The uncommon preoperative diagnosis of a De Garengeot hernia and its more novel laparoscopic treatment.

This case report involves an elderly woman who presented with a 3-day history of a tender groin swelling on her right side. Her admission bloods were fairly unremarkable, but a preoperative ultrasound impressively confirmed a femoral hernia containing the appendix (De Garengeot hernia) and she underwent emergency laparoscopic hernioplasty with a prosthetic mesh and appendicectomy. The procedure found an incarcerated hernia with a strangulated tip of the appendix that unexpectedly separated upon gentle manipulation and histopathology revealed appendiceal inflammation. There were no complications with the patient's recovery and she was discharged 2 days after surgery.

Multicenter analysis of immunosuppressive medications on the risk of malignancy following adult solid organ transplantation.

Objective: This study aimed to assess the risk of maintenance immunosuppression on the post-transplant risk of malignancy across all solid organ transplant types. Methods: This is a retrospective cohort study from a multicenter hospital system in the United States. The electronic health record was queried from 2000 to 2021 for cases of solid organ transplant, immunosuppressive medications, and post-transplant malignancy. Results: A total of 5,591 patients, 6,142 transplanted organs, and 517 post-transplant malignancies were identified. Skin cancer was the most common type of malignancy at 52.8%, whereas liver cancer was the first malignancy to present at a median time of 351 days post-transplant. Heart and lung transplant recipients had the highest rate of malignancy, but this finding was not significant upon adjusting for immunosuppressive medications (heart HR 0.96, 95% CI 0.72 - 1.3, p = 0.88; lung HR 1.01, 95% CI 0.77 - 1.33, p = 0.94). Random forest variable importance calculations and time-dependent multivariate cox proportional hazard analysis identified an increased risk of cancer in patients receiving immunosuppressive therapy with sirolimus (HR 1.41, 95% CI 1.05 - 1.9, p = 0.04), azathioprine (HR 2.1, 95% CI 1.58 - 2.79, p < 0.001), and cyclosporine (HR 1.59, 95% CI 1.17 - 2.17, p = 0.007), while tacrolimus (HR 0.59, 95% CI 0.44 - 0.81, p < 0.001) was associated with low rates of post-transplant neoplasia. Conclusion: Our results show varying risks of immunosuppressive medications associated with the development of post-transplant malignancy, demonstrating the importance of cancer detection and surveillance strategies in solid organ transplant recipients.

Application of Next-Generation Sequencing-Based Mutational Profiling in Acute Lymphoblastic Leukemia.

PURPOSE OF REVIEW: Recent efforts to characterize hematologic cancers with genetic and molecular detail have largely relied on mutational profiling via next-generation sequencing (NGS). The application of NGS-guided disease prognostication and clinical decision making requires a basic understanding of sequencing advantages, pitfalls, and areas where clinical care might be enhanced by the knowledge generated. This article identifies avenues within the landscape of adult acute lymphoblastic leukemia (ALL) where mutational data hold the opportunity to enhance understanding of disease biology and patient care. RECENT FINDINGS: NGS-based assessment of measurable residual disease (MRD) after ALL treatment allows for a sensitive and specific molecular survey that is at least comparable, if not superior, to existing techniques. Mutational assessment by NGS has unraveled complex signaling networks that drive pathogenesis of T-cell ALL. Sequencing of patients with familial clustering of ALL has also identified novel germline mutations whose inheritance predisposes to disease development in successive generations. While NGS-based assessment of hematopoietic malignancies often provides actionable information to clinicians, patients with acute lymphoblastic leukemia are left underserved due to a lack of disease classification and prognostication schema that integrate molecular data. Ongoing research is positioned to enrich the molecular toolbox available to clinicians caring for adult ALL patients and deliver new insights to guide therapeutic selection, monitor clinical response, and detect relapse.

Targeted Therapies for the Evolving Molecular Landscape of Acute Myeloid Leukemia.

Despite considerable growth in our understanding of the heterogeneous biology and pathogenesis of acute myeloid leukemia (AML) in recent decades, for nearly forty years, little progress was gained in the realm of novel therapeutics. Since 2017, however, nine agents have been FDA-approved for patients with AML in both the upfront and relapsed/refractory (R/R) settings. Most of these compounds function as inhibitors of key cell cycle enzymatic pathways or mediators of leukemic proliferation and survival. They have been approved both as single agents and in combination with conventional or reduced-intensity conventional chemotherapeutics. In this article, we review the molecular landscape of de novo vs. R/R AML and highlight the potential translational impact of defined molecular disease subsets. We also highlight several recent agents that have entered the therapeutic armamentarium and where they fit in the AML treatment landscape, with a focus on FLT3 inhibitors, IDH1 and IDH2 inhibitors, and venetoclax. Finally, we close with a survey of two promising novel agents under investigation that are poised to enter the mainstream clinical arena in the near future.

A case of endovascular management to gain control of a lower gastrointestinal haemorrhage caused by appendiceal artery bleeding.

Bleeding from the appendix is a rare cause of lower gastrointestinal haemorrhage. Previous publications have noted diagnosis via colonoscopy or computed tomography angiogram and treatment via surgical or endoscopy. We report a case of large volume per rectal bleeding from the appendix, with diagnosis and treatment via angiography and coil insertion, which is the first of its kind reported in the literature.

SARS-CoV-2 infection in acute pancreatitis increases disease severity and 30-day mortality: COVID PAN collaborative study.

OBJECTIVE: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection. DESIGN: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups. RESULTS: 1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection. CONCLUSION: Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.

