Clinical Conundrum Research Articles

Clinical conundrum

Clinical conundrum

Non-invasive molecular biomarkers for predicting outcomes of micro-TESE in patients with idiopathic non-obstructive azoospermia.

Non-obstructive azoospermia (NOA), the most severe type of male infertility, affects approximately 1% of men worldwide. However, the aetiology of most NOA cases is not definite, that is defined as idiopathic NOA (INOA), posing a clinical conundrum worldwide. Most of these patients must receive donor sperm treatment until the emergence of microdissection testicular sperm extraction (micro-TESE). Although this procedure has recently become a promising treatment for INOA, the low sperm retrieval rate and testicular trauma have prompted us to explore appropriate non-invasive molecular biomarkers to predict the outcomes of sperm recovery preoperatively. Previous studies have identified a spectrum of biomarkers to address this challenging issue at various levels in different tissues, such as DNAs, RNAs, protein and steroid levels in the blood and seminal fluid. To better understand and assess the predictive values of diverse molecular biomarkers from different tissues on the outcome of sperm retrieval by micro-TESE in patients with INOA, we summarised recent findings and discussed the potential applications of these methods. The ultimate goal of this study was to provide references for further studies and clinical management.

Deciphering chronic hypertension from preeclampsia: Utility of NT-proBNP in obstetric triage

Distinguishing between normal physiologic fluctuations of blood pressure among pregnant patients with chronic hypertension (cHTN) versus superimposed preeclampsia (SI preE) is a common clinical conundrum. A unique marker of preE is increased cardiac afterload due to increased systemic vascular resistance, which is reflected by N-terminal pro B-type natriuretic peptide (NT-proBNP). We evaluated the utility of NT-proBNP to discriminate between cHTN and SI preE.

COVID-19 vaccination-associated ipsilateral supraclavicular lymphadenopathy.

Lymphadenopathy associated with COVID-19 vaccination can be a clinical conundrum for clinicians.

564 Controversial role of intracardiac eletrophysiology study in Brugada syndrome: analysis of a single-centre retrospective cohort study

Abstract Aims According to European guidelines, aborted sudden cardiac death (SCD) in Brugada syndrome (BrS) is regarded as a I class recommendation for secondary prevention implantable cardioverter defibrillator (ICD). However, the risk stratification of BrS patients for primary prevention ICD still represents a clinical conundrum. Although intracardiac electrophysiology (EP) study proved useful for the selection of high-risk patients in this setting. Therefore, aim of this study was to assess all clinical and EP variables associated with the induction of VA at EP study and the rate of appropriate/inappropriate ICD interventions and/or clinical SCD events in these patients occurring at follow-up. Methods and results From 2001 to 2021, all EP studies performed in symptomatic/asymptomatic patients (46 ± 14 years, M 88%) with/without family history of SCD spontaneous/drug-induced type I pattern (TIP) on ECG and no spontaneous ventricular arrhythmias were retrospectively considered at our study centre. Clinical variables, BrS pattern, EP study data (including right ventricular site and type of stimulation protocol), and ICD interventions (DC-shocks or Anti-Tachycardia Pacing events, ATP) and/or SCD events occurring at follow-up were all evaluated. EP study was deemed positive for any polymorphic VA induced during programmed ventricular stimulation; non-sustained episodes included. ICD was routinely implanted in all patients with a positive EP study. Follow-up data were detected by the collection of medical and home-monitoring recordings at study-site level. Follow-up data were available in 50 patients (9 ± 6 years on average). Patients were generally young with few cardiovascular comorbidities. SCD history was known in 21 (42%) with a significant number of asymptomatic patients (48%). Br patterns were equally distributed in the investigated population (spontaneous and drug-induced TIP in 52% and 48%, respectively) and AF history was fairly common (16%). In the study population, EP study tested positive in 30 patients (60%): spontaneous TIP (P = 0.0518), few extrastimuli during programmed ventricular stimulation (P = 0.0015), and right ventricular stimulation at the apical site (P ≤ 0.0001) were the only variables to be clearly associated with a positive EP study in the appraised patients. At follow-up, appropriate ICD shocks were documented in 4 out of 30 implanted patients (13%) at generally 5 ± 7 years from EP study evaluation. Although three ICD interventions (75%) occurred in patients with spontaneous TIP, one patient with drug-induced TIP pattern and positive EP study referred to Emergency Department for unrelenting VT storm after roughly 13 years from ICD implantation. Inappropriate ICD interventions for fast rate AF were detected in 10% of cases. Finally, no SCD events were documented at follow up in patients with a negative EP study. Conclusions In a retrospective analysis, EP study proved useful in the risk stratification of SCD in BrS patients. A few ventricular extrastimuli delivered at the right ventricular apex seem sufficient to prompt the induction of life-threatening VA in high-risk BrS patients during EP study. Moreover, in this setting, a negative EP study seems protective against the development of VA/SCD events at follow-up. However, not only is spontaneous TIP associated with an increased risk of arrhythmic death, but a drug-induced TIP, generally regarded as a low-risk condition, might also be associated with a long-term hazard of SCD in these patients.

