk to ESKD or death in patients with both HIVAN and HIVICK.

The Fanconi anemia pathway and Breast Cancer: A comprehensive review of clinical data.

The development of breast cancer depends on several risk factors, including environmental, lifestyle and genetic factors. Despite the evolution of DNA sequencing techniques and biomarker detection, the epidemiology and mechanisms of various breast cancer susceptibility genes have not been elucidated yet. Dysregulation of the DNA damage response causes genomic instability and increases the rate of mutagenesis and the risk of carcinogenesis. The Fanconi Anemia (FA) pathway is an important component of the DNA damage response and plays a critical role in the repair of DNA interstrand crosslinks and genomic stability. The FA pathway involves 22 recognized genes and specific mutations have been identified as the underlying defect in the majority of FA patients. A thorough understanding of the function and epidemiology of these genes in breast cancer is critical for the development and implementation of individualized therapies that target unique tumor profiles. Targeted therapies (PARP inhibitors) exploiting the FA pathway gene defects have been developed and have shown promising results. This narrative review summarizes the current literature on the involvement of FA genes in sporadic and familial breast cancer with a focus on clinical data derived from large cohorts.

A Meta-Analysis of Extracorporeal Anticoagulants in Pediatric Continuous Kidney Replacement Therapy.

OBJECTIVE: Continuous kidney replacement therapy (CKRT) is the primary therapeutic modality utilized in hemodynamically unstable patients with severe acute kidney injury. As the circuit is extracorporeal, it poses an increased risk of blood clotting and circuit loss; frequent circuit losses affect the provider's ability to provide optimal treatment. The objective of this meta-analysis is to evaluate the safety and efficacy of the extracorporeal anticoagulants in the pediatric CKRT population. DATA SOURCES: We conducted a literature search on PubMed/Medline and Embase for relevant citations. STUDY SELECTION: Studies were included if they involved patients under the age of 18 years undergoing CKRT, with the use of anticoagulation (heparin, citrate, or prostacyclin) as a part of therapy. Only English articles were included in the study. DATA EXTRACTION: Initial search yielded 58 articles and a total of 24 articles were included and reviewed. A meta-analysis was performed focusing on the safety and effectiveness of regional citrate anticoagulation (RCA) vs unfractionated heparin (UFH) anticoagulants in children. DATA SYNTHESIS: RCA had statistically significantly longer circuit life of 50.65 hours vs. UFH of 42.10 hours. Two major adverse effects metabolic alkalosis and electrolyte imbalance seen more commonly in RCA compared to UFH. There was not a significant difference in the risk of systemic bleeding when comparing RCA vs. UFH. CONCLUSION: RCA is the preferred anticoagulant over UFH due to its significantly longer circuit life, although vigilant circuit monitoring is required due to the increased risk of electrolyte disturbances. Prostacyclin was not included in the meta-analysis due to the lack of data in pediatric patients. Additional studies are needed to strengthen the study results further.

COVID-19 in an Asymptomatic Renal Transplant Recipient Employed in the Health Care Setting: A Case Report.

During the ongoing pandemic, there have been varying presentations of coronavirus disease 2019 (COVID-19) infection, with the concern that patients who are immunosuppressed (due to underlying medical conditions and/or therapies) are at higher risk of severe disease. We report the case of an elderly renal transplant recipient working in a long-term health care facility who was being monitored by weekly surveillance testing and tested positive for COVID-19 by polymerase chain reaction (PCR) testing, despite having no clinical symptoms. He recovered with supportive care, despite being on multiple long-term immunosuppressant drugs and having multiple comorbidities. Additionally, it was found that he did not mount an antibody response, when he tested negative by serologic testing. Through this case, we wish to highlight the unique clinical scenario of asymptomatic patients who may have an underwhelming immune response to COVID-19, but may nevertheless be an important source of dissemination. We further discuss the probable mechanism of such asymptomatic presentations in immunosuppressed patients, while reinforcing the importance of self-isolation of COVID-19 patients (particularly in asymptomatic health care workers).

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial.