Implementing COVID-19 Mitigation in the Community Mental Health Setting: March 2020 and Lessons Learned.

In March 2020, at the beginning of the COVID-19 pandemic, state-funded community mental health service programs (CMHSP) in Michigan, organized into 10 regions known as a "Prepaid Inpatient Health Plan" (PIHP), grappled with the task of developing a modified plan of operations, while complying with mitigation and social distancing guidelines. With the premise that psychiatric care is essential healthcare, a panel of physician and non-physician leaders representing Region 5, met and developed recommendations, and feedback iteratively, using an adaptive modified Delphi methodology. This facilitated the development of a service and patient prioritization document to triage and to deliver behavioral health services in 21 counties which comprised Region 5 PIHP. Our procedures were organized around the principles of mitigation and contingency management, like physical health service delivery paradigms. The purpose of this manuscript is to share region 5 PIHP's response; a process which has allowed continuity of care during these unprecedented times.

Occlusive Hepatic Artery Thrombus in a Deceased-Donor Liver Procured From a Donor With Blunt Abdominal Trauma Following a Road Traffic Collision Accident.

Here, we describe a case of occlusive hepatic artery thrombus in a liver procured from an 18-year-old deceased donor after circulatory death. The donor had died of multiple trauma following a road traffic collision. Occlusive thrombus was found at the hepatic artery bifurcation during back-table preparation. Consequently, the liver transplant did not proceed. We suggest careful assessment of hepatic arteries of all donor livers before transplant, particularly those from donors who are involved in deceleration injuries. Transplanting such livers may lead to primary nonfunction.

Laparoscopic redo anti-reflux surgery: Case-series of different presentations, varied management and their outcomes.

BACKGROUND: A minority of patients undergoing surgery for refractory gastroesophageal reflux disease (GORD) will require revision antireflux surgery ("redo-ARS") for persistent symptoms or complications. Although a repeat minimally invasive procedure for revision may be technically challenging due to post-operative changes, studies are beginning to show favourable data for the laparoscopic approach. METHOD: From a single institution 41 consecutive cases of laparoscopic redo-ARS performed by the same surgeon were classified by mode of presentation to analyse their intra-operative findings, management and post-operative outcomes. Cases were classified as either early, emergency or late. RESULTS: There were 12 early, 4 emergency and 25 late redo-ARS cases. Complete resolution of symptoms, using the criteria of less than weekly symptoms and off all anti-reflux medications, were acquired in 6 (50%), 2 (50%) and 16 (64%) patients within the early, emergency and late groups respectively. Overall morbidity following revision was 7.3% with no mortality. There were no open conversions. CONCLUSION: Although fewer patients will achieve complete resolution of symptoms as compared with outcomes following primary ARS, laparoscopic revision of ARS is a safe and effective approach for the revision of anti-reflux surgery in the early, emergency and elective settings.

Utility of drain fluid amylase measurement on the first postoperative day after pancreaticoduodenectomy.

BACKGROUND: Early detection of pancreatic fistula (PF) may improve the outcome after pancreaticoduodenectomy, and exclusion of PF may allow earlier drain removal and accelerate recovery. The aim of the present study was to evaluate the relationship between drain fluid amylase on the first postoperative day (DFA(1)) and PF. PATIENTS AND METHODS: This work was designed as a prospective study and included patients undergoing pancreaticoduodenectomy in a single center. For each patient, DFA was measured on the first and fifth postoperative days, and PF was defined by drainage of amylase-rich fluid on the fifth postoperative day (DFA(5) >300 U/l). A cut-off value of DFA(1) was derived, which yielded sensitivity and negative predictive value of 100% for predicting a PF. RESULTS: A total of 70 patients (47% male) who underwent pancreaticoduodenectomy (Whipple procedure: 37; pylorus-preserving procedure: 33) between April 2009 and March 2010 were included. Nine of those patients developed a PF (grade A-2; B-5; C-2). There were two postoperative deaths (3%). The DFA(1) value significantly correlated with DFA(5) (Spearman rank coefficient 0.68; p < 0.0001). The median DFA(1) of patients with a PF (6,205; range 357-23,391) was significantly higher than in patients without a PF (69; range 5-5,180; p = 0.01; unpaired t test). No patient with a PF had a DFA(1) ≤350 U/l, compared to 48/61 patients (79%) without a PF. Using 350 U/l as a cut-off, a low DFA(1) excluded a PF with a sensitivity, specificity, positive and negative predictive values of 100, 79, 41, and 100%, respectively. CONCLUSIONS: Drain fluid amylase on the DFA(1) after pancreaticoduodenectomy stratifies patients according to likelihood of developing a PF.

Liver transplantation for acute intermittent porphyria: a viable treatment?

BACKGROUND: Acute intermittent porphyria (AIP) is the most common hepatic porphyria. Its clinical presentation includes severe disabling and life-threatening neurovisceral symptoms and acute psychiatric symptoms. These symptoms result from the overproduction and accumulation of porphyrin precursors, 5-aminoleuvulinic acid (ALA) and porphobilinogen (PBG). The effect of medical treatment is transient and is not effective once irreversible neurological damage has occurred. Liver transplantation (LT) replaces hepatic enzymes and can restore normal excretion of ALA and PBG and prevent acute attacks. METHOD: Two cases of LT for AIP were identified retrospectively from a prospectively maintained LT database. RESULT: LT was successful with resolution of AIP in two patients who suffered from repeated acute attacks. CONCLUSION: LT can correct the underlying metabolic abnormality in AIP and improves quality of life significantly.