Invasive aspergillosis is a critical determinant of mortality in cirrhosis: a systematic review with meta-analysis.

Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95% CI: 64.3-91.8, I2 = 59%, P < 0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis. LAY SUMMARY: We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study.

Acute kidney injury in COVID-19: Considerations in pregnancy.

The clinical manifestations of COVID-19 are diverse with the involvement of different organ systems. Renal involvement is particularly noteworthy with acute kidney injury (AKI) being an important disease manifestation, particularly in pregnancy. Pregnancy itself serves as a high-risk condition for COVID-19 disease and a risk factor for deterioration, developing a more severe illness than nonpregnant women, and subsequent higher intensive care unit admission, oxygen therapy, and ventilatory support. There are reports in the literature highlighting the involvement of vital organs in pregnancy; however, data pertaining to AKI in pregnancy during COVID-19 are lacking in terms of risk factors, disease management, and outcomes. The entire spectrum of hormonal changes and adaptive mechanisms in pregnancy can be adversely affected by this viral infection. A literature search regarding AKI in COVID-19 in pregnancy was performed on PubMed, Scopus, Google Scholar, and ScienceDirect, and the relevant articles were selected. Our review highlights key issues pertaining to AKI in COVID-19 in pregnancy in an attempt to overcome, albeit partly, the scarcity of corroborative literature regarding the same.

Advances in the Treatment of Polycythemia Vera: Trends in Disease Management.

Treatment modalities for polycythemia vera (PV) have evolved over time. Phlebotomy and low-dose aspirin suffice in low-risk patients, but cytoreductive therapies are indicated in all high-risk patients (age ≥ 65 years or those with a history of PV-related thrombotic event) and may be considered for low-risk patients with progressively increasing splenomegaly, progressively increasing leucocyte and platelet counts, and for those who do not tolerate phlebotomy. Hydroxyurea/hydroxycarbamide or interferons can be used as first-line drugs. Hydroxyurea may not be tolerated by some patients, and it also carries risk of myelosuppression. Interferon alfa is especially useful for PV symptoms, and the newer preparation, ropeginterferon alfa-2b, has lesser incidence of flu-like reactions. Ruxolitinib reduces the JAK2V617F mutation burden and is used as a second-line drug. Anagrelide reduces platelet production and can be used in conjunction with hydroxyurea in patients with excessive thrombocytosis. The alkylating agent, busulfan, can also be used as a last resort in patients with a limited life expectancy. Prospective future treatments include givinostat, a histone deacetylase inhibitor, and idasanutlin, a murine double minute 2 antagonist.

Atypical mucormycosis masquerading as non-resolving cavitatory pneumonia: A frequently misdiagnosed entity.

We are reporting an unusual case of cavitatory pulmonary mucormycosis in a patient with uncontrolled type 2 diabetes mellitus who was treated successfully. This is a unique case of pulmonary mucormycosis masquerading as cavitatory pulmonary disease. A 45-year-old female presented with fever, chest pain, cough and breathlessness. She was also found to have very high blood glucose due to previously undiagnosed diabetes. Diabetic ketoacidosis is the most common predisposing factor for mucormycosis. Our patient had uncontrolled diabetes and presented with bilateral cavitatory pulmonary lesions even in the absence of diabetic ketoacidosis. Appropriate investigations were ordered, and alternate causes of lung cavitation were diligently excluded. She was treated with amphotericin-B for three weeks followed by oral posaconazole for eight weeks with excellent outcome. A low threshold for detection as well as a differential of mucormycosis must be kept in immunocompromised patients presenting with cavitatory lung disease.

Expanding spectrum of DADA2: a review of phenotypes, genetics, pathogenesis and treatment.