Clinical conundrum

Sarah Shepherd presents the case of a Domestic Shorthair cat with pyrexia and ascites she saw when working as a small animal rotating intern at the Small Animal Teaching Hospital, University of Liverpool.

P.0530 Lithium-induced psoriasis: a clinical conundrum

P.0530 Lithium-induced psoriasis: a clinical conundrum

Management of Patients with Poor Prognosis First Permanent Molars Beyond 'Ideal' Timing.

The management of compromised first permanent molars is a common clinical conundrum in paediatric dentistry. Extensive guidance exists which supports the timed extraction of severely affected molars presenting at 8-10 years to allow favourable eruption of unaffected second permanent molars. However, treatment planning becomes more of a challenge when this window of opportunity is missed. In these situations, we are left with a tooth of guarded long-term prognosis in a patient where access and cooperation can be challenging. Delays to routine care as a result of the COVID-19 pandemic are likely to make this a more common clinical presentation so this article aims to discuss management options for these patients.

Challenges in Managing Isolated Subsegmental Pulmonary Embolism.

This commentary explores the clinical conundrums arising when caring for patients with acute pulmonary embolism isolated to the subsegmental pulmonary arteries. We discuss ways to confirm the radiologic diagnosis, how to distinguish patients for whom anticoagulation is indicated from those who are eligible for structured surveillance without anticoagulation, what surveillance entails, and why ensuring continuity of care matters. We report a case from our own experience that illustrates these decision-making crossroads and highlights the importance of cross-disciplinary collaboration. Because the evidence in the literature is currently weak and indirect, we draw on expert opinion in US and European guidelines, a recent statement from a multidisciplinary consensus panel, and several ongoing well-designed clinical trials. This discussion will help clinicians better manage the spectrum of patients who present with isolated subsegmental embolism.

Opioid Therapy in Cancer Patients and Survivors at Risk of Addiction, Misuse or Complex Dependency.

A clinical conundrum can occur when a patient with active opioid use disorder (OUD) or at elevated risk for the condition presents with cancer and related painful symptoms. Despite earlier beliefs that cancer patients were relatively unaffected by opioid misuse, it appears that cancer patients have similar risks as the general population for OUD but are more likely to need and take opioids. Treating such patients requires an individualized approach, informed consent, and a shared decision-making model. Tools exist to help stratify patients for risk of OUD. While improved clinician education in pain control is needed, patients too need to be better informed about the risks and benefits of opioids. Patients may fear pain more than OUD, but opioids are not always the most effective pain reliever for a given patient and some patients do not tolerate or want to take opioids. The association of OUD with mental health disorders (dual diagnosis) can also complicate delivery of care as patients with mental health issues may be less adherent to treatment and may use opioids for “chemical coping” as much as for pain control.

Next Steps: Advocating for Women in Orthopaedic Surgery.

Orthopaedic surgery is the least diverse of all medical specialties, by both sex and race. Diversity among orthopaedic trainees is the lowest in medicine, and growth in percentage representation is the lowest of all surgical subspecialties. Women comprise only 6% of orthopaedic surgeons and 16% of orthopaedic surgery trainees. This extreme lack of diversity in orthopaedics limits creative problem-solving and the potential of our profession. Women in orthopaedics encounter sexual harassment, overt discrimination, and implicit bias, which create barriers to training, career satisfaction, and success. Women are underrepresented in leadership positions, perpetuating the lack of diversity through poor visibility to potential candidates, which impedes recruitment. Correction will require a concerted effort, as acknowledged by the American Academy of Orthopaedic Surgeons leadership who included a goal and plan to increase diversity in the 2019 to 2023 Strategic Plan. Recommended initiatives include support for pipeline programs that increase diversity of the candidate pool; sexual harassment and implicit bias acknowledgement, education, and corrective action; and the active sponsorship of qualified, capable women by organizational leaders. To follow, women will lend insight from their diverse viewpoints to research questions, practice problems, and clinical conundrums of our specialty, augmenting the profession and improving patient outcomes.