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results: Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). Conclusions and Relevance: In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04401293.

Kidney involvement in multisystem inflammatory syndrome in children: a pediatric nephrologist's perspective.

The initial report of the multisystem inflammatory syndrome in children (MIS-C) was from the UK in April 2020; since then, cases have been reported worldwide. Renal involvement has been seen commonly, ranging from 10% to 46%. Kidney involvement following severe acute respiratory syndrome coronavirus 2 infection in children with MIS-C is more common than initially thought and is associated with higher morbidity and mortality. There are several reports of a direct viral tropism of coronavirus disease 2019 and MIS-C-associated renal damage. This study's objective was to systematically review the current understanding of kidney involvement in children suffering from MIS-C. Based on our systemic literature search, 19 studies have either partially or fully discussed kidney involvement in MIS-C patients. Furthermore, we discuss the multifactorial pathogenesis contributing to acute kidney injury (AKI) development in MIS-C. The current review gives a pediatric nephrologist's perspective of the renal involvement in MIS-C, the incidence of AKI, the pathophysiology of AKI in MIS-C and the proposed therapeutic regimens available, including the need for kidney replacement therapy for a child with AKI associated with MIS-C. As the disease is rapidly evolving, more detailed clinical prospective studies are required to understand MIS-C and its role in AKI better.

Use of rituximab in paediatric nephrology.

Rituximab is a chimeric monoclonal antibody capable of depleting B cell populations by targeting the CD20 antigen expressed on the cell surface. Its use in oncology, initially in B cell lymphoma and post-transplant lymphoproliferative disorders, predates its current utility in various fields of medicine wherein it has become one of the safest and most effective antibody-based therapies. It was subsequently found to be effective for rheumatological conditions such as rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis. Over the past decade, rituximab has generated a lot of interest in nephrology and has become an emerging or accepted therapy for multiple renal conditions, including systemic lupus erythematosus, lupus nephritis, vasculitis, nephrotic syndrome and in different scenarios before and after kidney transplantation. This review outlines its current use in paediatric nephrology practice, focusing on the knowledge required for general paediatricians who may be caring for children prescribed this medication and reviewing them on a shared care basis.

Primary Synovial Diffuse Large B-Cell Lymphoma Presenting as Loosening of Prosthetic Joint: A Case Report and Review of Literature.

Primary synovial diffuse B-cell lymphoma is a rare clinical condition. The condition presents primarily with localized joint symptoms such as swelling, pain and reduced range of motion. It may or may not be associated with lymphadenopathy, hepatosplenomegaly or B-type constitutional symptoms. We report a case of a 74-year-old woman who presented with persistent left knee pain and swelling after left knee replacement secondary to osteoarthritis. There was a concern for mechanical loosening of internal left knee prosthetic joint. On revision surgery (14 weeks after the initial surgery), hypertrophied synovium with areas of fibrotic scars, necrotic tissue and dark colored masses was resected. She was found to have diffuse large B-cell lymphoma (DLBCL) after histological analysis. In cases with persistent joint symptoms or postoperative complications, arthroscopy or arthrotomy should be considered and any atypical appearing tissue should be sent for histopathological analysis.

Lambert-Eaton Myasthenic Syndrome Secondary to Nivolumab and Ipilimumab in a Patient with Small-Cell Lung Cancer.

We present a case of a 59-year-old male with a confirmed diagnosis of small-cell lung cancer (SCLC). He had progressive disease even after four cycles of cisplatin and etoposide chemotherapy and 21 cycles of radiation. He was therefore started on immunotherapy with nivolumab every 2 weeks and ipilimumab every 6 weeks. After 4 months of starting immunotherapy, he reported extreme fatigue, muscular weakness, and poor appetite. He was diagnosed with hypothyroidism, primary adrenal insufficiency, and Lambert-Eaton Myasthenic Syndrome (LEMS). LEMS can be both a paraneoplastic syndrome of SCLC and an adverse effect of immunotherapy. Currently, there is no diagnostic test available to determine if a case of LEMS is a paraneoplastic syndrome or immunotherapy-related adverse effect. In our patient, we felt that LEMS was an immunotherapy-related adverse effect rather being a paraneoplastic syndrome. Our determination was based on the time of onset of muscular weakness, presence of other immunotherapy-mediated adverse events, and the appearance of symptoms in spite of SCLC that had been stabilized on immunotherapy. Accordingly, immunotherapy was stopped and a brief tapering course of steroids was initiated. Our patient's muscular weakness from LEMS responded well. His clinical improvement persisted even with radiologic progression of disease after cessation of immunotherapy.

