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The coronavirus disease-19 (COVID-19) pandemic has forced hospitals to prioritize COVID-19 patients, restrict resources, and cancel all non-urgent elective cardiac procedures. Clinical visits have only been facilitated for emergency purposes. Fewer patients have been admitted to the hospital for both ST-segment elevation myocardial infarctions (STEMI) and non-ST segment elevation myocardial infarctions (NSTEMI) and a profound decrease in heart failure services has been reported. A similar reduction in the patient presentation is seen for ischemic heart disease, decompensated heart failure, and endocarditis. Cardiovascular services, including catheterization, primary percutaneous coronary intervention (PPCI), cardiac investigations such as electrocardiograms (ECGs), exercise tolerance test (ETT), dobutamine stress test, computed tomography (CT) angiography, transesophageal echocardiography (TOE) have been reported to have declined and performed on a priority basis. The long-term implications of this decline have been discussed with major concerns of severe cardiac complications and vulnerabilities in cardiac patients. The pandemic has also had psychological impacts on patients causing them to avoid seeking medical help. This review discusses the effects of the COVID-19 pandemic on the provision of various cardiology services and aims to provide strategies to restore cardiovascular services including structural changes in the hospital to make up for the reduced staff personnel, the use of personal protective equipment in healthcare workers, and provides alternatives for high-risk cardiac imaging, cardiac interventions, and procedures. Implementation of the triage system, risk assessment scores, and telemedicine services in patients and their adaptation to the cardiovascular department have been discussed.
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COVID-19/epidemiologia , Cardiologia/organização & administração , Atenção à Saúde/organização & administração , Controle de Infecções/organização & administração , COVID-19/prevenção & controle , COVID-19/transmissão , Procedimentos Cirúrgicos Cardiovasculares , Humanos , Telemedicina , TriagemRESUMO
Point-of-care ultrasonography (POCUS), particularly venous excess ultrasound (VExUS) is emerging as a valuable bedside tool to gain real-time hemodynamic insights. This modality, derived from hepatic vein, portal vein, and intrarenal vessel Doppler patterns, offers a scoring system for dynamic venous congestion assessment. Such an assessment can be crucial in effective management of patients with heart failure exacerbation. It facilitates diagnosis, quantification of congestion, prognostication, and monitoring the efficacy of decongestive therapy. As such, it can effectively help to manage cardiorenal syndromes in various clinical settings. Extended or eVExUS explores additional veins, potentially broadening its applications. While VExUS demonstrates promising outcomes, challenges persist, particularly in cases involving renal and liver parenchymal disease, arrhythmias, and situations of pressure and volume overload overlap. Proficiency in utilizing spectral Doppler is pivotal for clinicians to effectively employ this tool. Hence, the integration of POCUS, especially advanced applications like VExUS, into routine clinical practice necessitates enhanced training across medical specialties.
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Hamman syndrome is defined as dissection of air in mediastinum and skin fascia usually due to increased intrathoracic pressure. The air leak tends to make its way into pleural and pericardial layers; however, in rare instances air can also dissect into epidural spaces, regarded as pneumorrhachis. We present a case of a young male with a history of polysubstance abuse and e-vaping, who presented with symptoms of altered mental status. Given the concerning physical examination, a computed tomography of the chest was undertaken, which showed pneumothorax, pneumomediastinum and pneumorrhachis. The patient was closely monitored in the intensive care unit and improved after symptomatic management. The symptoms of pneumorrhachis depend on the volume and location of air in intracranial and intraspinal space. Although asymptomatic in our case, it is crucial for clinicians to be aware that pneumorrhachis with Hamman syndrome can potentially cause neurological deficits and cardiopulmonary arrest in severe cases due to increased intraspinal and intracranial hypertension, emphasising the need for close monitoring. LEARNING POINTS: Elevated intrathoracic pressure generated by deep inhalation of an aerosolised product is one of the triggers of air dissection in pleural, pericardial, and mediastinal regions. In rare instances, air can also translocate into intracranial and intraspinal spaces, which is referred to as pneumorrhachis.Mostly asymptomatic, pneumorrhachis has the potential to develop acute neurological deficits due to increased intracranial and intraspinal pressure, validating the need for acute monitoring.Most cases of pneumorrhachis are managed conservatively. However, severe cases warrant decompression or high concentrations of oxygen administration to facilitate air absorption.