Deficiency of adenosine deaminase 2 (DADA2) is a monogenic disease caused by biallelic mutations in ADA2 gene (previously CECR1). The aim of this review was to describe the clinical phenotypes, genetics, pathogenesis and treatment of DADA2. ADA2 is highly expressed on myeloid cells and deficiency leads to polarisation of macrophages to an M1 inflammatory type and activation of neutrophils. The pathogenesis of immunological and haematological manifestations is less clear. The spectrum of clinical presentations varies widely from asymptomatic individual to severe vasculitis, several autoinflammatory, immunological and haematological manifestations. Initially considered a childhood disease, the first presentation is now being reported well into adulthood. Vasculitis closely resembles polyarteritis nodosa. Livedoid reticularis/racemosa like skin rash and central nervous system involvement in the form of ischemic or haemorrhagic stroke are dominant manifestations. Immunological manifestations include hypogammaglobulinemia and recurrent infections. Lymphopenia is the most common haematological manifestation; pure red cell aplasia and bone marrow failure has been reported in severe cases. The disease is extremely heterogeneous with variable severity noted in patients with the same mutation and even within family members. Tumour necrosis factor inhibitors are currently the treatment of choice for vasculitic and inflammatory manifestations and also prevent strokes. Haematopoietic stem cell transplantation is a curative option for severe haematological manifestations like pure red cell aplasia, bone marrow failure and immunodeficiency. Further research is required to understand pathogenesis and all clinical aspects of this disease to enable early diagnosis and prompt treatment. Key Points • Deficiency of adenosine deaminase 2 (DADA2) is a monogenic disease caused by biallelic mutations in ADA2 gene. • The clinical features include vasculitis resembling polyarteritis nodosa, autoinflammation, haematological manifestations and immunodeficiency. • The severity varies widely from mild to fatal even in patients within a family and with the same mutation. • The treatment of choice for inflammatory and vasculitic disease is tumour necrosis factor α blockers. Bone marrow transplant may be considered for severe haematological disease.

Helminthic Infection in the Background of Active Pulmonary Tuberculosis: An Underreported Co-infection.

Helminthic infections are widely prevalent in resource-poor countries. Tuberculosis, a disease contributing significantly to morbidity and mortality in endemic areas, often co-exists with helminthic infections. Poor living standards predispose to both of them. Moreover, untreated helminthic infection enhances the deleterious impact of tuberculosis, largely through immunological alteration. We are reporting the case of a 22-year-old male who presented with a month-long history of abdominal pain, nausea, vomiting, fever and cough complicated by hemoptysis, along with an episode of the passage of a worm in the vomitus. A thorough workup revealed active pulmonary tuberculosis co-existing with intestinal ascariasis. Anti-helminthic therapy was initiated along with anti-tubercular therapy, leading to significant improvement.

Systemic Lupus Erythematosus Induced Central Variant of Posterior Reversible Encephalopathy Syndrome: A Rare Association.

Involvement of the posterior cerebral structures is well established in patients with posterior reversible encephalopathy syndrome (PRES). In striking contrast to this, a subset of patients may have an atypical presentation characterized by the involvement of central structures. This is usually seen in the backdrop of systemic lupus erythematosus (SLE), a rare but known cause of PRES. Timely diagnosis with judicious use of radiological modalities and therapeutic intervention is key for successful recovery; however, the prognosis of PRES in patients with SLE is not very promising. We are describing an extremely rare case of a patient diagnosed with a central variant of PRES with previously undiagnosed SLE.

Splenic and Portal Vein Thrombosis With Concurrent Splenic Infarction: A Rare Manifestation of Essential Thrombocythemia.

Mesenteric venous thrombosis (MVT) presents with a wide range of clinical presentations depending on the vessel involved, degree of thrombosis, and the extent of bowel wall ischemia. MVT usually has an insidious presentation and is often a forerunner of an underlying disorder. Essential thrombocythemia (ET) presenting itself as MVT along with splenic infarction is a rare presentation. Here, we report the case of a 54-year-old female with massive splenomegaly, thrombocytosis, and acute splenic and portal venous thrombosis along with multiple splenic infarcts. Bone marrow suggested ET with JAK2V617F mutation positivity. She was managed conservatively and made an uneventful recovery.

Isolated Splenic Tuberculosis: A Diagnostic Conundrum.