Disseminated Intravascular Coagulation as an Initial Manifestation of Metastatic Prostate Cancer Emergently Treated with Docetaxel-Based Chemotherapy.

A 70-year-old male presented with hematuria and bruising of arms and legs for the last three days. He also complained of urinary frequency and hesitancy and weight loss of 40 pounds over a span of four months. Initial blood tests showed prothrombin time (PT) of 25.1 seconds, international normalized ratio (INR) of 2.5, partial thromboplastin time (PTT) of 43.9 seconds, fibrinogen of 60 mg/dl, fibrin degradation products (FDP) of more than 20 µg/ml, and platelets of 88,000/µl. The impression was disseminated intravascular coagulation (DIC). A search was initiated to determine the underlying etiology precipitating DIC. Due to urinary symptoms and weight loss, prostate-specific antigen (PSA) was ordered. PSA was elevated at 942 µg/dl. Computed tomography (CT) of the abdomen and pelvis without contrast showed an enlarged prostate with mass effect on the bladder base, left-sided hydronephrosis, and numerous enlarged pelvic lymph nodes. A bone scan of the whole body showed increased sclerosis of the L3 vertebral body. There was a concern for metastatic prostate cancer precipitating DIC. On first admission, our patient's DIC was stabilized with FFP and cryoprecipitate transfusions. He refused chemotherapy, and degarelix was not economically feasible. Accordingly, he was started on androgen deprivation therapy (ADT), bicalutamide, and leuprolide as an inpatient, pending the tissue biopsy. The patient refused a prostate biopsy. A bone marrow biopsy was performed which confirmed metastatic prostate adenocarcinoma. The patient was stable for discharge with a plan for outpatient chemotherapy. Subsequently, he was lost to follow-up with the oncology. Six months after the initial presentation, he was readmitted with hematuria. Repeat PSA worsened to 1,970 µg/dl. Blood work was consistent with acute DIC. He refused chemotherapy again. So, he was restarted on ADT. However, his hematuria and DIC panel were worsening. He was emergently started on docetaxel as an inpatient (after patient agreement). Within three days of starting chemotherapy, his hematuria resolved and DIC panel showed consistent improvement.

Atypical Presentation of Acute Myeloid Leukemia.

We present a case of a 48-year-old male who presented with worsening pleuritic chest pain for 2 h. He also complained of fever, malaise, headache and severe neck pain. Electrocardiogram (ECG) showed ST segment elevation in leads I, II, aVL and V5 with PR elevation and ST depression in aVR. On admission, troponin-I was 14.8 ng/mL. Based on ECG changes, elevated troponin and family history of early coronary artery disease, the patient was emergently taken to cardiac catheterization lab. Angiography showed non-obstructive coronaries, mild hypokinesis of mid inferior and anterolateral wall with ejection fraction (EF) of 40-45%. Based on above presentation and angiography findings, the diagnosis of acute myopericarditis was made. He was started on colchicine and ibuprofen. The other workup to determine etiology of myopericarditis was negative as shown below. Given the history of fever, headache and worsening neck pain, we also became suspicious of meningitis. Lumbar puncture was performed which was negative. On the day of admission, he was found to have blasts on complete blood count and peripheral smear. Bone marrow biopsy and flow cytometry confirmed the diagnosis of acute myeloid leukemia (AML). He received induction and salvage therapy. Repeat bone marrow confirmed complete remission and normal cytogenetics. Although pericardial or myocardial biopsies are unavailable for our patient, in the absence of other causes, it does appear that his acute myopericarditis was associated with AML.