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Acute myocardial infarction (MI) is one of the leading global healthcare emergencies, contributing to over three million global deaths. The purpose of this study is to investigate further the efficacy of sacubitril/valsartan over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in reducing the risk of heart failure (HF) in post-MI patients and providing a clear evidence-based medicine guideline for future use. An electronic database search was conducted on English databases. Eight articles were included, fulfilling our inclusion criteria, i.e., adult patients of ≥18 years with a recent diagnosis of acute MI. Pooled analysis was done using Review Manager version 5.4.1 (Cochrane Collaboration, London, England), and the data for each outcome were analyzed as dichotomous variables. A total of eight clinical trials were included in the meta-analysis. Six studies analyzed the sacubitril/valsartan and ACEI combination. The pooled analysis reported a significant increase in the risk of hypotension (relative risk {RR}: 1.29 {1.18, 1.41}) in the sacubitril/valsartan compared to the ACEI alone group. In addition, a significant increase was observed in the left ventricle ejection fraction (LVEF) after using the sacubitril/valsartan combination compared to using ACEI alone (RR: 3.08 {2.68, 4.48}). Furthermore, no significant difference was observed between the groups in terms of mortality rate (RR: 0.86 {0.73, 1.02}), the risk of heart failure (RR: 0.62 {0.39, 1.00}), the frequency of recurrent MI (RR: 0.86 {0.27, 2.76}), and the mean difference of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (weighted mean difference {WMD}: -174.36 {-414.18, 65.46}) between both the groups. However, the sacubitril/valsartan combination proved to be beneficial in significantly reducing the risk of major adverse cardiac events (MACE) (RR: 0.64 {0.48, 0.84}) and rehospitalizations (RR: 0.53 {0.39, 0.71}) as compared to ACEI post MI. Additionally, sacubitril/valsartan and ARB's combination was reported in two studies. This led to a significant decrease in NT-proBNP concentration (WMD: -71.91 {-138.43, -5.39}) post MI in the sacubitril/valsartan combination group compared to the ARB usage alone. However, no significant difference was observed in the improvement of LVEF (WMD: 0.88 {-5.11, 6.87}) between both groups. Although the sacubitril/valsartan combination has no difference in mortality and outcomes compared to ACEI, there is evidence that using it proves to be more beneficial post MI compared to ACEI and ARB usage alone.
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Deglutition syncope and carotid sinus hypersensitivity are neurally mediated events, leading to potentially dangerous arrhythmias and cardiovascular events. Mostly related to underlying gastroesophageal or cardiovascular causes, sometimes, this might not be the case. We report the first-ever documented case of deglutition syncope with acute suppurative parotitis, which resolved after resolving the parotid gland's swelling.
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Thrombotic thrombocytopenic purpura (TTP) is a known menace in hematology and is quite rare in practice with known triggers. Lately, in the COVID-19 pandemic, hematology has seen a new pathology amongst which TTP associated with COVID-19 messenger RNA (mRNA) vaccine is unique. We report a case of a 69-year-old male with multiple comorbidities who presented to the hospital with severe fatigue and shortness of breath. Labs were significant for thrombocytopenia, anemia, and hemolysis with schistocytes consistent with TTP with a second dose of BNT162b2 mRNA vaccine as a likely culprit been documented.