Tuberculosis is an established cause of pyrexia of unknown origin and can implicate practically any human organ system. Splenic involvement is common in disseminated or miliary tuberculosis following hematogenous spread, but isolated splenic involvement is a very rare phenomenon. We report the case of a 30-year-old immunocompetent female who presented with high-grade fever and dull aching pain in the left hypochondrium for three months. Laboratory data provided no diagnostic information. Abdominal ultrasonography revealed an enlarged spleen with multiple small hypoechoic lesions that were corroborated on computed tomography. No pulmonary involvement or primary focus of infection was discernible elsewhere. Splenic fine needle aspiration cytology helped clinch a histopathological diagnosis of isolated splenic tuberculosis. Administration of anti-tubercular therapy resulted in resolution of the disease and an excellent outcome in our patient.

Idiopathic Symmetrical Peripheral Gangrene: A Rare Clinical Entity.

Symmetrical peripheral gangrene (SPG) is a rare disorder leading to ischemic necrosis of extremities. We present a rare case of idiopathic SPG in a 58-year-old male who did not seek any medical care, and history was elucidated only after he presented one year later for treatment of pneumonia. Extensive investigations revealed no etiology. SPG can result from a variety of conditions that cause disseminated intravascular coagulation and lead to distal hypoperfusion. The treatment is aimed at the control of the underlying disease and wound management.

Postmenopausal Hormone Therapy and Its Association with Breast Cancer.

With the cessation of estrogen and progesterone at menopause, the hormone withdrawal affects various systems in the woman's body. In earlier days, menopausal hormone therapy (HT) was prescribed for primary prevention of coronary artery disease (CAD) and osteoporosis, which were thought to be because of estrogen deprivation and epidemiologic data supported a beneficial effect of estrogen on the heart and bone. Later on, robust data from the Women's Health Initiative study comparing two HT trials demonstrated adverse outcomes in terms of excess risk of CAD, stroke, venous thromboembolism, and breast cancer. Even with risk stratification based on family history, approximately only 15% of women diagnosed with breast cancer have such a risk factor. This implies that family history will not be elicited in more than 85% of women who develop breast cancer. Literature review suggests that the prior use of conjugated equine estrogen (CEE) alone has the potential to be effective as an intervention, leading to a reduction in mortality due to breast cancer. Therefore, it is time to reevaluate the risk reduction strategies for breast cancer that are currently in practice. In terms of absolute numbers, for every 10,000 person-years of prior use of CEE alone, there would be only two fewer deaths from breast cancer and two fewer deaths secondary to its sequelae. This translates into a significant number of women in our country with a population of 1.38 billion (of which 48%, nearly 650 million, are women).

A Case of Methyl Ethyl Ketone Peroxide Ingestion Complicated by Rhabdomyolysis.

Methyl ethyl ketone peroxide (MEKP) is a colorless-to-faintly-yellow liquid that is used as a cross-linking to harden plastics or resins in various industries. It is also an ingredient of paints, varnishes, and paint removers. Because of the high reactivity of MEKP, it is available only as a 40% to 60% solution in dimethyl phthalate or other phthalates. Post-ingestion, the spectrum of complications is vast, ranging from corrosive injury in the oral cavity and gastrointestinal tract to fulminant hepatic toxicity, sepsis, multi-organ failure, and disseminated intravascular coagulation. We report the case of a 40-year-old, self-employed, male worker in a lamination workshop, who presented with accidental ingestion of MEKP from an unlabeled container. He subsequently developed a multitude of complications, most noteworthy being rhabdomyolysis and in turn acute kidney injury. The patient was managed in the intensive care unit with supportive management and hemodialysis sessions; however, the patient succumbed to his illness, despite aggressive measures.

Reversible Myelosuppresion With Prolonged Usage of Linezolid in Treatment of Methicillin-Resistant Staphylococcus aureus.

Bone marrow suppression has a wide variety of causes. One of the overlooked causes is linezolid, a drug that is now being extensively used in the management of not only soft tissue infections but also hospital-acquired infections. Methicillin-resistant Staphylococcus aureus (MRSA) is widely being treated with linezolid. It becomes imperative that we comprehensively understand the hematological adverse effect profile of this drug. A reversible myelosuppression is seen with its extended use, though a number of risk factors like renal impairment are usually present. A prompt diagnosis can help us to timely discontinue the drug. We report one such case of an elderly patient with septic arthritis of the knee who developed pancytopenia after 32 days of linezolid therapy. Withdrawal of the drug led to a complete recovery of the blood counts in 21 days.