IL-1β, IL-17A, and IL-10: A Novel Axis Linked to Immunological Dysfunction May Pre-Empt Early Diagnosis of Sepsis after Cardiac Surgery

INTRODUCTIONSepsis caused by a dysregulated host response to infection, is a serious healthcare problem that results in very high mortality every year-round the globe. When left untreated, sepsis can potentially turn fulminant, making early diagnosis and intervention an essential component of the therapeutic strategy. Proinflammatory cytokines are necessary for initiating an effective inflammatory response against infection, whereas their excess production has been associated with tissue injury in multiple organ systems leading to increased mortality. In contrast, anti-inflammatory cytokines seem to be a prerequisite for controlling and down regulating the initial inflammatory response. But a sustained release of these biomolecules leads to a turn-down of immune activation within the host organism. In the clinical conundrums associated with sepsis, it was often observed that pathogen-responsive cells were exposed to a complex cytokine milieu. The excess production of proinflammatory cytokines is essential for the survival, replication and activation of phagocytic and cytotoxic immune cells. In conjunction with this proinflammatory activity, anti-inflammatory cytokines are also released which are involved in the occurrence of cellular anergy and impaired response to aetiologic agents, causing a compensatory anti-inflammatory response syndrome (CARS).Current practice in cardiac surgery is to review laboratory test results (CRP, PCT, blood culture) and clinical criteria (SOFA and STS) 48 h after surgery to diagnose sepsis. CRP and PCT lack sensitivity and specificity, whereas blood culture requires a long turnaround time and lacks sensitivity. Sepsis being an interplay between pro and anti-inflammatory response, the relative expression of immune biomarkers may provide a useful criterion for early diagnosis of sepsis. Thus, we aimed at investigating the variations in circulating levels of prominent cytokines and their potential use as a diagnostic marker of adult sepsis post cardiac surgery.MATERIALS AND METHODSIn this double-blinded cohort study, blood samples of adult patients undergoing cardiac surgery were collected before surgery (D -1), and on the post-operative day 1 (D +1) after the approval from the appropriate Institutional Ethics Committee. Patients who were deemed risky by EuroSCORE II risk stratification were included and immuno-compromised as well as patients with active infection before surgery were excluded. Plasma levels of IL-1β, IL-5, IL-6, IL-10, IL-17A and TNFα were determined using cytometric bead assay by flow cytometry and the results were analyzed using FCAP Array™ software. The data sets were analyzed (GraphPad Prism 5.02) and a p value of < 0.05 was considered statistically significant.RESULTSThe study was conducted with 34 patients (n=34) and un-blinded after retrieval of data. The cohort has 8 patients diagnosed with sepsis and 26 without sepsis based on STS criteria. Demographic details for both groups are summarized in Table 1. Cytokine and other biomarker expression levels before (D-1) and after (D+1) Surgery is summarized in Table 2. At D +1, IL-1β, TNF-α, IL-17A and IL-10 showed significantly higher concentration in sepsis group compared to non-sepsis group (Fig 1B). CRP, PCT, WBC and differential blood count were not showing any discriminatory potential between sepsis and non-sepsis patients at D +1. The ROC curves of the above four cytokine expression levels at D+1 was analyzed between sepsis and non-sepsis groups. A plasma IL-1β level of 0.25 pg/ml had a sensitivity of 87.5 % and a specificity of 53.8 % and a plasma IL-17A level of 1.78 pg/ml had a sensitivity of 75 % and specificity of 46.2 %. In addition, IL-10 level of 8.99 pg/ml in plasma showed a diagnostic sensitivity of 87.5 % and a specificity of 53.8% (Fig 1C). Based on the current observation we proposed a model of inflammatory cytokine dynamics involving IL-1β, IL-17A and IL-10 suggesting their role, which may lead to the development of sepsis (Fig 1D).CONCLUSIONWe identified a significant up regulation of circulating inflammatory cytokines at 24 h in patients who developed sepsis after cardiac surgery, earlier than any noticeable changes in conventional sepsis biomarkers. These results suggest the possibility of inflammatory cytokines as a diagnostic marker and may be a potential therapeutic target as well. The study needs to be validated further on a larger cohort of patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical conundrum

Thomas Natsiopoulos and Ferran Valls Sanchez invite Companion readers to consider a lethargic Staffordshire Bull Terrier with diarrhoea and alopecia they saw at Dick White Referrals.

Physiologic Timeline of Cranial-Base Suture and Synchondrosis Closure.