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Vacinas contra COVID-19/efeitos adversos , COVID-19 , Imunização Secundária/efeitos adversos , Pandemias , Púrpura Trombocitopênica Trombótica/etiologia , SARS-CoV-2 , Proteína ADAMTS13/imunologia , Idoso , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Terapia Combinada , Dispneia/etiologia , Fadiga/etiologia , Infecções por HIV/complicações , Hepatite B Crônica/complicações , Humanos , Hipertensão/complicações , Imunossupressores/uso terapêutico , Falência Renal Crônica/complicações , Masculino , Troca Plasmática , Púrpura Trombocitopênica Trombótica/sangue , Púrpura Trombocitopênica Trombótica/terapia , Trombose Venosa/complicaçõesRESUMO
Background: Duplication of the vas deferens, a rare congenital anomaly of the pelvic anatomy, is often an incidental finding during surgeries involving the spermatic cord, such as inguinal hernia repair, varicocelectomy, orchidopexy, and vasectomy. Case Report: A 25-year-old male presented to our surgical outpatient clinic with bilateral swelling in the inguinal region. A diagnosis of bilateral inguinal hernia was established. While performing spermatic cord dissection during hernioplasty, a duplicated vas deferens was revealed within the left spermatic cord. Doppler ultrasonography confirmed the absence of waveforms in both vasa deferentia, differentiating them from adjacent vessels. The hernia repair was performed without complications. Conclusion: Our case highlights the importance of radiologists' and surgeons' ability to recognize a duplicated vas deferens to avoid possible iatrogenic injury.
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Non-Hodgkin lymphoma is one of the most common hematological malignancies having both nodal and extranodal sites of involvement. The thyroid gland is one of the rarest primary sites. Most cases of primary thyroid lymphoma are diffuse large B-cell in nature; thus, aggressive and in extreme cases can rapidly lead to airway compromise, especially in patients who have been living with goiter for years. We present one such case of a 64-year-old female who presented with signs of airway compromise, requiring emergent airway intubation and surgical debulking. She was treated with emergent chemotherapy (DA-EPOCH-R regimen), without radiotherapy and this resulted in complete remission.
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The development of spontaneous pneumomediastinum and subcutaneous emphysema are few of the rare clinical manifestations observed in coronavirus disease-19 (COVID-19) patients which are yet to be fully understood. Most cases of spontaneous pneumomediastinum arise due to factors causing high intra-alveolar pressure. Herein, we report a case of a COVID-19 positive elderly male, who presented with spontaneous pneumomediastinum and subcutaneous emphysema unrelated to high-pressure ventilatory measures, detected on chest computed tomography (CT). Despite acute medical care, the patient progressed towards a more serious clinical course. Male gender and diffuse alveolar damage caused by COVID-19 seems to be the most relevant association in this case. However, we have enlightened other possible pathological mechanisms and their association with severity index of COVID-19.
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COVID-19/complicações , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Subcutâneo/diagnóstico por imagem , COVID-19/fisiopatologia , Progressão da Doença , Humanos , Masculino , Enfisema Mediastínico/virologia , Pessoa de Meia-Idade , Enfisema Subcutâneo/virologia , Tomografia Computadorizada por Raios XRESUMO
Restless leg syndrome (RLS) is a sleep disorder characterized by the sudden urge to move the lower limbs during periods of rest accompanied by an unpleasant sensation like tingling or burning in the legs. Often, this urge is partially relieved by the movement of legs. However, it causes disturbance of sleep leading to daytime fatigue. Herein, we present an unusual case of new-onset of restless leg syndrome in a COVID-19 infected patient who presented three weeks after an uncomplicated delivery via caesarean section. The patient was managed with sleep hygiene measures, oral iron and vitamin C tablets apart from general COVID-19 management medications, subsequently leading to significant improvements. Here we have discussed possible associated factors, pathophysiological mechanisms and management of RLS in the case of COVID infected individuals.
