Hackensack University Medical Center Mountainside

Assisted reproductive technologies (ART) have significantly impacted fertility treatment worldwide through innovations such as in vitro fertilization (IVF) and in vitro maturation (IVM). IVM holds promise as a technology for fertility treatment in women who cannot or do not wish to undergo conventional controlled ovarian hyperstimulation (COH). However, IVM has historically shown highly variable performance in maturing oocytes and generating oocytes with strong developmental capacity. Furthermore, novel IVM approaches are usually highly limited to use in cycles lacking human chorionic gonadotropin (hCG) triggers, which is not standard practice in fertility treatment. We recently reported the development of ovarian support cells (OSCs) generated from human induced pluripotent stem cells (hiPSCs) that recapitulate dynamic ovarian function in vitro. Here we investigate the potential of these OSCs in an IVM co-culture system to improve the maturation of human cumulus-enclosed immature oocytes retrieved from abbreviated gonadotropin stimulated cycles. We reveal that OSC-IVM significantly improves maturation rates compared to existing IVM systems. Most importantly, we demonstrate that OSC-assisted IVM oocytes are capable of robust euploid blastocyst formation, a key marker of their clinical utility. Together, these findings demonstrate a novel approach to IVM with broad applicability to modern ART practice.

Introduction: Post-vaccination arrhythmia is reported as a possible cardiovascular side effect of COVID-19 vaccination. We present a case of ventricular tachycardia (VT) storm in a young healthy man following the 2nd dose of COVID-19 vaccination in the absence of underlying structural heart disease, myocarditis or arrhythmic syndromes. Description: A 38-year-old male with no medical history was admitted after an out-of-hospital cardiac arrest and found to be in VT storm within 24 hours of receiving his 2nd dose of COVID-19 vaccination. He received 4 shocks en route and had another episode of pulseless VT on arrival where Amiodarone was initiated. Laboratory values showed elevated inflammatory markers, and COVID tests were negative. Troponin peaked at 1.5 ng/ml. Initial transthoracic echocardiogram (TTE) revealed normal left ventricular ejection fraction (LVEF) without regional wall motion abnormality. On Day 2, he developed VT storm and was given magnesium sulfate, lidocaine and an additional bolus of amiodarone. Repeat TTE revealed a significant decrease in EF. He became hypotensive requiring inotropes and was emergently taken to the cath lab where intra-aortic balloon pump (IABP) and temporary transvenous pacing (TVP) were placed. Cardiac catheterization revealed normal coronary arteries, elevated left ventricular end diastolic pressure and mildly dilated LV with global hypokinesis and EF of 30%. His condition slowly improved without further occurrences of VT storm. Follow up TTE revealed normal LVEF, IABP and TVP were removed, and he was extubated. Cardiovascular magnetic resonance imaging showed no evidence of myocarditis with normal LV size. An automatic implantable cardioverter-defibrillator was placed. Genetic testing for Brugada syndrome was negative. Discussion: VT storm typically occurs with underlying structural heart disease, inherited arrhythmic syndromes or myocarditis, and is often difficult to identify a specific trigger. Although this is the first case report of VT storm occurring after the COVID-19 vaccine, it is important to note that the lack of a definitive test to diagnose myocarditis such as biopsy is a major limiting factor. This case report also supports the need for structured studies regarding a possible relationship between VT storm and COVID-19 vaccination.

Introduction: Given the subjective nature of Irritable Bowel Syndrome (IBS), excess testing is often ordered. Prior studies have postulated IBS is due to overgrowth of intestinal bacteria and subsequent alteration in intestinal gas composition. Our pilot investigation with Bowel Sound Analysis (BSA) reveals correlation between bowel sound activity and IBS symptom severity. This study further explores BSA and its proposed correlation with Lactulose Breath Test (LBT) and IBS symptom severity. Point of Care analysis of bowel sounds is a potential diagnostic tool that is non-invasive and may provide objective data for evaluating the severity of IBS. Methods: This is a case-control study including IBS patients who met Rome IV criteria. Gastrointestinal Symptom Rating Scale IBS (GSRS-IBS) was used to quantify severity of symptoms. A score of >35 was considered an IBS flare-up. Bowel sounds were collected for 45 seconds from 3 points around the umbilicus with an electronic stethoscope. Audio files were analyzed based on proprietary computer software modeled after previous IBS patients. The model uses scores < 5 as normal, 5-10 as mildly abnormal, and >10 as abnormal. Patients were given a TrioSmart LBT provided by Gemelli Biotech to complete post-appointment. (Figure) Results: A total of 63 patients completed the GSRS and BSA. A scatterplot of GSRS vs BSA scores demonstrated an R2 of 0.591 with ANOVA calculated p-value < 0.0001. A total of 37 patients completed the LBT. Using the established thresholds of symptom severity, a chi-square test between 3 variables yielded a p-value < 0.005 with the tree map exhibiting the categories each patient fell into. We note, as seen in the proximity matrix Table, that the BSA had a greater overlap with symptom severity when compared to the LBT. This suggests the BSA captures audio data pertinent to the severity of IBS symptoms beyond bacterial dysbiosis. (Table) Conclusion: Point of Care BSA may serve as a promising objective assessment for IBS. The time-efficient and point-of-care application of BSA may allow it to serve as a screening procedure to help evaluate and treat patients with IBS. A large sample cohort study of the BSA between pre and post-treatment patients would need to be done to establish a better understanding. If validated, the BSA could provide clinicians with an objective marker to ascertain IBS presentation, response to therapy, as well as couple with the LBT to assess specific abnormal intestinal gas levels that may subsequently guide treatment plans.Figure 1.: A. Scatterplot of IBS symptom Score over the Bowel Sound Score: The above graph details a best of fit model to predict IBS symptom severity over the score received on the BSA. The data fits the model to an R^2 of 0.591 with an ANOVA of regression showing a p-value <0.0001 B. Proportional chart represents 3-way correlation between 3 given tests: The Treemap bins each patient into a category depending on the results of all 3 tests. The probabilities of each positive test within the 37 patient sample were used to create an expected value Table which was then used to perform a chi-square test of independence. The test of association showed a p-value of <0.005. Table 1. - Proximity Matrix (Percent agreement) between Gastrointestinal Symptom Rating Scale IBS (GSRS), Lactulose Breath Test (LBT), and Bowel Sound Analysis (BSA) GSRS LBT BSA GSRS 1 0.708 0.784 LBT 0.708 1 0.708 BSA 0.784 0.708 1

