Pulmonary Mucormycosis in Chronic Lymphocytic Leukemia and Neutropenia.

Pulmonary mucormycosis is a rare life-threatening fungal infection associated with high mortality. We present the case of a 61-year-old man with history of chronic lymphocytic leukemia who presented with fever and cough, eventually diagnosed with pulmonary mucormycosis after right lung video-assisted thoracoscopic surgery. The patient was successfully treated with amphotericin B and right lung pneumonectomy; however, he later died from left lung pneumonia

Atraumatic splenic rupture associated with apixaban.

Apixaban is a direct oral anticoagulant that works by inhibiting factor Xa. It has been associated with adverse bleeding outcomes including atraumatic splenic rupture. We present the case of an 86-year-old man who presented with features of left upper abdominal pain and hemorrhagic shock found to have atraumatic splenic rupture and hemoperitoneum on imaging

Acquired von Willebrand disease associated with monoclonal gammopathy of unknown significance

We present a case of a 79-year-old male who presented with retroperitoneal hematoma a week after motor vehicle accident. Prior history and family history of bleeding were nonsignificant. His activated partial thromboplastin time was found to be prolonged in the emergency department. Further workup with coagulation studies showed decreased factor VIII, vWF antigen, and vWF:ristocetin cofactor assay, and negative Bethesda assay, indicating acquired von Willebrand disease. Immunofluorescence to find an underlying etiology was suggestive of MGUS. Management of AvWD depends on controlling active bleeding and treating the underlying cause. He was treated with factor VIII, haemate-p, rituximab, two cycles of IVIg, and three weeks of oral steroids

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Celiac Disease Manifesting as Severe Malabsorption

Case Presentation: A 20-year-old man with type 1 diabetes, hypothyroidism, and hypomagnesemia presented for evaluation of hypocalcemia. Patient reported progressive lack of motivation and depression. He developed lower extremity swelling and abdominal distention over the past 3 months. He denied fatigue, heat or cold intolerance, weight change, polydipsia, polyuria, chest pain, palpitations, shortness of breath, abdominal pain, diarrhea, muscle spasms, perioral numbness or tingling. On exam, patient was ill-appearing. His BMI was 20.7 kg/m2. He had sparse facial and body hair and exhibited pallor. Heart was regular rate and rhythm. Abdomen was distended, and patient had pitting lower extremity edema extending to the knees. Chovstek’s sign was positive. Lab work revealed leukocytosis (WBC16.6 B/L), anemia (Hgb 8.6 g/dL), hypokalemia (3.1 Meq/L), hypomagnesemia (1.0 mg/dL), hypocalcemia (ionized calcium 0.76 mmol/L), hypoalbuminemia (2.7 g/dL), transaminitis (AST168 IU/L, ALT 81 IU/L) with normal total bilirubin, hypothyroidism (TSH 383.640 uIU/mL, FT4 0.56 ng/dL), hyperparathyroidism (PTH 193 pg/mL), and low vitamin D 25 Hydroxy (9.1 ng/mL). Hemoglobin A1c was 15%. EKG showed sinus tachycardia with no acute changes; QTc was prolonged at 495 msec. X ray of the abdomen revealed distended bowels without obstruction. Patient received intravenous calcium gluconate, calcitriol, and magnesium. CT abdomen revealed enteritis with extensive mesenteric adenopathy. AM cortisol, LH and FSH were normal. Total and free testosterone were low (130 ng/dL and 19 ng/dL respectively). Iron and ferritin were low (14 mcg/dL and 7 ng/mL respectively), vitamin B12 was normal, folate was low (5.5 ng/mL). Upon further questioning, patient revealed he had been avoiding bread and pasta, as these worsened his abdominal distention. Patient underwent esophogastroduodenoscopy which revealed scalloped duodenal folds without frank inflammatory changes. Endomysial antibodies were negative, tissue transglutaminase antibody was greater than 100 U/mL. Pathology showed chronic duodenitis with marked villous blunting with intraepithelial lymphocytosis consistent with celiac disease. Patient was initiated on gluten free diet and discharged on oral calcium, magnesium, vitamin D, and iron supplementation. At 2 weeks follow up, patient showed improvement in pallor and abdominal distention, and lower extremity edema had resolved. Patient’s calcium, magnesium, and TSH were all improved. Discussion: Celiac disease is a chronic inflammatory gluten mediated enteropathy with variable manifestations, although classically presenting with weight loss, chronic abdominal pain and diarrhea. Patient’s with autoimmune diseases such as type 1 diabetes and hypothyroidism are at elevated risk of developing this disorder. Untreated, it can lead to severe malabsorption and also increase the risk of certain malignancies such as lymphomas. Thus, early recognition and diagnosis is critical. Diagnosis is made with serologic testing of tissue transglutaminase-IgA antibody levels and bowel biopsy. Celiac disease is often easily treated with avoidance of consumption of gluten containing products. Conclusions: Celiac disease is a significant and often debilitating syndrome affecting multiple organs. Diarrhea is the most common manifestation. However, patients can lack gastrointestinal symptoms and only present with signs of malabsorption. Thus, patients with evidence of poor nutrient absorption should be tested for the disease