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COVID-19/complicações , Síndrome das Pernas Inquietas/terapia , Adulto , Ácido Ascórbico/administração & dosagem , Cesárea , Feminino , Humanos , Compostos de Ferro/administração & dosagem , Gravidez , Síndrome das Pernas Inquietas/virologia , Higiene do SonoRESUMO
Pharyngeal-cervical-brachial (PCB) variant of Guillain-Barré Syndrome (GBS) is characterized by weakness in cervicobrachial and oropharyngeal region, together with areflexia of upper limbs. Being an uncommon variant, it is often misdiagnosed as other neurological conditions resembling GBS. Although most of the cases occur as a post-infectious complication, no reports describing its development following dengue-chikungunya co-infection have been documented. A young female presented with a progressive history of swallowing difficulty, bilateral arm weakness and neck weakness. Three weeks earlier, she was presented with clinical features corresponding to dengue and was symptomatically treated. Currently, hypotonia and decreased muscle strength were observed in both upper limbs and neck. Detailed investigation revealed the presence of Immunoglobulin M (IgM) antibodies against dengue antigen (NS 1) and Chikungunya virus (CHIKV), confirming the possibility of previous dengue-chikungunya co-infection. Nerve conduction studies and electromyography of upper limbs pointed towards findings consistent with the early stages of acute motor demyelinating and possible axonal neuropathy. The detection of antiganglioside antibodies (anti-GT1a antibodies), confirmed the diagnosis of the pharyngeal-cervical-brachial variant of GBS. A five days treatment of intravenous immunoglobulin (IVIG) along with physical rehabilitation was started which led to significant improvement and the patient was discharged after 15 days. PCB is an unfamiliar variant of GBS for many clinicians. Diagnosis can be made by a thorough history, clinical examination and investigations that can rule out other potential causes of cervicobrachial and oropharyngeal weakness. It also necessitates careful monitoring and followups after mono- and co-arboviral infections to prevent any debilitating neurological complications.
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Febre de Chikungunya/complicações , Dengue/complicações , Síndrome de Guillain-Barré/diagnóstico , Adulto , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/terapia , Coinfecção , Dengue/diagnóstico , Dengue/terapia , Feminino , Síndrome de Guillain-Barré/fisiopatologia , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulina M/imunologia , Imunoglobulinas Intravenosas/administração & dosagemRESUMO
The risk of acute respiratory tract infections is particularly pronounced in patients deficient in 25-hydroxyvitamin D (25(OH)D). With respect to COVID-19, there are conflicting evidence on the association of 25(OH)D levels with disease severity. We undertook this study to evaluate the 25(OH)D status in COVID-19 patients admitted in Karachi, Pakistan, and associated vitamin D deficiency with primary outcomes of mortality, length of stay, intubation, and frequency of COVID-19 symptoms. A total of 91 patients were evaluated for 25(OH)D status during their COVID-19 disease course. 25-hydroxyvitamin D levels were classified as deficient (< 10 ng/mL), insufficient (10-30 ng/mL), or sufficient (> 30 ng/mL). The study population comprised 68.1% males (N = 62). The mean age was 52.6 ± 15.7 years. Vitamin D deficiency was significantly associated with intensive care unit (ICU) admission (RR: 3.20; P = 0.048), invasive ventilation (RR: 2.78; P = 0.043), persistent pulmonary infiltrates (RR: 7.58; P < 0.001), and death (RR: 2.98; P < 0.001) on univariate Cox regression. On multivariate Cox regression, only death (RR: 2.13; P = 0.046) and persistent pulmonary infiltrates (RR: 6.78; P = 0.009) remained significant after adjustment for confounding factors. On Kaplan Meier curves, vitamin D deficient patients had persistent pulmonary infiltrates and a greater probability of requiring mechanical ventilation than patients with 25(OH)D ≥ 10 ng/mL. Mechanical ventilation had to be initiated early in the deficient group during the 30-day hospital stay (Chi-square: 4.565, P = 0.033). Patients with 25(OH)D ≥ 10 ng/mL also demonstrated a higher probability of survival than those with 25(OH)D concentrations < 10 ng/mL. 25-hydroxyvitamin D deficient population had longer hospital stays and worse outcomes.