Fusion of cranial-base sutures/synchondroses presents a clinical conundrum, given their often unclear "normal" timing of closure. This study investigates the physiologic fusion timelines of cranial-base sutures/synchondroses. Twenty-three age intervals were analyzed in subjects aged 0 to 18 years. For each age interval, 10 head computed tomographic scans of healthy subjects were assessed. Thirteen cranial-base sutures/synchondroses were evaluated for patency. Partial closure in greater than or equal to 50 percent of subjects and complete bilateral closure in less than 50 percent of subjects defined the fusion "midpoint." Factor analysis identified clusters of related fusion patterns. Two hundred thirty scans met inclusion criteria. The sutures' fusion midpoints and completion ages, respectively, were as follows: frontoethmoidal, 0 to 2 months and 4 years; frontosphenoidal, 6 to 8 months and 12 years; and sphenoparietal, 6 to 8 months and 4 years. Sphenosquamosal, sphenopetrosal, parietosquamosal, and parietomastoid sutures reached the midpoint at 6 to 8 months, 8 years, 9 to 11 months, and 12 years, respectively, but rarely completed fusion. The occipitomastoid suture partially closed in less than or equal to 30 percent of subjects. The synchondroses' fusion midpoints and completion ages, respectively, were as follows: sphenoethmoidal, 3 to 5 months and 5 years; spheno-occipital, 9 years and 17 years; anterior intraoccipital, 4 years and 10 years; and posterior intraoccipital, 18 to 23 months and 4 years. The petro-occipital synchondrosis reached the midpoint at 11 years and completely fused in less than 50 percent of subjects. Order of fusion of the sutures, but not the synchondroses, followed the anterior-to-posterior direction. Factor analysis suggested three separate fusion patterns. The fusion timelines of cranial-base sutures/synchondroses may help providers interpret computed tomographic data of patients with head-shape abnormalities. Future work should elucidate the mechanisms and sequelae of cranial-base suture fusion that deviates from normal timelines.

Stuck between a rock and a hard place: The clinical conundrum of managing cardiac surgical patients during the SARS-CoV-2 pandemic.

Deferring nonemergent cardiac surgery became the strategy of choice for several international healthcare systems afflicted by high case burdens of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2/COVID‐19) to both conserve valuable healthcare resources and protect patients from possible exposure. Missing from the available dataset to help guide policy development has been a clear understanding of the extent to which COVID‐19 infection modulates cardiac surgery outcomes. In their investigation, Bonalumi et al. uncovered an inpatient COVID‐19 positivity rate of almost 10 times higher than that of the general Italian population, as well as a mortality rate over 20 times higher amongst cardiac surgery patients with perioperative COVID‐19 infection compared to those COVID‐negative. While the summation of available evidence points to the serious consideration cardiac surgeons must give to delaying surgeries during the COVID‐19 pandemic, recognition must be given to the risks that postponing cardiac surgery may have on patient outcomes. Emerging data is beginning to demonstrate the efficacy of vaccination in preventing postoperative COVID‐19 infection and morbidity.

O01 Post-transplant lymphoproliferative disorder (PTLD) in a patient with rheumatoid arthritis

O01 Post-transplant lymphoproliferative disorder (PTLD) in a patient with rheumatoid arthritis

Valvular Heart Disease in Athletes.

Valvular heart disease is prevalent in older athletes with primarily degenerative valvular disorders and younger athletes with congenital or genetic syndromes. Limited data exist on the risks and benefits of exercise for athletes with underlying valvular disorders, so current guidelines are primarily based upon expert consensus. This review focuses on the current data, guideline recommendations, and emerging clinical conundrums for athletes with common valvular heart conditions including aortic stenosis, bicuspid aortic valve (BAV), mitral regurgitation (MR), mitral valve prolapse (MVP), and thoracic aortic aneurysms.

Is bilevel PAP more effective than CPAP in treating hypercapnic obese patients with COPD and severe OSA?

Commentary on Zheng Y, Yee BJ, Wong K, Grunstein R, Piper A. A pilot randomized trial comparing CPAP versus bilevel PAP spontaneous mode in the treatment of hypoventilation disorder in patients with obesity and obstructive airway disease. J Clin Sleep Med. 20XX;XX(XX):XXX-XXX. doi:10.5664/jcsm.9506.

Clinical conundrum

Abstract Elisa Pompermaier, a rotating intern at Northwest Veterinary Specialists, describes a case of a Springer Spaniel with tetraparesis and seizures.

S1654 Clinical Conundrum in a Young Male With Severe Biliary Obstruction

S1654 Clinical Conundrum in a Young Male With Severe Biliary Obstruction