Non-hepatosplenic extramedullary hematopoiesis (NHS-EMH), the formation of blood cellular elements outside the medulla of the bone marrow and outside the liver and spleen, has been noted among patients with myeloproliferative neoplasms and other serious hematological diseases. However, NHS-EMH is rarely identified among individuals without concurrent hematological disease. Since the radiologic features of NHS-EMH are nonspecific, lesions may be mistaken for metastatic disease when observed in patients with known solid tumors. We report an unusual case of a patient with a simultaneous presentation of malignant melanoma and multiple NHS-EMH lesions. The biopsy revealed trilineage hematopoiesis resembling normal bone marrow tissue, in the absence of abnormalities of peripheral blood counts or presence of driver mutations associated with myeloproliferative neoplasms. The biopsy results were critical in downstaging the patient and thus permitted avoidance of unnecessary malignant melanoma therapy. This case emphasizes the importance of surgical biopsy of suspect lesions when treatment strategies will be impacted.

Introduction: Dropped gallstones (DG) refers to the spillage of gallstones into the abdominal cavity during laparoscopic cholecystectomy (LC). While the majority remain silent, it can result clinically significant complications. Case Description/Methods: A 58-year-old woman with alcoholic cirrhosis presented with acute cholecystitis. Model for End-Stage Liver Disease (MELD) score was 10, with post-operative mortality risk of 0.86% and 3.4% at 7 and 30 days respectively. She underwent an uneventful LC. She returned to the hospital two weeks later with fever and diffuse abdominal pain. Computerized Tomography (CT) imaging noted moderate ascites, an 8 x 4cm gallbladder fossa abscess with single calculi (Fig 1A), and multiple calculi in the pouch of Douglas and anterior cul-de-sac (Fig 1B). Paracentesis revealed 4690 polymorphonuclear (PMN) cells/mm3 consistent with secondary peritonitis, with ascitic culture growing methicillin-susceptible Staphylococcus aureus (MSSA). Abscess was drained percutaneously with cultures positive for MSSA. She was treated with intravenous antibiotics and transitioned to oral cephalexin. Her symptoms resolved. However, she returned to the hospital 6 weeks later with diffuse abdominal pain. CT again revealed moderate ascites along with the previously noted calculi but no abscess. Paracentesis revealed 1080 PMN cells/mm3 and she had no signs of other infection. She was treated with another course of antibiotics and declined surgical retrieval of the calculi. She had no recurrence of symptoms on 6-month follow-up. Discussion: We present here a case of abscess and secondary peritonitis due to DG. The incidence of gallstone spillage during LC varies between 10-40%, with location including the gallbladder fossa, cul-de-sac, peritoneum or Morison’s pouch. Median time to presentation is 5 months post-operatively, and complications include sepsis, peritonitis, abscess, fistula formation. The diagnosis is frequently missed on initial presentation, and not realized until recurrence of symptoms. Abscess drainage and antibiotics may only provide temporary symptom relief. However, complete evacuation and retrieval of stones either surgically or percutaneously will prevent symptom recurrence. DG is a rare source of immediate and delayed post-operative morbidity related to LC. Surgeons and gastroenterologists should be aware of this disease entity, and should have a high index of suspicion for early diagnosis especially in the setting of chronic liver disease, ascites and perihepatic abscess.Figure 1.: Computerized Tomography abdomen and pelvis imaging noted moderate ascites, an 8 x 4cm gallbladder fossa abscess with single calculi (Figure 1A), and multiple calculi in the pouch of Douglas and anterior cul-de-sac (Figure 1B).

Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. 67 hospitals in the United States. Adults with COVID-19 admitted to a participating ICU. Time to death, censored at hospital discharge, or date of last follow-up. Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). Observational design. Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. None.