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COVID-19/sangue , Vitamina D/sangue , Adulto , Idoso , Índice de Massa Corporal , COVID-19/complicações , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Paquistão/epidemiologia , Estudos Retrospectivos , Centros de Atenção TerciáriaRESUMO
Introduction Traumatic injury to peripheral nerves is a major medical problem worldwide. Moreover, injury to the hand and wrist can lead to extreme morbidity and disable the injured for life. In this study, we highlight the most commonly damaged nerves and tendons that get ruptured in different types of hand trauma patients. No recent study has been done to document the etiologies and quantify the patterns of nerve and tendon involvement in hand injuries to the best of our knowledge. Methodology This was a cross-sectional study conducted at the largest trauma center in the city and the Plastic and Reconstructive Surgery ward of Civil Hospital, Karachi. A convenient sampling of 200 patients was done with the help of a preformed, well-structured questionnaire. Patients whose hand was injured solely were included in the study and those with the involvement of the whole limb or other parts of the body were excluded. Results We found that most males between the ages of 11 and 20 years presented predominantly with right-hand injury while working with machines. Nerve injury proved to be a rare occurrence. However, combined nerve injury of the ulnar, median, and radial nerve was seen in poly digit trauma. The median nerve was the most commonly damaged nerve in poly digit trauma. Among the tendon injuries, the incidence of combined tendon injury was the greatest. The flexor digitorum superficialis was the most common tendon injured overall. Conclusion This study significantly states that tendons are frequently injured in hand accidents. Plastic surgeons must also be aware of optimal nerve repair and reconstruction techniques to limit the physical disabilities and economic burden arising from nerve injury of the dominant hand.
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Budd-Chiari associated with celiac disease is a rare phenomenon in the medical literature with annual incidence of less than five per million. The majority of the cases are reported from the North African region. Our patient presented in the out-patient department with symptoms of progressive abdominal distension, diffuse abdominal pain and shortness of breath for one year. She was a known case of celiac disease for the last three years. The clinical examination revealed ascites, jaundice, decreased air entry in basal segments bilaterally, and multiple hemangiomas all over the body. Haematological and biochemical investigations, including levels of pro-thrombotic factors and homocysteine level, turned out to be normal. However, computed tomography (CT) revealed hepatic vein obstruction. Hence, a diagnosis of Budd-Chiari syndrome was confirmed. The patient was managed with anticoagulants, diuretics and gluten-free diet. Within a month, the patient showed marked improvement with a significant reduction in ascites. To the best of our knowledge, this rare association is the first case to be reported from Pakistan and third from the region of South Asia.
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Mal de debarquement syndrome (MdDS) is a bizarre sensation of continued movement after the termination of motion. It is accompanied by disequilibrium, usually experienced after voyage or travel, however, it is not associated with vertigo. Although most cases resolve spontaneously, middle-aged women sometimes particularly experience protracted symptoms following an ocean cruise, with the persistence of symptoms for many years. We present the case of a young female with no known comorbidities who was misdiagnosed quite a few times before the actual diagnosis of this rare disease was established.
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Under the banner of cancers of unknown primary origin (CUPs), neuroendocrine tumours account for less than five percent of the neoplasms. The clinical manifestations and management depend upon the tumour's grade and differentiation and its site of growth. At times, despite of aggressive search for primary origin, cancer remains hidden. Herein, we present a case of a middle-aged woman who presented to our tertiary set-up with complaints of abdominal pain and distension. After a series of radiologic and interventional investigations including positron emission tomography with liver biopsy and immunohistochemical analysis, a diagnosis of the welldifferentiated neuroendocrine tumour was made, located in the right lobe of the liver. However, the primary origin could not be identified. The patient was managed with trans-arterial chemoembolization (TACE) followed by hepatic resection and was followed biennially afterwards. In our case, hepatic metastasis was treated with chemoembolization and stagedresection and provided a good prognosis to the patient. Our case is unique as only a few case reports have been published with following presentation and documentation of efficacious treatment is needed to contribute to the literature. Proper trials with exteriorization of bowel and radiological imaging is necessary to stage the primary tumour, even if end result is in vain. This will help to further improve the prognosis.