Perioperative Glucocorticoid Management in Patients with Rheumatologic Diseases Undergoing Elective Joint Surgeries

Over 7 million Americans are estimated to suffer from inflammatory rheumatologic diseases and the rate of joint arthroplasties are nearly 50 % higher among this population as compared to controls. Many of these patients are on glucocorticoids around the time of their joint surgeries. The optimum perioperative management of glucocorticoid dosing is not known and there is no established clinical practice. The most recent recommendation by American College of Rheumatology/ American Association of Hip and Knee Surgeons to continue home steroid dose rather than administer supraphysiologic stress dose for patients undergoing elective arthroplasties was based on a low level of evidence. The aim of our study was to compare the rates of peri- and postoperative outcomes after elective joint arthroplasties with continuing home glucocorticoid dosing versus administering stress dose steroid

Pelvic Lymphocele: An Obscure Cause of Unilateral Leg Swelling

Case Presentation: A 57-year-old man with robotic prostatectomy 2 months ago for prostate cancer presented with 2 days of right lower extremity swelling. His history was notable for a large right lower extremity deep vein thrombosis (DVT) for which he had an IVC filter placed, and pulmonary embolus for which he was on rivaroxaban. He denied fever, chills, joint pain, muscle aches, recent trauma or falls. On examination, he had uniform non- pitting edema of the right lower extremity from ankle to thigh, without associated tenderness, deformity or skin changes. Right lower extremity pulses and sensation were intact. He was afebrile without leukocytosis. Ultrasound of the right lower extremity revealed no evidence of acute DVT, and resolution of the previous thrombus. CT scan of abdomen and pelvis identified a right groin lymphocele that was compressing the right iliac vein. Interventional radiology placed a percutaneous drain and the patient was discharged home. On follow up, his swelling had significantly improved and as there was no further drainage, the percutaneous catheter was removed. Discussion: Unilateral leg swelling is commonly encountered and poses a diagnostic challenge. Acute unilateral lower extremity swelling is usually due to DVT or trauma, whereas lymphedema and venous insufficiency are common causes of chronic swelling. Lymphocele formation that leads to major complications after radical prostatectomy is rare, and is usually seen in the early postoperative period. However, it should be considered in patients with fever, abdominal pain or leg swelling during the late postoperative period in patients who underwent extensive lymph node dissection. Surgical treatment options are available, but percutaneous intervention is preferred. Conclusions: Pelvic lymphocele, a collection of lymphatic fluid that develops after extensive lymphadenectomies, is not an infrequent complication after radical prostatectomy and pelvic lymphadenectomy occurring in 20% of cases. Rarely pelvic lymphocele may cause unilateral leg swelling due to its mass effect causing a diagnostic dilemma

Mycobacterium mucogenicum Hand Infection in an Intravenous Drug Abuser

Mycobacterium mucogenicum is a rapidly growing mycobacterium found ubiquitously in water sources. It has been reported to cause widespread infections with infection entry from wound or central venous catheters especially in immunocompromised patients. Diagnosis is made from blood cultures which may take at least a week. Management includes removal of the source or drainage of wound infections and combination antimicrobial therapy