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Neoplasias Hepáticas , Neoplasias Primárias Desconhecidas , Tumores Neuroendócrinos , Quimioembolização Terapêutica , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologiaRESUMO
BACKGROUND: Stress and burnout have been soaring among doctors. It does not only have deleterious effects during working hours but also impact personal lives of the doctors. The primary focus of this study is to gauge level of burnout among surgical residents working in two major tertiary care hospital of Karachi, Pakistan. METHODS: This was a cross sectional study comprising of 118 candidates who completed the questionnaire based on demographics variables, professional details and Maslach Burnout Inventory (MBI), which scores the burnout level on the basis of three components namely emotional exhaustion, depersonalization and personal accomplishment. The duration of study was one month starting from 1st January to 31st January 2019. Residents working in Department of General Surgery were part of inclusion criteria. Consultants and medical students met the exclusion criteria. Data was analysed by SPSS-23. RESULTS: Mean MBI score was 57.15 with mean scores of Emotional Fatigue, Personal Fulfilment and Depersonalization were 22.42, 19.89 and 14.81 respectively. In terms of emotional fatigue, female residents (49.2%) were more likely to suffer than their male counterpart (50.8%) (p=0.018). Married residents (37.3%) tend to have higher mean personal fulfilment scores (p=0.02). Residents who were living alone (31%) have higher mean depersonalization score (p=0.02). With respect to personal factors, higher MBI scores were observed among doctors who were married, worked about 75-90 hours and remain sleep-deprived and those who were not able to sustain their families financially. CONCLUSIONS: On the basis of higher MBI scores in married, sleep deprived residents who were working for extensive hours and felt financial constraints, there is an extensive need of comprehensive support groups, humane number of working hours, improved salary packages, de-stressing activities like sports etc. to ameliorate the mental health of resident physicians and enhance their productivity.
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Esgotamento Profissional/epidemiologia , Internato e Residência , Cirurgiões , Estudos Transversais , Feminino , Humanos , Masculino , Paquistão , Cirurgiões/educação , Cirurgiões/estatística & dados numéricosRESUMO
Background The prevalence of chronic malnutrition and its associated morbid outcomes has been a significant cause of health loss globally, affecting millions of children hampering their mental, physical, social, and immune system development. World Health Organization's (WHO) recommendations presenting infant feeding guidelines have largely controlled this burden. However, developing countries including Pakistan have failed to promote these guidelines and still succumb to a huge burden of morbidity and mortality secondary to malnourishment among infants. Methodology Our study is a prospective cohort including 300 infants without predisposing congenital anomaly, followed from 6 months to 18 months of age. The primary outcome involved was classifying patients as malnourished based on anthropometric measurements, assessing the prevalence of co-morbidities and comparison of results in compliance with WHO guidelines. Results A total of 276 infants were included and the rest were lost to follow-up. Stratification on socioeconomic status was done; 53% of infants were diagnosed as malnourished, either due to stunted growth, underweight, or both. The odds of development of malnourishment based on non-adherence to WHO guidelines on breastfeeding were 2.87 (p=0.001). The incidence of morbid complications was higher in the malnourished group, including gastrointestinal and respiratory tract infections. Conclusion The implementation of WHO recommendations on infant feeding techniques can prove to be a pivotal instrument to control the soaring index of morbidities and mortalities associated with malnourishment. A strong focus on parental education and awareness among masses is required for its promulgation and controlling the infant health burden linked to this preventable condition.
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Wilkie's syndrome, also commonly known as superior mesenteric artery (SMA) syndrome, is an infrequent and rare cause of small bowel obstruction. It is caused by extrinsic compression of the duodenal segment of the intestine between the aorta and SMA, causing significant post-prandial abdominal pain and vomiting. The literature suggests the incidence of 0.01% to 0.3%. We present here an atypical presentation of SMA syndrome in which a young patient presented to our tertiary set-up with unusually constant abdominal pain and weight loss requiring invasive interventions.
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Paraneoplastic pemphigus (PNP), also known as paraneoplastic autoimmune multisystem syndrome (PAMS), is an autoimmune blistering disorder of the skin associated with various hematological and nonhematological malignancies. In most of the cases, it can be a harbinger of a concealed benign or malignant neoplasm. We report the case of a 23-year-old female patient who presented to the dermatology consult service with a previously known diagnosis of refractory pemphigus vulgaris but she failed to reach remission for her oral and skin lesions on steroid and intravenous immunoglobulin (IVIG). She was later investigated for underlying malignancy as the concern of PNP was raised. She was found to be diagnosed with a pelvic mass which was found to be Castleman's disease. Our patient responded well to surgery and postoperative course of pulsed methylprednisolone and IVIG. Here, we discuss the diagnosis and clinical course of this unique case and strive to create awareness about PNP that can present as a refractory polymorphous blistering dermatological disorder and can hinder the diagnosis and management of patients.